To analyze all-cause mortality among hepatitis C cases aged ≥18 years in Yuxi City from 2005 to 2023 and explore the interactions of factors influencing survival time. Baseline and follow-up data for hepatitis C cases reported during this period were extracted from the Chinese National Notifiable Disease Reporting System. Survival time and related factors were assessed using the Cox proportional hazards model. Kaplan-Meier cumulative mortality risk curves were generated for treated and untreated hepatitis C cases, and interactions among subgroups of various influencing factors were examined. A total of 5 110 hepatitis C cases aged ≥18 years were reported from 2005 to 2023, encompassing 35 349.25 person-years of observation with the follow-up time duration M ( Q1, Q3) was 6.17 (2.33, 11.08) person-years. There were 763 all-cause deaths, corresponding to a mortality density of 2.16 per 100 person-years. Survival analysis showed a statistically significant difference in cumulative mortality between the treated and untreated groups (Log-rank χ2=122.033, P<0.001), with a lower risk of death observed among treated patients. Additive model analysis showed that there was a synergistic interaction between treatment status and age group, with relative excess of interaction, attributable proportions of interaction, and synergy index of 6.16 (95 %CI: 2.70-9.61), 1.83 (95 %CI: 1.46-2.30), and 0.42 (95 %CI: 0.31-0.53), respectively; and between treatment status and gender. There was a synergistic interaction between treatment status and sex, with relative excess of interaction, attributable proportions of interaction, and synergy index of 2.63 (95 %CI: 1.14-4.13), 1.56 (95 %CI: 1.19-2.06), and 0.32 (95 %CI: 0.17-0.46), respectively. The cause of death composition were 38.53% (249 cases) attributed to hepatitis C-related causes.The leading non-hepatitis C-related causes of death were cardiovascular and cerebrovascular diseases, pulmonary diseases, malignancies, drug overdose, and injuries. In conclusion, hepatitis C cases ≥18 years of age in Yuxi City had a lower cumulative mortality rate when treated than when untreated. Treatment status interacted with age and gender on patient survival, respectively. Changes in patients with concomitant cardiovascular diseases, pulmonary diseases and malignancies should be focused.

Medical engineering in TCM medical institutions in Guizhou Province was described in terms of its development status and problems in functional positioning,professional title appraisal,unbalanced staff composition and discipline foun-dation.Some suggestions were put forward including determining the functional positioning and management mode of medical engineering institutions,promoting the professional title system for medical engineering staffs,strengthening medical engineering team and enhancing medical engineering discipline.References were provided for the development of medical engineering in TCM medical institutions in Guizhou Province.[Chinese Medical Equipment Journal,2025,46(5):84-90]

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

The accumulation of deoxyribonucleic acid (DNA) oxidative damage mediated by reactive oxygen species (ROS) is closely associated with liver diseases. 8-Oxoguanine (8-OxoG), a prevalent DNA oxidation product, plays a significant role in liver disease progression. The base excision repair (BER) pathway, comprising over 30 proteins including 8-OxoG DNA glycosylase1 (OGG1), MutY homolog (MUTYH), and MutT homolog protein 1 (MTH1), is responsible for the clearance and mismatch repair of 8-OxoG. Abnormally high levels of 8-OxoG and dysregulated expression and function of 8-OxoG repair enzymes contribute to the onset and development of liver diseases. Consequently, targeting the 8-OxoG production and repair system with agonists or inhibitors may offer a promising approach to liver disease treatment. This review summarizes the impact of 8-OxoG accumulation and dysregulated repair enzymes on various liver diseases, including viral liver disease, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), cholestatic liver disease (CLD), liver fibrosis, cirrhosis, and liver cancer. Additionally, we review natural constituents as potential therapeutic agents that regulate 8-OxoG production, repair enzymes, and repair system-related signal pathways in oxidative damage-induced liver diseases.
Humans ; Liver Diseases/genetics* ; Biological Products/pharmacology* ; DNA Repair/drug effects* ; Guanine/metabolism* ; Animals ; Disease Progression ; DNA Damage ; Oxidative Stress

Utilizing network pharmacology, molecular docking, and cellular experimental validation, this study delved into the therapeutic efficacy and underlying mechanisms of matrine in combating senescence. Databases were utilized to predict targets related to the anti-senescence effects of matrine, resulting in the identification of 81 intersecting targets for matrine in the treatment of senescence. A protein-protein interaction(PPI) network was constructed, and key targets were screened based on degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the key targets to elucidate the critical pathways involved in the anti-senescence effects of matrine. Molecular docking was conducted between matrine and key targets. A senescence model was established using human umbilical vein endothelial cells(HUVECs) induced with hydrogen peroxide(H_2O_2). Following treatment with varying concentrations of matrine(0.5, 1, and 2 mmol·L~(-1)), cell viability was assessed by using the CCK-8. SA-β-galactosidase staining was employed to observe the positive rate of senescent cells. Flow cytometry was utilized to measure the apoptosis rate. Real-time quantitative PCR(RT-PCR) was utilized to measure the mRNA expression of apoptosis-related cysteine peptidase 3(CASP3), albumin(ALB), glycogen synthase kinase 3β(GSK3B), CD44 molecule(CD44), and tumor necrosis factor-α(TNF-α). Western blot was performed to detect the protein expression of tumor protein p53(p53), cyclin-dependent kinase inhibitor 1A(p21), cyclin-dependent kinase inhibitor 2A(p16), and retinoblastoma tumor suppressor protein(pRb) in the senescence signaling pathway, p38 protein kinase(p38), c-Jun N-terminal kinase(JNK), and extracellular regulated protein kinases(ERK) in the mitogen-activated protein kinase(MAPK) pathway, and phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in the PI3K/Akt signaling pathway. The experimental results revealed that matrine significantly increased the viability of HUVECs(P<0.05), decreased the positive rate of senescent cells and the apoptosis rate(P<0.05), and reduced the mRNA expression levels of CASP3, ALB, GSK3B, CD44, and TNF-α(P<0.05). It also inhibited the protein expression of p53, p21, p16 and pRb in the senescence signaling pathway(P<0.05), upregulated the protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05), and downregulated the protein expression of p-p38/p38, p-JNK/JNK, and p-ERK/ERK(P<0.05). Collectively, these findings suggest that matrine exerts an inhibitory effect on HUVECs senescence, and its mechanism involves the modulation of the senescence signaling pathway, MAPK pathway, and PI3K/Akt signaling pathway to suppress cell apoptosis and inflammation.
Humans ; Matrines ; Quinolizines/chemistry* ; Alkaloids/chemistry* ; Human Umbilical Vein Endothelial Cells/cytology* ; Cellular Senescence/drug effects* ; Network Pharmacology ; Molecular Docking Simulation ; Signal Transduction/drug effects* ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology*

This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

AIM To explore the clinical effects of Huayu Ditan Linao Decoction combined with Suhexiang Pills on elderly patients with cerebral hemorrhage in convalescent stage.METHODS One hundred and ten patients were randomly assigned into control group(55 cases)for 1-month intervention of both conventional treatment and rehabilitation training,and observation group(55 cases)for 1-month intervention of Huayu Ditan Linao Decoction,Suhexiang Pills,conventional treatment and rehabilitation training.The changes in clinical effects,TCM syndrome score,NIHSS score,FMA score,BI index,cerebrovascular function indices(dynamic resistance,average flow velocity,peripheral resistance,average flow rate),serum inflammatory indices(IL-6,hs-CPR,TNF-α)and serum oxidative stress indices(SOD,MDA)were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome score,NIHSS score,dynamic resistance,peripheral resistance,serum inflammatory indices,MDA(P＜0.05),and increased FMA score,BI index,average flow velocity,average flow rate,SOD(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the elderly patients with cerebral hemorrhage in convalescent stage,Huayu Ditan Linao Decoction combined with Suhexiang Pills can enhance clinical effects,improve limb functions and nerve functions,regulate serum inflammatory and oxidative stress indice,and promote prognosis.

Objective To investigate the efficacy of an interpretable integrated learning model combining clinical indicators,CT image features and radiomics features for the differential diagnosis of lung squamous cell carcinoma and adenocarcinoma,so as to provide references for clincal treatment decisions.Methods A retrospective analysis was conducted on clinical and imaging data from 220 patients(231 lesions)with primary non-small cell lung cancer at Jiangjin Central Hospital of Chongqing(Center 1)and 83 patients(84 lesions)at Chongqing General Hospital(Center 2).In Center 1,the squamous cell carcinoma group consisted of 60 patients(60 lesions),while the adenocarcinoma group included 160 patients(171 lesions).In Center 2,the squamous cell carcinoma group comprised 18 patients(18 lesions),and the adenocarcinoma group involved 65 patients(66 lesions).The patients were categorized into squamous cell carcinoma and adenocarcinoma groups based on pathological findings.Center 1 was randomly partitioned into a training set and a validation set at a 7∶3 ratio,while Center 2 served as the independent test set.Firstly,a deep learning model,VB-Net,was used to automatically segment the tumor region on the lung window image;secondly,the SMOTE(synthetic minority oversampling technique)method was used to balance the categories in the training set and standardize the extracted features with Z-scores;thirdly,the least absolute shrinkage and selection operator(LASSO)were used to select the optimal radiomics features and calculate the radiomics score(Radscore),and univariate and multivariate logistic regression was used to screen clinical indicators and independent clinical factors for differentiating lung squamous cell carcinoma and adenocarcinoma in CT image features;finally,three ensemble learning algorithms(AdaBoost,Bagging decision tree and XGBoost)were used to combine independent clinical factors and Radscore to construct the model.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic performance of the models.SHAP technique was used to analyze the feature contribution and model decision-making process.Results Among the evaluated ensemble models,AdaBoost and Bagging decision trees demonstrated overfitting tendencies.In contrast,the XGBoost model showed the best performance,achieving AUC values of 0.939,0.887 and 0.853 in the training,validation and independent test sets,respectively.SHAP indicated that Radscore was the most important feature affecting the performance of the model.The decision diagram enabled the visualization of the diagnostic process of the model.Conclusion The interpretable integrated learning model based on clinical indicators,CT image and radiomics features is expected to non-invasively diagnose lung squamous cell carcinoma and adenocarcinoma before treatment and assist clinicians make treatment decisions as early as possible.[Chinese Medical Equipment Journal,2025,46(7):12-20]

Medical engineering in TCM medical institutions in Guizhou Province was described in terms of its development status and problems in functional positioning,professional title appraisal,unbalanced staff composition and discipline foun-dation.Some suggestions were put forward including determining the functional positioning and management mode of medical engineering institutions,promoting the professional title system for medical engineering staffs,strengthening medical engineering team and enhancing medical engineering discipline.References were provided for the development of medical engineering in TCM medical institutions in Guizhou Province.[Chinese Medical Equipment Journal,2025,46(5):84-90]