BACKGROUND:Liuwei Dihuang Wan takes"three tonifying and three reducing effects"as its compatibility feature to nourish yin and tonify the kidneys,while Zuogui Wan takes"seeking yin in yang"as its compatibility feature to nourish yin and tonify the kidneys by promoting yang.Both of them belong to the same method of nourishing yin and tonifying the kidneys,and have better curative effects at the symptomatic and cellular molecular levels. OBJECTIVE:To observe the effects of Liuwei Dihuang Wan and Zuogui Wan in bone metabolism,and to explore their mechanism of action in the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)osteoblastic pathway. METHODS:Thirty-two Sprague-Dawley rats were randomized into model,Liuwei Dihuang Wan,Zuogui Wan,and sham operation group,with eight rats in each group.Osteoporosis models were prepared using removal of both ovaries in the first three groups.Starting at 30 days postoperatively,rats in the Liuwei Dihuang Wan group were gavaged with Liuwei Dihuang Wan 1.125 g/kg/d;rats in the Zuoqui Wan group were gavaged with Zuogui Wan 2.25 g/kg/d;and rats in the sham operation group and the model group were gavaged with saline 10 mL/kg/d.After 12 weeks of gavage,the rat tibia was taken to measure bone mineral density.The serum levels of estrogen,bone alkaline phosphatase,and cAMP/cGMP were measured using ELISA,and the expression of OPG/RANKL in the femur was detected using western blot. RESULTS AND CONCLUSION:Compared with the sham operation group,the model group showed a decrease in bone mineral density and levels of estrogen and bone alkaline phosphatase(P＜0.05)and an increase in cAMP/cGMP level(P＜0.05).Compared with the model group,the Liuwei Dihuang Wan group and the Zuogui Wan group significantly increased bone mineral density(P＜0.05)and bone alkaline phosphatase levels(P＜0.05);the Zuogui Wan group significantly decreased cAMP/cGMP levels(P＜0.05)and upregulated OPG expression(P＜0.05);the Liuwei Dihuang Wan group upregulated OPG expression and downregulated RANKL expression(P＜0.05);and both groups were unable to significantly increase estrogen levels(P＞0.05).To conclude,Zuogui Wan,which seeks yin from yang,can effectively increase the expression of OPG but cannot downregulate the expression of RANKL.However,Liuwei Dihuang Wan,which has three tonifying and three reducing effects,can bidirectionally regulate the expression of OPG and RANKL.This result suggests that Liuwei Dihuang Wan can significantly inhibit osteoclastic function compared with Zuogui Wan,and further research is needed to verify this conclusion.

BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective:To develop a clinical predictive model for dampness constitution based on laboratory testing indicators.Methods:A retrospective cohort study was conducted on 1 355 healthy individuals who underwent physical examinations at the Health Examination Center of Guangdong Provincial Hospital of Traditional Chinese Medicine from October 1 st, 2022 to October 31 st, 2023. Basic information and blood routine, blood glucose, liver function, lipid metabolism, and kidney function test results of 1 355 apparently healthy individuals were collected. According to the diagnostic criteria for dampness constitution in traditional Chinese medicine, they were divided into a dampness constitution group (683 cases, including 394 with phlegm-dampness constitution and 289 with damp-heat constitution) and a non-dampness constitution group (672 cases). Among them, there were 547 males and 136 females in the dampness constitution group, with an age of 38.0 (32.0, 45.0) years; and there were 355 males and 317 females in the non-dampness constitution group, with an age of 33.0 (27.0, 41.0) years. A total of 1 355 apparently healthy individuals were randomly divided into a training set ( n=948) and a validation set ( n=407) using computer-generated random numbers in a 7∶3 ratio. Logistic regression analysis was employed to identify risk factors associated with dampness constitution. Utilizing these identified risk factors, a predictive model was constructed and subsequently visualized. The model′s predictive accuracy, consistency, and clinical utility were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), respectively. Results:Among 1 355 subjects, there were statistically significant differences ( P<0.05) in gender, age, body mass index (BMI), blood glucose, some indicators of renal function, some indicators of blood routine, liver function, and four indicators of lipid metabolism between the dampness constitution group and the non-dampness constitution group. Gender ( OR=0.434,95 %CI 0.253-0.738), Cr ( OR=0.981,95 %CI 0.967-0.996), BMI ( OR=1.366,95 %CI 1.290-1.450), and LDL-C ( OR=1.388,95 %CI 1.014-1.897) were independent risk factors for dampness constitution ( P<0.05). A nomogram was subsequently developed based on these identified risk factors. The areas under the ROC curves (AUC) of the training set and validation set were 0.810 (95 %CI 0.783-0.837) and 0.804 (95 %CI 0.762-0.846), respectively. Conclusion:Gender,BMI,Cr and LDL-C were risk factors for the development of dampness constitution, and the clinical predictive model has clinical application value in predicting the risk of dampness constitution.

Objective To investigate the effectiveness of a higher-order thinking-oriented BOPPPS-based blended teach-ing model in otolaryngology-head and neck surgery education,focusing on its impact on the academic performance and teaching satisfaction of undergraduate clinical medicine students.Methods A total of 199 undergraduate clinical medicine students from Guangzhou Medical University were enrolled,divided into a control group(2021-2022 academic year,n=118)and an experi-mental group(2022-2023 academic year,n=81).The control group received conventional blended teaching via Chaoxing plat-form combined with case discussions,while the experimental group implemented the BOPPPS-integrated blended teaching model.Results Students in the experimental group achieved significantly higher average scores than the control group(Δ=11.71 points),with the excellent rate increasing from 0% to 11.1% and the failure rate decreasing to 1.2% .Additionally,the experi-mental group reported high satisfaction with the BOPPPS-integrated blended teaching model,with an overall satisfaction rate of 80.25%.Furthermore,54.32% of students expressed a preference for blended teaching approaches.Students widely acknowl-edged that this model facilitated flexible knowledge application.Conclusion The BOPPPS-integrated blended teaching model ef-fectively enhances the academic performance and teaching satisfaction of undergraduate clinical medicine students,providing a valuable reference for medical education reform oriented toward fostering higher-order thinking and clinical competency.

Objective:To develop a clinical predictive model for dampness constitution based on laboratory testing indicators.Methods:A retrospective cohort study was conducted on 1 355 healthy individuals who underwent physical examinations at the Health Examination Center of Guangdong Provincial Hospital of Traditional Chinese Medicine from October 1 st, 2022 to October 31 st, 2023. Basic information and blood routine, blood glucose, liver function, lipid metabolism, and kidney function test results of 1 355 apparently healthy individuals were collected. According to the diagnostic criteria for dampness constitution in traditional Chinese medicine, they were divided into a dampness constitution group (683 cases, including 394 with phlegm-dampness constitution and 289 with damp-heat constitution) and a non-dampness constitution group (672 cases). Among them, there were 547 males and 136 females in the dampness constitution group, with an age of 38.0 (32.0, 45.0) years; and there were 355 males and 317 females in the non-dampness constitution group, with an age of 33.0 (27.0, 41.0) years. A total of 1 355 apparently healthy individuals were randomly divided into a training set ( n=948) and a validation set ( n=407) using computer-generated random numbers in a 7∶3 ratio. Logistic regression analysis was employed to identify risk factors associated with dampness constitution. Utilizing these identified risk factors, a predictive model was constructed and subsequently visualized. The model′s predictive accuracy, consistency, and clinical utility were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), respectively. Results:Among 1 355 subjects, there were statistically significant differences ( P<0.05) in gender, age, body mass index (BMI), blood glucose, some indicators of renal function, some indicators of blood routine, liver function, and four indicators of lipid metabolism between the dampness constitution group and the non-dampness constitution group. Gender ( OR=0.434,95 %CI 0.253-0.738), Cr ( OR=0.981,95 %CI 0.967-0.996), BMI ( OR=1.366,95 %CI 1.290-1.450), and LDL-C ( OR=1.388,95 %CI 1.014-1.897) were independent risk factors for dampness constitution ( P<0.05). A nomogram was subsequently developed based on these identified risk factors. The areas under the ROC curves (AUC) of the training set and validation set were 0.810 (95 %CI 0.783-0.837) and 0.804 (95 %CI 0.762-0.846), respectively. Conclusion:Gender,BMI,Cr and LDL-C were risk factors for the development of dampness constitution, and the clinical predictive model has clinical application value in predicting the risk of dampness constitution.

Objective To explore the risk factors associated with the occurrence of dampness syndrome based on peripheral blood multiple laboratory indicators,construct predictive model and validate it.Methods A retrospective analysis was conducted on 180 patients who visited the Preventive Treatment Center of Guangdong Provincial Hospital of Chinese Medicine from May 2022 to December 2023.They were divided into two groups according to the diagnostic criteria:the damp syndrome of TCM group(n=118)and the balanced yin-yang constitution group(n=62),with the latter serving as the"non-syndrome"control group for dampness syndrome.Serum biochemical indicators were detected by electrochemiluminescence(ECL),immune cell subsets were analyzed through flow cytometer,and routine blood parameters were assessed using an automatic hematology analyzed.Logistic regression analysis was employed to screen risk factors and develop a predictive model.The Bootstrap method was used for data resampling to draw the receiver operating characteristic(ROC)curve,calibration curve,and clinical decision curve analysis(DCA)to evaluate the predictive value,consistency,and clinical efficacy of the model.Results Compared with the balanced yin-yang constitution group,the damp syndrome of TCM group showed increased levels of insulin(INS),non-high-density lipoprotein cholesterol(non HDL-C),red blood cells(RBC)and the proportion of CD4+T cells,the proportion of triglyceride(TG)>1.70 mmol/L,total cholesterol(TC)>5.20 mmol/L,low-density lipoprotein cholesterol(LDL-C)>3.37 mmol/L,and high-density lipoprotein cholesterol(HDL-C)≤1.15 mmol/L were also significantly higher,with statistical significance(U/t/χ2=-2.900～4 626,all P＜0.05).Logistic regression analysis showed that INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and the proportion of CD4+T cells were independent risk factors for the occurrence of damp syndrome of TCM(all P＜0.05).Based on the screened risk factors,a forecasting model was established and a nomogram was plotted.The model had an area under the ROC curve area under curve(AUC)of 0.747(95%CI=0.672～0.822),a Brier score of 0.184 for the calibration curve,and demonstrated clinical net benefit at threshold probabilities ranging from 0.30 to 1.00.Conclusion The forecasting model constructed based on INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and CD4+T cells ratio has a high predictive value for damp syndrome of TCM.

Objective To explore the risk factors associated with the occurrence of dampness syndrome based on peripheral blood multiple laboratory indicators,construct predictive model and validate it.Methods A retrospective analysis was conducted on 180 patients who visited the Preventive Treatment Center of Guangdong Provincial Hospital of Chinese Medicine from May 2022 to December 2023.They were divided into two groups according to the diagnostic criteria:the damp syndrome of TCM group(n=118)and the balanced yin-yang constitution group(n=62),with the latter serving as the"non-syndrome"control group for dampness syndrome.Serum biochemical indicators were detected by electrochemiluminescence(ECL),immune cell subsets were analyzed through flow cytometer,and routine blood parameters were assessed using an automatic hematology analyzed.Logistic regression analysis was employed to screen risk factors and develop a predictive model.The Bootstrap method was used for data resampling to draw the receiver operating characteristic(ROC)curve,calibration curve,and clinical decision curve analysis(DCA)to evaluate the predictive value,consistency,and clinical efficacy of the model.Results Compared with the balanced yin-yang constitution group,the damp syndrome of TCM group showed increased levels of insulin(INS),non-high-density lipoprotein cholesterol(non HDL-C),red blood cells(RBC)and the proportion of CD4+T cells,the proportion of triglyceride(TG)>1.70 mmol/L,total cholesterol(TC)>5.20 mmol/L,low-density lipoprotein cholesterol(LDL-C)>3.37 mmol/L,and high-density lipoprotein cholesterol(HDL-C)≤1.15 mmol/L were also significantly higher,with statistical significance(U/t/χ2=-2.900～4 626,all P＜0.05).Logistic regression analysis showed that INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and the proportion of CD4+T cells were independent risk factors for the occurrence of damp syndrome of TCM(all P＜0.05).Based on the screened risk factors,a forecasting model was established and a nomogram was plotted.The model had an area under the ROC curve area under curve(AUC)of 0.747(95%CI=0.672～0.822),a Brier score of 0.184 for the calibration curve,and demonstrated clinical net benefit at threshold probabilities ranging from 0.30 to 1.00.Conclusion The forecasting model constructed based on INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and CD4+T cells ratio has a high predictive value for damp syndrome of TCM.

AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.

AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.