BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

Objective: To assess the current status of bacterial detection capabilities in various blood collection and supply and related laboratories across China, and to identify key factors affecting the consistency of test results. Methods: A pooled analysis was conducted on data from 21 external quality assessment (EQA) rounds for blood bacterial detection carried out by the China International Transfusion Infection Prevention and Control (CITIC) project from 2019 to 2025. The study covered three types of laboratories-blood centers, central blood stations, and commercial laboratories—across 23 provincial-level administrative regions in China. Statistics were compiled on the number of participating laboratories, and the concordance rates were calculated for different institution types, different automated blood culture systems, different bacterial concentrations, and different strains. Non-standard reporting issues were also reviewed, and statistical methods were applied for analysis. Results: Over the seven-year period, the number of participating laboratories increased from 161 to 236, with an average annual growth rate of 6.58%, and the annual concordance rates ranged from 82.61% to 94.92%. The overall laboratory concordance rates for the three types of participating laboratories were all>89.0% (P>0.05), while commercial laboratories showed a significant year-by-year increase (70.97%-100%, P<0.05). The concordance rates of automated blood culture systems from eight manufacturers showed no significant differences (97.98%-100%, P>0.05), indicating stable performance across all devices. The overall sample concordance rate was 98.88%, with negative samples showing a lower rate than positive samples (97.97% vs 99.14%); positive sample rates increased with higher concentrations; and low-concentration Gram-negative bacterial samples had a lower concordance rate than Gram-positive ones (93.15% vs 100%). A total of 50 instances of non-standard result reporting were identified, with incorrect time units accounting for the highest proportion (52.0%). Conclusion The participation scale and overall testing proficiency of blood collection and supply and related laboratories nationwide have improved year by year, and all types of automated blood culture devices can meet the requirements for blood bacterial screening. Detection of negative and low-concentration positive samples remains a weak link in current bacterial EQA, and the standardization of laboratory data reporting requires further strengthening. Continuous: external quality assessment, targeted training, and standardized reporting procedures can effectively enhance the homogenization level of blood bacterial testing across the country and ensure the safety of clinical transfusion.

Viral pneumonia in the Lancang-Mekong River Basin exhibits distinct regional epidemiological characteristics and pathogenic mechanisms. Filthy dampness constitutes the core pathogenic factor of the disease here， and the core pathogenesis lies in the yang failing to be stored in the you （酉） position. Clinically， the fundamental therapeutic principle is established as boosting qi to expel filth and guiding yang qi to descend and converge into the you position. In the early stage， the pathogenesis is characterized by the pervasive diffusion of filthy dampness， yang qi floating externally and failing to be stored， and the lung failing to diffuse qi. The treatment focuses on invigorating yang qi to dispel filth and dredging the you pathways， primarily using modified Ganlu Xiaodu Decoction （甘露消毒丹）. In the progressive stage， the pathogenesis involves the tenacious stagnation of filthy dampness， yang constraint transforming into heat， and the rampant spread of heat-toxins. The therapeutic approach shifts to acrid medicinals for opening and bitter medicinals for promoting descent， rectifying healthy qi to expel filth， utilizing modified Dayuan Beverage （达原饮）. In the recovery stage， filthy dampness gradually recedes， accompanied by the depletion of qi and yin， and insufficient kidney yang. The treatment emphasizes supplementing qi and nourishing yin， accompanied by warming yang， with modified Yunv Decoction （玉女煎）.

Objective To investigate the association between plasma homocysteine(Hcy)level and coronary artery calcification(CAC)and its clinical predictive efficacy.Methods A total of 172 patients who underwent coronary CT angiography North China University of Science and Technology Affiliated Hospital from April 2019 to May 2021 and CAC score(CACS)＞0 were enrolled.According to the CACS value,the subjects were divided into mild calcification group(n=136)and severe calcification group(n=36),and the clinical characteristics of two groups were compared and analyzed.Multivariate Logistic regression model was used to screen the independent influencing factors of CAC severity,and a prediction model was constructed based on the Hcy detection value.The clinical diagnostic value was evaluated by the receiver operating characteristic(ROC)curve.Results There were significant differences in Hcy,white blood cell count,triglyceride and magnesium ion levels between two groups(P＜0.05).Multivariate Logistic regression analysis showed that Hcy,white blood cell count and magnesium ion level were independent risk factors for the progression of CAC.Furthermore,a regression model based on Hcy was constructed and ROC curve was fitted to evaluate its predictive efficacy.The results suggested that the predictive model had the best performance when the critical value of Hcy was set at 27.4μmol/L:the sensitivity was 55.6％,the specificity was 97.1％,and the area under the curve was 0.765.Conclusion Hcy serves as an independent risk factor for the severity of CAC and can effectively predict the progression of CAC with high accuracy.

Objective To investigate the effects of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in rats with knee osteoarthritis(KOA).Methods Forty SD were divided randomly into a sham operation group(n=10)and a modeling group(n=30).A KOA model was established in the modeling group by anterior cruciate ligament transection of the right hind limb knee joint.The drawer test was used to confirm the successful establishment of the model.Post-surgery,the rats were subjected to 30 min of forced activity daily to induce KOA.Lameness and hopping movements were observed after 4 weeks,and hematoxylin and eosin staining confirmed cartilage surface damage,deformation,and inflammatory cell infiltration,indicating successful modeling.The model rats were then assigned randomly to a model group(n=8),celecoxib group(n=8),and Yishen Zhuyu Tongluo Decoction group(n=8).The sham operation and model groups received 10 mL/kg of saline by gavage,the celecoxib group received 12 mg/kg of celecoxib solution,and the Yishen Zhuyu Tongluo Decoction group received 5.4 g/kg of the herbal decoction,once daily for 8 weeks.After the interventions,the rats were anesthetized,blood was collected from the abdominal aorta and serum was separated,and the knee joints were isolated.Three samples were fixed in paraformaldehyde,while the remaining cartilage tissue was reserved.Pathological changes in joint cartilage were observed by hematoxylin and eosin and Safranin O-Fast Green staining.Bone microstructure was analyzed using micro-computed tomography.Serum interleukin(IL)-1β and IL-18 protein levels were detected by enzyme-linked immunosorbent assay.Relative mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,FTH-1,GPX-4,and cyclooxygenase(COX)-2 were detected by reverse transcription quantitative real-time PCR,and protein expression of NLRP3,Caspase-1,and COX-2 were detected by immunohistochemistry.Results Compared with the sham operation group,model rats showed surface damage and deformation of cartilage tissue,disordered cell arrangement in all layers,significant loss of Safranin O-Fast Green staining,and sparse and irregular trabecular bone distribution.Serum levels of the inflammatory factors IL-1β and IL-18 were elevated(P＜0.01).mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 were also significantly increased(all P＜0.01),while FTH-1 and GPX-4 mRNA expression levels were decreased(P＜0.01).Compared with the model group,rats in the celecoxib and Yishen Zhuyu Tongluo Decoction groups showed smoother and more intact cartilage surfaces,significantly increased cell counts,less loss of Safranin O-Fast Green staining,denser trabecular bone,and thicker cortical bone,with improved bone microstructure.Serum IL-1β and IL-18 levels were reduced(P＜0.01),NLRP3(P＜0.01,P＜0.05),ASC,Capase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 mRNA levels were decreased(all P＜0.01),and relative expression levels of FTH-1 and GPX-4 mRNA were significantly increased(P＜0.01).Conclusions Yishen Zhuyu Tongluo Decoction can treat KOA by inhibiting chondroptosis and ferroptosis in chondrocytes,reducing serum IL-1β and IL-18 levels,and improving bone microstructure.

Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Macrophages/immunology* ; Glucose/metabolism* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics* ; Male ; Mice, Inbred C57BL ; Humans ; Colitis/drug therapy* ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy* ; Metabolic Reprogramming

Objective To investigate the effects of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in rats with knee osteoarthritis(KOA).Methods Forty SD were divided randomly into a sham operation group(n=10)and a modeling group(n=30).A KOA model was established in the modeling group by anterior cruciate ligament transection of the right hind limb knee joint.The drawer test was used to confirm the successful establishment of the model.Post-surgery,the rats were subjected to 30 min of forced activity daily to induce KOA.Lameness and hopping movements were observed after 4 weeks,and hematoxylin and eosin staining confirmed cartilage surface damage,deformation,and inflammatory cell infiltration,indicating successful modeling.The model rats were then assigned randomly to a model group(n=8),celecoxib group(n=8),and Yishen Zhuyu Tongluo Decoction group(n=8).The sham operation and model groups received 10 mL/kg of saline by gavage,the celecoxib group received 12 mg/kg of celecoxib solution,and the Yishen Zhuyu Tongluo Decoction group received 5.4 g/kg of the herbal decoction,once daily for 8 weeks.After the interventions,the rats were anesthetized,blood was collected from the abdominal aorta and serum was separated,and the knee joints were isolated.Three samples were fixed in paraformaldehyde,while the remaining cartilage tissue was reserved.Pathological changes in joint cartilage were observed by hematoxylin and eosin and Safranin O-Fast Green staining.Bone microstructure was analyzed using micro-computed tomography.Serum interleukin(IL)-1β and IL-18 protein levels were detected by enzyme-linked immunosorbent assay.Relative mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,FTH-1,GPX-4,and cyclooxygenase(COX)-2 were detected by reverse transcription quantitative real-time PCR,and protein expression of NLRP3,Caspase-1,and COX-2 were detected by immunohistochemistry.Results Compared with the sham operation group,model rats showed surface damage and deformation of cartilage tissue,disordered cell arrangement in all layers,significant loss of Safranin O-Fast Green staining,and sparse and irregular trabecular bone distribution.Serum levels of the inflammatory factors IL-1β and IL-18 were elevated(P＜0.01).mRNA expression levels of NLRP3,ASC,Caspase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 were also significantly increased(all P＜0.01),while FTH-1 and GPX-4 mRNA expression levels were decreased(P＜0.01).Compared with the model group,rats in the celecoxib and Yishen Zhuyu Tongluo Decoction groups showed smoother and more intact cartilage surfaces,significantly increased cell counts,less loss of Safranin O-Fast Green staining,denser trabecular bone,and thicker cortical bone,with improved bone microstructure.Serum IL-1β and IL-18 levels were reduced(P＜0.01),NLRP3(P＜0.01,P＜0.05),ASC,Capase-1,GSDMD,IL-1β,IL-18,ACSL-4,and COX-2 mRNA levels were decreased(all P＜0.01),and relative expression levels of FTH-1 and GPX-4 mRNA were significantly increased(P＜0.01).Conclusions Yishen Zhuyu Tongluo Decoction can treat KOA by inhibiting chondroptosis and ferroptosis in chondrocytes,reducing serum IL-1β and IL-18 levels,and improving bone microstructure.

In recent years,there has been an increase in the prevalence and incidence of acute myocardial infarction.Despite advances in diagnostic and therapeutic technologies related to the disease,challenges remain in the management of the disease after patients are discharged from the hospital.Home-based cardiac rehabilitation has been demonstrated to be an effective means of improving the prognosis of the disease.The utilization of digital health technology has the potential to enhance patient compliance and quality of life in the context of home-based cardiac rehabilitation for those who have experienced an acute myocardial infarction.This article reviews the forms of intervention,specific applications and effects of digital health technologies in home-based cardiac rehabilitation,It analyses the existing problems and puts forward nursing countermeasures.The aim is to further help nursing staff to guide the practice of home cardiac rehabilitation for patients with acute myocardial infarction.