BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

Objective To investigate the effects of meridian massage on mitochondrial autophagy in ischemic stroke rats through the hypoxia-inducible factor-1α(HIF-1α)/BCL2/adenovirus E1B 19kDa interacting protein 3(BNIP3)pathway.Methods The ischemic model was made by blocking the right middle cerebral artery(MCA)of rats with thread embolism.The ischemic stroke rats with successful modeling were divided into model group,massage group,pathway agonist group,pathway inhibitor group and massage+inhibitor group.The rats in the blank control group received routine massage at non-meridian acupoints(including Baihui,Fengfu and Renzhong).The massage group was treated with circulation massage(including Biguan,Taichong,Fenglong and Zusanli),the pathway agonist group was treated with HIF-1α/BNIP3 activator,the pathway inhibitor group was treated with HIF-1α/BNIP3 inhibitor,and the massage+inhibitor group was treated with combination of circulation massage and HIF-1α/BNIP3 inhibitor.Another 10 healthy rats were selected for sham operation intervention,which only separated the blood vessels without inserting the plug.Neurological deficits were evaluated through the Zea Longa scoring system;TTC brain smear staining was used to determine the volume of cerebral infarction and the degree of hemispheric swelling in rats.The pathological changes of rat hippocampal tissue were observed by HE staining;Immunofluorescence was used to detect the expressions of HIF-1α and BNIP3 in rat brain tissue;The number of autophagosomes in the hippocampal region was observed by transmission electron microscopy.Western blot was used to detect the protein expressions related to autophagy(LC3B),apoptosis(Beclin-1),and HIF-1α/BNIP3 signaling pathways in mitochondria of brain tissue.Results ① The fluorescence expression intensity of HIF-1α and BNIP3 in hippocampus of model group was increased compared with that of sham group(P<0.05);The fluorescence expression intensity of HIF-1α and BNIP3 in hippocampus of massage group was significantly increased compared with that of model group(P<0.05).② Compared with model group,cerebral hemisphere swelling,nerve function deficit score and cerebral infarction volume in inhibitor group were increased(P<0.05);The levels of cerebral hemisphere swelling,nerve function deficit score and cerebral infarction volume in agonist group were decreased(P<0.05).The protein expressions of Beclin-1 and LC3B in agonist group were increased(P<0.05).The protein expressions of Beclin-1 and LC3B in inhibitor group were decreased(P<0.05).③ Compared with the massage group,the hippocampal cells in the massage+inhibitor group were more dispersed,the number of cells decreased,edema appeared,and tissue was damaged.④ Compared with model group,the protein expressions of LC3B,HIF-1α,Beclin-1 and BNIP3 in massage group were increased(P<0.05);The protein expressions of LC3B,HIF-1α,Beclin-1 and BNIP3 in massage+inhibitor group were decreased(P<0.05).Conclusion In the treatment of ischemic stroke,meridian massage can activate HIF-1α/BNIP3 signaling pathway,and then promote brain mitochondrial autophagy to improve nerve function,which provides a theoretical basis for the subsequent application of meridian massage in the clinical treatment of ischemic stroke patients.

Objective To explore the mechanism of malt alcohol extract improving depression-like behavior induced by CUMS in rats by regulating gut microbiota.Methods The depression model of rats was established using an 8-weeks CUMS procedure,and the administration group was given low(59.6 mg·kg-1)and high(178.8 mg·kg-1)doses of malt alcohol extract,respectively.The depression-like behavior of rats was evaluated by classic behavioral test.The composition of intestinal microbiota of rats was analyzed by 16S rRNA sequencing.The morphological changes of colon were observed by hematoxylin and eosin(HE),the expression of ZO-1 and Occludin in colon was detected by immunofluorescence(IF),and the expression of IL-10,IL-1βand 5-HT were detected by ELISA.Results The low dose of malt alcohol extract attenuated the depressive behavior and restored the expression of 5-HT in the brain of CUMS rats.16S rRNA sequencing results showed that the diversity and relative abundance of gut microbiota changed after treatment with the low dose of malt alcohol extract.ELISA results showed that the low dose of malt alcohol extract significantly reversed the CUMS-induced reduction of IL-10 and elevation of IL-1 β.HE results showed that the low dose of malt alcohol extract significantly ameliorated CUMS-induced structural damage in colon.IF results showed increased protain expression of intestinal epithelial barrier tight junction proteins ZO-1 and Occludin by the low dose of malt alcohol extract.Conclusion The low dose of malt alcohol extract can ameliorate CUMS-induced depressive-like behavior in rats by modulating intestinal flora,restoring 5-HT expression in the brain,inhibiting inflammation,and repairing the intestinal barrier.

Objective A high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was developed to quantify galantamine concentrations in rat blood following intramuscular injection of galantamine hydrobromide and to investigate its pharmacokinetic profile.Methods Male and female SD rats were randomly divided into four groups,each with six rats(three males and three females).The single intramuscular injection group received a single intramuscular dose of hydrobromide galantamine at low,medium,and high doses(0.25,0.50 and 1.00 mg·kg1)in rats.The single intravenous injection group received a single intravenous dose of hydrobromide galantamine at 0.25 mg·kg-1.The multiple intramuscular injection group received hydrobromide galantamine at 0.50 mg·kg-1 via intramuscular injection once daily for 7 consecutive days with a 24-hour interval between doses.Pharmacokinetic parameters of galantamine were calculated for each treatment group.Results The peak concentrations(Cmax)of galantamine following a single intramuscular injection in the low,medium,and high-dose groups were(80.54±9.31),(168.25±47.92)and(314.33±46.51)ng·mL-1,respectively.The area under the concentration-time curve(AUC0-t)was(95.23±20.42),(182.21±36.63)and(380.43±70.71)ng·mL-1·h,respectively.Additionally,the accumulation index of galantamine in the multiple intramuscular dosing group was 1.09.Conclusion Intramuscular injection of galantamine hydrobromide has good bioavailability in rats.Meanwhile,when administered multiple times,the drug accumulates low in the body.The experimental results provide valuable reference for the clinical pharmacokinetic study and clinical application of hydrobromide galantamine injection.

Objective To investigate the current clinical practices regarding perioperative discontinuation,bridging,and resumption of antiplatelet therapy in coronary heart disease(CHD)patients undergoing elective non-cardiac surgery or procedures,aiming to optimize perioperative antithrombotic management strategies.Methods A retrospective study was conducted on CHD patients requiring long-term oral antiplatelet therapy after percutaneous coronary intervention(PCI)who underwent elective non-cardiac surgery or procedures at a tertiary hospital in Hubei Province from January 1 to June 30,2024.Data on perioperative discontinuation,bridging,and resumption of antithrombotic drugs,as well as in-hospital bleeding events,were analyzed.Results A total of 338 hospitalized patients were included,with males accounting for 79.88%and the majority aged over 60 years.High bleeding-risk procedures comprised 56.61%of cases.Among 171 patients on single antiplatelet therapy(SAPT)preoperatively,8.19%continued therapy without interruption.Of the 157 patients who discontinued SAPT,67.25%received bridging therapy with low molecular weight heparin(LMWH),and 4.68%with sulodexide.Among 167 patients on dual antiplatelet therapy(DAPT)preoperatively,17.37%(29 cases)continued DAPT,while 122 discontinued it,with 85 receiving LMWH bridging.Postoperatively,58.64%(173/295)had not resumed antiplatelet therapy by discharge.Three intraoperative and 17 postoperative bleeding events(predominantly minor)were recorded.Conclusions Current perioperative antithrombotic management strategies for patients on long-term antiplatelet therapy undergoing elective surgery lack standardization,both domestically and internationally.Practices at this institution regarding drug discontinuation,bridging,and resumption diverged from guideline recommendations.However,the low observed bleeding rate and insufficient evidence highlight the need for well-designed clinical studies to address unresolved issues in perioperative antithrombotic management.

Objective To establish a method for quantitative control of multi-pharmacological components in Kanggan Jiedu capsules,and to evaluate the quality of Kanggan Jiedu capsules by chemometrics and weighted technique for order preference by similarity to an ideal solution(TOPSIS)method.Methods HPLC was performed on an Apollo C18 column with acetonitrile-0.1%formic acid gradient elution as mobile phase.The volume flow rate was 1.0 mL/min,and the detection wavelength was 327,238 and 298 nm.The contents of 3,5-O-dicaffeoylquinic acid,4,5-dicaffeoylquinic acid,gardenoside,geniposide,3'-hydroxy puerarin,puerarin,3'-methoxy puerarin,baicalin,wogonoside,oxypeucedanin,imperatorin,isoimperatorin,pseudoaspidin and tetraalbaspidin ABBA in 15 batches of Kanggan Jiedu capsules were determined by quantitative analysis of multi-components by single marker(QAMS),and then statistical software was used to analyze the difference of 15 batches of samples to find out the main potential markers affecting the quality of Kanggan Jiedu capsules.Results The f value of the 3,5-O-dicaffeoylquinic acid was 0.9119,with 4,5-dicaffeoylquinic acid as the internal reference.The f of the gardenoside,3'-hydroxy puerarin,puerarin and 3'-methoxy puerarin were 1.4941,1.2423,0.9281 and 1.0860,respectively,with geniposide as the internal reference.The f of the baicalin,wogonoside,oxypeucedanin,isoimperatorin,pseudoaspidin and tetraalbaspidin ABBA were 1.4551,0.7414,0.8796,0.6949,1.3248 and 0.8240,respectively,with imperatorin as the internal reference.The f values of each component were robust.There was no significant difference in the content determined by the two methods.The chemometrics method results showed that 15 batches of Kanggan Jiedu capsules could be clustered into three categories,there were certain differences between batches.Baicalin,geniposide,imperatorin,puerarin,3,5-O-dicaffeoylquinic acid and wogonoside were the main potential markers affecting the quality of Kanggan Jiedu capsules.The results of weighted TOPSIS method results showed that the Ci values of 15 batches of samples were between 0.2018 and 0.7346,among which S13 ranked the top with Ci value of 0.7346.Conclusion The established method for quantitative detection of 14 pharmacodynamic components is convenient and accurate.The quality of Kanggan Jiedu capsules can be evaluated by chemometrics and weighted TOPSIS method.

Objective Through reviewing the herbs,medical books and classic prescriptions of the past dynasties,the herbal examination of Gypsum fibrosum and its analogs was carried out to clarify the relationship between them.The qualitative analysis was carried out by single-point Raman,infrared,near infrared and XRD techniques,the quantitative analysis of the main components was carried out by EDTA titration and Raman surface scanning technique,the elemental analysis was carried out by ICP-OES,and the differences between gypsum and argillite were observed by scanning electron microscope.Results Gypsum fibrosum is mixed with marble,feldspar,north cold-water stone,south cold-water stone and xuanjing stone and so on.Before the Ming Dynasty,there was no differentiation between soft and anhydrite,and after the Ming Dynasty,it was clear that gypsum was soft gypsum and feldspar was anhydrite;in modern times,marble is also made to be gypsum for medicinal use;Feldspar is anhydrite and is no longer made to be used for medicinal use,north cold-water stone is red gypsum,and south cold-water stone is calcite.Gypsum,south coldwater stone is calcite.The peaks of argillite appeared to be buried in the Raman spectrum compared with Gypsum fibrosum,and the original profiles of both infrared and near-infrared were basically the same,and the near-infrared model established by the preprocessing method of the first-order derivatives plus vector normalization(5-point smoothing)could effectively differentiate between Gypsum fibrosum and its analogues,but it could not differentiate between argillite and Gypsum fibrosum with high content.XRD showed that there are differences in the relative intensities of the peaks of argillite and Gypsum fibrosum,and some XRD shows that there are differences in the relative intensities of the peaks of basalt and Gypsum fibrosum,and some of the peaks of basalt are characterized by impurities such as quartz,and the contents of trace elements such as Fe,Mn,Cr,Pb,Hg and As are higher in basalt.The peak shapes of XRD,Raman spectra,infrared spectra and near-infrared spectra of Gypsum fibrosum and calcined gypsum are closer but can still be distinguished,and the Ca content of calcined gypsum is higher than that of gypsum.Commercially available south chrysocolla and stalactite source are carbonate minerals calcite calcite.Spectral detection can not be distinguished,the trace element content is basically the same,but the traits are different.North chrysocolla(red gypsum)is higher than the Fe content of commercially available white gypsum.Raman surface scanning not only can be a qualitative and quantitative determination of minerals such as gypsum and other minerals,and the results of the content of the titration is basically similar,but also to determine the state of Gypsum fibrosum and calcined gypsum calcined water loss status and the degree of calcined gypsum.The results of Raman surface scanning are similar to the titration results.Conclusion This study can provide a scientific basis for the traceability of Gypsum fibrosum,and can better guide the clinical use of medicine and the rational use of resources.

Objective:To analyze the key points,deficiencies,and typical experience of the policy system for improving provincial primary Traditional Chinese Medicine(TCM)service capacity in China,so as to provide references for policy optimization.Methods:Top-level design documents related to the primary TCM service capacity improvement project in different provinces during the"14th Five-Year Plan"period were retrieved.The Latent Dirichlet Allocation(LDA)topic model model was used for thematic mining of policy texts,and the Policy Modeling Consistency(PMC)index model was constructed to analyze the common problems of various policies.Results:A total of 18 relevant policies were included,with an average PMC index of 5.52.Among the selected policies,10 were perfect policies,6 were excellent policies,and 2 were good policies,with no poor policies.The indicators of policy objects,policy objectives,and policy tools showed excellent performance,while the main problems were lack of supervision,insufficient interdepartmental coordination,and blind spots in policy content.Conclusion:In the"15th Five-Year Plan"period,the construction of TCM medical consortiums should be the main body to promote the expansion and sinking of high-quality TCM medical resources;the advantages of TCM in maintaining the full-life cycle health of the masses at the primary level should be valued;and internal and external policy coordination should be strengthened to form policy synergy and promote the high-quality development of primaiy TCM.

Objective To compare the efficacy and safety of perioperative chemotherapy regimens based on docetaxel administered in different cycles for locally advanced gastric cancer(LAGC)and gastroesophageal junction cancer(GEJC)through a network Meta-analysis.Methods PubMed,Embase,Cochrane Library,and Web of Science databases were electronically searched to collect randomized controlled trials(RCTs)evaluating docetaxel-based perioperative regimens for the treatment of LAGC and GEJC from inception to February 28,2025.Two researchers independently screened the literature,extracted relevant data,and assessed the risk of bias in the included studies.Subsequently,a network Meta-analysis was performed using R 4.5.0 software.Results A total of 10 RCTs involving 2,064 patients were included.The results of the network Meta-analysis showed that,compared with three cycles of epirubicin,cyclophosphamide,and fluorouracil(ECF regimen)and four cycles of platinum and fluorouracil(PF regimen),both three-cycle and four-cycle docetaxel,platinum,and fluorouracil(TPF regimen)significantly increased the complete tumor resection rate(R0 resection rate).Compared with surgery alone,the three-cycle TPF regimen significantly improved the R0 resection rate.Additionally,the four-cycle TPF regimen significantly improved 3-year and 5-year progression-free survival(PFS)compared with the two-cycle PF regimen,and significantly improved overall survival(OS)at 3 and 5 years compared with the three-cycle ECF regimen.Compared with surgery alone,the three-cycle TPF regimen also significantly increased the pathological complete response rate(pCR rate).Furthermore,compared with the two-cycle TPF and three-cycle ECF regimens,the four-cycle TPF and PF regimens were associated with a lower risk of surgical complications.Conversely,the two-cycle TPF and three-cycle ECF regimens significantly increased the risk of surgical complications compared with surgery alone.No statistically significant differences were observed in the incidence of grade 3 to 4 adverse events among the treatment regimens(P＞0.05).Based on the surface under the cumulative ranking curve(SUCRA)plot and pairwise comparisons,the three-cycle PF regimen appeared to be the most effective in achieving the highest R0 resection rate,the three-cycle TPF regimen appeared to be the most effective in achieving the highest pCR rate,while the four-cycle TPF regimen was associated with the best outcomes in terms of 3-year and 5-year PFS and OS.Conclusion The four-cycle TPF regimen may be associated with the optimal PFS and OS among perioperative chemotherapy regimens.No statistically significant differences were observed between the four-cycle TPF and the three-cycle PF in terms of R0 resection rate,between the four-cycle TPF and the three-cycle TPF in terms of pCR rate,or between the four-cycle TPF and the other seven regimens included in the study in terms of safety assessment.The four-cycle TPF regimen may represent the optimal perioperative chemotherapy regimen for patients with LAGC and GEJC.