30 July 2022, Volume 49 Issue 04

    

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  Biocompatibility assessment of mesoporous TiO₂ nanoparticles for the application of sonodynamic treatment of hepatocellular cancer

  WANG Xi, TANG Yang, ZHANG Xiao-long, XU Ya-dan, WANG Wen-ping

  jms. 2022, 49(04): 475-483. https://doi.org/10.3969/j.issn.1672-8467.2022.04.001

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  Objective To evaluate the biosafety of mesoporous titanium dioxide(TiO₂)nanoparticles in sonodynamic therapy against human HepG2 tumors. Methods Mesoporous TiO₂ nanoparticles were synthesized by soft-templating strategy,and toxicity was assessed after co-culture with HepG2 cells,and its generation of ROS in HepG2 cells mediated by sonodynamic therapy was measured by applying fluorescent probe. Blood coagulation assay was used to measure hemocompatibility,and safety was assessed by blood biochemical indices and HE staining of organ tissue sections in mice after intravenous injection. After intravenous administration of the drug in Kunming mice and HepG2 implanted tumor nude mice,the organs and tumors were taken at the designated time and digested in aqua regia,and inductively coupled plasma emission spectroscopy was applied to map the distribution of the drug organs. Results Mesoporous TiO₂ nanoparticles were highly dispersed and homogeneous,showed no toxicity after cell co-culture,and produced ROS in HepG2 cells by combined ultrasound. all indices of blood agglutination assay,blood biochemical indices of mice and organ tissue sections(highest dose 150 mg/kg) were not significantly different from the control group. The drug was mainly distributed in the liver and spleen after intravenous administration,peaking at 8 h(containing 51.32%)and reaching 6.74% in the tumor tissue at 1h. The maintenance concentration was revealed within 24 h. Conclusion Mesoporous TiO₂ nanoparticles as an sono-sensitizer can effectively generate ROS,have good safety of intravenous injection,metabolize mainly through the reticuloendothelial system,and can accumulate in the tumor tissue to provide a good time window for sonodynamic therapy.
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  Establishment of thymoma PDC model and screening of chemotherapeutics

  AO Yong-qiang, GAO Jian, WANG Shuai, DING Jian-yong, JIANG Jia-hao

  jms. 2022, 49(04): 484-491,506. https://doi.org/10.3969/j.issn.1672-8467.2022.04.002

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  Objective To establish the patient-derived tumor cells(PDC) model of thymoma to simulate the activity of chemotherapeutic drugs in vivo,and to screen effective chemotherapeutic schemes to guide clinical medication. Methods The fresh surgical specimens of thymoma were digested and dissociated within 24 hours,and viable thymic tumor cells were cultured in the culture medium. The PDC model was established and passaged stably. Seven different cisplatin-containing chemotherapy regimens were selected for drug sensitivity test to observe their killing effect on thymoma cells. Results Ninteen specimens of thymoma were collected and 8 cases of thymoma PDC model were successfully established, success rate was 42%(8/19).Models included 1 case of type A,3 cases of type AB,3 cases of type B2,and 1 case of thymic carcinoma. Based on Masaoka staging,there were 3 cases in stage Ⅱ,3 cases in stage Ⅲ, and 2 cases in stage Ⅳa. Among the 7 selected cisplatin-containing drug regimens,drug sensitivity test was carried out in 6,7 and 8 cases of thymoma PDC models,respectively. Albumin paclitaxel,vinorelbine or epirubicin combined with cisplatin regimens had higher killing efficacies on thymoma cells,which were 6/8, 6/7 and 5/6 respectively. The drug resistance rates were 2/8,1/7 and 1/6 respectively;while docetaxel, paclitaxel,gemcitabine or pemetrexed combined with cisplatin regimens have lower killing efficacies,which were 4/8,3/8,5/8 and 3/8 respectively. The drug resistance rates were higher,4/8,5/8,3/8 and 5/8 respectively.A thoracoscopic biopsy was performed on a patient with unresectable thymic tumor,and part of the tissue was collected to successfully establish a PDC model. The drug sensitivity test result of the patient's PDC model showed that gemcitabine combined with cisplatin has a strong killing effect,therefore this treatment plan was performed and the tumor size was significantly reduced after chemotherapy. Conclusion The thymoma PDC models was successfully established to simulate the drug activity in the tumor via drug sensitivity test. According to test results,we performed chemotherapy on a patient with unresectable thymoma and achieved significant effects.Therefore we recommend to use albumin paclitaxel, vinorelbine or epirubicin combined with cisplatin for thymoma chemotherapy.
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  Assessment of left atrial function and the association with left ventricular filling pressure in patients with paroxysmal atrial fibrillation by threedimensional speckle tracking echocardiography: a case-control study

  BAO Li-wen, CHENG Lei, BAO Li-lian, SHEN Jun, HONG Shang-zhi, SHI Hai-ming, HUANG Guo-qian

  jms. 2022, 49(04): 492-498. https://doi.org/10.3969/j.issn.1672-8467.2022.04.003

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  Objective To evaluate the left atrial(LA)function in paroxysmal atrial fibrillation(PAF) using three-dimensional echocardiography at sinus rhythm,and the correlation between left atrial function and left ventricular filling pressure was observed. Methods This small-scale,single center and casecontrol study included patients with PAF and healthy controls matched by age and gender. LA structure and function were measured by three-dimensional echocardiography and the acquired parameters was analyzed by specific software. Left ventricle structure and function were assessed by conventional echocardiography methods. Results There were 23 cases with average age of(66.2±4.3)years old in PAF group,and 73.9% were male. There were 23 cases with average age of(64.3±7.5)years old in control group,and 69.6% were male. LA ejection fraction(45.2%±8.8% vs. 54.0%±7.0%,P<0.01), peak atrial longitudinal strain(16.1±5.4 vs. 20.5±6.6,P=0.01),peak atrial circumferential strain(21.7±10.1 vs. 32.8±7.6,P<0.01),early diastolic circumferential strain(-6.9±5.8 vs. -10.3±5.0,P=0.02)and late diastolic circumferential strain(-14.6±9.3 vs. -22.1±7.2,P=0.01)were all significantly reduced in PAF group compared with controls group,but not correlated with E/A and E/e'. All LA volume parameters were significantly larger in PAF group[LA maximum volume:(52.1±14.1)mL vs.(45.3±11.9) mL,P=0.05;LA minimum volume:(29.3±8.7) mL vs. (21.4±6.6) mL,P<0.01;pre-LA contractile volume:(43.1±12.4)mL vs.(35.3±9.2)mL,P=0.01]apart from LA maximum volume index which didn't reach a significant level(29.4±7.4 vs. 26.0±6.6,P=0.09). LA maximum volume,LA minimum volume and pre-LA contractile volume were correlated with E/A(r=0.54,P=0.02;r=0.56,P=0.01;r=0.61,P=0.01)while LA maximum volume index was correlated with E and E/e'(r=0.47,P=0.03;r=0.43,P=0.05). Conclusion Three-dimensional speckle tracking evaluates the morphological and functional reconstruction of left atrial in PAF more comprehensively. LA volume of PAF is increased,LA ejection fraction is reduced,the longitudinal and circumferential deformation function of whose are dampened compared with the control ones. LA volume parameters are strongly correlated with filling pressure.
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  Analysis of clinical and imaging characteristics of cryptococcal meningitis and tuberculous meningitis co-infection in AIDS patients

  MA Qiong, YAN Qin-qin, SHI Xiu-dong, HOU Qin-guo, SHI Yu-xin

  jms. 2022, 49(04): 499-506. https://doi.org/10.3969/j.issn.1672-8467.2022.04.004

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  Objective To investigate the clinical and MRI characteristics of cryptococcal meningitis and tuberculous meningitis co-infection in aquired immunodeficiency syndrome(AIDS)patients,and to improve its diagnostic efficacy. Methods The clinical data of 39 AIDS patients with cryptococcal meningitis and tuberculous meningitis co-infection(AIDS/CM/TBM) who were admitted to Shanghai Public Health Clinical Center from Sept 2015 to Oct 2021 were retrospectively analyzed. Their clinical manifestations,laboratory results and MRI findings were compared with 61 AIDS patients with cryptococcal meningitis(AIDS/CM)and 42 AIDS patients with tuberculous meningitis(AIDS/TBM).Results The incidence rate of headache of the AIDS/CM/TBM patients was higher than that of the AIDS/TBM patients,and the incidence rate of convulsion,visual disorders,consciousness disorders were higher than those in the AIDS/CM patients and AIDS/TBM patients(P<0.05).The CD4⁺ T cell counts of 32 (82.0%) AIDS/CM/TBM patients were ≤ 100 cells/μL. The white blood cell counts and the cerebrospinal fluid(CSF)protein levels in the AIDS/CM/TBM patients were significantly higher than those in the AIDS/CM patients,and the CSF glucose levels were significantly lower than those in the AIDS/CM patients(P<0.05).The CSF opening pressure and the CSF chloride levels in the AIDS/CM/TBM patients were significantly higher than those in the AIDS/TBM patients(P<0.05). Thirty-four (87.2%) AIDS/CM/TBM patients showed intracranial lesions in MRI examination, and the main manifestations were meningitis and meningoencephalitis.The incidence of brain lobe lesions in the AIDS/CM/TBM patients was higher than that of the AIDS/CM patients,and the incidence of dilated VirchowRobin spaces(VRS) or pseudocysts was lower than that of the AIDS/CM patients (P<0.05). Multivariate Logistic regression analysis showed that headache,consciousness disorders,and CSF glucose levels ≤ 1.85 mmol/L were correlated with the multiple infection of AIDS/CM/TBM(P=0.009,0.005, 0.002). Conclusion The clinical manifestations of AIDS/CM/TBM are more severe,the changes of laboratory examination are more significant,and the manifestations of brain MRI are meningitis and meningoencephalitis. Headache,consciousness disorders,and CSF glucose levels ≤ 1.85 mmol/L have suggestive significance for clinical diagnosis,which are helpful for timely intervention.
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  Clinical application of color Doppler ultrasound in evaluation of transplant renal artery stenosis

  ZOU Zi-ran, YANG Ping, YANG Cheng, HE Wan-yuan, WANG Wen-ping

  jms. 2022, 49(04): 507-513,521. https://doi.org/10.3969/j.issn.1672-8467.2022.04.005

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  Objective To explore the clinical value of color Doppler ultrasound in the diagnosis of transplant renal artery stenosis(TRAS),the assessment of stenosis degree and the efficacy evaluation of interventional therapy. Methods The data of patients with kidney transplantation admitted to Zhongshan Hospital,Fudan University from Feb 2013 to May 2020 were analyzed retrospectively. Twenty-seven patients diagnosed with TRAS by digital substraction angiography (DSA) or magnetic resonance angiography (MRA) were enrolled as the stenosis group (6 patients were moderate stenosis and 21 patients were severe stenosis). Fourty-eight patients with stable kidney function during the same period were randomly selected as the control group. All the patients underwent color Doppler ultrasound. Peak systolic velocity(PSV)and resistance index(RI)from the main renal artery,segmental renal artery and interlobular artery of the transplanted kidney were recorded,respectively. The parameters derived from color Doppler ultrasound between the stenosis group and the control group as well as between the moderate stenosis group and the severe stenosis group were compared,and the diagnostic efficacy of commonly used parameters was calculated. Furtheremore,changes of color Doppler hemodynamic parameters before and after treatment were analyzed in the stenosis group. Results Compared with the control group,PSV from main renal artery[(3.42±1.31)m/s vs.(1.26±0.48)m/s,P<0.001]and the ratio of PSV between main renal artery and interlobar artery(14.75±7.30 vs. 3.91±1.77,P<0.001)were significantly higher in the stenosis group. While PSV of segmental renal artery[(0.43±0.19)m/s vs.(0.53±0.16)m/s,P=0.021],RI of segmental renal artery(0.52±0.11 vs. 0.63±0.08,P<0.001),PSV of interlobular artery[(0.26±0.11)m/s vs.(0.34±0.10)m/s,P=0.002],RI of interlobular artery(0.49±0.10 vs. 0.61±0.09, P<0.001)and RI of main renal artery(0.60±0.12 vs. 0.71±0.09,P<0.001)were much lower than those in the control group. With PSV of main renal artery ≥ 2.50 m/s,ratio of PSV between main renal artery and interlobar artery ≥ 10,and RI of interlobular artery<0.55 as the cut-off value for TRAS diagnosis,the sensitivity were 77.8%,77.8% and 70.4%,the specificity were 50.0%,75.0% and 50.0%,and the accuracy were 70.4%,50.0% and 67.7%,respectively. Ratio of PSV between main renal artery and interlobar artery of severe stenosis group was higher than that of moderate stenosis group(16.41±7.00 vs. 8.96±5.41,P=0.024).For those with TRAS treated with interventional therapy,great changes occurred in all color Doppler ultrasound related parameters. After treatment,PSV from main renal artery[(1.48±0.43)m/s vs.(3.50±1.35)m/s,P<0.001)]and ratio of PSV between main renal artery and interlobar artery(4.20±1.90 vs. 16.78±9.35,P<0.001)significantly decreased,while PSV of segmental renal artery[(0.52±0.19)m/s vs.(0.40±0.14)m/s,P=0.008],RI of segmental renal artery(0.64±0.07 vs. 0.52±0.17,P<0.001),PSV of interlobular artery[(0.39±0.11)m/s vs.(0.25±0.11)m/s,P<0.001],RI of interlobular artery (0.62±0.11 vs. 0.50±0.18,P=0.001) and RI of main renal artery (0.67±0.09 vs. 0.62±0.15,P=0.035)increased. Conclusion Color Doppler ultrasound is an simple,noninvasive,and highly accurate technique that can be used as the preferred method for screening TRAS,assessing the degree of stenosis and evaluating the treatment efficacy of interventional therapy.
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  Nomenclature curation of genes and variants in the genetic disease annotation databases

  WANG Xiao, WANG Ya-qiong, DONG Xin-ran, WU Bing-bing, WANG Hui-jun, LU Yu-lan, ZHOU Wen-hao

  jms. 2022, 49(04): 514-521. https://doi.org/10.3969/j.issn.1672-8467.2022.04.006

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  Objective To evaluate the consistency and updating state of gene and variant nomenclatures in the widely used disease databases,we curated gene names in the genetic disease database (OMIM)and variant nomenclatures in the disease variant annotation databases(HGMD,ClinVar),and corrected mismatched names to the current version based on the GENCODE v34 reference. Methods For OMIM genes,we examined if the disease gene symbols were the same as the standard gene symbols in HGNC and GENCODE through their accession numbers. For the variant transcripts in HGMD and ClinVar,we evaluated if the transcripts existed in the RefSeq and Ensembl references,and whether their versions were up to date. Results Curation results showed that 86.7% of genes in OMIM were correct. In ClinVar,83.47% of variants passed the curation. Only 18.78% of variants in HGMD whose transcripts matched the reference,and another 78.33% of variants whose transcripts were not up to date.We labeled information for mismatched genes and variants according to their missing type;provided standard gene names,corrected transcript accession numbers for variants that were inconsistent in our curation. Conclusion We found that there are still some problems such as information missing,version inconsistency or abandonment in the commonly used disease annotation databases. By examining and correcting the nomenclatures of genes and variants,we can facilitate the analysis,interpretation,verification, and communication of genetic data in molecular clinical diagnosis and related scientific work.
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  Association study of SNPH gene polymorphisms with schizophrenia in Chinese Han population

  WU Jun, LU Jia-jing, HUANG Xin-xin, HUANG Ru-yan, LYU Qin-yu, YI Zheng-hui

  jms. 2022, 49(04): 522-528. https://doi.org/10.3969/j.issn.1672-8467.2022.04.007

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  Objective To investigate the relationship between syntaphilin (SNPH) gene and schizophrenia(SZ)in Chinese Han population. Methods TaqMan probe genotyping technique was used to detect 5 single nucleotide polymorphisms(SNPs)of SNPH gene in 389 SZ patients(case group)and 433 healthy controls(control group),including rs3764714,rs3795139,rs3803947,rs3803949 and rs6134520. Then we conducted linkage disequilibrium analysis and analyzed whether there were differences in the frequency distribution of alleles,genotypes and haplotypes. At last,we compared the differences in genotype distributions under different genetic patterns between the two groups. Results The linkage disequilibrium analysis showed that the five locus could constitute a haplotype block(D' >0.8). However,in subsequent studies,there was no statistical significance in the frequency distribution of haplotypes A-AA-C-T,G-A-G-T-T,and G-G-G-C-C composed of the five genes between the case group and the control group(P=0.978,P=0.535,P=0.524). There was no significant difference in allele and genotype frequency distributions between the two groups. Besides,under the co-dominant,dominant,recessive and log-additive inheritance patterns,there was still no statistical significance in the genotype frequency distributions between the case group and the control group. Conclusion SNPH gene may not be a susceptible gene for SZ in Chinese Han population.
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  Role of SIRT1-cAMP in the improvement of ovarian reserve by resveratrol in mice

  GUO Lu, LIU Xiao-cheng, GU Chao, LI Bin

  jms. 2022, 49(04): 529-536. https://doi.org/10.3969/j.issn.1672-8467.2022.04.008

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  Objective To explore the effects of Sirtuin1(SIRT1)agonist on ovarian reserve and the possible role of SIRT1-cAMP pathway in oxidative stress induced ovarian dysfunction in mice. Methods Resveratrol(Res) and H₂O₂ were used to intervene human ovarian luteinized granulosa cells,and the apoptosis and mitochondrial membrane potential of granulosa cells were detected by flow cytometry,and the estrogen secretion capacity of granulosa cells was determined by enzyme-linked immunosorbent assay. Western blot and RT-PCR were used to detect the expression of functional receptors and genes related to estrogen synthesis in granulosa cells.Finally,oxidative stress injured premature ovarian insufficiency(POI) model mice induced by 3-nitropropionic acid were pretreated with Res,and its protective function on ovarian reserve was evaluated from estrous cycle,ovarian index,hormone level and follicular counting. PCR was used to detect the expression of key genes in the cyclic adenosine monophosphate (cAMP) signaling pathway in mouse ovarian tissues. Results Res could improve the estrogen synthesis ability of human granulosa cells,the expression of functional receptors and genes related to estrogen synthesis in oxidative-stress damaged granulosa cells through SIRT1. Meanwhile,Res could improve the ovarian function of oxidative-stress damaged POI mice and increase the ovarian expression of key genes in cAMP signaling pathway including EPAC,RAP1b,RAP1a,PLCb3,CREB1,CAMK2α and SIRT1. Conclusion Res can improve the ovarian reserve of oxidative-stress injured mice,and SIRT1-cAMP signaling pathway may be the potential mechanism,and positive feedback may function between them.
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  On the improvement of family services in public health events: a qualitative case study based on COVID-19 responses

  CHEN Bo-hao, XUE Cheng, REN Jun, YIN Xiao-ya, ZHU Ying, TANG Biao-qian, WANG Shu-mei

  jms. 2022, 49(04): 537-541,547. https://doi.org/10.3969/j.issn.1672-8467.2022.04.009

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  Objective To understand the status of family services and residents'demands for services in Shanghai in order to construct and improve the key elements of family services in public health events. Methods We used a combining method of individual in-depth interviews and focused group interviews. The informants were domestic and foreign experts in public health,health services,education,safety, etc.,community workers and residents. The interview questions were as follow:problems in family services,residents'demands and suggestions for family services,etc. Results We found 7 major family services problems in Shanghai's response to public health events:The boundary of authorities and responsibilities were not clearly defined between the upper and lower departments. The team construction of public health professions at the community level was flawed. There were miscommunications between upper and lower medical institutions during the epidemic outbreaks. Residents were not aware of the available family services provided by their communities. Unnoticed insanitary spots still existed in public spaces,and the maintenance of residential emergence equipment needs to be strengthened. The public opinion guidance required further strengthening,and the elderly people lack an effective medium for information acquisition. The emergency plan of closed management to solve practical problems after Shanghai's COVID lockdown was insufficient. The residents'demands included the following 6 aspects:comprehensive family services,supply and guarantee of basic living materials and special materials, professionals providing family services as a means of support,emergency medical services,receiving psychological intervention and understanding knowledge of mental health,security of food and food supply chain security. Conclusion 'Government led''cross-border cooperation''clear executive body'and 'based on the needs of residents'were key factors. Therefore,we suggest family services are included in the normalizing construction of government.
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  Long-term outcomes and adverse reactions of intensity-modulated radiation therapy in patients with early stage nasopharyngeal carcinoma

  YIN Huan, XUE Fen, HE Xia-yun, MENG Xiao-yan

  jms. 2022, 49(04): 542-547. https://doi.org/10.3969/j.issn.1672-8467.2022.04.010

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  Objective To observe the long-term follow-up results of intensity-modulated radiation therapy(IMRT)in patients with stage Ⅰ -Ⅱ nasopharyngeal carcinoma(NPC)and analyze the related prognostic factors and adverse reactions. Methods A retrospective analysis was conducted from Jun 2005 to Dec 2015 in 210 NPC patients with T1-2N0-1 disease treated with IMRT. Among them,35 patients(16.7%)were stage Ⅰ and 175 patients(83.3%)were stage Ⅱ.Of stage Ⅱ patients,113 patients (64.6%)received chemoradiotherapy and the rest received radiotherapy alone. The primary dose was 66 Gy/30Fx. Results The median follow-up time was 91 months,and the 5- and 10-year overall survival rates(OS)were 97.1% and 87.8%,respectively. The 5- and 10-year local control rates(LC),regional control rates(RC)and distant metastasis-free survival rates(DMFS)were 95.7% and 92.8%,98.6% and 98.6%,96.2% and 94.1%,respectively.There were no differences in 5- and 10-year OS,RC and DMFS between stage Ⅱ patients with or without(P=0.535,0.942,0.754). The LC of chemoradiotherapy group was higher than that of radiotherapy alone group(P=0.009). There were no grade 4 late toxicities,and the incidence of grade 3 late toxicities were rare,mainly including hearing loss,dental caries,dry mouth. And incidence of cranial nerve injury and temporal lobe injury was 1.4% and 3.3%,respectively. The incidence of the second tumor was 6.7%. Conclusion Stage Ⅰ -Ⅱ NPC patients treated with IMRT can achieve high LC,RC,DMFS,OS and low adverse reactions. The addition of chemotherapy in stage Ⅱ patients did not improve survival.
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  Analysis of 7-year medical record data characteristics and medical assistance of pediatric inpatients in one counterpart support hospital in Yunnan Province

  SHI Yu, LI Rui, ZHANG Guo-wen, HUANG Yan, ZHOU Gao-feng, ZHAI Xiao-wen

  jms. 2022, 49(04): 548-553. https://doi.org/10.3969/j.issn.1672-8467.2022.04.011

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  Objective To analyze the date of 7 years of inpatient cases in the pediatric ward of Lüchun County People's Hospital in Yunnan Province,in order to meet the support needs of the pediatric hospital. Methods In this study,medical records of discharged patients from Jan 2013 to Dec 2019 were extracted.Based on the first diagnosis of discharged children,the statistics of disease types are carried out. The disease classification is based on the International Classification of Diseases(ICD-10)standards to analyze the characteristics and changing trends,clinical characteristics of the main diseases,and the changes in hospitalization expenses. Results From 2013 to 2019,a total of 14 934 children were discharged,and the number of discharged children showed an increasing trend. The top ten diseases were bronchial pneumonia,acute upper respiratory tract infection,acute bronchitis,acute gastroenteritis,neonatal asphyxia,jaundice,premature infants,herpetic angina,convulsions,and acute pharyngitis. The average age of children,mainly infants was(22.7±32.8)months. The Hani ethnic group accounted for 91.0%. The median of overall hospitalization expenses increased from 1 841.0 Yuan(95%CI:2 525.4-2 716.9)in 2013 to 2 045.6 Yuan(95%CI:2 525.4-2 716.9)in 2019(P<0.05). The median inspection fee dropped from 156.0 Yuan(95%CI:349.5-419.7)in 2013 to 143.9 Yuan(95%CI:210.0-229.8)in 2019(P<0.05).The referral rate was 2.2%,and the mortality rate was 0.3%. Conclusion By summarizing the medical information of the patients discharged from the pediatric wards of the recipient hospital,we can fully evaluate the disease spectrum and medical treatment situation in the recipient areas,accurately provide medical support for the recipient hospitals,and better complete the rural revitalization plan.
Medical Experience Communications
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  Expression of plasma miR-21 and miR-222 in primary central nervous system lymphoma and its correlation with prognosis

  XU Hui-wen, WANG Zhen-zhen, LI Qing, MA Jing-jing, CHEN Kun, LIN Zhi-guang, MA Yan, CHEN Bo-bin

  jms. 2022, 49(04): 554-561. https://doi.org/10.3969/j.issn.1672-8467.2022.04.012

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  Objective To evaluate correlation of plasma-derived miR-21 and miR-222 with prognosis of primary central nervous system lymphoma (PCNSL). Methods A total of 41 patients newly diagnosed with PCNSL in our hospital between Sep 2011 and Dec 2016 were enrolled. Peripheral blood samples were collected before initiation of treatment,and qRT-PCR was performed for the measurement of plasma miR-21/miR-222. Prognostic value was assessed by Kaplan-Meier,Log-rank,and Cox regression analyses. Results According to the median expression level of miR-21 and miR-222,patients were divided into the high expression and low expression group,respectively.During a median follow-up of 44.47 months,miR-21-high-expressing group exhibited long progression free survival(PFS)with median PFS of 22.63 months,higher than that of miR-21-low-expressing group(15.50 months,P=0.049),while no significant difference was found in the overall survival(OS)of the two groups. Moreover,there was no significant difference between the groups of high and low miR-222 expression in both PFS and OS. Univariate analyses demonstrated that plasma miR-21 levels,ECOG performance status(PS),serum lactic dehydrogenase(LDH)and high-dose methotrexate(HD-MTX)plus teniposide(Vm26)regimen,were associated with PFS of PCNSL.Cox regression analysis showed that miR-21,ECOG PS and LDH were independent prognostic risk factors for PCNSL survival. No association of plasma miR-222 levels with prognosis of PCNSL were observed. Conclusion HD-MTX combined with Vm26 chemotherapy regimen improved the PFS of patients with PCNSL. Plasma miR-21 may be valuable in the prognosis evaluation of PCNSL.
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  First line nivolumab combined regimen for meningeal carcinomatosis: a real-world follow-up observation

  CHU Zhao-hui, LIU Tao, CHEN Kun, ZHAN Qiong, WANG Yu

  jms. 2022, 49(04): 562-566. https://doi.org/10.3969/j.issn.1672-8467.2022.04.013

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  Objective To observe the efficacy of first line regimen containing nivolumab in the treatment of meningeal carcinomatosis(MC). Methods Four patients diagnosed by cerebrospinal fluid (CSF)cytology in the Department of Oncology,Huashan Hospital,Fudan University from Apr 1 to Oct 1 2019 were enrolled. They all received nivolumab combined regimen in the first line. The clinical characteristics of CSF tumor burden(TB),meningeal enhancement,hydrocephalus,and central nervous system(CNS)symptoms were summarized,and their relevance with short-term and long-term efficacy was analyzed. Results The primary tumor included two cases of lung cancer treated by multi-line targeted treatment,one case of cholangiocarcinoma,and one case of unknown primary tumor. Two patients had low CSF TB. The other two patients with high CSF TB complicated with hydrocephalus were treated with CSF shunt first. The median course of treatment with nivolumab combined with chemotherapy and/or antiangiogenic drugs was 5.5(5-33). Until the final follow-up on May 1,2022,the median follow-up was 610(153-947)days,one patient had no progression,two were still alive,all patients had no CNS side effect. The CNS symptoms of all patients were relieved on the first assessment after treatment,and the median follow-up was 46(37-65)days. Three patients had decreased CSF TB,and their CNS progression free survival(PFS)were 108,134 and >944 days,respectively. One patient had no change in CSF TB, and his PFS was only 76 days. Patients with low CSF TB had longer overall survival(OS)than those with high CSF TB(>947 days and >944 days vs. 153 days and 275 days). Conclusion In the first line treatment of MC patients with nivolumab,the decrease of CSF TB in the short term may indicate a longer CNS PFS,and the low CSF TB may indicate a longer OS. The efficacy is worthy of further verification.
Methods and Techniques
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  Two-step genetically variant peptide detection tool development without‘next-generation’sequencing

  LI Xin, SONG Li-li, SONG Na-na, XING Qing-he, ZHOU Feng

  jms. 2022, 49(04): 567-573. https://doi.org/10.3969/j.issn.1672-8467.2022.04.014

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  Objective To construct a reference protein sequence database containing genetically variant peptide(GVP)and develop a toolkit for identifying GVPs in proteomics data. Methods Based on the single nucleotide polymorphism (SNP) in dbSNP and the reference protein database in the SwissProt,we constructed the GVP-containing databases ComVarDB and several databases which only contained GVPs of some high expression proteins. Then we tested the database using proteomics data collected from hair shaft sample. Results A Python-based toolkit 2Steps_GVPtool was developed to identify GVPs in proteomics data. 14 GVPs were identified in search against ComVarDB database. A maximum of 18 GVPs were identified when only GVPs of 500 high expression proteins were added to the database. Conclusion Through iterative search steps,database construction can be optimized based on the result of conventional proteomics analysis,that is,database only containing GVPs of some high expression proteins can help identify more GVPs.
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  Effect of Care kV technology on image quality and radiation dose in dual-source CT triple rule out CT angiography for chest pain

  WANG Kun, JIN Liang, LI Cheng, TIAN Quan-kai, ZHANG Lu-kai, LI Ming

  jms. 2022, 49(04): 574-581. https://doi.org/10.3969/j.issn.1672-8467.2022.04.015

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  Objective To investigate the effect of new generation dual source CT combined with Care kV technology on image quality and radiation dose in triple rule out CT angiography(TRO-CTA)for chest pain. Methods Ninety patients who attended the Chest Pain Center of Huadong Hospital,Fudan University from Mar to Sep 2021 and were proposed for TRO-CTA were retrospectively collected. They were divided into two groups A and B according to the different scanning methods. The tube voltage of CT scan in group A was determined by the Care kV technique,while group B used a fixed tube voltage of 120 kV. The image quality and radiation dose were compared between the two groups. Results The mean CT dose index volume(CTDIvol)was significantly lower in group A than in group B[(20.42±9.60)mGy vs.(32.27±13.41)mGy,P<0.001)].The mean dose length product(DLP)in Group A was significantly lower than that in Group B[(525.28 ±240.12)mGy×cm vs.(944.20±408.36)mGy×cm, P<0.001)].Thus,the mean effective radiation dose(ED)was significantly lower in group A than in group B[(7.35 ±3.36)mSv vs.(13.22 ±5.72)mSv,P<0.001)]. The CT values of all vessels in group A were significantly higher than those in group B(P<0.05),except for the distal segment of the left anterior descending and the distal segment of the left circumflex. Image noise was significantly higher in group A than in group B(15.79±3.81 vs. 11.37±3.40,P<0.001).The differences in signal-to-noise ratio of vessel segments between the two groups were not statistically significant except for the distal segment of the LAD. The differences in contrast-to-noise ratio of pulmonary artery and aorta in group A and group B were not statistically significant,but the CNR of coronary artery in group A was generally higher than that in group B.The differences in subjective scores of pulmonary artery,aorta and coronary artery in images from group A and B were not statistically significant. Conclusion The use of Care kV technology for TROCTA angiography of chest pain on a new generation dual-source CT can significantly reduce radiation dose while guaranteeing the diagnostic quality of the images.
Reviews
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  Advances in microbiota culturomics and its application in dermatological research

  YU Tian-ze, QIU Zhuo-qiong, LI Wei

  jms. 2022, 49(04): 582-587. https://doi.org/10.3969/j.issn.1672-8467.2022.04.016

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  The skin microbiota plays a crucial role in maintaining skin homeostasis and participates in the occurrence and development of many skin diseases.Previous studies have mainly revealed the composition and characteristics of the human skin microbiome through high-throughput sequencing. However,this technique has biases and limitations;it is difficult to conduct further studies on the function of specific individual strains. Culturomics can isolate isolates by high-throughput bacteria culture and identify isolates by mass spectrometry technology and 16S rRNA sequencing,and then further analyze the function of the isolated strains,which can explore the diversity of skin microbiota in healthy people and catalyze research on species and strain levels of skin commensal bacteria under disease conditions. The culturomics of the skin microbiota in healthy people increases the number of culturable skin bacteria and reveals the diversity of skin microbiota carbon source utilization patterns and individual specificity of skin microbiota. Culturomics can dynamically observe changes of the skin microbiota during the treatment of skin diseases, reveal the importance of maintaining the diversity of skin microbiota to skin homeostasis,and select specific strains beneficial in the treatment of psoriasis,chronic skin trauma,and other skin diseases. With the continuous improvement of culturomics methods and the development of multi-omics combined application,bacterial culturomics will become an indispensable method in dermatological research.
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  Treatment progress of biologic agents in Behçet’s syndrome

  BAO Hua-fang, GUAN Jian-long

  jms. 2022, 49(04): 588-595. https://doi.org/10.3969/j.issn.1672-8467.2022.04.017

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  The pathogenesis of Behçet's syndrome(BS)is unclear,and the clinical phenotypes of BS are complicated. Interferon-α and monoclonal anti-tumor necrosis factor-α antibodies has improved the prognosis and the life quality of the BS patients with visceral involvement,but there are still some patients who do not respond well. Other biological agents have achieved some clinical effects in BS patients. Anakinra and canakinumab can improve the uveitis,mucocutaneous involvement in BS patients. Secukinumab may be effective to the mucocutaneous phenotype and joint involvement phenotype. The BS patients with uveitis, central nervous system involvement and vascular involvement had a satisfying reaction to tocilizumab,while phenotypes of skin and mucosa,joint and intestine responded badly.Ustekinumab seemed to be eutherapeutic to refractory mucocutaneous involvement and uveitis.Multicenter large-sample clinical trials are necessary to clarify the efficacy and safety of these drugs in the treatment for BS.
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  Research progress on the early diagnosis of abnormal morphological and biomechanical characteristics of keratoconus

  XIAN Yi-yong, SHEN Yang, ZHAO Jing, ZHANG Xiao-yu, ZHOU Xing-tao

  jms. 2022, 49(04): 596-605. https://doi.org/10.3969/j.issn.1672-8467.2022.04.018

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  Keratoconus is a primary,noninflammatory corneal ectatic disease,resulting in severe vision loss. Early or subclinical keratoconus has an insidious or asymptomatic onset which is hard for accurate diagnosis,comprising one of the major risk factors for corneal ectasia after laser refractive surgery. In recent years,researches utilizing instruments such as the Oculus Pentacam,the Corvis ST,the anterior segment optical coherence tomography(OCT)and the in-vivo confocal microscopy(IVCM)have been made to investigate early changes of keratoconus from the aspect of corneal topography,tomography, pachymetry,biomechanics and micro-structures,contributing to the early diagnosis and intervention of keratoconus. In this review,we discuss the advances of new techniques and methods for the early diagnosis of keratoconus.
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  Research progress on assessment of left atrial function using speckle tracking echocardiography and its clinical value in atrial fibrillation

  BAO Li-lian, CHENG Lei, HUANG Guo-qian, BAO Li-wen

  jms. 2022, 49(04): 606-613. https://doi.org/10.3969/j.issn.1672-8467.2022.04.019

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  Speckle tracking echocardiography(STE)is a novel technique in the field of echocardiography which can be used to conduct direct deformation analysis of the heart mechanic function. STE derived myocardium strain is considered a more sensitive index to evaluate myocardial function.So far,studies on STE mainly focus on the left ventricle,while its application in assessing left atrial(LA) function and measuring LA strain is limited and methodology controversies exist. This review summarized the application of STE in LA function evaluation,methodology pivots,current controversies,advantages and limits,technical progresses,and the clinical value of LA strain in patients with atrial fibrillation.
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  Research progress of epithelial-mesenchymal transition on idiopathic pulmonary fibrosis and signaling pathway

  DENG Ling-ling, OUYANG Bo-shu, WEI Ying, DONG Jing-cheng

  jms. 2022, 49(04): 614-619,627. https://doi.org/10.3969/j.issn.1672-8467.2022.04.020

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  Idiopathic pulmonary fibrosis(IPF)is a chronic fatal disease and its pathogenesis remains unclear. Epithelial-mesenchymal transition(EMT)is a biological process in which differentiated alveolar epithelial cells lose epithelial characteristics and obtain mesenchymal cell morphology and migration,which is a transient and reversible process. Blocking the signal transduction mediated by TGF-β-Smad,Wnt/β- catenin,Hippo would be beneficial to the inhibition of EMT,thus help inhibit the progression of IPF. The authors summarized the research progress of signal transduction pathways related to epithelialmesenchymal transition in IPF,which would provide scientific basis for the preclinical use of drugs targeting EMT as a therapeutic strategy for pulmonary fibrosis patients.
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  Research progress of perioperative cerebral blood flow monitoring methods in adults

  ZHOU Xue-hua, LI Yu-feng, SHEN Xia

  jms. 2022, 49(04): 620-627. https://doi.org/10.3969/j.issn.1672-8467.2022.04.021

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  Normal brain function is maintained by the supply of cerebral oxygen which depends on the constant and adequate cerebral blood flow. Either ischemic or hyper-perfusion brain injury can be prevented by monitoring the cerebral blood flow perioperatively,so that to improve recovery for patients postoperatively.Until now,none of the methods is perfect for cerebral blood flow monitoring in clinic. Each has its own advantages and limitations. This article is aimed to review the commonly used and new monitoring methods used for adult patients in terms of the time,principle,clinical application,advantages and limitations.
Case Report
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  Mixed phenotype（B-lymphocytic/myeloid）acute leukemia with expression of TEL-ABL1 fusion gene: a case report

  WANG Lu-ting, LU Li-na, HE Da-bao, LIU Xiao-min, CAO Shu-ya, WANG Su-yun

  jms. 2022, 49(04): 628-632. https://doi.org/10.3969/j.issn.1672-8467.2022.04.022

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  Mixed phenotype acute leukemia(MPAL)is rare,accounting for approximately 2%-5% of acute leukemia cases. TEL(exon 1-5)-ABL1 fusion gene(TEL-ABL1)as case reports,is mainly seen in malignant hematological diseases,such as acute myeloid leukemia(AML),acute lymphocytic leukemia (ALL),and myeloproliferative neoplasm (MPN). Positive MPAL and TEL-ABL1 suggest a poor prognosis. This case is the first report of B lymphocytic/myeloid mixed-phenotype acute leukemia with positive TEL-ABL1 fusion gene. Complete remission was achieved after chemotherapy for lymphoid and myeloid leukemia and targeted therapy with tyrosine kinase inhibitors.After consolidation chemotherapy, the patient underwent human leucocyte antigen (HLA)-identical sibling allogeneic peripheral blood hematopoietic stem cell transplantation,then died due to intestinal rejection.