ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy （DCM） of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group （186 cases） and non-exposure group （185 cases） according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months， and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events （MACE） in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE， and subgroup analysis was performed. Changes in traditional Chinese medicine （TCM） syndrome score， left ventricular ejection fraction （LVEF）， left ventricular fractional shortening （LVFS）， left ventricular end-diastolic diameter （LVEDD）， and Minnesota Living with Heart Failure Questionnaire （MLHFQ） score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy （before treatment） and 1 year after receiving the therapy （after treatment）. ResultsMACE occurred in 31 cases （16.67%） in the exposure group and 47 cases （25.41%） in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group ［HR=0.559， 95%CI（0.361，0.895）， P=0.014］. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients ［HR=0.623， 95%CI（0.396，0.980）， P=0.041］， and consistent results were observed in different subgroups. Compared with pre-treatment， the exposure group showed decreased TCM syndrome score and MLHFQ score， reduced LVEDD， and increased LVEF and LVFS after treatment （P＜0.05）； in the non-exposure group， TCM syndrome score decreased， LVEF and LVFS increased， and LVEDD reduced after treatment （P＜0.05）. After treatment， the exposure group had higher LVEF and LVFS， smaller LVEDD， and lower TCM syndrome score and MLHFQ score compared with the non-exposure group （P＜0.05）. ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome， meanwhile improving their clinical symptoms， cardiac function， and quality of life.

OBJECTIVE To investigate the clinical characteristics and risk factors for batroxobin-related severe hypofibrinogenemia （HFIB） and construct a risk prediction model. METHODS A retrospective analysis was conducted on inpatients treated with batroxobin in the First Medical Center of a tertiary hospital from January 1， 2020， to December 31， 2024. Patients were categorized into non-severe HFIB group and severe HFIB group based on the severity of HFIB. Univariate and multivariate Logistic regression analyses were performed to identify the independent influencing factors for batroxobin-related severe HFIB. A nomogram was developed using the “rms” package in R 4.5 software. The predictive performance of the model was evaluated using the receiver operating characteristic curve. Calibration was assessed via the Bootstrap resampling method， and goodness-of-fit was evaluated with the Hosmer-Lemeshow test. RESULTS A total of 1 472 patients were included in this study. Of these， 1 445 developed HFIB， yi elding an incidence of 98.17%. Furthermore， 895 were classified as severe HFIB， accounting for 60.80% of the cohort. Multivariate Logistic regression analysis showed that increased age， high initial dose per 10 kg body weight， use of maintenance dose， and concomitant glucocorticoid use were independent risk factors for batroxobin-related severe HFIB， while high baseline fibrinogen （FIB） level was identified as a protective factor. The model demonstrated an area under the curve of 0.760 （95% CI： 0.735-0.785）. The mean absolute error of the calibration curve was 0.006. The P value of the Hosmer-Lemeshow test was 0.609. CONCLUSIONS Batroxobin can rapidly and significantly reduce FIB levels and carries a risk of inducing severe HFIB. Patients with advanced age， high initial dose per 10 kg body weight， use of maintenance dose and concomitant glucocorticoid use had a higher risk of batroxobin-related severe HFIB， while high baseline FIB level had a lower risk of batroxobin-related severe HFIB. The risk prediction model developed based on these factors can be used to predict the likelihood of batroxobin-related severe HFIB.

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective:To establish a predictive model for the risk of cognitive impairment in patients with hypertension.Methods:Data were obtained from the China Health and Retirement Longitudinal Study(CHARLS),and 17 indicators were analyzed,including demographic features,behavioral factors,and health status.The study cohort was randomly divided into a training set(n=2 918)and an internal validation set(n=1 249)at a ratio of 7∶3,and 1 457 patients with hypertension who were treated in Chongqing Traditional Chinese Medicine Hospital from January to December 2024 were included as an external validation set.The least absolute shrinkage and selection operator regression analysis was used to identify predictive variables,and 10-fold cross-validation was used to determine the optimal model.A logistic regression model was used to investigate the risk factors for cognitive impairment in patients with hypertension,and then a nomogram prediction model was established.The calibration curve was used to assess the accuracy of the model,and the area under the ROC curve(AUC)and the decision curve analysis were used to assess the predictive performance of the model.Results:A total of 4167 hypertensive patients aged≥45 years were included from the CHARLS database,among whom 668 had cognitive impairment.The multivariate logistic regression analysis showed that age(odds ratio[OR]=1.408,95%CI=1.040-1.056),sex(OR=0.570,95%CI=0.492-0.660),body mass index(OR=0.931,95%CI=0.914-0.948),educational level(OR=0.235,95%CI=0.200-0.277),place of residence(OR=1.674,95%CI=1.447-1.936),physi-cal activity(OR=0.459,95%CI=0.373-0.562),depression(OR=1.386,95%CI=1.198-1.604),and total cholesterol level(OR=0.997,95%CI=0.995-0.999)were predictive variables.The ROC curve analysis showed that the nomogram model had good performance,with an AUC of 0.814(95%CI=0.802-0.826)in the training set,0.817(95%CI=0.788-0.846)in the internal validation set,and 0.725(95%CI=0.699-0.752)in the external validation set.Conclusion:The nomogram model developed in this study can effectively predict the risk of cognitive impairment in Chinese patients with hyperten-sion and has a good application value.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Diabetic cognitive dysfunction （DCD） is one of the complications of diabetes， which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide， DCD has become a serious medical and social problem. However， its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms， and the prevention and treatment require multi-link and multi-target therapeutic measures. At present， there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction， but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases， and it has many unique advantages such as multiple components， multiple targets， side effects， and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD， which can improve insulin resistance， synaptic dysfunction， inflammation， oxidative stress， endoplasmic reticulum stress， and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase （PI3K）/protein kinase B （Akt）， advanced glycation end products （AGEs）/advanced glycation end products receptor （RAGE）/nuclear transcription factor-κB （NF-κB）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， and endoplasmic reticulum stress and nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years， so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

Japanese encephalitis is an acute central nervous system infectious disease caused by Japanese encephalitis virus (JEV) with brain parenchyma inflammation, characterized by high fever, headache, positive meningeal irritation, impaired consciousness, convulsion, and respiratory failure, with mortality rate as high as 20%-30%, and with neurological sequelae in 30%-50% of survivors. The mechanism of brain damage caused by JEV infection is still unclear, and some studies imply its close relation with immune-inflammatory response. This article reviews the research progress on immune-inflammatory response mechanism of Japanese encephalitis to help to understand its pathogenesis.

Currently， evidence on the efficacy and risk of traditional Chinese medicine （TCM） injections is seriously insufficient， and it is difficult to evaluate TCM injections comprehensively， truly and objectively using available efficacy evaluation indicators. Therefore， establishing a clinical efficacy evaluation system that can effectively reflect TCM injections is imperative. Core outcome set （COS） has played an important role in screening TCM efficacy evaluation indicators， however， there are still certain problems， such as large differences in efficacy indicators， non-standardization， and lack of featured and specific TCM indicators. Mixed method research （MMR） has the advantages of looking at problems from both quantitative and qualitative perspectives. It is thereby proposed to use COS and MMR integrated model to establish a clinical efficacy evaluation indicator system that not only fully considers the cha-racteristics of TCM injections， but also highlights the efficacy and advantages of TCM injections from the perspective of TCM intervention. Simultaneously， an indicator screening method using MMR to optimize COS research model is formulated， which can provide ideas for the research on efficacy evaluation indicators of TCM injections.