[Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy].

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

[Monitoring and analysis on host animals of hemorrhagic fever with renal syndrome in Henan Province from 2019 to 2022].

Objective: To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022. Methods: Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed. Results: A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024. Conclusion: The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

[Clinical significance of Epstein-Barr Virus detection in the cerebrospinal fluid of patients who underwent hematopoietic stem cell transplantation].

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.

[Clinical study of antinib combined with radiotherapy in the treatment of third-line extensive small cell lung cancer].

Objective: To explore whether the survival benefit of the third-line extensive small-cell lung cancer (ES-SCLC) will be obtained by the combination of anlotinib and radiotherapy, and evaluate the safety of this treatment regimen. Methods: Twenty-seven patients with ES-SCLC who received third-line treatment with less than three metastatic organs at the Cancer Hospital of Xinjiang Medical University from November 2018 to July 2021 were collected and treated with radiotherapy based on anlotinib. Kaplan-Meier curve was used to estimate the overall survival (OS) and progression-free survival (PFS), descriptive statistical analysis was used to evaluate the safety, and European organisation for research and treatment of cancer quality of life questionnaire-core 30 (EORTC QLQ-C30) was used to evaluate the quality of life. Results: The follow-up cut-off date was July 1, 2021, and the follow-up time ranged from 4.8 to 31.0 months, with a median follow-up time of 10.2 months for the entire group. Among the 27 patients, 4 achieved partial remission, 17 had stable disease and 6 had progression of disease. The objective remission rate (ORR) was 14.8%, and the disease control rate (DCR) was 77.8%. Median PFS and the median OS were 5 months and 11 months, respectively. The most common adverse reactions included fatigue (33.3%, 9/27), anorexia (14.8%, 4/27), bleeding (14.8%, 4/27) and hand-foot syndrome (11.1%, 3/27). Most of them were grade 1 to grade 2, 3 cases were more than grade 3, and there was no grade 5 toxicity recorded. After radiotherapy combined with amlotinib treatment, patients showed improvement in general health, somatic functioning, social functioning, and emotional functioning (all P<0.05). Conclusion: For the third-line ES-SCLC patients, radiotherapy based on the anlotinib can significantly prolong their PFS and OS, and the adverse reactions can be tolerated.

[The epidemiology and pathogeny investigation of two clusters of severe fever with thrombocytopenia syndrome disease outbreaking in Henan Province, 2022].

To investigate two clusters of severe fever with thrombocytopenia syndrome virus (SFTSV) in Xinyang City, Henan Province, in 2022, and analyze their causes, transmission route, risk factors, and the characteristics of virus genetic variation. Case search and case investigation were carried out according to the case definition. Blood samples from cases, family members and neighbors and samples of biological vectors were collected for RT-PCR to detect SFTSV. The whole genome sequencing and bioinformatics analysis were performed on the collected positive samples. A total of two clustered outbreaks occurred, involving two initial cases and ten secondary cases, all of which were family recurrent cases. Among them, nine secondary cases had close contact with the blood of the initial case, and it was determined that close contact with blood was the main risk factor for the two clustered outbreaks. After genome sequencing analysis, we found that the SFTSV genotype in two cases was type A, which was closely related to previous endemic strains in Xinyang. The nucleotide sequence of the SFTSV in the case was highly homologous, with a total of nine amino acid mutation sites in the coding region. It was not ruled out that its mutation sites might have an impact on the outbreak of the epidemic.

[Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation].

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Therapeutic effects and safety of apatinib mesylate on patients with gastric carcinoma peritoneal metastasis in SOX scheme.

OBJECTIVE: The aim of this study was to investigate the diagnostic values of serum tumor markers in gastric carcinoma peritoneal metastasis and the therapeutic efficacy as well as safety of apatinib mesylate combined with Geo+Oxaliplatin (SOX) scheme treatment in gastric carcinoma peritoneal metastasis. PATIENTS AND METHODS: Sixty patients with gastric carcinoma peritoneal metastasis and 11 patients without gastric carcinoma peritoneal metastasis were selected as the research subjects. The levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9] and abdominal irrigating solution exosome [micro ribonucleic acid (miR)-21 and miR-320c] and the differences in their diagnostic values were compared and analyzed. The patients with gastric cancer peritoneal metastases are then divided into two groups, one for control (30 cases receiving just SOX scheme treatment) and the other for the experiment (30 cases receiving SOX scheme treatment plus apatinib mesylate). Besides, the differences in serum tumor marker level, therapeutic efficacy, overall survival (OS), complication rating, and Quality of Life Questionnaire-Core-30 (QLQ-C30) score among patients after treatment were compared. RESULTS: Demonstrated that serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9 levels of patients in the transfer group were remarkably enhanced compared with those of patients in the non-transfer group, and the levels of abdominal irrigating solution exosome (miR-21 and miR-320c) were reduced compared with those in non-transfer group (p<0.05). The area under the curve (AUC) of the diagnosis of gastric carcinoma peritoneal metastasis by each index were 0.553, 0.880, 0.832, 0.619, 0.863, 0.651, 0.918, and 0.903, respectively. Patients in the experimental group's serum levels of CEA, CA125, CA211, CA242, CA724, and CA19-9 were noticeably lower after therapy compared to those in the control group, and their median OS was also noticeably longer (p<0.05). After treatment, the objective remission rate (ORR) and disease control rate (DCR) of the control group and experimental group amounted to 6.7% vs. 30.0% and 50.0% vs. 86.7%, respectively. ORR and DCR of the experimental group were notably higher (p<0.05). Between the patients in the control group and the experimental group, there were no glaring variations in the frequency of problems (hypertension, nausea, vomiting, bone marrow suppression, hand-foot syndrome, and leucopenia) (p>0.05). The cognitive function, emotional function, and life health scores of patients in the experimental group were significantly higher than those in the control group (p<0.05), which suggested that serum tumor markers and miR-21 as well as miR-320c showed high diagnostic efficiency in gastric carcinoma peritoneal metastasis. CONCLUSIONS: Apatinib mesylate combined with SOX scheme treatment was more effective in treating gastric carcinoma peritoneal metastasis and possessed the same safety as single SOX scheme treatment. Hence, it is worthy of clinical promotion.

An evaluation of pelvic organ prolapses in perimenopausal and menopausal Chinese females.

OBJECTIVE: The aim of the study was to evaluate the prevalence of pelvic organ prolapse (POP) and correlate the various factors including, but not limited to, educational status, socio-economic condition, body mass index (BMI), menstrual history, with the status and severity of POP. PATIENTS AND METHODS: A retrospective cross-sectional study was conducted between August 2021 and September 2022 and suspected patients of POP were considered from the outpatient Department of Gynecology and Obstetrics. The study has mainly used 3 indicators of socio-economic status, namely, occupation, education, and income. These factors were correlated and statistically analyzed with that of POP. RESULTS: The study findings revealed that there are more symptomatic patients who are illiterate as compared to asymptomatic POP and with increasing education status, there is a decrease in symptomatic POP patients (p<0.05). Also, there is a significant proportion of symptomatic POP patients in the lower class and lower middle class as compared to asymptomatic patients in each class, respectively (p<0.05). It also found that micturition difficulty and vaginal bulging are significantly correlated with the stages of POP (p<0.05). CONCLUSIONS: Educational status and socio-economic condition are significant indicators of the presence of symptoms or severity of POP. The study further concluded that menopausal females have more symptomatic POP as compared to pre-menopausal females.

[Analysis of the status of occupational disease prevention and control of enterprises in mining and manufacturing industries in China in 2019].

Objective: To analyze the status of prevention and treatment of occupational diseases among mining and manufacturing industries in China in 2019, provide the scientific basis for the formulation and revision of policies and standards of prevention and treatment of occupational diseases. Methods: In May 2022, Collecting data of a project named Surveillance of Occupational Hazards in the Workplace in 2019 through the National Surveillance System for Occupational Hazards in the workplace. Compare the status of prevention and treatment of occupational diseases in 63 563 enterprises of mining and manufacturing industries among different dimensions. Results: The training rate of managers was 76.17% and that of occupational health managers was 76.97%. The rate of reporting of occupational diseases hazardous items was 67.58%, the rate of launching of the detection of occupational hazards was 57.16%, and the rate of launching of occupational health examination was 62.42%. Excluding the distribution rate of dust mask, the installation rate of various occupational prevention facilities and the distribution rate of gas mask and hearing protector were less than 80%. The differences in all the indicators among different areas, enterprise scales, economic types were statistically significant (P<0.05) . Conclusion: There are still some enterprises which are relatively weak in the ability of the prevention and treatment of occupational diseases in China. Measures such as special support, guidance and strengthen supervision should be taken towards those enterprises toimprove the awareness of prevention and treatment of occupational diseases and the level of that.

[Periodic dynamic observation and analysis of cellular and humoral immunity indexes of adults infected with Omicron BA.1].

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.

[Effect analysis of the modified wire-loop snare technique in retrieving severely tilted inferior vena cava filters].

Objective: To examine the application effect of the modified wire-loop snare technique in retrieving severely tilted inferior vena cava filters (IVCF). Methods: The clinical data of 18 patients (12 males and 6 females, aged (62.1±13.1) years (range: 29 to 78 years)) who underwent the modified wire-loop snare technique to retrieve IVCF at the Affiliated Hospital of Qingdao University, Qingdao Eighth People's Hospital, and Jimo District Hospital of Traditional Chinese Medicine from November 2017 to April 2022 were retrospectively analyzed. The applied filters included drum-type filters (OptEase in 7 cases, Aegisy in 2 cases) and conical filters (Celect in 6 cases and Denali in 3 cases). Preoperative CT angiography and intraoperative digital subtraction angiography showed that the filter was severely tilted and the hook was covered by hyperplastic intima of the vena cave vein. A modified wire-loop snare technique was used to retrieve drum-type filters and conical filters via femoral and jugular vein approaches, respectively. After successful puncture, the long sheath was placed, the 4 F (1 F≈0.33 mm) vertebral catheter and a snare were inserted through the long sheath, and the 5 F pigtail catheter was inserted simultaneously to guide a 0.035 inch soft guide-wire (260 cm in length) to pass through the top of the filter and turning back. The tip of the soft guide-wire was snared by the vertebral catheter and pulled out of the sheath. The 4 F vertebral catheter was inserted following the tip of the guide-wire to form a wire-loop using the vertebral catheter and the pigtail catheter. After fixing the tip and tail of the soft guide-wire in vitro, the long sheath was pushed forward to cut the hyperplastic intima and the hook was pulled away from the vena cava wall to retrieve the filter under the support of two catheters. Results: The filters were successfully retrieved in 17 cases, the operation time was (25.5±8.7) minutes (range: 15 to 45 minutes), no complication occured. The hook of one filter (Celect) penetrated out of the vena vava wall and the wire-loop could not pull the hook back into the vena cava. Then the filter was removed by laparotomy. Conclusion: The modified wire-loop snare technique could retrieve the severely tilted retrivable drum-type filters and conical filters, even when serve adhesion exists between the filter and the vena cava wall.

Ingestion of Lactobacillus helveticus WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice.

Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.

[Analysis of epidemiological characteristics of bacillary dysentery with multiple-onset in Henan Province from 2005 to 2020].

Objective: To understand the epidemiological characteristics of bacillary dysentery with multiple-onset in Henan province from 2005 to 2020. Methods: The reported cases of bacillary dysentery (including confirmed cases and clinically diagnosed cases) in Henan Province from January 2005 to December 2020 were collected through China's National Disease Supervision Information Management System. The main information included gender, age, home address, date of onset and date of diagnosis. The interval between two episodes of the same case was more than 15 days, which was judged as two episodes. The incidence characteristics of bacillary dysentery patients with two or more cases in Henan Province from 2005 to 2020 were analyzed, and the regional distribution map of cases was drawn using ArcGIS software. Results: From 2005 to 2020, a total of 250 430 cases of bacillary dysentery were reported in Henan Province, with a cumulative incidence rate of 228.66/100 000. There were 2 342 cases with two or more attacks. The incidence of recurrent cases of bacillary dysentery increased year by year (χ2trend=2 932.28, P<0.001). There was no significant difference in the incidence of two or more cases of different sexes (χ2=0.39, P=0.540). There was significant difference in the incidence among different age groups (χ2=438.40, P<0.001). The incidence of two or more cases in the 60-69 age group was relatively high (1.70%). The shortest time interval between the onset of the disease was 16 days, and the longest was 5 579 days, with M (Q1, Q3) about 428 (237, 843) days. Compared with healthy people, those with a history of bacterial diseases had a higher risk of developing bacillary dysentery (RR: 4.12, 95%CI: 3.95‒4.29). Conclusion: The proportion of patients with multiple-onset shows an increasing trend, and there is an age difference.

[Novel MFN2, BSCL2 and LRSAM1 variants in a cohort of Chinese patients with Charcot-Marie-Tooth disease].

Objective: Charcot-Marie-Tooth disease (CMT) comprises a group of clinically and genetically heterogeneous inherited neuropathies with an estimated prevalence of 1 in 2500. This study aimed to analyze the clinical and mutational characteristics of Chinese CMT patients with MFN2, BSCL2 and LRSAM1 variants. Methods: In this study, genetic analysis was performed in 206 Chinese patients at Chinese PLA General Hospital from December 2012 to March 2020 with clinical diagnosis of CMT, and reported variants of MFN2, BSCL2 and LRSAM1 related to CMT2. Results: We reported ten MFN2 mutations in ten unrelated patients (7 male, 3 female), two of whom had positive family history. Three novel mutations were detected including c.475-2A>G (splicing); c.687dupA (p.E230Rfs*16) and c.558dupT (p.S186fs). We reported three BSCL2 mutations of four unrelated patients, including c.461C>G (p.S154W), c.461C>T(p.S154L), and novel variants of c.1309G>C (p.A437P) and c.845C>T (p.A282V). Furthermore, two novel variants of LRSAM1, including c.1930G>T (p.G644C) and c.1178T>A (p.L393Q) were detected in two unrelated patients. Conclusion: Mutational spectrum of MFN2-, BSCL2-and LRSAM1-related CMT disease is expanded with the identification of novel variants in Chinese patients.

[Two-dimensional equivalent mechanical modeling and finite element analysis of normal female pelvic floor system].

Objective: To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure. Methods: A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed. Results: In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH2O (1 cmH2O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body. Conclusions: The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.

[Comparison and thoughts of the training system for thoracic surgeons].

There is no unified thoracic surgery training system in China, neither in the trainee selection or evaluation, nor in the training curriculum or the graduation requirements. A literature review was performed for available publications regarding international thoracic surgical training. A brief comparison was made regarding the thoracic surgery residency programs in China, Japan, United States and United Kingdom, including training pathway, recruitments, training content, performance assessment and academic experience. In conclusion, there are four key aspects worth noting. Firstly, an effective residency programme is invaluable to specialty training, and effort should be made to create a unified training programme that allows trainee to progress from residency to specialty training smoothly. Secondly, flexibility and personalization should be allowed in higher specialty training, so that trainee can develop their subspecialty interests. Thirdly, a unified clinical curriculum, selection and standardized income should be promoted to minimalize the variation of training outcome between provinces. Fourthly, additional training and time should be allowed for trainee who wants to pursue an academic career, and academic outcomes should be evaluated alongside with the standard clinical training.

[Clinical study on the relationship between the exosomes in bronchoalveolar lavage fluid and plasma and the severity of lung injury and outcome in early acute respiratory distress syndrome patients].

Objective: To investigate the relationship between the levels of exosomes in bronchoalveolar lavage fluid (BALF) and plasma and the severity of lung injury and its outcome in patients with acute respiratory distress syndrome (ARDS). Methods: Patients who were admitted to the Department of Critical Care Medicine, Zhongda Hospital Affiliated to Southeast University and received invasive mechanical ventilation were selected from August 2020 to April 2021, and they were divided into ARDS group and non-ARDS group. Finally, 33 ARDS patients were included, including 18 males and 15 females, aged (65.5±15.5) years; 10 non-ARDS patients, 8 males and 2 females, aged (57.2±15.3) years. The BALF and plasma of the two groups of patients were collected within 24 hours after enrollment, and the total exosomes of the samples were collected by ultracentrifugation. Nanoparticle tracking analysis (NTA) was used to detect and compare the differences in exosome content between the two groups. Correlation of content with the severity and prognosis of lung injury in ARDS patients. Results: There was no significant difference in gender and age between ARDS group and non-ARDS group (both P>0.05). The exosome in plasma of ARDS group was significantly higher than that of non-ARDS group [(25.3±1.2)/ml vs (24.2±1.6)/ml, P=0.031], while the exosomes in BALF of ARDS group was also higher than that of non-ARDS group [(26.5±1.6)/ml vs (24.6±1.1)/ml, P=0.001]. The exosomes in BALF of patients with ARDS caused by intrapulmonary causes was higher than that in ARDS group caused by extrapulmonary causes [(26.9±1.5)/ml vs (25.2±0.9)/ml, P=0.01], and the infection caused by bacterial shows that the highest exosome level in BALF. The exosomes in the BALF of the mild ARDS group was significantly lower than that of the severe ARDS group [(25.7±1.3)/ml vs (27.2±1.5)/ml, P=0.038]; the exosomes in BALF of ARDS patients was negatively correlated with P/F ratio (r=-0.38, P=0.03); and it was positively correlated with Murray lung injury score (r=0.47, P=0.01). However, the static compliance levels, length of hospital stay, duration of mechanical ventilation, and 28-day outcome were not associated with the exosomes in BALF. Conclusion: Compared with non-ARDS patients, ARDS patients have significantly higher levels of exosomes in BALF and plasma, there is a certain correlation between exosomes derived from BALF and the severity of lung injury in ARDS.

[An area under curve-based nomogram to predicts vancomycin-associated nephrotoxicity in critically ill patients: a retrospective cohort study].

Objective: To develop an area under curve (AUC)-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill patients. Methods: This retrospective cohort study included adult patients treated with vancomycin in the intensive care unit at a tertiary teaching hospital from January 2015 to December 2017. Baseline clinical characteristics before vancomycin treatment and pharmacokinetic parameters were collected to establish a prediction model of nephrotoxicity. Univariate analysis was used to screen variables, and multivariate logistic regression analysis was used to establish the prediction model and nomogram. Results: A total of 159 patients met the inclusion criteria, sixty-four were included in the final analysis. Sixteen patients (25%, 16/64) developed vancomycin-associated nephrotoxicity. The following variables were incorporated into the prediction model: vancomycin AUC, estimated glomerular filtration rate (GFR), and combined nephrotoxic drugs. The following equation was established to calculate the probability of nephrotoxicity: logit (P)=-4.83+0.009×AUC-2.87×1 (if GFR>60 ml/min)+2.53×1 (if number of combined nephrotoxic drugs≥2). A nomogram was generated based on the equation. The receiver-operating characteristic curve demonstrated that the AUC of the prediction model was 0.927 (95%CI 0.851-1.000). The cut-off value of the probability of nephrotoxicity was 26.48%. The sensitivity and specificity were 87.5% and 87.5% respectively. Conclusion: The incidence of vancomycin-associated nephrotoxicity is high. The AUC-based nomogram can effectively predict vancomycin-associated nephrotoxicity in critically ill patients.

[Analysis of disease progression rate and related factors in amyotrophic lateral sclerosis patients at initial visit].

Objective: To find out the relationship of the progression rate of amyotrophic lateral sclerosis (ALS) patients with relevant clinical indicators at initial visit so as to enrich the knowledge of ALS at its early stage. Methods: The clinical data of 282 patients diagnosed with ALS at Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to March 2021 were collected in order to make a retrospective analysis of the dynamic change of the progression rate (ΔFS) and influencing factors, and thus a classification of the progression rate will be summarized. Results: Among 282 patients, 164 were males and 118 were females. The age of onset was (53±11) years old. The ΔFS had a negative exponential relationship with delay time of diagnosis no matter what kinds of onset the patients experienced (upper limb onset, lower limb onset or bulbar onset). The ΔFS for the limb function sub-group had a similar functional relationship with diagnostic delay in patients with either upper limb onset or lower limb onset. The statistical model indicated that the disease progression rate of ALS at initial visit can be classified into three types (high speed type: ΔFS≥1.0 score/month; moderate speed type: 0.5≤ΔFS<1.0 score/month; low speed type: ΔFS<0.5 score/month). The critical values of the three types in patients with upper limb onset were 8 and 20 months, while 9 and 24 months for lower limb onset patients, and 9 and 36 months for bulbar onset patients. At initial visit, there were significant statistical differences among these three types in age at onset (P=0.008), diagnostic delay (P<0.001), ALS functional rating scale-revised (ALSFRS-R) score (P<0.001) and onset site (P=0.006). The age at onset in moderate speed type was significantly greater than that of the slow speed type [(54.9±10.4) years vs (50.2±9.6) years, P=0.002]. The diagnostic delay in high speed type [6 (4, 10) months] was significantly shorter than that in moderate speed type [12 (8, 19) months, P<0.001] and low speed type [22 (14, 36) months, P<0.001], and the moderate speed type was shorter in comparison with low speed type (P<0.001). As for the ALSFRS-R score, the high speed type [36(32, 39)] was significantly lower than the moderate speed type [39 (36, 42), P<0.001] and low speed type [42 (39, 44), P<0.001], and the moderate speed type was lower in comparison with low speed type (P=0.002). The proportion of cases with upper limb onset in high speed type (20.3%) was significantly lower than that in low speed type (42.2%, P<0.001) and moderate speed type (37.5%, P=0.014). By contrast, the proportion of cases with lower limb onset in high speed type (39.2%) was significantly higher than that in low speed type (28.9%, P=0.023), however no difference was shown between the fast speed type and moderate speed type (32.0%, P=0.061). There was no difference among these three progression types in patients with bulbar onset. Conclusions: The disease progression rate of ALS at initial visit can be classified into three types including high speed, moderate speed and low speed. At early stage of ALS, ΔFS is affected by onset age, onset site, diagnostic delay and ALSFRS-R score.