ObjectiveTo evaluate the effects and safety of the optimized new Shengmai Powder （优化新生脉散方） on exercise tolerance in patients with chronic heart failure （CHF） of qi deficiency， blood stasis， and fluid retention syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 78 CHF patients with qi deficiency， blood stasis， and fluid retention syndrome were recruited and randomly assigned to a treatment group （39 cases） and a control group （39 cases）. On the basis of conventional western medical therapy， patients in the treatment group additionally received the optimized new Shengmai Powder granules， while the control group was given an oral placebo of optimized new Shengmai Powder granules. Patients in both groups took 30.6 g each time， twice a day， mixed with water for administration， with a total treatment course of 4 weeks. The primary outcomes were 6-minute walk distance （6MWD） and peak oxygen uptake （Peak VO₂） measured by cardiopulmonary exercise testing. Secondary outcomes included New York Heart Association （NYHA） functional classification， B-type natriuretic peptide （BNP） levels， cardiac function indexes including left ventricular ejection fraction （LVEF）， left ventri-cular end-systolic diameter （LVESD） and left ventricular end-diastolic diameter （LVEDD）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） scores， and scores of four diagnostic information of traditional Chinese medicine （TCM）. All indicators were assessed once before and after treatment respectively. Safety indicators were evaluated， and adverse events during the trial were recorded. ResultsAll patients in both groups were included in the full ana-lysis set （FAS） and safety set （SS）. Compared with baseline， the 6MWD and Peak VO₂ of cardiopulmonary exercise test in the treatment group significantly increased after treatment， while the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information significantly decreased， and the NYHA cardiac function grade significantly improved （P＜0.01）. After treatment， the 6MWD and Peak VO₂ of cardiopulmonary exercise test， as well as their changes from baseline in the treatment group were higher than those in the control group； the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information in the treatment group were lower than those in the control group； and the improvement of NYHA cardiac function grade in the treatment group was superior to that in the control group （P＜0.01）. There was no statistically significant differences in all indicators after treatment in the control group （P＞0.05）. The incidence of adverse events was 5.1% （2/39） in the treatment group and 2.6% （1/39） in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionOn the basis of conventional western medicine treatment， the addition of the optimized new Shengmai Powder can further improve exercise tolerance， cardiac function and quality of life in patients with CHF of qi deficiency， blood stasis and fluid retention syndrome， and show good safety.

Objective To construct a diagnostic model for phlegm-dampness syndrome in hypertension based on multimodal feature fusion.Methods Clinical text information(physiological/lifestyle data,symptoms,pulse characteristics)and tongue image data were collected from 261 hypertension patients.For clinical text data,statistical analyses,including ANOVA,Mann-Whitney U test,and Chi-square test,were performed to identify significant features(P<0.05),which were incorporated into a clinical text-based diagnosis model(CTDM)using a multilayer perceptron algorithm.For tongue images,a tongue image-based diagnosis model(TIDM)was constructed based on channel attention mechanisms and residual networks.A multimodal diagnostic model(MDM)was built by fusing clinical text and tongue image features using a feature concatenation method.The diagnostic performance of each model was evaluated using five-fold cross-validation with the area under the receiver operating characteristic curve(AUC),accuracy,specificity,and sensitivity.Results Seven clinical text features,including physiological/lifestyle factors(disease duration,body mass index),symptoms(chest tightness,loss of appetite,excessive phlegm),and pulse characteristics(slippery pulse,damp pulse),were identified as risk factors for phlegm-dampness syndrome in hypertension.The AUC of the CTDM was 0.831±0.021,the AUC of the TIDM was 0.878±0.035,and the MDM achieved an AUC of 0.972±0.015.Conclusion The multimodal diagnostic model that integrates clinical text and tongue image features demonstrates high diagnostic accuracy and provides valuable guidance for AI-assisted diagnosis of phlegm-dampness syndrome in hypertension.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Objective To establish and validate a method for simultaneous analysis of fluconazole,linezolid,voriconazole and cont-ezolid by liquid chromatography-tandem mass spectrometry,and conduct preliminary assessment its value of application value in clinical therapeutic drug monitoring.Methods Using an isotopic internal standard method,the serum samples were pretreated with protein precipitation.The supernatant was diluted after centrifugation,and detected by liquid chromatography-tandem mass spectrometer.Refer-ring to the Recommendations for Clinical Application of Liquid Chromatography-Mass Spectrometry(LC-MS)and Clinical and Labora-tory Standards Instituhe(CLSI)C62A,the performance of the LC-MS method was verified,including quantitation limits,linearity,trueness,precision,matrix effect,carry-over,interference,dilution consistency and stability.The blood samples from patients who were treated with fluconazole,linezolid,voriconazole,and contezolid were collected and measured for trough or peak concentrations.Results The quantitation limits of fluconazole,linezolid,voriconazole and contezolid by this method were 1 μg/mL,0.25 μg/mL,0.25 μg/mL and 0.1 μg/mL,respectively.The linear ranges were 1-100 μg/mL,0.25-25 μg/mL,0.25-25 μg/mL,and 0.1-10μg/mL,respectively.The recovery rates were 103.0％-105.7％,103.1％-108％,102.4％-106.2％and 101.0％-109.9％,respectively.The precisions,expressed as coefficient of variation(CV),were 1.7％-3.4％,2.1％-4.8％,1.9％-3.1％,and 3.1％-6.8％,respective-ly.No obvious matrix effect,carry-over contamination and interference were found.The dilution consistency and stability were satisfac-tory.The concentrations of fluconazole,linezolid and voriconazole within the reference interval accounted for 49.1％,52.5％and 80.7％of the total samples,respectively.The peak concentration of contezolamide was(14.02±4.94)μg/mL(n=4),and the trough concen-tration was(0.34±0.20)μg/mL(n=5).Conclusion In this study,a method for simultaneous analysis of the concentrations of flu-conazole,linezolid,voriconazole and contezolid was successfully established and verified by liquid chromatography-tandem mass spec-trometry.This method is simple,rapid,and suitable for therapeutic drug monitoring,and providing a basis for the optimization of drug regimens.

Objective:? To summarize the achievements in improving the consistency of clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing results.Methods:? From 2021 to 2024, Zhongshan Hospital Affiliated to Fudan University recruited laboratories voluntarily participating in the MSHP (Clinical LC-MS/MS Testing Consistency Program). As of Batch 202404, a total of 76 laboratories had enrolled, including 60 medical institutions (all tertiary hospitals) and 16 third-party laboratories. Test items were established, and comparative samples were distributed regularly-each item′s samples covered three concentrations (high, medium, and low). Samples were shipped via cold chain and tested within one week. Our laboratory′s measurements served as the target, with participating labs′ results within ±25% of the target deemed qualified. Passing-Bablok regression and Bland-Altman analysis were used to assess consistency.Results:Taking 3-MT (3-methoxytyramine) as an example, the coefficients of variation (CVs) for the project′s three concentration levels improved from 17.00%, 47.18%, and 4.88% in the first comparative batch to 9.59%, 9.59%, and 6.1% in Batch 202404. Passing-Bablok regression results for the 5 units participating in 3-MT testing showed that Laboratory A had proportional bias but no systematic bias (regression slope [95% CI]: 0.903 [0.862-0.952]; intercept [95% CI]: 0.912 [-1.921-6.073]). The remaining laboratories exhibited no proportional or systematic bias with the target (Laboratory B: slope 1.031 [0.961-1.147], intercept-0.733 [-4.641-8.272]; Laboratory C: slope 0.982 [0.940-1.009], intercept-0.576 [-2.675-1.891]; Laboratory D: slope 0.973 [0.939-1.066], intercept-1.168 [-6.108-1.649]; Laboratory E: slope 0.999 [0.905-1.051], intercept-1.876 [-6.111-3.508]). Bland-Altman analysis indicated that all 5 laboratories′ results generally showed good consistency with the target. Through quality feedback and optimizing sample preparation concentrations, result consistency was enhanced.? Conclusion:? Clinical LC-MS/MS testing consistency programs contribute to improving the comparability of test results.

Objective To construct a diagnostic model for phlegm-dampness syndrome in hypertension based on multimodal feature fusion.Methods Clinical text information(physiological/lifestyle data,symptoms,pulse characteristics)and tongue image data were collected from 261 hypertension patients.For clinical text data,statistical analyses,including ANOVA,Mann-Whitney U test,and Chi-square test,were performed to identify significant features(P<0.05),which were incorporated into a clinical text-based diagnosis model(CTDM)using a multilayer perceptron algorithm.For tongue images,a tongue image-based diagnosis model(TIDM)was constructed based on channel attention mechanisms and residual networks.A multimodal diagnostic model(MDM)was built by fusing clinical text and tongue image features using a feature concatenation method.The diagnostic performance of each model was evaluated using five-fold cross-validation with the area under the receiver operating characteristic curve(AUC),accuracy,specificity,and sensitivity.Results Seven clinical text features,including physiological/lifestyle factors(disease duration,body mass index),symptoms(chest tightness,loss of appetite,excessive phlegm),and pulse characteristics(slippery pulse,damp pulse),were identified as risk factors for phlegm-dampness syndrome in hypertension.The AUC of the CTDM was 0.831±0.021,the AUC of the TIDM was 0.878±0.035,and the MDM achieved an AUC of 0.972±0.015.Conclusion The multimodal diagnostic model that integrates clinical text and tongue image features demonstrates high diagnostic accuracy and provides valuable guidance for AI-assisted diagnosis of phlegm-dampness syndrome in hypertension.

Objective To establish and validate a method for simultaneous analysis of fluconazole,linezolid,voriconazole and cont-ezolid by liquid chromatography-tandem mass spectrometry,and conduct preliminary assessment its value of application value in clinical therapeutic drug monitoring.Methods Using an isotopic internal standard method,the serum samples were pretreated with protein precipitation.The supernatant was diluted after centrifugation,and detected by liquid chromatography-tandem mass spectrometer.Refer-ring to the Recommendations for Clinical Application of Liquid Chromatography-Mass Spectrometry(LC-MS)and Clinical and Labora-tory Standards Instituhe(CLSI)C62A,the performance of the LC-MS method was verified,including quantitation limits,linearity,trueness,precision,matrix effect,carry-over,interference,dilution consistency and stability.The blood samples from patients who were treated with fluconazole,linezolid,voriconazole,and contezolid were collected and measured for trough or peak concentrations.Results The quantitation limits of fluconazole,linezolid,voriconazole and contezolid by this method were 1 μg/mL,0.25 μg/mL,0.25 μg/mL and 0.1 μg/mL,respectively.The linear ranges were 1-100 μg/mL,0.25-25 μg/mL,0.25-25 μg/mL,and 0.1-10μg/mL,respectively.The recovery rates were 103.0％-105.7％,103.1％-108％,102.4％-106.2％and 101.0％-109.9％,respectively.The precisions,expressed as coefficient of variation(CV),were 1.7％-3.4％,2.1％-4.8％,1.9％-3.1％,and 3.1％-6.8％,respective-ly.No obvious matrix effect,carry-over contamination and interference were found.The dilution consistency and stability were satisfac-tory.The concentrations of fluconazole,linezolid and voriconazole within the reference interval accounted for 49.1％,52.5％and 80.7％of the total samples,respectively.The peak concentration of contezolamide was(14.02±4.94)μg/mL(n=4),and the trough concen-tration was(0.34±0.20)μg/mL(n=5).Conclusion In this study,a method for simultaneous analysis of the concentrations of flu-conazole,linezolid,voriconazole and contezolid was successfully established and verified by liquid chromatography-tandem mass spec-trometry.This method is simple,rapid,and suitable for therapeutic drug monitoring,and providing a basis for the optimization of drug regimens.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective To explore the effects of Buyang Huanwu Decoction on neuronal cell apoptosis after cerebral ischemia based on mediating Cav1 in regulating Wnt pathway.Methods Male wild-type(WT)and Cav1-/-(KO)C57BL/6 mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group(18.5 g/kg).Cerebral ischemia model was prepared using middle cerebral artery occlusion method,and drug intervention was given for 14 days.Neurobehavioral score was performed,HE staining was used to observe the morphology of ischemic cortical area of brain tissue,TUNEL staining was used to detect neuronal apoptosis in ischemic cortical area,immunohistochemistry was used to detect the expressions of apoptosis related proteins and Wnt1,glycogen synthase kinase 3β(GSK3β)and β-catenin protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurobehavioral score of the model group mice significantly increased,neuronal cells in the ischemic cortical area showed vacuolar changes,with nuclear condensation and widened intercellular spaces,the apoptosis rate of nerve cells significantly increased,with increased expressions of Bax,GSK3β and decreased expressions of Bcl-2,Wnt1 and β-catenin(P<0.01).Compared with the same genotype model group,the neurobehavioral score of mice in Buyang Huanwu Decoction group were significantly decreased,the pathological damage of the ischemic cortical area improved,the apoptosis rate of nerve cells decreased,the expressions of Bax and GSK3β decreased,and the expressions of Bcl-2,Wnt1 and β-catenin increased(P<0.01).Compared with the WT model group,the KO model group showed an increase in neurobehavioral score,aggravated damage in ischemic cortical area,significantly increased neuronal apoptosis rate,and increased expression of GSK3β(P<0.05).Compared with the WT Buyang Huanwu Decoction group,the KO Buyang Huanwu Decoction group showed an increase in neurobehavioral score,aggravated damage in ischemic cortical area,significantly increased neuronal apoptosis rate,increased expressions of Bax and GSK3β,and decreased expressions of Bcl-2,Wnt1 and β-catenin(P<0.01).Conclusion Buyang Huanwu Decoction can inhibit neuronal cell apoptosis after cerebral ischemia,and its mechanism may be related to regulating the expressions of apoptosis-related proteins by mediating Cav1 to regulate the Wnt signaling pathway.

Objective To explore the mechanism of Buyang Huanwu Decoction against cerebral ischemia-reperfusion injury in rats by regulating lipid metabolism through the cAMP/PKA/PPARγ pathway.Methods 60 rats were randomly divided into sham operation group(Sham),model group(Model),Buyang Huanwu Decoction low-dose group(BHD-L),Buyang Huanwu Decoction medium-dose group(BHD-M),Buyang Huanwu Decoction high-dose group(BHD-H)and Butylphthalide group(NBP).The cerebral ischemia-reperfusion model was prepared by transient middle cerebral artery embolization.The BHD low-,medium-and high-groups were given different doses of Buyang Huanwu Decoction(6.413,12.825,25.65 g·kg-1)by intragastric administration.The NBP group was administered with Butylphthalide(54 mg·kg-1).The sham operation group and the model group were administered with an equal volume of distilled water,all given for 14 days.The rats were subjected to neurobehavioral scoring.HE staining was used to observe brain pathological changes,and the kit was used to detect the levels of phosphocholine(PC),phosphatidylethanolamine(PE),diacylglycerol(DAG),and free fatty acid(FFA)on the ischemic side.RT-qPCR and Western Blot were applied to detect the mRNA and protein expressions of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),and peroxisome proliferator-activated receptor γ(PPARγ).Results Compared with the sham group,the neurological deficit score was significantly increased(P＜0.01),pathomorphological damage in ischemic cortex was found,the contents of PC and PE were reduced,the contents of DAG and FFA were increased(P＜0.01),and cAMP mRNA expression increased(P＜0.05)in the model group.Compared with the model group,the neurological deficit score of the BHD-L group was decreased(P＜0.05),and the neurological deficit score of the BHD-M,BHD-H and NBP groups was significantly decreased(P＜0.01),the cells in each treatment group were regularly arranged,the intercellular spaces were reduced,and the normal cells were increased.PC and PE were significantly increased,DAG and FFA were significantly decreased(P＜0.01)in the BHD-M,BHD-H and NBP groups.PC was increased,FFA and DAG were decreased in the BHD-L group(P＜0.05,P＜0.01).The mRNA level of PPARγ was increased in the BHD-L group(P＜0.05),and the mRNA and protein levels of cAMP,PKA,and PPARγ were increased in the other treatment groups(P＜0.05,P＜0.01).Conclusion Buyang Huanwu Decoction has a neuroprotective effect on cerebral ischemia-reperfusion injury rats,and its mechanism may be related to regulating the expression of key factors in the cAMP/PKA/PPARγ signaling pathway and lipid metabolism.