Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.

Currently， there are many difficulties in formulating recommendations of traditional Chinese medicine （TCM） clinical practice guidelines. This paper analyzed and summarized the unique or prominent difficult issues in the formulation of recommendations faced by TCM guidelines， such as experts' professional background and experience bringing about the preferance from the academic emotion， inconsistency between different academic schools making it difficult to reach consensus， lack of guiding principles of the decision weight of different dimensions for recommendations. Therefore， methodological suggestions have been put forward， including organizing parallel TCM and western medicine consensus group， improving the method of combining TCM and western medicine paradigm， attaching great importance to the evidence-based governance of academic schools， and promoting the research on different dimensions for recommendation formulation， which may provide a methodological reference for the guideline development.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

Objective:Based on the accounting results of total health expenditure in different regions since the 18th National Congress of the Communist Party of China,to analyze the regional disparity and evolution trend of health financing level and financing structure in 2012-2022,so as to provide references for subsequent adjustment and improvement.Methods:Range,standard deviation and coefficient of variation were used to analyze the degree of absolute and relative differences of total regional health expenditure in China and the changing characteristics of regional total health expenditure differences since the New Era(2012-2022).Results:Since 2012,the total health expenditure in various regions has been increasing continuously,and the average annual growth rate of total health expenditure is higher than that of the economy in this region.The relative difference of the proportion of total health expenditure to GDP in 31 provinces has converged in the fluctuation,but the absolute difference is still very large;the relative gap and absolute gap of per capita total health expenditure are expanding;the absolute difference in the proportion of out-of-pocket payments to total health expenditure has narrowed,while the relative difference has gradually narrowed.Conclusion:There are obvious differences in the growth rate of total health expenditure in different regions,so it is suggested that"appropriate growth"and"accurate control of health expenditure"should be carried out in parallel;the regional disparity of health investment in China has not improved,especially the regional disparity of per capita investment level continues to increase,so narrowing the regional disparity is a long-term task.The gap of regional financing structure has converged,but the gap is still large.

Objective:Based on the accounting results of total health expenditure in different regions since the 18th National Congress of the Communist Party of China,to analyze the regional disparity and evolution trend of health financing level and financing structure in 2012-2022,so as to provide references for subsequent adjustment and improvement.Methods:Range,standard deviation and coefficient of variation were used to analyze the degree of absolute and relative differences of total regional health expenditure in China and the changing characteristics of regional total health expenditure differences since the New Era(2012-2022).Results:Since 2012,the total health expenditure in various regions has been increasing continuously,and the average annual growth rate of total health expenditure is higher than that of the economy in this region.The relative difference of the proportion of total health expenditure to GDP in 31 provinces has converged in the fluctuation,but the absolute difference is still very large;the relative gap and absolute gap of per capita total health expenditure are expanding;the absolute difference in the proportion of out-of-pocket payments to total health expenditure has narrowed,while the relative difference has gradually narrowed.Conclusion:There are obvious differences in the growth rate of total health expenditure in different regions,so it is suggested that"appropriate growth"and"accurate control of health expenditure"should be carried out in parallel;the regional disparity of health investment in China has not improved,especially the regional disparity of per capita investment level continues to increase,so narrowing the regional disparity is a long-term task.The gap of regional financing structure has converged,but the gap is still large.

Objective:Based on the accounting results of total health expenditure in different regions since the 18th National Congress of the Communist Party of China,to analyze the regional disparity and evolution trend of health financing level and financing structure in 2012-2022,so as to provide references for subsequent adjustment and improvement.Methods:Range,standard deviation and coefficient of variation were used to analyze the degree of absolute and relative differences of total regional health expenditure in China and the changing characteristics of regional total health expenditure differences since the New Era(2012-2022).Results:Since 2012,the total health expenditure in various regions has been increasing continuously,and the average annual growth rate of total health expenditure is higher than that of the economy in this region.The relative difference of the proportion of total health expenditure to GDP in 31 provinces has converged in the fluctuation,but the absolute difference is still very large;the relative gap and absolute gap of per capita total health expenditure are expanding;the absolute difference in the proportion of out-of-pocket payments to total health expenditure has narrowed,while the relative difference has gradually narrowed.Conclusion:There are obvious differences in the growth rate of total health expenditure in different regions,so it is suggested that"appropriate growth"and"accurate control of health expenditure"should be carried out in parallel;the regional disparity of health investment in China has not improved,especially the regional disparity of per capita investment level continues to increase,so narrowing the regional disparity is a long-term task.The gap of regional financing structure has converged,but the gap is still large.

Objective:Based on the accounting results of total health expenditure in different regions since the 18th National Congress of the Communist Party of China,to analyze the regional disparity and evolution trend of health financing level and financing structure in 2012-2022,so as to provide references for subsequent adjustment and improvement.Methods:Range,standard deviation and coefficient of variation were used to analyze the degree of absolute and relative differences of total regional health expenditure in China and the changing characteristics of regional total health expenditure differences since the New Era(2012-2022).Results:Since 2012,the total health expenditure in various regions has been increasing continuously,and the average annual growth rate of total health expenditure is higher than that of the economy in this region.The relative difference of the proportion of total health expenditure to GDP in 31 provinces has converged in the fluctuation,but the absolute difference is still very large;the relative gap and absolute gap of per capita total health expenditure are expanding;the absolute difference in the proportion of out-of-pocket payments to total health expenditure has narrowed,while the relative difference has gradually narrowed.Conclusion:There are obvious differences in the growth rate of total health expenditure in different regions,so it is suggested that"appropriate growth"and"accurate control of health expenditure"should be carried out in parallel;the regional disparity of health investment in China has not improved,especially the regional disparity of per capita investment level continues to increase,so narrowing the regional disparity is a long-term task.The gap of regional financing structure has converged,but the gap is still large.

Objective:Based on the accounting results of total health expenditure in different regions since the 18th National Congress of the Communist Party of China,to analyze the regional disparity and evolution trend of health financing level and financing structure in 2012-2022,so as to provide references for subsequent adjustment and improvement.Methods:Range,standard deviation and coefficient of variation were used to analyze the degree of absolute and relative differences of total regional health expenditure in China and the changing characteristics of regional total health expenditure differences since the New Era(2012-2022).Results:Since 2012,the total health expenditure in various regions has been increasing continuously,and the average annual growth rate of total health expenditure is higher than that of the economy in this region.The relative difference of the proportion of total health expenditure to GDP in 31 provinces has converged in the fluctuation,but the absolute difference is still very large;the relative gap and absolute gap of per capita total health expenditure are expanding;the absolute difference in the proportion of out-of-pocket payments to total health expenditure has narrowed,while the relative difference has gradually narrowed.Conclusion:There are obvious differences in the growth rate of total health expenditure in different regions,so it is suggested that"appropriate growth"and"accurate control of health expenditure"should be carried out in parallel;the regional disparity of health investment in China has not improved,especially the regional disparity of per capita investment level continues to increase,so narrowing the regional disparity is a long-term task.The gap of regional financing structure has converged,but the gap is still large.