OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

Objective:To investigate the occurrence of work-related musculoskeletal disorders (WMSDs) among underground coal mine workers, identify the risk factors for WMSDs, and provide a scientific evidence for the prevention and treatment of WMSDs.Methods:In March 2024, through cluster sampling, the on-the-job workers who underwent questionnaire surveys and health examinations at a certain coal mine from July to August 2018 were selected as the research subjects. Basic information of employees, ergonomics-related characteristics, and the occurrence status of WMSDs in each part were collected, and multivariate logistic regression was used for analysis.Results:The incidence rate of WMSDs in at least one site among underground coal mine workers within the past year was 62.22% (219/352). The top three sites in sequence were the lower back (44.32%, 156/352), neck (26.14%, 92/352), and knee (26.14%, 92/352). Multivariate logistic regression analysis showed that frequently exerting great force with arms or hands during work ( OR=2.223, 95% CI: 1.022-4.836), prolonged static forward bending ( OR=1.544, 95% CI: 1.305-1.972), and frequently exerting great effort to operate tools or machines ( OR=2.206, 95% CI: 1.011-4.813), absence of external support systems ( OR=1.589, 95% CI: 1.349-1.996), and repetitive full-body twisting ( OR=1.523, 95% CI: 1.298-1.916) were all risk factors for the occurrence of WMSDs in the lower back ( P<0.05). Both night shift work ( OR=1.564, 95% CI: 1.339-1.939) and frequent forward neck flexion ( OR=1.532, 95% CI: 1.312-1.907) were all risk factors for the occurrence of WMSDs in the neck ( P<0.05). Lifting heavy objects above the shoulder ( OR=1.333, 95% CI: 1.142-1.782), uncomfortable posture and inability to exert force ( OR=1.873, 95% CI: 1.104-2.712), the use of vibration tools ( OR=2.958, 95% CI: 1.255-6.972), and length of service >10 years ( OR=1.525, 95% CI: 1.105-1.967) were all risk factors for the occurrence of WMSDs in the knee ( P<0.05) . Conclusion:The incidence of WMSDs among underground coal miners is relatively high, mainly concentrated in the lower back, neck and knee, and is related to factors such as poor working postures, and work organization. Coal mining enterprises should strengthen work organization, provide appropriate working equipment, and ensure reasonable distribution of workloads.

Objective:To identify risk factors influencing the incidence of hypertension among steelworkers (Homo sapiens) and establish an effective and easily implementable hypertension prediction model.Methods:In September 2023, 2214 steelworkers (Homo sapiens) were selected as study subjects. Basic demographic information, lifestyle, and occupational exposure data were collected, along with physiological measurements such as height, weight, and blood pressure. Multivariate unconditional logistic regression analysis was employed based on relevant literature to determine influencing factors for hypertension among steelworkers (Homo sapiens). Python 3.9 software was used to construct and compare logistic regression, support vector machine (SVM), random forest, extreme gradient boosting tree (XGBoost), and LGBM models. Model performance was evaluated using metrics such as receiver operating characteristic (ROC) curves, accuracy, calibration curves, and F1 scores. The Shapley Additive Explanations (SHAP) model was introduced for feature importance analysis to enhance the interpretability of the prediction model.Results:A total of 432 cases of hypertension were detected among 2214 study subjects, with a detection rate of 19.51%. Age, smoking status, salt intake, use of cooling equipment, carbon monoxide exposure, family history of hypertension, fasting blood glucose, triglycerides, and hemoglobin were identified as independent risk factors for hypertension ( P<0.05). A comparison of the five models revealed the following performance metrics: logistic regression achieved an accuracy of 0.853, F1 score of 0.680, Brier score of 0.108, and AUC of 0.907; SVM demonstrated an accuracy of 0.863, F1 score of 0.687, Brier score of 0.081, and AUC of 0.910; random forest showed an accuracy of 0.857, F1 score of 0.603, Brier score of 0.105, and AUC of 0.861; XGBoost yielded an accuracy of 0.850, F1 score of 0.684, Brier score of 0.117, and AUC of 0.899; and the LGBM model exhibited an accuracy of 0.838, F1 score of 0.625, Brier score of 0.112, and AUC of 0.870. Conclusion:The SVM model demonstrated strong predictive performance, effectively assessing the risk of hypertension among steelworkers (Homo sapiens) and facilitating targeted health management interventions.

Balo′s concentric sclerosis (BCS) is a rare demyelinating disease of the central nervous system, once considered a variant of multiple sclerosis. It is characterized by alternating layers of demyelinated and myelinated regions in a concentric pattern, resembling tree rings. The disease typically has an acute onset and diverse clinical manifestations. In the past, diagnosis of BCS primarily relied on autopsy; however, with the widespread application of magnetic resonance imaging, the number of confirmed cases has gradually increased, significantly improving the efficiency of clinical diagnosis and treatment. Nevertheless, most reports both domestically and internationally remain limited to individual cases. This article provides a review of the epidemiology, etiology, predisposing factors, pathogenesis, neuropathological features, clinical manifestations, differential diagnosis, relationship with multiple sclerosis, auxiliary examinations, and treatment of BCS.

Objective To observe the clinical efficacy of Huangqi Danggui Compound Decoction(mainly composed of Astragali Radix,Angelicae Sinensis Radix,etc.)combined with Shi's Acupuncture Therapy in the treatment of postpartum low back pain due of qi and blood depletion type.Methods A total of 138 patients diagnosed with postpartum low back pain from March 2021 to February 2024 in the outpatient and inpatient departments of the Second Affiliated Hospital of Hebei University of Chinese Medicine were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 69 cases in each group.The control group was treated with Ibuprofen Sustained-Release Capsules combined with Shi's Acupuncture Therapy,while the observation group was additionally treated with Astragalus and Angelica Compound Decoction on the basis of the control group's treatment.Both groups were treated for 4 weeks.After treatment,the clinical efficacy of the two groups was evaluated.The changes in Oswestry Disability Index(ODI)and Visual Analogue Scale(VAS)scores before and after treatment,as well as the SF-36 Quality of Life Scale scores,were observed.The changes in follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E2)levels were compared before and after treatment,and the safety and incidence of adverse reactions in the two groups were evaluated.Results(1)The total effective rate in the observation group was 92.75%(64/69),while it was 79.71%(55/69)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the ODI and VAS scores of both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in ODI and VAS scores compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the SF-36 Quality of Life Scale scores of both groups improved significantly(P＜0.05),and the observation group showed significantly better improvement in SF-36 scores compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the FSH,LH,and E2 levels in the observation group were significantly improved(P＜0.05),and the observation group showed significantly better improvement in FSH,LH,and E2 levels compared to the control group,with a statistically significant difference(P＜0.05).In the control group,the FSH,LH,and E2 levels improved slightly,but there was no statistically significant difference compared to before treatment(P＞0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the observation group and the control group(P＞0.05).Conclusion Huangqi Danggui Compound Decoction combined with Shi's Acupuncture Therapy in the treatment of postpartum low back pain due to qi and blood depletion can significantly alleviate pain symptoms,improve lumbar function,regulate sex hormone levels,and enhance the quality of life of patients,with significant efficacy and good safety.

Objective To explore the mechanisms of Qingre Lidan Jiedu Recipe(QLJR)for improving cognitive dysfunction in rats with high copper load.Methods Seventy-five male SD rats were randomized into normal control group,model group,QLJR group,penicillamine(PCA)group,and QLJR+PCA group.Except for those in the control group,all the rats were fed a high-copper diet for 12 weeks.The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests.Hippocampal expressions of NIX,FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining,and changes in mitochondrial morphology were observed with transmission electron microscopy.Results Behavioral tests showed prolonged target hole latency,shortened latency to enter the dark chamber,and increased error counts of the rats in the model group,which were significantly improved in QLJR+PCA group;the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group.Among all the groups,the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group;NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group.Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups,but their expressions did not differ significantly between QLJR and PCA groups.The rats in the model group showed obvious structural disarray of the mitochondria,which were improved in all the treatment groups.Conclusion QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.

AIM:To investigate the mechanism by which the Z-DNA-binding protein 1(ZBP1)/receptor-in-teracting protein kinase 1(RIPK1)/mixed lineage kinase domain-like protein(MLKL)pathway modulates the necroptosis of neurons in a mouse model of Alzheimer disease(AD).METHODS:Thirty mice were randomly divided into three groups:normal control(NC)group,APP/PS1 model(MOD)group,and necroptosis inhibitor necrostatin-1(Nec-1)group,each with 10 mice.The learning and memory capacities of mice were assessed using the Morris water maze assays.The pathological morphology of hippocampal tissue was examined based on the HE staining assay.The expression levels of tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)in serum samples were measured by ELISA.The phosphory-lation of amyloid precursor protein(APP),Tau protein and the expression levels of proteins related to the ZBP1/RIPK1/MLKL pathway in hippocampal tissue were measured by Western blot.Immunofluorescence analysis was performed to de-tect the positive expression of p-RIPK1,while the mRNA level of ZBP1 was measured by RT-qPCR.RESULTS:Com-pared with NC group,the escape latency of mice in the MOD group was significantly longer(P<0.05),the number of crossing platforms was reduced(P<0.05),and the arrangement of hippocampal neurons was disordered accompanied with nuclear condensation.The concentration of TNF-α in serum was increased,whereas the concentration level of IL-10 was decreased(P<0.05).The expression levels of APP,p-Ttau and ZBP1 proteins in the hippocampal tissue and the ratios of p-RIPK1/RIPK1,p-RIPK3/RIPK3 and p-MLKL/MLKL were significantly upregulated(P<0.05).Similarly,the positive expression level of p-RIPK1 and the mRNA level of ZBP1 in hippocampal tissue were significantly upregulated(P<0.05).Compared with the MOD group,the cognitive function of AD mice,pathological damage of hippocampal tissue,and the levels of TNF-α and IL-10 in serum were reversed in the Nec-1 group(P<0.05).Moreover,the Nec-1 treatment signifi-cantly downregulated the expression levels of the above proteins(P<0.05),and the positive expression of p-RIPK1 and the mRNA level of ZBP1 were significantly decreased(P<0.05).CONCLUSION:The ZBP1/RIPK1/MLKL pathway is involved in the occurrence of neuronal necroptosis and the pathological process of AD mice.Inhibition of this pathway sig-nificantly ameliorates cognitive dysfunction and neuroinflammatory responses in AD mice.

Objective:To analyze the factors influencing the lung function of coal miners, identify the optimal combination of indicators for evaluating lung function, develop a risk assessment model using machine learning, and offer personalized risk assessment for workers.Methods:In June 2023, through cluster sampling, male underground workers who participated in occupational health examinations at a coal mine in North China from July to August 2018 were selected as the research subjects. Their health examination results and occupational environmental data were collected. A total of 3, 320 coal miners were included. Randomly divide the research subjects into a training set (2324 people) and a validation set (996 people) in a ratio of 7∶3, and the balance of the two sets was tested. Perform LASSO regression analysis using R 4.2.2 software to select relevant important variables, and determine the model's input variables by combining them with relevant literature. Utilize Python 3.8 to construct logistic regression, random forest, support vector machine, and XG Boost models, assess the models' discriminative ability using metrics like accuracy, sensitivity, specificity, F1 score, ROC curve, and AUC, evaluate the models' calibration using Brier score, Log loss score, and calibration curve, and further analyze the clinical performance of the developed models through DCA decision curve analysis.Results:Among the 3 320 coal miners, 856 had abnormal lung function (25.78%). The XG Boost model was identified as the optimal model, achieving a training set accuracy of 87.39%, sensitivity of 86.60%, specificity of 87.67%, F1 score of 0.779, AUC of 0.945, Brier score of 0.071, Log loss of 0.267 and demonstrated good calibration curve consistency.Conclusion:The XG Boost model exhibits superior predictive performance compared to other models, and the model has high application value. The Shapley Additive Explanation (SHAP) method is employed for interpretation, making it a reliable basis for preventing abnormal lung function in coal miners.