Objective:The aim of this study was to assess the frailty status of patients with heart failure undergoing CRT-D and then explore the predictive value of frailty for all-cause mortality and heart failure-related readmissions in these patients.Methods:We retrospectively included 374 patients with chronic heart failure who underwent CRT-D treatment at the First Affiliated Hospital of Xinjiang Medical University between June 2020 and June 2024. Based on the Tilburg Debilitation Assessment Scale, 175 patients (46.8%) were classified as frail while 199 (53.2%) were classified as non-frail. The baseline data between the two groups was compared using Cox regression analysis and Kaplan-Meier curves were used for survival analysis. P-values of <0.05 indicated statistically significant differences. Results:A total of 374 patients aged 25-93 (68±11) years were enrolled in this study, 101 (27.0%) of which were female. Among these, 175 (46.8%) were categorized as frail, and 199 (53.2%) were classified as non-frail. Over a median follow-up time of 23 (5, 45) months, 35 (9.4%) patients experienced all-cause mortality, with 30 (17.1%) deaths occurring in the frail group and 5 (2.5%) in the non-frail group; meanwhile, readmission events due to heart failure occurred in a total of 174 (46.5%) patients, including 122 (70.1%) in the frail group, and 52 (29.9%) in the non-frail group. Cox analysis showed that frailty was a significant determinant of all-cause mortality ( HR=21.25, 95% CI 3.99-113.30, P<0.001) and readmission among heart failure patients receiving CRT-D ( HR=2.52, 95% CI 1.73-3.68, P<0.001). Log-rank tests showed that the survival rate of patients in the frail group was significantly lower than that of patients in the non-frail group ( HR=7.22, 95% CI 2.80-18.60, P<0.001) and the risk of readmission events due to heart failure was significantly higher among patients in the frail group than among those in the non-frail group ( HR=2.75, 95% CI 1.98-3.81, P<0.001). Conclusions:Frailty is an independent predictor of postoperative all-cause mortality and the occurrence of heart failure-related readmissions in patients with heart failure treated receiving CRT-D.

BACKGROUND:Stem cell transplantation has a promising therapeutic prospect in the treatment of myocardial infarction,but the efficacy of stem cell transplantation is limited by the low homing efficiency of transplanted cells to the heart and the low retention rate and survival rate in the heart.Exercise therapy is an important integral component of cardiac rehabilitation for patients with myocardial infarction.However,the role of exercise in stem cell therapy for myocardial infarction has not yet been clarified.OBJECTIVE:To investigate the effect of exercise(including acute exercise and chronic exercise)on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction.METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group or combination group with random number table method(n=20).Myocardial infarction model of rats in model group,transplantation group,or combination group was made by coronary artery ligation.24 hours after the model was made,the combination group underwent aerobic exercise for 8 weeks(chronic exercise,30 min/d,5 days per week),and within 5 minutes after the first exercise(acute exercise).SD rat bone marrow mesenchymal stem cells labeled with green fluorescent protein were injected into the tail vein of the transplantation group and the combination group.A part of animals from each group were taken 24 hours after the first exercise.The survival rate of stem cells transplanted into rat myocardium,sex-determining region of Y,protein expression of homing factors,oxidative stress,and inflammatory response parameters were measured.After 72 hours of the last exercise,the remaining rats were taken to detect cardiac structure and function,myocardial histological changes,and the number of Ki67+cells.RESULTS AND CONCLUSION:(1)After acute exercise:Compared with sham operation group,myocardial reactive oxygen species level,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression increased(P<0.05),and superoxide dismutase activity decreased(P<0.05)in model group.Compared with model group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression reduced(P<0.05),superoxidation dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in transplantation and combination groups.Compared with the transplantation group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression decreased(P<0.05),stem cell survival rate,sex-determining region of Y mRNA expression,superoxide dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in combination group.(2)After chronic exercise:Compared with sham operation group,cardiomyocyte cross-sectional area and collagen content increased(P<0.05),left ventricular ejection fraction and left ventricular short-axis shortening rate decreased(P<0.05)in model group.Compared with model group,cardiomyocyte cross-sectional area and collagen content decreased(P<0.05),Ki67+cells increased(P<0.05)in transplantation group.Compared with transplantation group,collagen content decreased(P<0.05),cardiomyocyte cross-sectional area,left ventricular ejection fraction,left ventricular short-axis shortening rate,and Ki67+cells increased(P<0.05)in the combination group.(3)Acute exercise improves the survival rate of exogenous stem cells by promoting stem cell homing and improving myocardial microenvironment,while chronic exercise can stimulate cardiomyocyte proliferation,inhibit cardiac remodeling,and enhance cardiac function after stem cell transplantation.Therefore,exercise can help to optimize the efficacy of stem cell transplantation after myocardial infarction in rats.

Primary hyperaldosteronism(PHA),the most common cause of secondary hypertension,can lead to cardiovascular and renal damage events.Early diagnosis and accurate typing of PHA is crucial to the choice of treatment options,and its diagnostic modalities usually include prone test screening,captopril test characterization and adrenal vein blood sampling for localization and typing diagnosis.However,with the development of imaging,molecular biology and morphology technologies,the use of nuclear medicine PET-CT,genetic testing and pathological diagnostic methods can also be used to accurately typify PHA.New technologies such as adrenal artery embolization and adrenal radiofrequency ablation are also increasingly being used in the treatment of PHA,which have the advantages of shorter and less costly surgery,fewer postoperative complications,and quicker recovery.This article provides a review of the developments in the screening,diagnosis and treatment of PHA with a view to informing clinical practice.

Primary hyperaldosteronism(PHA),the most common cause of secondary hypertension,can lead to cardiovascular and renal damage events.Early diagnosis and accurate typing of PHA is crucial to the choice of treatment options,and its diagnostic modalities usually include prone test screening,captopril test characterization and adrenal vein blood sampling for localization and typing diagnosis.However,with the development of imaging,molecular biology and morphology technologies,the use of nuclear medicine PET-CT,genetic testing and pathological diagnostic methods can also be used to accurately typify PHA.New technologies such as adrenal artery embolization and adrenal radiofrequency ablation are also increasingly being used in the treatment of PHA,which have the advantages of shorter and less costly surgery,fewer postoperative complications,and quicker recovery.This article provides a review of the developments in the screening,diagnosis and treatment of PHA with a view to informing clinical practice.

Objective:To explore the independent risk factors for predicting the right adrenal dominant secretory side in patients with primary hyperaldosteronism (PHA), so as to construct and verify the prediction model of the dominant secretory side, and provide evidence for the diagnosis and treatment of PHA patients.Methods:Clinical data of 82 PHA patients undergoing adrenal vein sampling (AVS) admitted to the Second Affiliated Hospital of Guangzhou Medical University from January 2015 to July 2023 were retrospectively analyzed, and divided into the training set (58 cases) and the verification set (24 cases) according to the ratio of 7∶3. Single factor and multiple factor logistic regression analysis were used to screen out the risk factors for predicting the right adrenal dominant secretory side, and then combined with the risk factors to build the prediction model of the dominant secretory side. The predictive efficiency and clinical applicability of the predominance secretory nomogram prediction model were verified by drawing receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA curve).Results:(1) Univariate and multivariate logistic analysis showed that the concentration of aldosterone (ALD2) in inferior vena cava and the results of adrenal CT imaging suggested that the right adrenal unilateral nodule (RJJ) were independent risk factors for the occurrence of right adrenal dominant secretion in PHA patients undergoing AVS (all P<0.05). (2) The area under ROC curve (AUC) corresponding to ALD2 variable was 0.898(95% CI: 0.735 7-0.986 1), and the sensitivity and specificity were 95.2% and 81.1%, respectively. The corresponding AUC of RJJ variable was 0.750(95% CI: 0.683 1-0.976 3), and the sensitivity and specificity were 90.5% and 86.7%, respectively. The AUC of the two variables in the verification set were 0.926 and 0.778, respectively. (3) Calibration curve and DCA curve showed that the prediction model had good consistency and clinical applicability, and can produce good clinical benefits. Conclusions:ALD2 and adrenal CT results suggest that RJJ is an independent risk factor for the prediction of the right adrenal dominant secretory side, and the prediction model based on these risk factors has good predictive efficacy and clinical applicability.

Objective:To explore the independent risk factors for predicting the right adrenal dominant secretory side in patients with primary hyperaldosteronism (PHA), so as to construct and verify the prediction model of the dominant secretory side, and provide evidence for the diagnosis and treatment of PHA patients.Methods:Clinical data of 82 PHA patients undergoing adrenal vein sampling (AVS) admitted to the Second Affiliated Hospital of Guangzhou Medical University from January 2015 to July 2023 were retrospectively analyzed, and divided into the training set (58 cases) and the verification set (24 cases) according to the ratio of 7∶3. Single factor and multiple factor logistic regression analysis were used to screen out the risk factors for predicting the right adrenal dominant secretory side, and then combined with the risk factors to build the prediction model of the dominant secretory side. The predictive efficiency and clinical applicability of the predominance secretory nomogram prediction model were verified by drawing receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA curve).Results:(1) Univariate and multivariate logistic analysis showed that the concentration of aldosterone (ALD2) in inferior vena cava and the results of adrenal CT imaging suggested that the right adrenal unilateral nodule (RJJ) were independent risk factors for the occurrence of right adrenal dominant secretion in PHA patients undergoing AVS (all P<0.05). (2) The area under ROC curve (AUC) corresponding to ALD2 variable was 0.898(95% CI: 0.735 7-0.986 1), and the sensitivity and specificity were 95.2% and 81.1%, respectively. The corresponding AUC of RJJ variable was 0.750(95% CI: 0.683 1-0.976 3), and the sensitivity and specificity were 90.5% and 86.7%, respectively. The AUC of the two variables in the verification set were 0.926 and 0.778, respectively. (3) Calibration curve and DCA curve showed that the prediction model had good consistency and clinical applicability, and can produce good clinical benefits. Conclusions:ALD2 and adrenal CT results suggest that RJJ is an independent risk factor for the prediction of the right adrenal dominant secretory side, and the prediction model based on these risk factors has good predictive efficacy and clinical applicability.

BACKGROUND:Stem cell transplantation has a promising therapeutic prospect in the treatment of myocardial infarction,but the efficacy of stem cell transplantation is limited by the low homing efficiency of transplanted cells to the heart and the low retention rate and survival rate in the heart.Exercise therapy is an important integral component of cardiac rehabilitation for patients with myocardial infarction.However,the role of exercise in stem cell therapy for myocardial infarction has not yet been clarified.OBJECTIVE:To investigate the effect of exercise(including acute exercise and chronic exercise)on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction.METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group or combination group with random number table method(n=20).Myocardial infarction model of rats in model group,transplantation group,or combination group was made by coronary artery ligation.24 hours after the model was made,the combination group underwent aerobic exercise for 8 weeks(chronic exercise,30 min/d,5 days per week),and within 5 minutes after the first exercise(acute exercise).SD rat bone marrow mesenchymal stem cells labeled with green fluorescent protein were injected into the tail vein of the transplantation group and the combination group.A part of animals from each group were taken 24 hours after the first exercise.The survival rate of stem cells transplanted into rat myocardium,sex-determining region of Y,protein expression of homing factors,oxidative stress,and inflammatory response parameters were measured.After 72 hours of the last exercise,the remaining rats were taken to detect cardiac structure and function,myocardial histological changes,and the number of Ki67+cells.RESULTS AND CONCLUSION:(1)After acute exercise:Compared with sham operation group,myocardial reactive oxygen species level,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression increased(P<0.05),and superoxide dismutase activity decreased(P<0.05)in model group.Compared with model group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression reduced(P<0.05),superoxidation dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in transplantation and combination groups.Compared with the transplantation group,reactive oxygen species,malondialdehyde content,tumor necrosis factor-α,and interleukin-1β protein expression decreased(P<0.05),stem cell survival rate,sex-determining region of Y mRNA expression,superoxide dismutase activity,stromal cell-derived factor 1α,and CXC chemokine receptor 4 protein expression increased(P<0.05)in combination group.(2)After chronic exercise:Compared with sham operation group,cardiomyocyte cross-sectional area and collagen content increased(P<0.05),left ventricular ejection fraction and left ventricular short-axis shortening rate decreased(P<0.05)in model group.Compared with model group,cardiomyocyte cross-sectional area and collagen content decreased(P<0.05),Ki67+cells increased(P<0.05)in transplantation group.Compared with transplantation group,collagen content decreased(P<0.05),cardiomyocyte cross-sectional area,left ventricular ejection fraction,left ventricular short-axis shortening rate,and Ki67+cells increased(P<0.05)in the combination group.(3)Acute exercise improves the survival rate of exogenous stem cells by promoting stem cell homing and improving myocardial microenvironment,while chronic exercise can stimulate cardiomyocyte proliferation,inhibit cardiac remodeling,and enhance cardiac function after stem cell transplantation.Therefore,exercise can help to optimize the efficacy of stem cell transplantation after myocardial infarction in rats.

Objective:The aim of this study was to assess the frailty status of patients with heart failure undergoing CRT-D and then explore the predictive value of frailty for all-cause mortality and heart failure-related readmissions in these patients.Methods:We retrospectively included 374 patients with chronic heart failure who underwent CRT-D treatment at the First Affiliated Hospital of Xinjiang Medical University between June 2020 and June 2024. Based on the Tilburg Debilitation Assessment Scale, 175 patients (46.8%) were classified as frail while 199 (53.2%) were classified as non-frail. The baseline data between the two groups was compared using Cox regression analysis and Kaplan-Meier curves were used for survival analysis. P-values of <0.05 indicated statistically significant differences. Results:A total of 374 patients aged 25-93 (68±11) years were enrolled in this study, 101 (27.0%) of which were female. Among these, 175 (46.8%) were categorized as frail, and 199 (53.2%) were classified as non-frail. Over a median follow-up time of 23 (5, 45) months, 35 (9.4%) patients experienced all-cause mortality, with 30 (17.1%) deaths occurring in the frail group and 5 (2.5%) in the non-frail group; meanwhile, readmission events due to heart failure occurred in a total of 174 (46.5%) patients, including 122 (70.1%) in the frail group, and 52 (29.9%) in the non-frail group. Cox analysis showed that frailty was a significant determinant of all-cause mortality ( HR=21.25, 95% CI 3.99-113.30, P<0.001) and readmission among heart failure patients receiving CRT-D ( HR=2.52, 95% CI 1.73-3.68, P<0.001). Log-rank tests showed that the survival rate of patients in the frail group was significantly lower than that of patients in the non-frail group ( HR=7.22, 95% CI 2.80-18.60, P<0.001) and the risk of readmission events due to heart failure was significantly higher among patients in the frail group than among those in the non-frail group ( HR=2.75, 95% CI 1.98-3.81, P<0.001). Conclusions:Frailty is an independent predictor of postoperative all-cause mortality and the occurrence of heart failure-related readmissions in patients with heart failure treated receiving CRT-D.

In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

The famous classical formulae are epitomes of the clinical practice experience created by doctors in history， as an important symbol of traditional Chinese medicine （TCM） theory and clinical treatment approaches， it has been given a new concept connotation and become one of the breakthroughs for the development of TCM in the new era. Due to the limitations of historical literature and different cognitive perspectives of literature research， there are still common problems in determination of the dosage， original materials， processing and decocting method for the famous classical formulae， which hinder its development and registration process. In the history of more than 2 000 years， famous classical formulae have been developed in the continuous clinical application of practice. This paper systematically reviewed the evolution of the concept and history of the famous classical formulae， and introduced the evolution of the famous classical formulae in terms of name， composition， medicine， dosage， decocting method and clinical functions， including the stability of basic prescription composition， differentiation of drug bases， the progress of processing methods， the characteristics of dosages in different historical periods and the expansion of functions. In view of the research of the key information for famous classical formulae， the paper puts forward the suggestion of paying more attention to the evolution of prescriptions in the past dynasties. In textual research， we should combine the changes of medicinal resources， habits of drug use and production technology of the past dynasties， so as to bridge the ancient and modern. As to the dosage selection， we should be based on the weights and measures of all dynasties and current clinical practice to select rational dosage and decocting method. On the basis of inheriting the essence， follows the ancient but not be bounded by it， and solves the common problems in the textual research of key information from the perspective of history and development.