ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

Objective To compare the clinical characteristics of pneumococcal meningitis in different age groups, and to provide a basis for early diagnosis of pneumococcal meningitis. Methods Cerebrospinal fluid and/or serum samples were collected from 1742 suspected cases of meningitis in Baoji, Shaanxi Province from August 2013 to July 2019. Streptococcus pneumoniae was detected by isolation culture and real-time fluorescence quantitative polymerase chain reaction. Retrospective analysis of clinical manifestations, biochemical indicators and other information of laboratory confirmed cases was conducted by χ² test or Fisher's exact test. Results A total of 1742 samples of encephalitis or meningitis cases were detected, and 41 cases were confirmed as laboratory-confirmed Streptococcus pneumoniae infection. Among them, there were 12 cases (29.27%) in the infant group, 14 cases (34.15%) in the child group, and 15 cases (36.59%) in the adult group. The proportion of the adults with headache was significantly higher than that of the infants (χ²=11.408，P＜0.017). The proportion of the adults with consciousness disorder, elevated white blood cells and elevated neutrophils were significantly higher than those in the infant and the child groups（Fisher's exact test, P＜0.017；χ² =6.428，P＜0.017；χ² =10.898，P＜0.017；χ² =6.421，P＜0.017；χ² =9.758，P＜0.017；χ² =7.744，P＜0.017). The proportion of the infants with cerebrospinal fluid turbidity was significantly higher than that of the children (Fisher's exact test，P＜0.017). The proportion of the infants with decreased white blood cells and reduced glucose in cerebrospinal fluid was significantly higher than that of the children group and the adult group（Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.017; Fisher's exact test, P＜0.017). Conclusion Most adult patients with pneumococcal meningitis have headache and consciousness disorders, with significantly increased proportion of white blood cells and neutrophils. Infant patients tend to have cloudy appearance of cerebrospinal fluid, leukopenia in blood, and decreased glucose in cerebrospinal fluid.

Biosensors based on acetylcholinesterase (AChE) are crucial for early diagnosis, less invasive treatment, and drug evaluation of Alzheimer's disease (AD). However, existing technologies often suffer from enzyme conformational changes, leading to altered activity and loss and reduced sensor efficacy. To address this challenge, we developed a novel right-side-out-oriented red blood cell membrane-coated electrochemical biosensors (ROCMCBs) to evaluate AChE inhibitors from traditional Chinese medicines (TCMs) as potential anti-AD agents. The developed right-side-out-oriented coating based on immunoaffinity not only fully exposed the binding sites of AChE on the cell membrane but also ensured its conformation and stability as a peripheral membrane-anchoring protein, which was conducive to maintaining its biological activity and producing optimal interaction with drugs. At the same time, the biosensors exhibited a satisfactory sensitivity (limit of detection = 0.41 pmol/L). Ultimately, six potentially active compounds against AD (baicalin, geniposide, gastrodin, berberine, rhynchophylline, and senkyunolide A) were rapidly identified and evaluated from TCMs. This project provides a promising strategy for developing cell membrane-coated electrochemical biosensors. The application of cell membrane-coated electrochemical biosensors with well-defined cell membrane orientation further expands new perspectives and methods for AChE-targeted anti-AD research.

Objective To investigate whether the pyroptosis-related Toll-like receptor 4(TLR4)signaling pathway influences the malignant transformation of actinic keratosis(AK)into cutaneous squamous cell carcinoma(SCC).Methods A total of 6 lesion tissue samples each from patients with AK and SCC,as well as 5 normal skin tissue samples from healthy subjects as controls,were collected from the First Affiliated Hospital of Kunming Medical University between August 2020 and August 2021.Quantitative PCR(qPCR)and Western blot analysis were performed to determine the mRNA and protein expression levels of TLR4 pathway-related factors,including TLR4,CPB1,NLRP3,IL-1β,and IL-18.TLR4/TUNEL double immunofluorescence staining was used to evaluate TLR4 expression and the level of cellular pyroptosis in tissue samples.In addition,Western blotting was performed to analyze the expression differences of pyroptosis-related core proteins(pro-caspase-1,cleaved caspase-1/p20,GSDMD,and cleaved N-terminal GSDMD)and TLR4 among the normal keratinocyte cell line HaCaT and SCC cell lines A431 and SCL-1.Results Quantitative PCR and Western blot results showed that the mRNA and protein expression levels of TLR4,CPB1,NLRP3,IL-1β,and IL-18 were significantly higher in SCC tissues than in AK and normal skin tissues(P<0.05).TLR4/TUNEL double immunofluorescence results revealed a progressive increasing trend in TLR4 expression and pyroptosis levels from normal skin to AK and further to SCC(P<0.05).Furthermore,in SCL-1 cells,the expression levels of pro-caspase-1,cleaved caspase-1/p20,cleaved N-terminal GSDMD,and TLR4 were significantly upregulated(P<0.05),whereas in A431 cells,only TLR4 expression was increased(P<0.05),and the levels of other pyroptosis-related proteins were downregulated compared to HaCaT cells(P<0.05).Conclusion The expression of the TLR4 signaling pathway gradually increased from AK to SCC,and its activation status varied among different cutaneous squamous cell carcinoma cell lines.

Depressive disorder is one of the common mental diseases, which seriously affects the daily work and life of patients. In recent years, transcranial magnetic stimulation (TMS) treatment has shown satisfactory effects in the clinical application of depression. However, depressive disorder involves complex symptoms, including functional impairment in different dimensions such as emotion, cognition, body and behavior, which leads to significant individual differences in the efficacy of TMS intervention. Therefore, with different symptoms as the starting point, this article systematically reviewed the clinical studies of TMS treatment for different symptom groups of depressive disorder, in order to provide scientific reference for individualized treatment of depressive disorder using TMS treatment.

Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.

Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.

Depressive disorder is one of the common mental diseases, which seriously affects the daily work and life of patients. In recent years, transcranial magnetic stimulation (TMS) treatment has shown satisfactory effects in the clinical application of depression. However, depressive disorder involves complex symptoms, including functional impairment in different dimensions such as emotion, cognition, body and behavior, which leads to significant individual differences in the efficacy of TMS intervention. Therefore, with different symptoms as the starting point, this article systematically reviewed the clinical studies of TMS treatment for different symptom groups of depressive disorder, in order to provide scientific reference for individualized treatment of depressive disorder using TMS treatment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.