Advances in the treatment of acute hepatic porphyria / 临床肝胆病杂志

Acute hepatic porphyria （AHP） is a rare disease with abnormal heme metabolism， and breakthroughs have been made in the treatment of this disease in recent years. In addition to conventional treatment methods， this article reviews new therapies for AHP that are in the stage of initial clinical application or are still in the research stage， including RNAi therapy， enzyme replacement therapy， genetic supplementation of DNA or mRNA， drug molecular chaperones， and glycine transporter inhibitors for reducing heme synthesis. Moreover， this article also reviews the treatment of AHP-related comorbidities and complications， such as hyponatremia and posterior reversible encephalopathy syndrome. High glucose infusion is the main treatment method for AHP in China， and the improvement in diagnosis and increased attention to rare diseases in China has promoted the development of the diagnosis and treatment of AHP， and it is expected to explore more suitable treatment methods for AHP in the Chinese population in the future.

Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10-3 g·kg-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3（TGF-β1/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β1 proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Clinical application of Mimics software system to three-dimensional reconstruction to guide thoracoscopic anatomic pulmonary segmentectomy / 中国胸心血管外科临床杂志

@#Objective    To investigate the clinical effect of 3D computed tomography bronchial bronchography and angiography (3D-CTBA) and guidance of thoracoscopic anatomic pulmonary segmentectomy by Mimics software system. Methods    A retrospective analysis was performed on patients who underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of Affiliated People's Hospital of Jiangsu University from June 2020 to December 2022. The patients who underwent preoperative 3D-CTBA using Materiaise's interactive medical image control system (Mimics) were selected as an observation group, and the patients who did not receive 3D-CTBA were selected as a control group. The relevant clinical indicators were compared between the two groups. Results    A total of 59 patients were included, including 29 males and 30 females, aged 25-79 years. There were 37 patients in the observation group, and 22 patients in the control group. The operation time (163.0±48.7 min vs. 188.8±43.0 min, P=0.044), intraoperative blood loss [10.0 (10.0, 20.0) mL vs. 20.0 (20.0, 35.0) mL, P<0.001], and preoperative puncture localization rate (5.4% vs. 31.8%, P=0.019) in the observation group were better than those in the control group. There was no statistically significant difference in the thoracic tube placement time, thoracic fluid drainage volume, number of intraoperative closure nail bin, postoperative hospital stay, or postoperative air leakage incidence (P>0.05) between the two groups. Conclusion    For patients who need to undergo anatomical pulmonary segmentectomy, using Mimics software to produce 3D-CTBA before surgery can help accurately identify pulmonary arteriovenous anatomy, reduce surgical time and intraoperative blood loss, help to determine the location of nodules and reduce invasive localization before surgery, and alleviate patients' pain, which is worthy of clinical promotion.

Genetic Diversity Analysis and Molecular ID Card Construction of Pinellia ternata Based on Phenotypic Traits and SSR Markers / 中国实验方剂学杂志

ObjectiveTo study the genetic diversity and genetic relationship of Pinellia ternata germplasm resources and provide the basis for germplasm identification， variety breeding， and resource conservation. MethodIn this study， 27 P. ternata were used as experimental materials to determine seven phenotypic characters， such as plant height， leaf length， and leaf width. Simple sequence repeats （SSR） primers were designed based on P. ternata transcriptome data， and polymerase chain reaction （PCR） amplification was performed on 27 P. ternata samples. The genetic diversity of P. ternata germplasm was analyzed by POPGENE32， PowerMarker V3.25， and NTSYS-PC 2.10e software. ResultA total of 10 pairs of highly polymorphic primers （PIC>0.5） and four pairs of moderately polymorphic primers （0.25<PIC<0.5） were selected. The average number of alleles detected was 3.928 6， and the average Nei's diversity index （H） and Shannon's index （I） were 0.557 8 and 1.002 9， respectively， indicating a high level of genetic diversity. Cluster analysis divided the Pinellia ternata into seven categories， and P. ternata in the same province were in the same categories. The SSR molecular ID cards of 27 P. ternata germplasm were constructed with 14 pairs of primers， and the rapid identification of P. ternata in each region was realized. ConclusionThe results of this study can lay a foundation for the genetic diversity and population structure of P. ternata and provide a scientific basis for the identification of P. ternata germplasm resources， map construction， and molecular-assisted breeding.

Preoperative MR T2WI signal characteristics of adenomyosis are closely related with the outcome of high-intensity focused ultrasound ablation: a propensity score-matched cohort study / 南方医科大学学报

OBJECTIVE@#To evaluate the correlation of magnetic resonance (MR) T2-weighted image (T2WI) signal characteristics of adenomyosis and the efficacy of high-intensity focused ultrasound (HIFU) ablation.@*METHODS@#Based on the presence or absence of patchy hyperintense foci on preoperative MR T2WI, the patients with adenomyosis undergoing HIFU treatment were divided into homogeneous signal group and heterogeneous signal group, and the heterogeneous group was further divided into heterogeneous hypointense group and heterogeneous isointense group according to signal intensity of the lesions. The patients in heterogeneous signal group were matched with the patients in the homogeneous group at a 1:1 ratio using the propensity score matching, and similarly, the patients in the heterogeneous hypointense group were matched with those in the heterogeneous isointense group at a 1:1 ratio. The non-perfused volume ratio (NPVR) and relief of dysmenorrhea were used to assess the therapeutic efficacy in the 4 groups.@*RESULTS@#A total of 299 patients were enrolled, who had a median preoperative dysmenorrhea score of 7.0 (6.0, 8.0) and a median NPVR of 53.5% (35.4, 70.1)%. After propensity score matching, the NPVR in homogeneous signal group was significantly higher than that in heterogeneous signal group [(60.3 ± 21.8)% vs (44.6±21.6)%, P < 0.05]. At 3, 6 and 12 months after HIFU, dysmenorrhea relief rates were higher in homogeneous signal group than in heterogeneous signal group, and the difference was statistically significant at 12 months (91.1% vs 76.8%, P < 0.05). The NPVR of heterogeneous hypointense group was higher than that of heterogeneous isointense group [(54.0±22.0) % vs (47.3± 22.9) %, P < 0.05]. At 6 months after HIFU, dysmenorrhea relief rate was significantly higher in heterogeneous hypointense group than in heterogeneous isointense group (91.5% vs 80.9%, P < 0.05).@*CONCLUSION@#The signal characteristics of adenomyosis on T2WI are closely related with the outcome of HIFU ablation, and its efficacy is better for homogeneous than for heterogeneous adenomyosis, and better for heterogeneous hypointense adenomyosis than for heterogeneous isointense adenomyosis.

Progress in the prevention and treatment of traditional Chinese medicine based on the mechanism of intestinal injury of various chemotherapy / 中国临床药理学与治疗学

Intestinal injury is a common adverse reaction of clinical chemotherapy drugs, which limits the further application of chemotherapy drugs and causes serious physical and mental burden to patients. At present, the mechanism of chemotherapy-induced intestinal injury is complex, and traditional Chinese medicine has an excellent preventive effect. This article reviews the related mechanisms of intestinal flora imbalance, oxidative stress, inflammatory response, cell apoptosis, and immune damage caused by chemotherapy, and summarizes the role of traditional Chinese medicine in prevention and treatment of oxidative stress, inflammatory response, cell apoptosis, and immune damage.

Effects of long working hours on the health of food-delivery workers / 中国职业医学

{L-End}Objective To investigate the current status of long working hours of food-delivery workers from food-delivery platform, and analyze its impact on their health such as occupational stress, depressive symptoms, insomnia symptoms, fatigue accumulation, and life satisfaction. {L-End}Methods A total of 2 145 food-delivery workers from two food-delivery platforms in Guangzhou City were selected as the research subjects using convenience sampling method. The occupational stress, depressive symptoms, insomnia symptoms, fatigue accumulation, and life satisfaction were investigated using the Core Occupational Stress Scale, Patient Health Questionnaire-9 items, Self-sleep Management Questionnaire, Self-diagnosis Questionnaire of Fatigue Accumulation of Workers, and World Health Organization Five-item Well Being Index. {L-End}Results The median and the 25th and 75th percentiles of weekly working hours were 63 (49,77) hours. And 92.2% (1 978/2 145) of workers, who worked more than 40 hours per week, were long working hours workers. While 70.1% (1 504/2 145) workers, who worked 55 hours or more per week, were ultra-long working hours workers. The detection rate of occupational stress, depressive symptoms, insomnia symptoms, fatigue accumulation, and low life satisfaction was 30.1%, 27.5%, 34.7%, 40.8%, and 75.1%, respectively. The longer the weekly working hours of the research subjects, the higher the detection rate of occupational stress and fatigue accumulation (all P<0.01). The results of multivariate logistic regression analysis showed that ultra-long working hours (weekly working hours ≥55 hours) was the influencing factor of occupational stress and fatigue accumulation after excluding the influence of confounding factors among workers (all P<0.05). {L-End}Conclusion The food-delivery workers of food-delivery platforms generally work long hours. Ultra-long working hours is a risk factor for occupational stress and fatigue accumulation among these workers.

Targeting the HIV reservoir: chimeric antigen receptor therapy for HIV cure / 中华医学杂志(英文版)

Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.

Virome in immunodeficiency: what we know currently / 中华医学杂志(英文版)

Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.

Effects of neuropathic pain induced by selective nerve injury model on intestinal microflora diversity in mice / 西安交通大学学报(医学版)

【Objective】 To investigate the effects of neuropathic pain induced by selective nerve injury (SNI) on intestinal microflora diversity in C57 mice. 【Methods】 36 C57 mice were randomly divided into SNI model group (n=18), sham-operation group (n=8), and control group (n=10). At day 0,1, 3, 7, and 14 after modeling, mechanical pain threshold and thermal pain sensitivity tests were carried out. At day 14 after modeling, colon content (fresh feces) from all the mice were collected for intestinal microflora diversity analysis. 【Results】 One day after modeling, the mechanical pain threshold in SNI group decreased significantly (more than 70%) due to nerve injury, and the thermal pain threshold decreased by 40%, while sham group and control group had no significant decrease. SNI group showed foot hyperalgesia, and the difference was statistically significant compared with sham group and control group (P<0.001). Compared with control group, sham-operation group had a transient decrease in thermal pain threshold on the first day after modeling (P=0.006), but there was no difference in pain threshold between the two groups on the third day after modeling. The α-diversity analysis showed that the abundance of Observed, Chao1, ACE and Simpson in SNI group was significantly lower than that in control group (P<0.05). That is, SNI group had flora disorder due to pain stimulation. Observed, Chao1, ACE, and Simpson were less abundant in sham group than in control group (P<0.05) and the change was between SNI group and control group. 【Conclusion】 Neuropathic pain induced by SNI model resulted in the decrease of mechanical pain threshold and thermal pain threshold, which leads to the reduction of intestinal flora diversity in C57 mice.

Occupational health literacy level and its influencing factors among key populations in China in 2022 / 中国职业医学

Objective To analyze the level of occupational health literacy (OHL) and its influencing factors among key populations in China. Methods The front-line workers from 31 provinces, autonomous regions, municipalities, and Xinjiang Production and Construction Corps in China were selected as the research subjects using a combination of stratified cluster random sampling and probability proportional sampling. The Occupational Health Literacy Questionnaire of National Key Populations was used to investigate the OHL level. Results In 2022, a total of 340 506 people from 23 industries were surveyed. Among them, 168 455 and 172 051 people were surveyed in the secondary and tertiary industries, respectively. The OHL level of the research subjects was 52.6%. The OHL levels of workers in the secondary and tertiary industries were 56.5% and 48.9%, respectively. The results of multivariate logistic regression analysis showed that gender, age, marital status, educational level, household registration, monthly income, employment nature, years of service and industry category were independent influencing factors for OHL level of the research subjects (all P<0.01). Specifically, females had a higher OHL level than males (P<0.01); the older the age, the higher the education level, the higher the monthly income level, the higher the OHL level (all P<0.01); the level of OHL in unmarried people was higher than that in married people (P<0.01); the OHL level of workers with non-agricultural household registration was higher than that of workers with agricultural household registration (P<0.01); the OHL levels of workers in state-owned enterprises, foreign-funded enterprises and public institutions were higher than those in private enterprises (all P<0.01); the level of OHL in the group with 21.0-43.0 years of service was lower than that in the other years of service groups (all P<0.01); the OHL level of workers in the secondary industry was higher than that in the tertiary industry (P<0.01). Conclusion The workers in the key industries selected by the tertiary industry, the private enterprises in the secondary industry, those with more than 21.0 years of service, and the disadvantaged groups with younger age low income, low education level, and the agricultural household registration are the key groups for the improvement of OHL level in the future. Appropriate intervention methods and strategies should be actively explored to improve the OHL of these key populations.

Clinical research advances in chimeric antigen receptor T-cell therapy for primary liver cancer / 临床肝胆病杂志

Primary liver cancer (PLC) has the features of insidious onset and difficulties in early diagnosis, with limited and ineffective therapeutic options. Chimeric antigen receptor (CAR) T-cell therapy is a genetically modified T-cell therapy that recognizes tumor-specific antigens and activates T cells to exert a tumor-killing effect. CAR T-cell therapy has made great progress in the treatment of hematological tumors and has achieved a good clinical effect in the field of solid tumors in recent years, and although CAR T-cell therapy has developed from the first to the fifth generation, there are still many challenges in the field of solid tumors. This article comprehensively reviews the mechanisms of CAR T-cell therapy for PLC and related research advances, including the main targets such as GPC3, AFP, MUC1, and NKG2D in CAR T-cell therapy for PLC, CAR T-cell therapy for PLC and oncolytic virus, and combined treatment with immune checkpoint inhibitors, as well as the advances in the biological, preclinical, and clinical studies on these targets and treatment modalities and the challenges and solutions for CAR T-cell therapy in the treatment of PLC, so as to provide a reference for the future clinical development of CAR T-cell therapy in liver cancer.

Prevalence of job burnout and associated influencing factors among healthcare workers in China / 环境与职业医学

Background Healthcare workers suffer from great internal and external pressure and are prone to burnout. Existing studies have shown that depressive symptoms are important influencing factors of burnout, both of which are closely related to job stress. Objective To analyze overall prevalence of burnout among healthcare workers using a new survey tool developed by our team, and to reveal potential influencing factors related to burnout. Methods A cross-sectional multi-center study was conducted in August–October 2019 and June–September 2020, using multi-stage stratified cluster sampling. A total of 8738 healthcare workers from 22 hospitals in 5 provinces (Shandong, Hubei, Hunan, Guangdong, and Chongqing) of China were selected in this study. A set of survey questionnaires, including the general information questionnaire and the Chinese versions of General Burnout Scale, Core Occupational Stress Scale, Patient Health Questionnaire-9, and Self-administered Sleep Questionnaire were distributed. Independent samples t-test or one-way ANOVA were employed for inter-group comparison of burnout. Spearman correlation was used to evaluate correlations among burnout, depressive symptoms, and occupational stress. Stepwise linear regression was conducted to identify factors independently associated with burnout. Process plug-in was used to test potential mediating effect of depressive symptoms on occupational stress and burnout. Results Of the 8738 questionnaires distributed, 8456 valid questionnaires were collected, and the recovery rate was 96.77%. Among the 8456 healthcare workers, the prevalence of burnout was 58.0%, that of occupational stress was 31.8%, and that of depressive symptoms was 31.0%. Among those with depressive symptoms and occupational stress, the proportions of burnout were 86.7% and 83.7%, respectively. According to the stepwise linear regression analysis, depressive symptoms, occupational stress, work experience, drinking, and marital status were all independent influencing factors of burnout. Especially, depressive symptoms, social support, and organization and reward had significant influences on burnout (b'=0.455, −0.183, 0.220, P<0.001). Depressive symptoms showed mediating effects on occupational stress (and its subscales) and burnout, and the contribution rates of the mediating effects were 41.00%, 47.02%, 43.44%, 56.62%, and 59.45%, respectively. Conclusion Burnout is a prominent problem among healthcare workers in the 5 provinces, with the prevalence of 58.0%. And nearly 1/3 suffering from depressive symptoms and occupational stress, which has a great impact on burnout.

Job burnout and influencing factors among Chinese manufacturing employees / 环境与职业医学

Background Manufacturing industry is the main body of China's national economy, and manufacturing employees provide solid guarantee and support for the vigorous development of China's manufacturing industry. The research on job burnout of manufacturing employees is helpful to prevent or alleviate the health damage and economic loss caused by job burnout. Objective To investigate the status and influencing factors of job burnout among manufacturing employees in China, and evaluate the potential mediating effect of job burnout between job stress and depressive symptoms. Methods A cross-sectional study was performed from August to October 2019 and from June to September 2020 in seven provinces of China. Study participants were recruited from 21 manufacturing companies covering 11 manufacturing subdivisions using multistage stratified cluster sampling. General Burnout Scale, Core Occupational Stress Scale, and Patient Health Questionnaire-9 were used to evaluate job burnout, job stress, and depressive symptoms. Mann-Whitney U test and Kruskal-Wallis H test were used to compare data between two independent samples and multiple independent samples of measurement data; Pearson χ2 test was used to compare the rate of enumeration data; Spearman rank correlation analysis was used to evaluate correlation between selected variables; binary logistic regression was used for multivariate analysis; stepwise regression and bias-corrected Bootstrap method were used to test potential mediating effect. Results A total of 10973 valid questionnaires were collected. The M (P25, P75) scores of exhaustions, cynicism, professional efficacy, job burnout, job stress, and depressive symptoms were 1.6 (0.4, 3.0), 1.0 (0.2, 2.2), 4.8 (3.2, 5.7), 1.6 (0.8, 2.5), 45.0 (40.0, 50.0), and 7.0 (4.0, 11.0), respectively. The positive rates of job burnout, job stress, and depressive symptoms were 53.4% (5865/10973), 28.4% (3116/10973), and 29.4% (3231/10973), respectively. The influencing factors of job burnout were gender (versus male; OR for female=0.852), age (versus≤25 years old; ORs for 26-30, 31-40, 41-50, 51-60 years old=0.824, 0.819, 0.738, 0.677), education level (versus junior high school or below; ORs for senior high school/technical secondary school, junior college/vocational college, graduate school or above=1.119, 1.345, 1.331), income per month (versus＜3000 yuan; ORs for 3000-4999, 5000-6999, 7000-8999, 9000-10999, ≥11000 yuan=0.513, 0.470, 0.430, 0.375, 0.411), position (versus assembly line; OR for non-assembly line=0.814), average weekly working hours (versus ≤40 h; ORs for 61-70, ＞70 h=1.199, 1.519), and drinking (versus non-drinking; OR for drinking=1.261). Job burnout was positively correlated with job stress and depressive symptoms (r=0.556, 0.508, P<0.001). Job burnout played a partial mediating role between job stress and depressive symptoms, and its contribution value accounted for 63.2% of the total effect. Conclusion Manufacturing industry employees' job burnout problem is prominent in China, and there are many factors affecting job burnout. Job burnout may play a partial mediating role between job stress and depressive symptoms in the target group.

Five profiles and influencing factors of burnout-engagement continuum in working populations of China / 环境与职业医学

Background With the rise and deepening of positive psychology research, theoretical research on job burnout is also deepening worldwide, and some new theoretical models are proposed, such as the burnout-engagement continuum, but there is still a lack of empirical research and application in China. Objective To analyze the current situation and influencing factors of five profiles in the burnout-engagement continuum in working populations of China: job engagement, ineffective, overextended, disengaged, and burnout. Methods From August to October 2019 and June to September 2020, a total of 27344 subjects of key occupations in six typical industries, including teachers, firefighters, manufacturing workers, medical staff, flight attendants, and traffic police, were selected from 10 provinces (cities) in the eastern, middle, and western regions of China by multistage stratified cluster sampling method for cross-sectional investigation. Maslach Burnout Inventory-General Survey and Core Occupational Stress Scale were used to evaluate job burnout and occupational stress respectively. χ2 test was used to compare rates of count data. Binary logistic regression was used for multivariate analysis of the five profiles. Results Among the subjects, 24.4%, 61.9%, 31.9%, 12.7%, and 11.8% were the prevalence rates of job engagement, ineffective, overextended, disengaged, and burnout, respectively. Flight attendants (35.7%), firefighters (29.0%), traffic police (28.5%), and manufacturing workers (26.5%) had high prevalence rates of job engagement profile. Medical stuff (62.9%) and manufacturing workers (61.8%) had high prevalence rates of ineffective profile. Teachers (39.2%), traffic police (37.2%), and medical stuff (35.5%) had high prevalence rates of overextended profile. Traffic police (17.9%), medical staff (14.3%), and teachers (13.4%) had high prevalence rates of disengaged profile. Traffic police (16.9%), medical staff (13.4%), and teachers (13.3%) had high prevalence rates of burnout profile. The results of multivariate analysis showed that gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress entered into the regression equations of job engagement, ineffective, overextended, disengaged, and burnout. The risks of overextended (OR=1.456-2.970), disengaged (OR=1.306-4.092), and burnout (OR=1.302-4.102) among the high rating groups of the four factors of occupational stress were higher than those among the low rating groups. Flight attendants (OR=0.296) and firefighters (OR=0.329) had lower risks of burnout than teachers, and flight attendants (OR=0.392) and firefighters (OR=0.466) had lower risks of disengaged than teachers. Conclusion Among the prevalence rates of the five profiles in the burnout-engagement continuum in the 6 typical occupational populations in China, ineffective profile is the highest, followed by overextended, and burnout is the lowest. Gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress have different effects on the five profiles, but industry and occupational stress have greater impacts on job burnout.

Reliability and validity of General Burnout Scale in multiple populations / 环境与职业医学

Background As one of the common tools for job burnout assessment, Maslach Burnout Inventory-General Survey (MBI-GS), its reliability and validity across different populations in China have not been examined yet. Objective To evaluate the reliability and validity of General Burnout Scale (GBS) by multiple occupational groups through the translation and preliminary test of MBI-GS. Methods Based on the Special Project of Occupational Hazards in Key Populations led by the Institute of Occupational Health and Poison Control, China CDC, key occupational groups in five typical industries were selected by multi-stage stratified cluster sampling, including teachers, firefighters, manufacturing workers, medical staff, and traffic police. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of GBS by single-factor, two-factor, and three-factor structure models. The model fitness was assessed by ratio of the chi-square statistic to the respective degrees of freedom (χ2/ν), root mean square error of approximation (RMSEA), goodness-of-fit index (GFI), comparative fit index (CFI), and parsimony-adjusted non-normed fit index (PNFI). Spearman correlation analysis was used to calculate the criterion validity of GBS with occupational stress, depressive symptoms, and sleep disorders. Cronbach's α coefficient and composite reliability (CR) coefficient were used to evaluate the internal consistency reliability of GBS. Results A total of 3485 subjects were surveyed in this study, 3375 valid questionnaires were recovered with a valid response rate of 96.84%. The results of CFA showed that in the adjusted three-factor structure model of GBS (exhaustion, cynicism, and professional efficacy), the χ2/ν < 4, the RMSEA ranged from 0.032 to 0.069, the GFI > 0.90, the CFI > 0.90, and the PNFI > 0.70, which illustrated a good fitness than that of the single- or the two-factor structure models in different occupational groups. The Spearman correlation analysis results showed that occupational stress, depressive symptoms, and sleep disorders were positively correlated with exhaustion and cynicism dimensions, and negatively correlated with professional efficacy dimension of the GBS, with the \begin{document}$ \left| r \right| $\end{document} ranging from 0.139 to 0.662 (P<0.05) in overall subjects. For traffic police and firefighters, professional efficacy was not correlated with depressive symptoms or sleep disorders (P>0.05). The Cronbach's α coefficients ranged from 0.819 to 0.899, and the CR values ranged from 0.941 to 0.978 in different occupational groups. Conclusion The GBS shows high reliability and validity, as well as good application effects in different occupational groups.

Hepatitis B virus X protein promotes podocyte pyroptosis in hepatitis B virus-associated glomerulonephritis by down-regulating microRNA -223 targeting NLRP3 inflammasome / 中华肝脏病杂志

Objective: To investigate the potential function and related mechanism of microRNA-223 (miRNA-223) in the podocyte pyroptosis of hepatitis B virus (HBV)-associated glomerulonephritis induced by HBV X protein (HBx). Methods: HBx-overexpressing lentivirus was transfected into human renal podocytes to mimic the pathogenesis of HBV-GN. Real-time fluorescence quantitative PCR and Western blotting experiments were used to detect the mRNA and protein expression of pyroptosis-related proteins [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1], and inflammatory factors (interleukin-1β and interleukin-18), respectively.TUNEL staining and flow cytometry were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression of podocytes biomarkers desmin and nephrin; Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to measure caspase-1 activity. The dual luciferase reporter gene assay was used to verify the downstream target of miRNA-223. Podocytes were divided into the following nine groups: control group (no special treatment), empty plasmid group (transfected with empty plasmid), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+miRNA-223 mimic group (transfected with HBx overexpression lentivirus and miRNA-223 mimic), HBx overexpression+miRNA-223 inhibitor group (transfected with HBx overexpression lentivirus and miRNA-223 inhibitor), HBx overexpression+miRNA-223 mimic+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 mimic+ NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 siRNA), HBx overexpression+miRNA-223 inhibitor+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 inhibitor+NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 siRNA). Results: miRNA-223 was down-regulated in HBx overexpression group compared with the control group (P < 0.05). TUNEL and immunofluorescence staining showed that NLRP3 knockdown attenuated podocyte injury and pyroptosis induced by HBx overexpression (P < 0.05). Dual luciferase reporter gene assay demonstrated that NLRP3 was one of the downstream targets of miRNA-223. Rescue experiments revealed that NLRP3 overexpression weakened the protective effect of miRNA-223 in podocyte injury (P < 0.05). The addition of miRNA-223 mimic and NLRP3 siRNA decreased the expression of NLRP3 inflammasome and cytokines, and reduced the number of pyroptosis cells induced by HBx overexpression (all P < 0.05); The addition of miRNA-223 inhibitor and NLRP3 overexpression plasmid significantly increased the expression of NLRP3 inflammasome and cytokines, caspase-1 activity, and the number of pyroptosis cells (all P < 0.05). Conclusion: HBx may promote podocyte pyroptosis of HBV-GN via downregulating miRNA-223 targeting NLRP3 inflammasome, suggesting that miRNA-223 is expected to be a potential target for the treatment of HBV-GN.

Biomechanical analysis of four internal fixations for Pauwels Ⅲ femoral neck fractures with defects / 中国骨伤

OBJECTIVE@#To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture.@*METHODS@#Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared.@*RESULTS@#When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS.@*CONCLUSION@#For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Modification of C20 oxidase in tanshinone biosynthesis pathway / 中国中药杂志

Tanshinones are one of the main effective components of Salvia miltiorrhiza, which play important roles in the treatment of cardiovascular diseases. Microbial heterogony production of tanshinones can provide a large number of raw materials for the production of traditional Chinese medicine(TCM) preparations containing S. miltiorrhiza, reduce the extraction cost, and relieve the pressure of clinical medication. The biosynthetic pathway of tanshinones contains multiple P450 enzymes, and the catalytic element with high efficiency is the basis of microbial production of tanshinones. In this study, the protein modification of CYP76AK1, a key P450-C20 hydroxylase in tanshinone pathway, was researched. The protein modeling methods SWISS-MODEL, Robetta, and AlphaFold2 were used, and the protein model was analyzed to obtain the reliable protein structure. The semi-rational design of mutant protein was carried out by molecular docking and homologous alignment. The key amino acid sites affecting the oxidation activity of CYP76AK1 were identified by molecular docking. The function of the obtained mutations was studied with yeast expression system, and the CYP76AK1 mutations with continuous oxidation function to 11-hydroxysugiol were obtained. Four key amino acid sites that affected the oxidation acti-vity were analyzed, and the reliability of three protein modeling methods was analyzed according to the mutation results. The effective protein modification sites of CYP76AK1 were reported for the first time in this study, which provides a catalytic element for different oxidation activities at C20 site for the study of the synthetic biology of tanshinones and lays a foundation for the analysis of the conti-nuous oxidation mechanism of P450-C20 modification.