BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective:To analyze the cost of diagnosis-intervention packet(DIP) in a certain hospital in 2021 based on hospital intelligent agents, so as to provide feasible ideas for refined management of DIP costs.Methods:On the basis of the construction of the hospital intelligent agent platform and the results of project cost accounting in the early stage, a total of 60 187 cases and 4 860 DIP diseases in the hospital in 2021 were selected as the research objects. The project superposition method was applied to calculate the unit cost of all DIP diseases in the hospital. Based on the results of DIP cost accounting, the ideas and methods of fine management of DIP costs were explored from the perspectives of DIP disease classification, management of all hospital diseases and medical insurance diseases, vertical and horizontal comparative analysis of DIP costs, and management of medical insurance cases and non medical insurance cases under the same DIP disease category.Results:Twenty-two advantageous DIP disease types, 67 key disease types, 1 590 potential disease types, and 3 181 disadvantageous disease types were identified. Introducing medical income as an intermediate indicator facilitated the classification of DIP disease types under medical insurance, 1 072 advantageous disease types, 917 key disease types, 458 potential disease types, and 815 disadvantageous disease types in medical insurance were identified. Through refined accounting, it was found that the average cost of non medical insurance cases under the same DIP disease category was generally higher than that of medical insurance cases, and there were differences in DIP costs at different levels during different time periods.Conclusions:By determining and analyzing the advantages and disadvantages of disease types in the entire hospital, common problems of disease types under the same category can be identified, and targeted control measures can be proposed. By analyzing the two dimensions of medical insurance surplus and medical surplus, the advantages and disadvantages of medical insurance diseases can be quickly determined, providing a lever for the control of medical insurance diseases. The horizontal and vertical comparative analysis of DIP costs, as well as the analysis of medical insurance cases and non medical insurance cases under the same DIP disease category, can provide feasible methods for hospitals to manage DIP costs at multiple levels and dimensions.

In recent years, public hospitals have been facing pressure from the reform of medical insurance payment methods. It is urgent to strengthen the operation and management of public hospitals. In June 2022, a tertiary public hospital utilized hospital intelligent agents to carry out refined cost management practices for medical service charging projects, sorted out medical service charging projects, designed management paths, and calculated project costs. The hospital conducted refined management on the cost of medical service charging items from three control dimensions of project unit cost with manpower, equipment and consumables, and two comparative directions with horizontal and vertical. The refined cost management practice not only pointted out the direction for global refinement cost control within the hospital, but also reduced the proportion of hospital consumption, which provided reference for improving the level of refined operation and management of public hospital hospitals.

Objective:To investigate the effect of nonalcoholic fatty liver (NAFLD) at different ages of onset with new-onset diabetes mellitus.Methods:The cohort study was conducted in Kailuan Group Company. Active and retired employees were used as study subjects. After excluding NAFLD diagnosed at baseline, previous history of diabetes mellitus, and long-term history of heavy drinking, 43 317 cases were finally included in the cohort. The study subjects were divided into five groups according to age (<30 years old as group 1, 30-39 years old as group 2, 40-49 years as group 3, 50-59 years as group 4, and ≥60 years as group 5). The prevalence and incidence density of new-onset diabetes mellitus were compared between each NAFLD and non-fatty liver population group. The effect of NAFLD at different ages of onset with new-onset diabetes mellitus was analyzed by multivariate Cox's regression model. Statistical analysis was performed using one-way ANOVA, χ2 test or multivariate Cox's regression model. Results:The prevalence and incidence density of diabetes mellitus was significantly higher in NAFLD than non-fatty liver population. The prevalence of diabetes mellitus in different age groups were 6.45%, 6.88%, 9.94%, 10.83%, and 11.43%, respectively. The incidence density of each age group was 9.21/1 000 person-years, 11.10/1 000 person-years, 16.17/1 000 person-years, 18.72/1 000 person-years, and 22.13/1 000 person-years, and the differences were statistically significant ( P<0.001). Multivariate Cox's regression model result showed that after adjusting for confounding factors such as gender, systolic blood pressure, and fasting blood glucose, the HRs (95% CI) for diabetes mellitus in each age group were 3.992 (1.897, 8.400), 2.321 (1.589, 3.392), 2.041 (1.667, 2.500), 2.007 (1.708, 2.360), and 1.908 (1.570, 2.319), and the differences were statistically significant ( P＜0.001). Conclusion:Newly developed NAFLD is an independent risk factor for new-onset diabetes mellitus. Early exposure to NAFLD increases the risk of developing diabetes mellitus compared with the same age group. Younger age of onset of NAFLD should be given attention and active treatment.

Malaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of

Objective:To explore the effectiveness of the Exowalk gait training robot in improving the walking ability of stroke survivors.Methods:Forty stroke survivors were randomly divided into a control group and an experimental group, each of 20. In their rehabilitation, the control group was given routine walking training, while the experimental group′s training was assisted with the Exowalk robot. Both groups trained for 60 minutes a day, five days a week for four weeks. Before as well as after 2 and 4 weeks of training functional ambulatory categories (FACs), the Berg balance scale (BBS), the 6-minute walking test (6MWT), the 10-minute walking test (10MWT), the Rivermead mobility index and an exercise index were used to evaluate those in both groups.Results:After 2 weeks significant improvement was observed in the average FAC, BBS, 6MWT and 10MWT results of both groups, without significant differences between them. After 4 weeks there was still no significant difference in the groups′ average BBS scores. However, the average FAC rating in the experimental group had improved significantly while there was no significant increase in the control group′s average score.Conclusions:The Exowalk robot can help to improve the balance and walking ability of hemiplegic stroke survivors.

Objective:To investigate the association of abdominal fat distribution with glycolipid metabolism and diabetic complications in patients with T2DM.Methods:Totally 357 inpatients with T2DM were collected from the Endocrinology Department of our hospital. All patients received quantitative computed tomography to measure the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and were divided into three groups depending on the tertile of VAT value: T1 group (VAT<162.0 cm 2), T2 group (162.0≤VAT<221.1 cm 2), T3 group (VAT≥221.1 cm 2). The incidences of diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy, peripheral atherosclerosis, and cardia-cerebrovascular disease were examined in all patients. Results:HbA 1C level in T1 group was higher than that in T3 group( P<0.05). High density lipoprotein-cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) in T1 group were higher compared with those in T2 and T3 groups ( P<0.05). Male proportion, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), 24h urinary albumin, diabetic kidney disease and peripheral atherosclerosis in T2 and T3 groups were higher than those in T1 group ( P<0.05). Fasting C- peptide (FCP) and modified homeostasis model assessment for insulin resistance (HOMA-IR) in T3 group were higher than those in T1 and T2 group ( P<0.01). VAT and SAT were positively correlated with BMI, FCP, and HOMA-IR (p<0.01). VAT was positively correlated with age, SBP, DBP, TG, 24h urinary albumin, diabetic kidney disease, peripheral atherosclerosis, and cardia-cerebrovascular disease ( P<0.05), while inversely correlated with HbA 1C, HDL-C, and eGFR ( P<0.05). SAT was positively correlated with total cholesterol and low density lipoprotein-cholesterol ( P<0.01), while negatively correlated with peripheral atherosclerosis ( P<0.01). Multivariate logistic regression analysis showed that VAT was still a risk factor for diabetic kidney disease after adjusted by age, BMI, SBP and fasting plasma glucose( P=0.013). Conclusion:VAT and SAT are associated with blood lipids and insulin resistance, while VAT seems to be a risk factor for diabetic kidney disease.