BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

BACKGROUND:Periprosthetic fracture of the femoral of the knee after total knee arthroplasty is one of the common complications,and there is a lack of biomechanical research on the periprosthetic fractures of the femoral of the knee under different bone strength conditions.The three-dimensional finite element analysis can provide a biomechanical basis for clinical practice. OBJECTIVE:To investigate the biomechanical changes of anterior femoral notching after total knee arthroplasty under different bone strengths,and to provide a mechanical basis for the clinical prevention of supracondylar femoral periprosthetic fractures after knee arthroplasty. METHODS:The femoral CT data of healthy adults were obtained,and the three-dimensional model of femoral lateral replacement of the knee joint was established by Mimics,Geomagic studio,and Solidworks software.Anterior femoral notching models of different depths were constructed,and the models were imported into ANSYS software to analyze the changes of biological stress on the femoral condyle with different bone strengths and different anterior femoral notching depths.The stress changes of the femoral anterior condyle section after and before the filling of anterior femoral notching with bone cement were analyzed. RESULTS AND CONCLUSION:(1)Under any bone strength,the supracondylar stress increased with the depth of anterior femoral notching.In normal bone conditions,there was a stress abrupt change point when the anterior femoral notching depth was between 3 mm and 4 mm.In the case of osteoporosis,there was a stress abrupt point when the anterior femoral notching depth was between 2 mm and 3 mm.(2)When anterior femoral notching occurred during knee arthroplasty and the depth exceeded the thickness of the bone cortex,the supracondylar stress of the femoral gradually increased as the bone strength decreased.(3)The stress of the anterior femoral condyle section decreased when the model with an anterior femoral notching depth of 3 mm was filled with bone cement.(4)The results show that anterior femoral notching should be avoided during knee arthroplasty,especially in patients with osteoporosis.If anterior femoral notching occurs during surgery,bone cement can be used to evenly fill the anterior femoral notching to reduce the supracondylar stress of the femur and reduce the incidence of periprosthetic fractures of the femoral joint

Objective: To analyze the temporal variation patterns of sickness absenteeism among primary and secondary school students in Shanghai, so as to explore models suitable for predicting peaks and intensity of absenteeism rates. Methods: The seasonal and trend decomposition using loess (STL) method was used to analyze the seasonal and long term trend changes in sickness absenteeism among primary and secondary school students from September 1 in 2010 to June 30 in 2018, in Shanghai. A hierarchical clustering method based on Dynamic Time Warping (DTW) was employed to classify absenteeism symptoms with similar temporal patterns. Based on historical data, the study constructed and evaluated different time series algorithms and machine learning models to optimize the accuracy of predicting the trend of sickness absenteeism. Results: During the research period, the average new absenteeism rate due to illness was 16.86 per 10 000 person day for every academic year, and the trend of sickness absenteeism exhibited both seasonality and a long term upward trend, reaching its highest point in the 2017 academic year (22.47 per 10 000 person day). The symptoms of absenteeism were divided into three categories: high incidence in winter and spring (respiratory symptoms, fever and general discomfort, etc.), high incidence in summer (eye symptoms, nosebleeds, etc.) and those without obvious seasonality (skin symptoms, accidental injuries, etc.).The constructed time series models effectively predicted the trend of absenteeism due to illness, although the accuracy of predicting peak intensity was relatively low. Among them, the multi layer perceptron (MLP) model performed the best, with an root mean squared error (RMSE) of 8.96 and an mean absolute error (MAE) of 4.37, reducing 36.51% and 39.02% compared to the baseline model. Conclusion Time series models and machine learning algorithms could effectively predict the trend of sickness absenteeism, and corresponding prevention and control measures can be taken for absenteeism caused by different symptoms during peak periods.

Background The adverse effects of long working hours, shift rotation, and job stress on the physical and mental health of occupational populations require urgent attention. Objective To investigate and compare the positive rates of WMSDs between different industries, analyze the exposure status of long working hours, shift rotation, and job stress among key occupational groups, and evaluate the impacts of these factors on WMSDs in the manufacturing and service industries. Methods The study subjects were derived from key occupational populations in Yunnan Province, recruited by the Chinese National Occupational Health Literacy Monitoring Survey in 2022. A cross-sectional design was used for this survey. The key occupational populations were recruited from the secondary industry (manufacturing industry, metal mining and beneficiation industry, and non-metal mining and beneficiation industry) by stratified random sampling and from the tertiary industry (medical and healthcare industry, education industry, environmental sanitation industry, transportation industry, and express/takeaway delivery industry) by proportional probability sampling, and 12014 front-line workers were finally included as survey participants. General information, work-related factors (shift rotation, weekly working hours, job stress, etc.) and WMSDs assessment results were obtained through a web-based self-reported questionnaire, and the associations of long working hours, shift rotation, and job stress with WMSDs were analyzed using χ² test and logistic regression. Results The average positive rate of WMSDs among the key occupational groups in Yunnan Province was 77.2%. The positive rate of WMSDs in the secondary industry group was 69.4%, while it was 81.6% in the tertiary industry group, with a statistically significant difference (P<0.001). Among the eight surveyed sectors, the education sector had the highest positive rate of WMSDs (94.2%). The single-site WMSDs mainly involved the neck, shoulders, and low back. In the secondary industry, WMSDs was reported in 1−2 body parts, while in the tertiary industry, WMSDs was mainly reported in multiple (≥5) body parts. Long working hours (OR: 1.119, 1.165, 1.163, respectively), shift rotation (OR: 1.094, 1.199, 1.230, respectively), and job stress (OR: 1.795, 1.854, 2.006, respectively) were risk factors for WMSDs in the neck, shoulder, or low back, and all three were also risk factors for multi-site WMSDs. Moreover, as the number of involved body parts increased, the effects of long working hours and job stress became more pronounced. For 1-2, 3-4, and 5 or more body parts compared to no pain reported, their OR values were 0.971 (95%CI: 0.871, 1.082), 1.133 (95%CI: 1.004, 1.279), and 1.285 (95%CI: 1.155, 1.429) for long working hours, respectively, and the OR values were 1.009 (95%CI: 0.878, 1.160), 1.360 (95%CI: 1.174, 1.575), and 2.797 (95%CI: 2.471, 3.166) for job stress, respectively. Conclusion The positive rate of WMSDs is higher in the tertiary industry than that in the secondary industry among the key occupational groups in Yunnan Province. Long working hours, rotating shift work, and job stress could significantly increase the risk of WMSDs.

Background Staff in tertiary hospitals are a high-risk group for occupational burnout. Timely identification and precise intervention are crucial for improving healthcare service quality. However, comparative studies on perceived stress and occupational burnout among hospital staff in different positions are lacking. Objective To describe the status of perceived stress and occupational burnout among hospital staff in different positions and compare the differences, explore the relationship between perceived stress and occupational burnout, and identify the influencing factors of occupational burnout. Methods In May 2022, 1526 hospital staff members were selected by convenience sampling from six tertiary hospitals in Guangzhou. Data were collected using a general information questionnaire, the Chinese Perceived Stress Scale (CPSS), and the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) to assess demographic characteristics, perceived stress, and occupational burnout. Chi-square test, one-way ANOVA, and Kruskal-Wallis H test were used to compare differences in perceived stress and occupational burnout among staff in different positions. Pearson correlation analysis was used to explore possible correlation between perceived stress and occupational burnout. Multiple linear regression was conducted to identify influencing factors of occupational burnout. Results A total of 1388 valid questionnaires were collected, with an effective response rate of 90.96%. Among them, 437 nurses (57.0%), 273 physicians (58.6%), 24 pharmacists (57.1%), and 62 administrators (54.9%) reported positive perceived health risk stress (P=0.892). Additionally, 392 nurses (51.1%), 213 physicians (45.7%), 19 pharmacists (45.2%), and 53 administrators (46.9%) reported positive occupational burnout (P=0.005). Perceived stress was positively correlated with occupational burnout among nurses, physicians, pharmacists, and administrators (r=0.5973, 0.5687, 0.5464, and 0.5276, respectively; P＜0.01). The multiple linear regression identified perceived stress (b=1.4587, P＜0.001), job satisfaction (b=−7.4195, P＜0.001), self-rated health (b=−2.0428, P＜0.001), working years (b=−0.1135, P=0.016), and being a nurse (compared with an administrators) (b=3.2435, P=0.045) as significant factors for occupational burnout (P<0.001). Conclusion Perceived health risk stress and occupational burnout are common among hospital staff, with nurses experiencing significantly higher levels of occupational burnout compared to other positions. Hospital managers should pay more attention to staff with higher perceived stress, lower job satisfaction, poorer self-rated health, and shorter working years, particularly nurses.

Dignity is a core concept in bioethics. With the development of emerging life science technologies， maintaining human dignity has become the main reason for restricting the use and development of these new technologies. In bioethics， this dignity-based conservatism manifests in two forms， namely religious conservatism and secular conservatism. However， they face some difficulties respectively. Compared with conservatism， the concept of dignity advocated by the capability approach can not only avoid these difficulties but also provide a reasonable justification for people’s rational utilization and development of emerging biotechnologies.

ObjectiveTo explore the current situation of forensic ethics practice and education by designing a questionnaire on forensic ethics， with a view to exploring the path of forensic ethics education construction. MethodsA total of 667 valid questionnaires were collected using the online survey method， basically covering various regions across the country and all sub-specialties of forensic medicine. Descriptive analysis was used to analyze the relevant data. ResultsMost practitioners had relevant ethical reflections in the process of forensic practice. 69.12% of the respondents indicated that they had studied the relevant rules， but approximately half stated that there were no corresponding ethical norms or standard operating manuals. The specific behaviors violating ethics in different units were diverse. 23.04% of the respondents reported that they had encountered unethical behaviors， but only 4.9% of them reported such violations. In terms of forensic ethics education， 87.75% of the respondents believed that there were issues with the current model of forensic ethics education. Meanwhile， the respondents showed a high degree of recognition for receiving forensic ethics education， with 84.15% of respondents expressing willingness to participate in relevant courses. More than half of respondents were willing to participate in forensic ethics education during undergraduate studies， new employee training， and regular post-employment training. ConclusionCurrently， there is a problem of ethical neglect in forensic work in China. Combining ethics courses with professional courses at the practitioner training stage and providing regular training at the practice stage are effective measures to popularize forensic ethics knowledge， enhance ethical awareness， and improve the quality of practice.

OBJECTIVE To conduct a rapid and comprehensive evaluation of commonly used oral dihydropyridine calcium channel blockers （DHP CCBs） in Guangxi， and provide scientific basis for clinical medication and drug selection in medical institutions. METHODS Based on the actual drug use data of public medical institutions at the second level and above in Guangxi Zhuang Autonomous Region， and based on the national centralized collection catalog， commonly used oral DHP CCBs were selected. The Professional Committee of Evidence-based Pharmacy of the Guangxi Pharmaceutical Association organized relevant experts from multiple medical institutions in the region to conduct a quantitative scoring of the selected oral DHP CCBs from five key dimensions of pharmaceutical characteristics， effectiveness， safety， economy， and other attributes， by referring to the Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions （the Second Edition）， combined with the latest evidence-based medical research results， and widely soliciting suggestions from clinical and pharmaceutical experts. Finally， the Guangxi Expert Consensus on Rapid Comprehensive Evaluation of Oral Dihydropyridine Calcium Channel Blockers in the Treatment of Cardiovascular Disease was formulated. RESULTS A total of 30 commonly used oral DHP CCBs were selected. Among them， Amlodipine besylate tablets （Huizhi） demonstrated superior comprehensive performance （81.79 points）， excelling particularly in pharmaceutical properties， effectiveness and other attributes. The compound scores of Amlodipine besylate tablets （Chongqing Yaoyou） and Amlodipine besylate tablets （Suzhou Dongrui） ranked second and third respectively， with scores of 81.66 and 81.60 points. CONCLUSIONS This consensus can provide guidance and decision-making support for the rational clinical application of oral DHP CCBs in Guangxi Region and the selection of drug directories in medical institutions.