Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Effects of HMGB1 on phenotypes, phagocytosis and ERK/JNK/P38 MAPK signaling pathway in dendritic cells / 中国药理学通报

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Influence of quercetin on aging of bone marrow mesenchymal stem cells induced by microgravity / 中国药理学通报

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study

Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

The predictive value of platelet-to-lymphocyte ratio for weaning failure in septic patients receiving mechanical ventilation / 中华预防医学杂志

Objective: To determine the ability of the ratio of platelet to lymphocyte (PLR) for predicting extubation failure in septic patients receiving invasive mechanical ventilation (IMV). Methods: The retrospective cohort study was conducted in ICU at Beijing Chao-Yang Hospital Shijingshan District, Capital Medical University in China from January, 2010 to December, 2019, including patients with sepsis who received IMV. 180 patients were enrolled in the study, including 111 male and 69 female, with the age range of 23-93 years and the median age of 76 years, and with an average age of 71.22 years. The medical records were reviewed, such as age, sex, acute physiology and chronic health evaluation II (APACHEII), sequential organ failure assessment (SOFA), spontaneous breathing trial (SBT) outcome, weaning outcome, complete blood count before SBT. According to weaning outcome, patients were divided into weaning failure and weaning success group. The difference of PLR, white blood cell(WBC), C-reaction protein (CRP) and procalcitonin (PCT) were compared between weaning failure and success group. Receiver-operating characteristics (ROC) curves and multivariate logistical regression analysis were employed to analyze the performance of these inflammatory markers for predicting weaning failure in patients with sepsis. Results: 180 patients with sepsis were included in the study and 37 patients (20.5%) experienced weaning failure (31 SBT failure and 6 extubation failure after successful SBT). PLR was higher in weaning failure group than that in weaning success group (Z=-5.793,P<0.001). Other inflammation biomarkers such as WBC, CRP and PCT were also higher in weaning failure group than that in weaning success group(Z=-4.356, -3.118 and -2.743, P<0.001, 0.002 and 0.006, respectively). According to ROC curves, PLR has a better predictive ability for weaning failure (AUC=0.809,95%CI 0.733-0.885) when compared to WBC (AUC=0.773,95%CI 0.648-0.817), CRP (AUC=0.666,95%CI 0.577-0.755) and PCT (AUC=0.603,95%CI 0.508-0.698). The cutoff value of PLR for predicting weaning failure was 257.69 with sensitivity 78.38%, specificity 76.22%, and diagnostic accuracy 71.66%. According to multivariate logistic regression analyses, PLR>257.69 was an independent risk factor for predicting weaning failure in patients with sepsis. Conclusions: PLR may be a valuable biomarker for predicting weaning failure in septic patients receiving IMV, and the patients with higher PLR should be handled with caution since they are at higher risk of weaning failure, and some more effective treatment should be in consideration after extubation.

Research on rapid detection technology of airborne pathogenic organisms based on up-conversion phosphor technology / 中华预防医学杂志

Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 107 CFU/ml and 108 CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 104 CFU/ml. Detection sensitivity of Yersinia pestis ≥103 CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥103 CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 104 CFU/m3, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.

Analysis of the core knowledge level of chronic diseases in Chinese adults and related factors / 中华预防医学杂志

Objective: To understand the core knowledge level and influencing factors of chronic disease prevention and control in Adults in China, and to provide a scientific basis for formulating chronic disease prevention and control measures. Methods: In this study, cross-sectional survey and quota sampling were used to recruit 173 819 permanent residents aged 18 and above from 302 counties of adult chronic diseases and nutrition surveillance in China to conduct an online questionnaire survey, including basic information and core knowledge of chronic diseases. The scores of the core knowledge of chronic disease prevention and control were described by median and interquartile range, the Wilcoxon rank sum test or the Kruskal Wallis test was used for the inter-group comparison, and the correlation factors of the total score were analyzed by the multilinear regression model. Results: A total of 172 808 participants were surveyed in 302 counties and districts, of which 42.60%(73 623) were male and 57.40%(99 185) were female; The proportion of respondents aged 18-44, 45-59, and 60 years old and above was 54.74% (94 594), 30.91% (53 423) and 14.35% (24 791), respectively. The total score of the core knowledge of chronic prevention and control in the total population was 66(13), and the scores of different characteristic groups were different, and the differences were statistically significant: the eastern region had the highest score at 67(11) (H=840.66, P<0.01), the urban 66(12) was higher than the rural 65(14) (Z=-31.35, P<0.01), and the male 66(14) was lower than female 66(12) (Z=-11.66, P<0.01), 18-24 years old 64(13) was lower than other age groups(H=115.80, P<0.01), and undergraduate degree and above had the highest score compared to other academic qualifications, with 68(9) points(H=2 547.25, P<0.01). Multivariate analysis showed that eastern (t=27.42, P<0.01), central (t=17.33, P<0.01), urban (t=5.69, P<0.01), female (t=17.81, P<0.01), high age (t=46.04, P<0.01) and high education (t=57.77, P<0.01) had higher scores of core knowledge of chronic disease prevention and control than other groups, the scores of core knowledge of chronic disease prevention and control of professional and technical personnel (t=8.63, P<0.01), state enterprises and institutions (t=38.67, P<0.01), agriculture, forestry, animal husbandry, fishery and water conservancy production (t=5.30, P<0.01), production, transportation and commercial personnel (t=24.87, P<0.01), and other workers (t=8.89, P<0.01) were higher than those of non-employed people. Conclusion: There are differences in the total scores of the core knowledge of chronic disease prevention and control in different characteristics of people in China, and in the future, health education on the prevention and treatment of chronic diseases should be strengthened for specific groups to improve the knowledge level of residents.

Association between urinary arsenic level and serum testosterone in Chinese men aged 18 to 79 years / 中华预防医学杂志

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.

Development and validation of prognostic nomogram for malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project / 老年心脏病学杂志（英文版）

BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Clinical Characteristics and Survival Analysis of Carbapenem-Resistant Pseudomonas Aeruginosa Colonized or Infected Patients with Hematological Disorders / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA.@*METHODS@#The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed.@*RESULTS@#A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034).@*CONCLUSIONS@#Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.

Clinical characteristics and survival of patients with HIV/AIDS and pulmonary tuberculosis / 公共卫生与预防医学

Objective To analyze the clinical characteristics of patients with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) and pulmonary tuberculosis, and investigate their survival and influencing factors of survival. Methods A total of 107 patients with HIV/AIDS and pulmonary tuberculosis were selected. The relationships of clinical symptoms, CT findings and CD4 cell count with positive laboratory tests were analyzed. Th survival of patients was investigated, and independent risk factors for death were analyzed. Results Most the 107 patients had symptoms such as cough, chest pain and fatigue. CT findings mainly included patchy shadow (75.70%), tree-in-bud sign (46.73%), nodular shadow (35.51%) and pulmonary hilar or mediastinal lymph node enlargement (86.92%). The proportion of lesions ≥ 3 pulmonary fields (47.66%) was higher. The positive rates of purified protein derivative (PPD), acid-fast bacilli and Mycobacterium tuberculosis were significantly higher in the CD4 cell count > 200/µL group than in the ≤200/µL group (P<0.05). There were statistically significant differences in body mass index (BMI), baseline CD4 cell count, multidrug resistant tuberculosis (MDR-TB) and standard anti-tuberculosis treatment between the survival group and the death group (P<0.05). Baseline CD4 cell count ≤200/µL, MDR-TB, and no standard anti-tuberculosis treatment were independent risk factors for death of patients with HIV/AIDS and pulmonary tuberculosis (P<0.05). Conclusion The clinical symptoms and imaging manifestations of patients with HIV/AIDS and pulmonary tuberculosis are complex and diverse, but characteristic. Baseline CD4 cell count ≤200/µL, MDR-TB and no standard anti-tuberculosis treatment are main risk factors for death of the patients.

Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis / 中华劳动卫生职业病杂志

Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.

Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review / 中华儿科杂志

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study / 中华妇产科杂志

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.

CT findings and dynamic changes of COVID-19 in the patients younger than 18 years old infected with SARS-CoV-2 Omicron variant / 中国热带医学

@#navirus disease 2019 (COVID-19) in the patients younger than 18 years old infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and to provide a basis for determining the chest CT changes and efficacy of COVID-19 caused by Omicron virus variant in patients younger than 18 years old. Methods　The clinical and imaging data of 30 cases of patients younger than 18 years old infected with COVID-19 Omicron variant, who admitted to the Third People's Hospital of Shenzhen from February 11 to March 26, 2022 were collected and retrospectively analyzed. The clinical manifestations, imaging features and dynamic changes of lesions were summarized. Results A total of 41 intrapulmonary lesions in 30 patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The main manifestations were patchy or nodular ground-glass opacities and/or consolidation, with focal subpleural distribution, lesions mainly occur in the right lung (70.73%, 29/41). There were 42 lesion morphologies, with 22 (52.38%) striped shadows and 16 (38.10%) nodular shadows, with small lamellar and patchy shadows predominating. There were 36 lesion density variations, with ground glass shadows being the most common, with a total of 24 ground glass shadows (66.66%) in each lobe of the lung, and also 6 consolidation lesions (16.67%) and 6 mixed ground glass opacity and consolidation lesions (16.67%). With the progression of the disease, lesions gradually enlarged, appeared on the 2nd day (312.93 mm3), peaked on the 9th day (1 837.18 mm3). The average absorption time of the lesions was (16±3) days, and there was no significant difference between the absorption time of patchy and nodular lesions (ground glass and/or consolidation) (t=0.853, P>0.05). The lesions showed focal ground-glass opacity in the early stage, 77.78% lesions were absorbed after treatment in the late stage. Inflammatory nodules were absorbed slowly (9-19 days), without residual fibrotic changes. Conclusions　The imaging manifestations of COVID-19 in patients younger than 18 years old infected with SARS-CoV-2 Omicron variant have certain characteristics, showed patchy or nodular ground glass opacities and/or consolidation, mainly distributed in the subpleural area, with small and few lesions and slow change, didn't remain fibrosis. Being familiar with its clinical and imaging manifestations can assist in early diagnosis, but confirming the diagnosis requires a combination of epidemiological history, clinical symptoms, SARS-CoV-2 nucleic acid and radiological manifestations.

The value of peripheral blood and pleural effusion T-SPOT.TB combined with pleural effusion adenosine deaminase in diagnosis of tuberculous pleurisy / 中国热带医学

@#Abstract: Objective To explore the relationship between peripheral blood and pleural effusion tuberculosis (TB) infection effector T cells, and to further evaluate the value of combined pleural effusion adenosine deaminase (ADA) for rapid diagnosis of tuberculous pleurisy. Methods The test data of 80 cases of tuberculous pleurisy and 70 cases of nontuberculous pleurisy treated in the Sixth People's Hospital of Nantong City from January 2017 to December 2020 were analyzed. The TBinfected effector T cells were also detected simultaneously in the peripheral blood and the pleural effusion by the T-SPOT technique, and the pleural effusion ADA was detected by the rate method. The subject operating characteristic curve (ROC) was applied to take the optimal pleural effusion ADA threshold to compare the sensitivity and specificity of different critical values. Person phase analysis was applied to analyze the correlation between peripheral blood and pleural effusion T-SPOT.TB. Data of peripheral blood, pleural effusion T-SPOT.TB and ADA were integrated. Results When pleural effusion ADA>45 U/L, the sensitivity and specificity for the diagnosis of tuberculous pleurisy were 50.0% and 94.3%, respectively; when ADA > 25.15 U/ L, the sensitivity and specificity were 80.0% and 72.9%. When ADA > 45 U / L, pleural/ blood T-SPOT.TB spot ratio (spot forming cells, SFCs) > 2 times, the specificity for the diagnosis of tuberculous pleurisy was 100% (highest); when 25.15 U/L< pleural effusion ADA ≤ 45 U/L, pleural/blood T-SPOT.TB spot ratio > 2 times, the specificity for the diagnosis of tuberculous pleurisy was 92.3% (second). When pleural effusion ADA ≤ 25.15 U/L, and the pleural effusion/blood T-SPOT.TB spot number ratio > 2 times, with 83.3% specificity (the lowest of the three groups). Conclusions The level of pleural effusion ADA is one of the most used methods for diagnosing tuberculous pleurisy. Further combination of pleural effusion and blood T-SPOT.TB, if the ratio of pleural effusion / blood T-SPOT. TB spots is greater than 2 times, it can further improve the diagnosis rate of tuberculous pleurisy.

Recombinant Schistosoma japonicum egg ribonuclease SjCP1412 inhibits the activation of LX-2 hepatic stellate cells in vitro / 中国血吸虫病防治杂志

Objective To investigate the effect of recombinant Schistosoma japonicum egg ribonuclease SjCP1412 (rSjCP1412) on proliferation, cell cycle, apoptosis and activation of human hepatic stellate cells LX-2 in vitro, and explore the underlying mechanisms. Methods The rSjCP1412 protein was expressed in Escherichia coli BL21 by prokaryotic expression, and the highly purified soluble rSjCP1412 protein was prepared by Ni NTA affinity chromatography and urea gradient refolding dialysis. Yeast RNA was digested using 12.5, 25.0, 50.0 µg rSjCP1412 proteins at 37 °C for 2, 3, 4 h, and the enzymatic products were electrophoresed on 1.5% agarose gel to observe the RNAase activity of rSjCP1412 protein. The proliferation of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was measured using CCK-8 assay, and the apoptosis of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was detected using the Annexin V-FITC/PI double staining, while the percentage of LX-2 cells at G0/G1, S and G2/M phases of cell cycle following stimulation with different doses of rSjCP1412 protein for 48 h was detected by DAPI staining. The type I collagen, type III collagen and α-smooth muscle actin (α-SMA) mRNA expression was quantified using quantitative florescent real-time PCR (qPCR) assay and Western blotting at transcriptional and translational levels in LX-2 cells following stimulation with different doses of rSjCP1412 protein for 48 h, while soluble egg antigen (SEA) served a positive control and PBS without rSjCP1412 protein as a normal control in the above experiments. The expression of collagen I, α-SMA and Smad4 protein was determined using Western blotting in LX-2 cells following stimulation with rSjCP1412 protein, transforming growth factor-β1 (TGF-β1) alone or in combination, to examine the signaling for the effect of rSjCP1412 protein on LX-2 cells. Results The rSjCP1412 protein was successfully expressed and the highly purified soluble rSjCP1412 protein was prepared, which had a RNase activity. Compared with the normal group, the survival rates of LX-2 cells significantly decreased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein and SEA for 48 h (F = 22.417 and 20.448, both P values < 0.05). The apoptotic rates of LX-2 cells significantly increased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h (F = 11.350, P < 0.05), and treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h resulted in arrest of LX-2 cells in G0/G1 phase (F = 20.710, P < 0.05). Treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h caused a significant reduction in relative expression levels of collagen I (F = 11.340, P < 0.05), collagen III (F = 456.600, P < 0.05) and α-SMA mRNA (F = 23.100, P < 0.05) in LX-2 cells, and both rSjCP1412 protein and SEA treatment caused a significant reduction in collagen I (F = 1 302.000, P < 0.05), α-SMA (F = 49.750, P < 0.05) and Smad4 protein expression (F = 52.420, P < 0.05) in LX-2 cells. In addition, rSjCP1412 protein treatment inhibited collagen I (F = 66.290, P < 0.05), α-SMA (F = 31.300, P < 0.05) and Smad4 protein expression (F = 27.010, P < 0.05) in LX-2 cells activated by TGF-β1. Conclusion rSjCP1412 protein may induce apoptosis of LX-2 cells and inhibit proliferation, cell cycle and activation of LX-2 cells through down-regulating Smad4 signaling molecules.

Value of Reduced Field-of-view DWI in Quantitative Assessment of Axial Spondyloarthritis / 中山大学学报(医学科学版)

ObjectiveTo investigate the value of reduced field-of-view DWI （r-FOV DWI） in quantitative assessment of axial spondyloarthritis. MethodsA total of 112 patients with chronic back pain or suspected axial spondyloarthritis receiving full field-of-view DWI （f-FOV DWI） and reduced field-of-view DWI （r-FOV DWI） from December 2019 to December 2021 were enrolled. Next， subjective image quality assessment （anatomical detail， artifacts， distortion， overall image quality） and objective image quality assessment including （signal to noise ratio and contrast to noise ratio） were conducted by two experienced radiologists. In addition， the Apparent Diffusion Coefficient （ADC） values of three groups （active group， inactive group， and control group） on the two DWI sequences were measured by the two radiologists， respectively. Finally， the consistency of measurement between the two researchers was evaluated and the differences in ADC values was compared. Results102 patients were included and were divided into three groups， including the active group （n=32）， inactive group （n=29）， and control group （n=41） according to ASAS diagnostic criteria. All subjective and objective image quality metrics were rated in favor of r-FOV DWI images compared with f-FOV DWI images ［overall image quality： DWI 4（3~4） vs. 3（3~3） and SNR： 6.58（5.05~10.38） vs. 4.46（2.37~10.04）， CNR： 2.04（-1.14~8.29） vs. 0.97（-8.19~7.12）；P＜0.05］. Inter-rater consistency of the two researchers were 0.60~0.74. According to the AUC curve， group inactive vs. control showed r-FOV DWI was better than f-FOV DWI. In other groups （lesion vs. control， active vs. inactive）， there were no differences between both sequences（P＜0.05）. ConclusionThe subjective image quality score and signal to noise ratio of r-FOV DWI were higher than those of f-FOV DWI， which could be used for quantitative assessment of axial spondyloarthritis.