Objective: To explore the severity of loneliness among the elderly in communities in Shanghai, and to identify factors associated with social and emotional loneliness respectively. Methods: A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area, Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021. In Pudong New Area, multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai, while in Huangpu District and Jing'an District convenience sampling was conducted. A total of 635 samples were included in the study. Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales. Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness. Results: Among the 635 participants, only 53 older adults (8.4%)were not lonely. Female (OR=0.46, 95%CI: 0.31-0.70), higher self-efficacy (OR=0.97, 95%CI: 0.94-1.00), more objective social support (OR=0.96, 95%CI: 0.93-0.99) were associated with less severe social loneliness. Meanwhile, higher level of education (secondary education, OR=0.56, 95%CI: 0.34-0.95; college or above, OR=0.30, 95%CI: 0.11-0.83) and higher self-efficacy (OR=0.96, 95%CI: 0.93-0.99) were associated with less severe emotional loneliness, while depression (OR=3.41, 95%CI: 1.76-6.60) and worse social capital (OR=2.02, 95%CI: 1.29-3.16) were associated with more severe emotional loneliness. Conclusion: Up to 91.6% of the elderly in our study sample were moderately lonely or above. The factors associated with social loneliness include self-efficacy, gender and social support. The factors associated with emotional loneliness are self-efficacy, education level, depression, and social capital.

This article introduced the basic theory of quantile regression and its application in medical and public health research for methodological reference. We fit the quantile regression model to cross-sectional data from the National Health and Nutrition Examination Survey to estimate the association between sleep duration and depression levels at different quantiles of depression levels. The method showed that among people with low levels of depression, sleep duration was not significantly associated with depression level. While among people with higher levels of depression, the association of sleep duration with depression level became much more pronounced. The real data analysis shows that quantile regression can provide a comprehensive analysis of association between exposure and continuous outcome, and identify subgroups that are more sensitive to exposure, providing recommendations for targeted interventions. The method showed promising application value in medical and public health research.

Ultrasound measurement of fetal biological parameters is an important indicator for evaluating fetal intrauterine growth and development, and its corresponding fetal growth standards are important criteria for determining whether the measurement parameters are normal or have fetal growth restriction. There are classic regional standards of prenatal ultrasonic measurement that have been used for many years, as well as international standards that have received widespread attention in recent years. However, there is no unified global standard. This paper reviewed the development process and clinical application status of fetal growth standards, explore future research trends, with a view to providing reference value for clinical practice.

This article introduced the basic theory of non-parametric regression and its application in medical and public health research for methodological reference. We conducted Cox proportional hazard models with restricted cubic splines using chronic disease management data from a Center for Disease Control and Prevention. We aimed to explore the separate and combined effects of mean fasting blood glucose level and glucose variability on all-cause mortality among individuals with type 2 diabetes. A non-linear association was observed between glucose variability and the risk of all-cause mortality. The association between glucose variability and all-cause mortality was stronger at higher mean fasting blood glucose levels compared to lower levels. The non-parametric regression methods comprehensively explored dose-response relationships between continuous exposure and outcome, revealing the combined effects of continuous exposures, which provided recommendations for targeted interventions. The method showed promising application value in medical and public health research.

Objective: To investigate the human papillomavirus (HPV) infection and genotype distribution characteristics among male reproductive health outpatients, and to compare the differences among different age groups of outpatients. Methods: A total of 1 658 males, visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022, were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization. Results: Among the 1 658 subjects, the overall HPV infection rate was 22.50%. Single infection accounted for 66.76%, which was the main infection type. HPV infection among different age groups were statistically significant (P < 0.001), with HPV infection of 16.83%, 22.87%, 34.63%, and 29.35% for 18-30, 31-40, 41-50, and ≥51 years, respectively. The top 5 high risk HPV genotypes were HPV52 (3.56%), HPV16 (3.26%), HPV39 (2.41%), HPV51 (2.17%), HPV58 (2.17%), and the top 1 low risk HPV genotype was HPV81 (2.90%). The proportions of infected individuals in this study that could be completely covered by bivalent, quadrivalent, and nine-valent HPV vaccines were 7.77%, 12.33%, and 26.27%, respectively. Conclusion: The predominant infection type among male reproductive health outpatients was single infection type. HPV 52, 16, 39, 51 and 58 were the most common high risk genotypes, while HPV 81 was the most common low risk genotype. Individuals aged 41-50 years had the highest HPV infection rate.

Objective: By analyzing relevant literature of long COVID, we aimed to understand the current research status, hotspots and trends in this field. Methods: Based on Web of Science core collection data, bibliometric analysis was used as the main research method. The results were visualized with VOSviewer. A comprehensive analysis was performed from various perspectives including trends in publication, journal distribution, highly cited papers, international research collaboration networks, and clusters of keywords, etc. Results: The field of long COVID has garnered significant global academic attention. A total of 7 877 related articles were retrievable, with a total citation count of 103 389 and an average citation count of 13.13 per article. Among them, the United States published the most articles (1 780 articles, 22.59%), while China ranked fifth in publication volume (686 articles, 8.71%). The international scientific cooperation network reflected the close collaborative relationships between countries in long COVID research, predominantly involving the United States, the United Kingdom, Italy, India, and China. Keywords clustering indicated that the current main research focuses in the long COVID field include: clinical manifestations, epidemiological characteristics, risk factors, and mechanisms of occurrence, treatment and rehabilitation measures of long COVID, and its impact on public and social life. Conclusion: This article reveals the current state, research hotspots and trends in the long COVID field, providing valuable references for related research institutions, scholars as well as health administrative office.

Objective: To compare the performance of machine learning (ML) and individualized treatment effect (ITE) models based on deep learning in providing personalized treatment recommendations using real-world clinical datasets, and construct personalized drug treatment recommendation models for pegylated liposomal doxorubicin (PLD) and epirubicin (EPI) in postoperative breast cancer patients, and assist clinical decision-making by evaluating the treatment effects of these drugs. Methods: Clinical data of 904 breast cancer patients admitted at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine was collected retrospectively, including 387 cases treated with PLD and 517 cases treated with EPI. The two groups were compared using propensity score matching to assess the 5-year disease free survival (DFS) outcome. Six ITE models, including CFR_WASS, were used to predict the 5-year DFS probability of patients under two drug treatments. Six machine learning (ML) models, including Random Forest, were used as baselines for performance analysis and comparison. Model's Predictive performance was evaluated based on the AUROC. The effectiveness of treatment recommendations was assessed by calculating the difference of 5-year rates between the group where the actual treatment used was consistent with the treatment recommended by the model and the control group. Results: Among the 153 matched cases, there was no statistically significant difference in 5-year DFS outcomes between the two groups. In 16 pairs of cases, the PLD group showed better clinical outcomes than the EPI group, and in 12 pairs of cases, the EPI group had better clinical outcomes than the PLD group, confirming individual differences in treatment benefit between the two drugs. The CFR_WASS model achieved the optimal predictive performance (AUROC value was 0.736 8), and there was no significant difference in 5-year DFS rates between most ML groups and the control group; The 5-year DFS rate in the ITE group was lower than that in the control group (P < 0.01), showing significant differences. Among them, the 5-year DFS rate in the CFR_WASS group was 2.13% lower than that in the control group. Conclusion: The ITE model is more accurate in estimating the individualized treatment effects of two drugs compared to the ordinary ML model, providing effective individualized treatment recommendations, and has certain clinical application value.

Propensity score weighting methods are crucial tools for adjusting confounding and conducting causal inference in observational studies. This paper introduces various propensity score weighting methods, and details the key features of each to aid researchers in selecting the most suitable method for their analyses. Additionally, the application of these methods in the fields of medicine and public health is demonstrated through an example data analysis. The example is based on data from 996 patients who underwent percutaneous coronary intervention (PCI). Different propensity score weighting methods are used to explore the effect of PCI combined with abciximab on six-month post-operative survival rates. The results indicate that different propensity score weighting methods provide treatment effect estimates tailored to different inference goals, highlighting the importance of selecting the appropriate method based on the specific inference objective. Propensity score weighting methods enhance the balance of covariate distribution between treatment and control groups, making them powerful tools for adjusting confounding factors in observational studies. Their applicability and value in medical and public health research are significant.

Objective: To explore the relationship and internal path between activities of daily living (ADL), sleep quality and mental health of community elderly people in Shanghai. Methods: A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec, 2021 using convenience sampling. Activities of Daily Living (ADL), Pittsburgh Sleep Quality Index (PSQI) and 10-item Kessler Psychological Distress Scale (K10) were adopted in the survey. Single factor analysis, correlation analysis and multiple linear regression were used to analyze the data. The effect relationship between the variables was tested using Bootstrap's mediated effects test. Results: A total of 1 864 participants were included in the study. The average score was 15.53±4.47 for ADL, 5.60±3.71 for PSQI and 15.50±6.28 for K10. The rate of ADL impairment, poor sleep quality, poor and very poor mental health of the elderly were 23.6%, 27.3%, 11.9% and 4.9%, respectively. ADL and sleep quality were all positively correlated with mental health(r=0.321, P < 0.001; r=0.466, P < 0.001); ADL was positively correlated with sleep quality(r=0.294, P < 0.001). Multiple linear results of factors influencing mental health showed that ADL (β=0.457, 95%CI: 0.341-0.573), sleep quality(β=0.667, 95%CI: 0.598-0.737) and mental health were positively correlated (P < 0.001). Sleep quality partially mediated the relationship between ADL and mental health (95%CI: 0.078-0.124) with an effect size of 33.0%. Conclusion: Sleep quality is a mediator between ADL and mental health among community elderly people. Improving ADL and sleep quality may improve mental health in the population.

Objective: To evaluate the patient-reported outcome (PRO) of patients with breast cancer who underwent autologous breast reconstruction and implant breast reconstruction. Methods: Patients who underwent breast reconstruction in Shanghai Cancer Center, Fudan University from Jan 2020 to Jun 2021 were selected, including 111 patients who underwent autologous breast reconstruction and 108 patients who underwent implant breast reconstruction. Chinese version Breast-Q2.0 scale, breast cancer specificity scale QLQ-BR23 and EORTC quality of life scale QLQ-C30 were used to investigate the PRO of the two groups 18 months after operation. Results: The rate of stage Ⅲ breast cancer in the self-weight construction group was higher than that in the implant reconstruction group (64.9% vs. 44.4%, P < 0.001). The preoperative neoadjuvant therapy and postoperative radiotherapy in the autologous reconstruction group were higher than those in the implant reconstruction group (P < 0.001). Postoperative chemotherapy and endocrine therapy in the autologous reconstruction group were lower than those in the implant reconstruction group (P < 0.001). The study based on Breast-Q scale showed that the breast satisfaction of autologous reconstruction group was higher than that of implant reconstruction (59.28±17.20 vs. 54.94±14.48, P < 0.05). The study based on QLQ-BR23 showed that the self-weight construction group was higher than the implant reconstruction group in the field of arm symptoms (20.02±20.80 vs. 12.65±16.18, P < 0.05). The study based on QLQ-C30 scale showed that there was no significant difference in all functional areas and symptom areas of patients. There was no significant difference in the number and time of social regression between the two groups. Conclusion: Breast reconstruction can improve the PRO of breast cancer patients, and oncology factors will affect the choice of breast reconstruction. Patients with autologous breast reconstruction are more satisfied with breast appearance, but upper limb symptoms such as swelling and pain are more obvious than implant reconstruction, which is related to the higher proportion of axillary lymph node dissection in patients with autologous reconstruction.There is no significant difference in quality of life and social regression between the two groups.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis (NASH). NASH is characterized by persistent liver damage, inflammation, and fibrosis which significantly increases the risk of end-stage liver diseases, such as liver cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD/NASH is not yet fully understood, but its recent epigenetic advances have provided new insights into the mechanisms of this disease. This review summarized recent progress in this area which has laid a solid foundation for elucidating the pathogenesis of NAFLD and provides potential targets for early detection, diagnosis, and treatment of this disease.

Since the World Health Organization (WHO) officially announced COVID-19 as a global pandemic in 2020, 114 countries or regions in the world have been affected to varying degrees. The arrival of the post-epidemic era requires countries to take new epidemic prevention and control measures to deal with the problems and challenges that may arise in the future. In order to help China consolidate its epidemic prevention achievements over the years and gain a larger development window in the post-epidemic era, this study explored the changes in the global epidemic situation and the major national prevention and control policies in different countries, summarized the development and changes of China's epidemic prevention and control policies, and proposed new family-centered precision prevention and control measures that adapt to China's national conditions.

This paper briefly introduced the varying coefficient model and used the varying coefficient Cox model as an example to demonstrate its application in the fields of medicine and public health through real data analysis, thereby provided methodological references for related research. The example was based on chronic disease management data from a Center for Disease Control and Prevention, fitting a varying coefficient Cox model to explore the time-varying association between body mass index (BMI) and mortality risk among a hypertensive population. The results showed that being underweight (BMI < 18.5 kg/m²) was associated with a higher risk of mortality, but this association weakened over time; being overweight (23 kg/m²≤BMI < 25 kg/m²) was associated with a lower risk of mortality, and this association also weakened over time. The varying coefficient model captured how the impact of exposure factors on outcomes changed with other variables, helping to comprehensively understand the complex relationships between variables, and had significant application and promotion value in medical and public health research.

Objective: To analyze the combined effect of body mass index (BMI) and age with cancer occurrence among a hypertensive population in Minhang District, Shanghai. Methods: Participants of this study were 212 394 hypertensive patients without cancer in Minhang District, Shanghai, registered in the electronic health information system from 2007 to 2015. Age and BMI were included as smoothing functions in the generalized additive Cox proportional risk model. The bivariate response model was constructed to visualize results using surface plots and to comprehensively analyze the association of BMI and age with the risk of cancer occurrence. Results: A total of 22 141 participants developed cancer by Dec 31, 2018. The association between age and the risk of cancer incidence showed an overall linear trend while the association between BMI and the risk of cancer incidence showed an overall "U" shape. BMI at about 26 kg/m² showed the lowest risk of cancer incidence. The risk of cancer occurrence increased with increasing age in people with different BMIs. The associations between BMI and the risk of cancer incidence were different at different age groups: there was no significant association between BMI and the risk of cancer incidence in the young people (20-44 years). While in the middle-aged and older people aged over 45 years, BMI was associated with the risk of cancer incidence in a "U" shape. The lowest risk of cancer incidence was around the BMI of 26 kg/m². Conclusion: BMI among the population with hypertension should be controlled in a reasonable range, especially in the middle-aged and older population, to prevent cancer occurrence.

Objective: To explore the operation effect of the improved full-appointment mode of ambulatory chemotherapy, so as to provide reference for further improving the treatment process. Methods: The enhanced full-appointment mode had been implemented in Fudan University Shanghai Cancer Center outpatient information system, which seamlessly integrated daytime chemotherapy assessment with comprehensive information management, formulated precise rules for chemotherapy appointments, and ensured efficient integration of relevant data.A comparative analysis was conducted between the period after optimization (Jan to Sep 2022) and the corresponding period in the previous year (Jan to Sep 2021), considering factors such as patient waiting time, human involvement, patient safety during chemotherapy, as well as nurse and patient satisfaction. Results: After optimization, the time spent by patients was reduced from 52.12 (32.73-83.05) to 20.04 (11.87-41.10) minutes, with statistically significant difference (z=-78.144, P < 0.001). Additionally, the time spent by patients before and after optimization was significantly different in the distribution of < 30 minutes, 30-60 minutes, and > 60 minutes (χ²=5 958.455, P < 0.001). Previously, one nurse and 2-3 security personnel were required to schedule appointments in the daytime chemotherapy center, while after optimization, there was no longer a need for nurses to arrange appointment windows and the number of security personnel was reduced to one, thereby optimized human operations. It was observed that the number of cases involving chemotherapy infusion reactions decreased from 59 to 46 following optimization, and the number of patients requiring rescue observation reduced from four to one. Notably, no rescue events occurred during non-day shifts, thus enhanced patient safety during treatment hours outside regular working hours. Furthermore, there was a statistically significant improvement in both nurses' and patients' satisfaction levels before and after implementation of these optimizations (P < 0.05). Conclusion: The modified full appointment mode reduced patient waiting time, optimized human resources utilization, enhanced patient safety during chemotherapy, and improved satisfaction levels among both nurses and patients. The implementation of the modified full appointment mode for daytime chemotherapy centers was beneficial to their overall operation.

Objective: To observe the effect of esketamine on postoperative recovery in children after endoscopic adenoidectomy. Methods: Sixty pediatric patients who underwent adenoidectomy with endoscope from Jan 2022 to Jan 2023 in Eye & ENT Hospital, Fudan University were enrolled. The pediatric patients were randomly divided into hydro-morphine group(n=30)and esketamine group(n=30). Anesthesia induction: lidocaine 1.5 mg/kg, propofol 2.5 mg/kg and remifentanil 4 μg/kg were injected intravenously, and then the endotracheal tube was used for airway management. Anesthesia maintenance: remifentanil infusion was at 0.2-0.5 μg·kg^-1·min^-1 and the end tidal concentration of sevoflurane was at 0.7-1.0 minimum alveolar concentration (MAC). At the end of surgery, either hydromorphone 0.01 mg/kg or esketamine 0.5 mg/kg were administered for postoperative pain control. Time to resume spontaneous breathing was recorded. Other parameters included respiratory rate per minute, duration of stay in the post-anesthesia care unit, hemodynamic profiles. The adverse events including agitation and desaturation were also of note. Results: Children in esketamine group resumed spontaneous breathing faster (P=0.048), had faster respiratory rate when recovery of spontaneous breathing (P=0.001) and lower concentration of end tidal CO₂ (P=0.005). The findings suggested that esketamine did not impair respiratory function. Compared to hydro-morphine group, children in esketamine group had shorter stay in the post-anesthesia care unit with statistical difference (P=0.020). Esketamine had no effect on heart rate and blood pressure, so there were less adverse events. Conclusion: Compared with 0.01 mg/kg hydro-morphine, 0.5 mg/kg esketamine does not impair respiratory function and it facilitate fast recovery in children undergoing endoscopic adenoidectomy after general anesthesia.

Objective: To investigate the expression and clinical relevance of heterogeneous nuclear ribonucleoproteins F (HNRNPF) in prostate cancer and its effect on the proliferation, migration and invasion of prostate cancer cells. Methods: The expression and immune infiltration characteristics of HNRNPF in prostate cancer and its correlation with the clinicopathological characteristics of prostate cancer patients were analyzed using TCGA database and GEO database. The HNRNPF gene was silenced by RNA interference in prostate cancer cell PC-3 and DU145, then the changes in cell proliferation ability was detected by CCK-8, EdU and colony formation assays, and the changes in cell migration and invasion abilities were detected by Transwell and wound-healing assays. Results: The expression of HNRNPF was significantly increased in prostate cancer compared with normal prostate tissue and significantly associated with T stage, Gleason score, prostate specific antigen and the infiltration level of multiple immune cells of prostate cancer patients. The prostate cancer patients with high expression of HNRNPF had shorter overall survival and disease-specific survival. HNRNPF silencing decreased the proliferation, migration, and invasion abilities of prostate cancer cells PC-3 and DU145. Conclusion: HNRNPF is a gene that is highly expressed in prostate cancer, has significant clinical relevance, and can promote the proliferation, migration, and invasion of prostate cancer cells.

Objective: To study and verify the function of de novo interferon regulatory factor (IRF8) frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level. Methods: The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells, or packed into lentivirus to infect two kinds of immune cell lines. Q-PCR, Western blot, immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation. Results: The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully, and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well. Compared with wildtype, the molecular weight of IRF8 variant was slightly increased, while the expression level presents in opposition, even if on transcription level. Moreover, the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm, and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein. Conclusion: The de novo frameshift mutation was presumed as gain-of-function (GOF) mutation.

Cantharidin is a terpenoid compound secreted by Mylabrisphalerata Pallas. In a variety of cancer types, cantharidin has shown the effects of inhibiting cancer cell growth, proliferation and migration. The anticancer mechanism of cantharidin involves inducing cell cycle arrest and apoptosis, inhibiting autophagy, enhancing DNA damage, inhibiting DNA repair, and regulating various cell signaling pathways. This article reviews the mechanism and research progress of cantharidin and its derivatives in common cancer types, in order to identify novel targets of cancer treatment using cantharidin, and provide new direction for clinical research to improve anticancer therapy.

Objective: To investigate the contribution of microglia in the basolateral amygdala (BLA) to pain hypersensitivity and pain-related aversion in knee-joint monoarthritis mice. Methods: A total of 61 mice were used for behavioral tests (14 mice in the control group and 47 mice in the model group), and other 6 mice were used for cell morphology (3 mice in each group). An animal model of knee-joint monoarthritis was established by injection of complete Freund's adjuvant (CFA) into the knee-joint cavity of mice. The von Frey and Hargreaves tests were used to examine mechanical allodynia and thermal hyperalgesia in mice, respectively. The place escape/avoidance paradigm test was used to examine pain-related aversion. Open field test and elevated plus maze test were used to examine anxiety-like behaviors in mice. Morphological changes of microglia in the BLA area after CFA injection were assessed by 3D reconstruction of microglia in the BLA brain region using immunofluorescence staining and Imaris software. Results: Compared with the control group, CFA-arthritic mice produced significant mechanical and thermal hyperalgesia in the ipsilateral hindpaw and maintained for at least 12 and 19 days, respectively. Meanwhile, CFA injection induced pain-related aversion and anxiety-like behaviors in mice, accompanied by significant activation of BLA microglia. Inhibition of BLA microglia activation alleviated CFA-induced hyperalgesia and aversive behaviors but had no significant effects on anxiety-like behaviors. Conclusion: CFA-arthritic mice produce hyperalgesia, pain-related aversion, and anxious behavior, in which hyperalgesia and pain-related aversion may be mediated by the activation of microglia in BLA.

Objective: To obtain guiding recommendations for the development of fertility preservation in female patients of reproductive age, so as to promote the scientific, standardized and orderly implementation of fertility preservation work. Methods: A previous questionnaire survey was used to determine the preliminary recommendations, a modified Delphi method was used to invite 18 domestic experts of fertility preservation to conduct two rounds of expert consultation. Then we adjusted and summarized recommendations according to the results of the consultation. Results: Finally, 14 guiding recommendations for the development of fertility preservation in female patients of reproductive age were obtained according to the results of the Delphi consultation, including 5 recommendations at technical level, 5 recommendations at political level and 4 recommendations at educational level. At technical level, it was proposed to establish a standardized operation process; at political level, it was proposed to improve the relevant legislation of fertility preservation in China to protect the safety and interests of patients; at educational level, it was suggested to take various forms to promote the mass dissemination of fertility preservation knowledge. Conclusion: Guiding recommendations for fertility preservation in female patients of reproductive age can provide detailed and comprehensive guidance for promoting fertility preservation in female patients of reproductive age in Shanghai, and provide reference for carrying out fertility preservation in other regions.

Objective: To investigate deep neuromuscular blockade (NMD) and moderate NMD on hepatic perfusion and liver function during laparoscopic hepatectomy. Methods: A total of 60 patients who received laparoscopic hepatectomy in Fudan University Shanghai Cancer Center were recruited from Dec 2021 to Dec 2022. They were randomly divided into two groups: deep NMD group (D group, n=30) and moderate NMD group (M group, n=30). D group was induced by administration of rocuronium 0.9 mg/kg followed by continuous infusion to maintain intraoperative post-tetanic count (PTC) of 1-2, while M group was induced by administration of rocuronium 0.6 mg/kg followed by continuous infusion to maintain intraoperative train-of-four (TOF) of 1-2. Indocyanine green (ICG) of 0.25 mg/kg was given intravenously both after induction and after specimen excision, and retention rate at fifteen minutes (ICG_R15) was recorded. In addition, intraoperative rocuronium dosage, surgical operation satisfaction score, postoperative shoulder pain, and the occurrence of vomiting on postoperative day 1 (POD1) were also recorded. Results: Compared with M group, the dosage of rocuronium in D group was significantly increased (P < 0.01), but there was no difference of ICG_R15 between the two groups (P=0.581), even other parameters of perioperative liver function. The surgical operation satisfaction score was significantly higher (P < 0.05), while the postoperative shoulder pain (P=0.037, OR=1.37, 95%CI: 1.01-1.86) and the occurrence of vomiting on POD1 (P=0.017, OR=1.64, 95%CI: 1.07-2.53) were significantly lower in D group than those in M group. Conclusion: Compared with moderate NMB, deep NMB can significantly improve surgery condition, reduce postoperative shoulder pain and vomiting. However, there was no significant difference between them on the hepatic perfusion and perioperative liver function.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a very rare malignant tumor that is considered to be associated with Epstein-Barr virus. Two patients in this report were generally healthy, and the spleen tumor was found during physical examination. After completing the examination, laparoscopic total splenectomy was performed, and the pathological result showed IPT-like FDCS. Postoperative chemoradiotherapy was not performed in either case. The disease has no characteristic clinical manifestations, and imaging overlaps with sarcoma. Microscopic manifestation showed CD21, CD23 and EBER positive spindle tumor cells in the inflammatory background with matted arrangement. Due to the interwoven distribution of tumor cells and lymphocytes, diagnosis is difficult. In this article, we report this two cases with literature review and summarize their clinical and pathological features to improve diagnostic cognition.

Objective: To analyze the budget impact of a price increase for carotid endarterectomy (CEA) on the total expenditure of health insurance expenditure in China. Methods: We set 2021 as the base year, and 2022-2026 as the study years. A budget impact analysis model was developed to calculate the expenditure of health insurance funds over the next 5 years following a 30% price increase for carotid endarterectomy. Data on the target population, treatment costs, and market share changes both nationwide and in four sample cities were used. The data was collected in May to Jul 2022. Results: The price increase for carotid endarterectomy will reduce total health insurance fund expenditures nationwide by 143.176 2 million yuan over five years. Total health insurance fund expenditures in the sample cities will also decrease to varying degrees. The higher the price increase for the surgical procedure, the greater the decrease in total expenditure of the health insurance fund. The market share of the surgical procedure has the greatest impact on the total expenditure of the health insurance fund. Conclusion: Increasing the price of carotid endarterectomy may lead to increase in its market share and decline in the health insurance fund expenditures in future five years.

Objective: To investigate the role of the TNFRSF12A molecule in the pathogenesis of liver cancer. Methods: Through comprehensive analysis of the Cancer Genome Atlas Program (TCGA) database and single-cell sequencing data, we studied the expression of TNFRSF12A in liver cancer and its correlation with prognosis. HPA database was utilized to analyze the subcellular localization of TNFRSF12A, and GO and KEGG analyses were performed by DAVID. TIME 2.0 was employed to analyze the correlation between TNFRSF12A and immune cell infiltration in liver cancer tissues. Results: TNFRSF12A was found to be highly expressed in liver cancer tissues, significantly correlating with patient survival prognosis (OS: HR=1.61, P=0.007 0; RFS: HR=1.45, P=0.037 0;PFS: HR=1.30, P=0.099 0; DSS: HR=1.67, P=0.027 0), as well as age (P=0.046 7) and BCLC stage (P=0.045 6). TNFRSF12A co-expressed with tumor stem cell markers (CD24, SOX4, ANPEP), indicating a strong link to malignancy. Furthermore, molecular functional analysis unveiled that IL-2R primarily existed in the cell cytoplasm and played a role in processes such as cell apoptosis, invasion, and protein binding. Moreover, TNFRSF12A was associated with Treg cells and immune cell infiltration, further suggesting its role in tumor immune regulation. Conclusion: TNFRSF12A exhibits a significant elevation within liver tumors and shows a notable correlation with patients' prognosis. Tumor cells engage in interactions with cytokines produced by Tregs, thereby reshaping the tumor microenvironment. The potential clinical significance of TNFRSF12A as a prognostic marker for tumors holds promise in offering novel avenues for personalized treatment and prognosis prediction.

Objective: To compare the clinical characteristics, peripheral blood inflammatory cells and levels of oxidative stress indicators between severe asthma and non-severe asthma patients, analyze the effects of neutrophils and oxidative stress molecules on the severity of asthma, and build a biological model for early prediction of severe asthma. Methods: From Aug 2018 to Jul 2019, 67 adult patients with stable asthma in our hospital were enrolled in this study. The clinical characteristics, peripheral blood inflammatory cells and levels of oxidative stress indicators of severe asthma group and non-severe asthma group were compared. Single factor Logistic regression analysis was conducted on severe asthma to screen out the most important five variables. Multifactor Logistic regression analysis was further conducted to establish a prediction model for severe asthma. Results: There were 25 severe asthma patients in this cohort, who had a longer course of disease, more frequent acute attacks, poorer asthma control, higher peripheral neutrophils, more severe obstructive ventilation dysfunction, lower myeloperoxidase (MPO) level and higher superoxide dismutase (SOD) than non-severe asthma patients. The patients with higher peripheral blood neutrophil count or proportion were more likely to show severe asthma, more frequent acute attacks, and more obvious reduction of pulmonary ventilation function. A panel of biomarkers, centered on peripheral blood neutrophil count and oxidative stress indicators SOD, human 8-epi-prostaglandin F2α (8-iso-PGF2α), could build a model to predict severe asthma. Conclusion: There are significant differences in clinical characteristics, peripheral blood inflammatory cells, and oxidative stress index levels between severe asthma patients and non-severe asthma patients. In stable asthma patients, levels of neutrophils and oxidative stress indicators such as SOD had an impact on the severity of asthma. The prediction model of severe asthma established on this basis provides a new idea for early recognition of severe asthma.

Objective: To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants. Methods: A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study. Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing, and the relationship between germline variants and clinical factors such as age of onset, family history and personal history was analyzed. Results: The rate of germline P/LP variants was 6.3% in unselected pancreatic cancer patients, but was high as 17.1% in genetic high-risk group patients (those with a family or personal history of cancer, or early-onset). Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2, BRCA2, and ATM. Conclusion: The rate of germline variants in overall pancreatic cancer patients is not high, but it increases significantly in genetic high-risk group, proving the importance of clinical factors in the screening of hereditary pancreatic cancer.

Objective: To explore the relationship between the types of bicuspid aortic valves (BAV) and the outcome of functional mitral regurgitation (FMR) and the affecting factors of FMR. Methods: From Jun 2018 to Sep 2022, patients with severe BAV aortic valve stenosis (AS) complicated with FMR underwent post transcatheter aortic valve replacement (TAVR) in Zhongshan Hospital, Fudan University were retrospectively analyzed. The baseline information and imaging data of different BAV patients were collected. Logistic regression was used to analyze the factors affecting the outcome of FMR (improvement and non-improvement). Result: A total of 100 patients with TAVR were included, including 49 patients with type 0 of BAV and 51 patients with type 1 of BAV. Compared with patients of type 1, patients of type 0 had younger age [(72.78±6.09)y vs. (77.00±8.35)y, P=0.050], lower male ratio (47% vs. 73%, P=0.009) higher BMI [(23.19±2.62)kg/m² vs. (21.99±3.13)kg/m², P=0.041], and lower incidence of aortic regurgitation (69% vs. 92%, P=0.040). Compared with the non-improvement group, the improvement group had a lower incidence of coronary heart disease (5% vs.18%, P=0.042), higher incidence of pulmonary hypertension (20% vs. 2%, P=0.007), larger left ventricular diastolic diameter [(51.98±6.74) mm vs.(48.04±7.72) mm, P=0.009] and higher maximum flow velocity [(4.86±0.95) cm/s vs.(4.47±0.75) cm/s, P= 0.023] of the aortic valve. The results of Logistic regression analysis showed that preoperative pulmonary hypertension, left ventricular end-diastolic diameter and maximum valvular flow velocity of BAV patients were the potential affecting factors of FMR improvement after TAVR. Conclusion: No significant difference was found in FMR improvement between BAV patients of type 0 and type 1 after TAVR. For BAV patients with AS, preoperative pulmonary hypertension, larger left ventricular end-diastolic diameter, and faster aortic valve flow velocity were associated with higher FMR improvement rate.

Objective: To retrospectively investigate the efficacy of pelvic floor muscle training (PFMT) using APP-based home device in the real-world scenario. Methods: A retrospective survey was conducted among 171 000 Chinese female users over 18 years old who freely registered APP and performed PFMT using a domestic manufactured home device from Oct 1, 2019 to Mar 31, 2021. The Patient Global Impression of Improvement (PGI-I) questionnaires concerning pelvic floor general condition, sexual satisfaction and other three major symptoms related to pelvic floor muscle laxity such as stress urinary incontinence (SUI), pelvic organ prolapse (POP), and vaginal laxity (VL) were broadcast public online for users to self-assess the improvement. The vaginal muscle strength values prior and post training recorded by APP were also reported. All data were collected anonymously for further stratified analysis. Results: A total of 984 valid questionnaires were collected by systematic sampling. The PGI-I scores of pelvic floor general condition (P=0.000 1), sexual satisfaction (P=0.009), SUI (P=0.000 1), POP (P=0.044) and VL (P=0.034) were statistically significant in users who reported to use the device for 3 months or more compared with those less than 3 months. In addition, the increase of vaginal muscle strength was related to the improvement of PGI-I scores in SUI and POP with statistical significance. There were no significant difference in subgroups such as age, education, parity, and delivery mode. Conclusion: The subjective benefit of pelvic floor function-related symptoms and the improvement of vaginal muscle strength could be observed after PFMT for three months or more using APP-based home device in Chinese women in the real-world scenario.

Objective: To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique. Methods: A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital, Fudan University was used to assess the size (length, width, and area) and morphology (sphericity index, i.e., the ratio of length to width) of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique. Repeated inter- and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients (ICCs). Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses. Results: The inter- and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980. Fetal four-chamber view and ventricular size increased with gestational week (all P < 0.001), the end-diastolic length of the left ventricle was larger than that of the right ventricle, and the end-diastolic diameter was smaller than that of the right ventricle (both P < 0.001), while there was no significant difference in the end-diastolic area of the two ventricles (P=0.050). The spherical index of four-chamber view did not correlate with gestational week (P=0.811). The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle, and the sphericity index of the apical segment was less than that of the right ventricle, the differences were statistically significant (all P < 0.01). Conclusion: The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility. The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.

Objective: To study the effect of drinking carbohydrate drinks before cesarean section on mothers and neonates, and to explore the application value of drinking carbohydrate drinks before cesarean section. Methods: The clinical data of 206 singleton women who underwent selective cesarean section in Obstetrics and Gynecology Hospital, Fudan University from Jun 2020 to Jun 2021 were retrospectively studied. Patients were divided into enhanced recovery after delivery (ERAD)group and control group according to whether drinking carbohydrate drinks before cesarean section. A retrospective cohort study was conducted to analyze the effect of preoperative carb drinks on preoperative fluid supplementation, postoperative rehabilitation and neonatal prognosis. Results: Among patients who fasted for less than 12 hours, the ERAD group had a lower fluid supplementation rate and a smaller average fluid supplementation volume compared to the control group (P < 0.05). The ERAD group had a lower rate of prokinetic agent using after surgery (P < 0.05). Among women without a history of abdominal surgery, the ERAD group had less blood loss 24 hours after surgery (P < 0.05). There were no significant differences in postoperative fever rate, incidence of nausea and vomiting, time of first flatus, neonatal apgar score, exit observation room neonatal blood, and neonatal neonatal intensive care unit (NICU) admission rate between the two groups. Among newborns with high-risk factors for hypoglycemia, the ERAD group had lower enter observation room neonatal blood compared to the control group, and a higher incidence of hypoglycemia (P < 0.05). Conclusion: Oral intake of carbohydrate drinks before cesarean section may be beneficial in reducing fluid supplementation before elective cesarean section, promoting postoperative gastrointestinal function recovery, and reducing postoperative bleeding. However, it may be related to the occurrence of neonatal hypoglycemia.

Objective: To investigate the imaging features of intestinal schwannoma (IS) in order to improve the diagnostic ability of the disease. Methods: The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed, including the location, size, morphology, nature, growth pattern, CT density, MRI signal, PET/CT metabolism and other characteristics of the tumors. Results: Of the 14 IS cases, the lesions of 3 cases were located in the duodenum, 2 cases in the cecum, 8 cases in the colon and 1 case in the rectum. The lesions were all round or oval, with an average maximum diameter of (2.4±1.1) cm. The lesions were solid in 13 cases, extraluminal growth in 10 cases, cystic degeneration in 1 case and myxoid degeneration in 1 case. Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases, and the short diameter of lymph nodes was greater than 5 mm in 6 cases. All 14 cases of IS showed low attenuation on plain CT scan, and progressive enhancement after contrast injection, including 1 case of mild enhancement, 2 cases of moderate enhancement, and 11 cases of obvious enhancement. Two cases of IS showed low signal intensity on T1WI, slightly high signal intensity on T2WI, significantly high signal intensity on DWI, and obvious progressive enhancement after contrast injection on MRI. Two cases of IS showed high metabolism on ¹⁸F-FDG-PET/CT, and the SUVmax was 9.4 and 8.8, respectively. Conclusion: The imaging findings of IS were characteristic to a certain extent. They mainly manifested as solid nodules or masses derived from the intestinal submucosa, with uniform attenuation or signal intensity, obvious progressive enhancement after contrast injection, obvious hypermetabolism on ¹⁸F-FDG-PET/CT, and slightly larger homogeneous lymph nodes were common around the lesions.

Objective: To investigate the relationship between triglyceride-gluscose (TyG) index in early pregnancy and the delivery of small for gestational age infant (SGA) in patients with gestational diabetes mellitus (GDM). Methods: A total of 1 532 pregnant women from Shanghai Fifth People's Hospital and the Second People's Hospital of Kashgar Region, who were enrolled in the study between Jan 2018 and Jun 2023 and met the inclusion criteria, were categorized into the group with GDM (754 cases) and the group without GDM (778 cases) based on the results of the oral glucose tolerance test (OGTT) conducted at 24-28 weeks of pregnancy. Within the GDM group, patients were further categorized into 3 groups based on neonatal weight: SGA group, large for gestational age infant (LGA) group, and appropriate for gestational age infant (AGA) group. A Logistic regression model was used to analyze the independent influences on SGA delivery in patients with GDM to analyze the correlation between the TyG index and the occurrence of SGA. The predictive value of the TyG index in early pregnancy for SGA delivery in GDM patients was analyzed using ROC curves. Results: The TyG index in the SGA group of GDM patients was significantly lower than that in the LGA, AGA and control without GDM group (P < 0.05). Multifactorial logistic regression analysis revealed that the TyG index was independently correlated with the SGA in GDM patients (P < 0.05). The ROC curve analysis demonstrated a good predictive value of the TyG index in early gestation for SGA delivery in GDM patients (AUC=0.821, 95% CI: 0.763-0.879, P < 0.001). Conclusion: The TyG index in early pregnancy among GDM patients is independently correlated with the occurrence of SGA infants and has a good predictive value for SGA delivery in GDM patients.

Objective: To achieve automatic segmentation of cell nuclei in gastrointestinal cancer pathological images by using a deep learning algorithm, so as to assist in the quantitative analysis of subsequent pathological images. Methods: A total of 59 patients with gastrointestinal cancer treated in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from Jan 2022 to Feb 2022, were selected as the research objects. Python and LabelMe were used for data anonymization, image segmentation, and region of interest annotation of patients' pathological images. A total of 944 pathological images were included, and 9 703 nuclei were annotated. Then, a new semantic segmentation model based on deep learning was constructed. The model introduced deformable attention transformer (DAT) to realize automatic, accurate and efficient segmentation of pathological image nuclei. Finally, multiple segmentation evaluation criteria are used to evaluate the model's performance. Results: The mean absolute error of the segmentation results of the model proposed in this paper was 0.112 6, and the dice coefficient (Dice) was 0.721 5. Its effect was significantly better than the U-net baseline model, and it was ahead of models such as ResU-net++, R2Unet and R2AttUnet. Moreover, the segmentation results were relatively stable with good generalization. Conclusion: The segmentation model established in this study can accurately identify and segment the nuclei in the pathological images, with good robustness and generalization, which is helpful to play an auxiliary diagnostic role in practical applications.

HHIP gene encoded human hedgehog-interacting protein, locating on chromosome 4q31.21-31.3. As an endogenous antagonist of Hedgehog (Hh) signaling pathway, HHIP inhibits the activation of Hh signaling pathway. In human cancers, the Hh signaling pathway has always been abnormally activated, and HHIP expression is generally down-regulated in most types of tumor tissues. The expression level of HHIP is positively correlated with overall survival of tumor patients, which is expected to be used as an independent prognostic marker. This review focused on the progress of HHIP research regarding its biological function, mechanism, and clinical value in tumor.

Glomerulocystic kidney disease (GCKD), a rare nephrocystic disorder, was the focus of this study. The FAT1 gene, comprising 27 exons, encoded a single-pass transmembrane protein with multiple biological functions. The extracellular portion of this protein consisted of 33 cadherin repeat sequences, 5 epidermal growth factor-like domains, and a G-layer associated domain. This report detailed a case of glomerular cystic disease caused by a mutation in the FAT1 gene, which was treated with the traditional Chinese medicine formula 'Shen Jiu Fang Modified'. This formula included Astragalus, Atractylodes, Poria, Angelica, Clematis, Silkworm, Hedyotis diffusa, Hibiscus leaf, among other ingredients, and aimed to invigorate the spleen and promote diuresis, as well as to nourish the kidneys and promote blood circulation. This case demonstrated the potential of traditional Chinese medicine in addressing rare kidney diseases, offering new insights for the diagnosis and treatment of similar complex cases.

Objective: To establish a scoring model for predicting the prognosis and drug sensitivity of colorectal cancer (CRC) based on the expression of disulfidptosis-related genes by bioinformatics analyses combined with the validation with CRC patient-derived organoids (CRC-PDOs). Methods: NMF (non-negative Matrix Factorization) algorithm, Cox and LASSO regression analyses were used to identify disulfidptosis-related genes with predictive value for CRC prognosis, and disulfidptosis-related risk scoring formula was constructed. The differential genes and enrichment pathways among different clusters were analyzed by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes). The sensitivity of the high/low-risk clusters of CRC patients to chemotherapy drugs was predicted using the GDSC database and validated using CRC-PDOs. Results: The results of NMF algorithm showed that CRC patients could be grouped into two clusters based on the disulfidptosis-related genes. COX regression analysis demonstrated that LRPPRC and SLC7A11 were the only two genes with significance to predict the prognosis of CRC patients (P=0.047, 0.033). Low expression of SLC7A11 or high expression of LRPPRC in tumors of CRC patients was significantly correlated with overall survival (OS) (P=0.004, 0.003). Based on LASSO regression analysis, the mortality risk scoring formula for disulfidptosis was as follows: Risk score=LRPPRC×(-0.670 5)+SLC7A11×0.311 2, and the GSE161158 dataset could be re-grouped into high-risk and low-risk clusters accordingly. There were 125 differentially expressed genes (DEGs) between the two clusters. According to the GO and KEGG results, the up-regulated genes in high-risk cluster were mainly enriched in immune regulation, such as leukocyte chemotaxis, granulocyte migration and toll-like receptor binding. Low-risk cluster was characterized by pathways associated with sulfide metabolism, such as sulfur compound transmembrane transporter activity. Based on the GDSC database, the expression level of SLC7A11 and LRPPRC could predict chemotherapy drug sensitivity. As a representative, the efficacy of chemotherapy drug (irinotecan) on inhibiting the growth of CRC-PDOs was shown to be linearly correlated with the relative gene expression levels of SLC7A11 and LRPPRC in CRC tissues of patients (P=0.007, 0.040). Conclusion: According to the results based on the bioinformatics analyses and drug sensitivity testing on CRC-PDOs, disulfidptosis risk score could predict the prognosis and drug sensitivity of CRC patients, with potential clinical application prospect.

Tricuspid regurgitation (TR) cases are widely distributed in China. Poor clinical drug efficacy, high surgical risk, and poor prognosis for right heart failure are found in patients with moderate or severe TR. In recent years, with the innovation of valve instruments and the development of technology, transcatheter tricuspid valve treatment could be a new choice for high-risk TR patients in surgery. Many TR animal models have emerged these years for the research of the mechanism of TR and for the clinical verification of instruments. Therefore, this review focuses on how to develop an animal model of TR and discusses the advantages and disadvantages of these techniques.

This article reports the diagnosis and treatment of a patient with primary hyperparathyroidism (PHPT) and vitamin D deficiency. The patient was a young male with a insidious onset. Multiple tests have shown hypercalcemia, hypophosphatemia, hypercalciuria, and hyperparathyroidism. There was no renal dysfunction, and the diagnosis of PHPT was clear. There were kidney stones and vitamin D deficiency at the same time. The patient met the surgical indications, but the difficulty in preoperative localization was that ultrasound examination showed suspicious masses in both parathyroid regions, and the ^99mTc-MIBI imaging result was negative. Finally, accurate preoperative localization was achieved through ¹⁸F-fluorocholine PET/CT, and the patient was cured after surgery.

Objective: An isotemporal substitution model was used to explore the associations between activities including 10 minutes per day of physical activity (PA), sedentary behavior (SB), and sleep (SLP), and depressive symptoms among vocational school students with and without depressive symptoms. Methods: Questionnaire survey was conducted on grade one to grade three students attending vocational schools in Shanghai and Jiangsu Province from Dec 2021 to Jan 2022. Fourteen schools were selected using the convenience cluster sampling method. The selected students were categorized into depressive symptoms group and non-depressive symptoms group according to the Centre for Epidemiologic Studies Depression Scale (CES-D) scores. Results: A total of 40 339 questionnaires were collected, of which 10 086 were able to clearly remember the time of physical activity in the past week, and 8 149 were valid after data cleaning. According to the valid questionnaires, 5 496 students (67.44%) were in the non-depressive symptoms group and 2 653 (32.56%) were in the depressive symptoms group. The mean age of the students were (16.70±1.19) years. In the non-depressive symptoms group, substituting moderate physical activity (MPA) for all the other behaviors was negatively associated with CES-D scores, while substituting vigorous physical activity (VPA) for MPA and SB was positively associated with CES-D scores. In the depressive symptoms group, substituting walking, SB, and SLP with MPA was negatively associated with CES-D scores, respectively. The associations of MPA substituted for walking, SB, and SLP with CES-D scores were much stronger in the depressive symptoms group than in the non-depressive symptoms group. Conclusion: The detection rate of depressive symptoms was high among vocational students. Substituting MPA for walking, SB, and SLP were negatively associated with CES-D scores, with a stronger association observed in the depressive symptoms group than in the non-depressive symptoms group.