ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Objective: To analyze the changes in classroom lighting environment of schools in Suzhou and their impact on refractive progression among primary and secondary school students, so as to provide the basis for accurate provention and control of myopia. Methods: A baseline investigation was conducted in October 2022 by using a stratified cluster random sampling method to recruit primary and secondary school students from Suzhou. A follow up visit was performed in October 2023. A total of 12 302 students and 360 classrooms that participated in both surveys were included analysis. The visual acuity progression over one year and classroom lighting conditions were assessed. Group comparisons were performed by using the Wilcoxon or Kruskal-Wallis rank-sum, and Chi-square tests. Multivariate Logistic regression was employed to identify the major factors influencing refractive changes. Results: The compliance rate of average illuminance on classroom blackboard surface increased from 72.22% to 75.28%, while the compliance rate of average illuminance on desks decreased from 89.44% to 87.22%, the overall myopia rate among students rose from 59.63% to 66.99% from 2022 to 2023. The average annual progression of equivalent spherical power(SE) in the right eye of students was -0.25(-0.75,0.06)D. Significant statistical differences were observed in the annual mean changes across different school levels, regions, baseline refractive statuses, and classroom lighting environment change groups ( Z/H =316.59, -8.27, 38.80 , 51.01, all P <0.05). Multivariate Logistic regression analysis showed that pre myopia, low myopia, junior high school, senior high school, vocational high school, and improved classroom lighting environment were protective factors of reducing the risk of rapid progression in refractive error ( OR =0.58, 0.69, 0.81, 0.50, 0.28, 0.82, all P <0.05). Conversely, female students and rural students had higher risks of rapid myopia progression ( OR =1.09, 1.42, both P <0.05). Conclusions Over one year follow up, the complance rate of classroom lighting indicators in Suzhou remaines stable, while students refractive status shows a trend toward myopia. Improving classroom lighting environment can reduce the risk of rapid myopia progression.

This article reports 2 cases of urinary retention in Alzheimer's disease with agitation treated by acupuncture. Based on patients' clinical symptoms, the etiology and pathogenesis were determined, and acupuncture was applied to Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), and bilateral Ciliao (BL32), Zhongliao (BL33), Fengchi (GB20), Taiyang (EX-HN5), etc. to regulate the mind and promote water metabolism. The positive and negative electrodes of the SDZ-Ⅴ type electroacupuncture device were attached to ipsilateral Ciliao (BL32), Zhongliao (BL33) respectively, with continuous wave, at the frequency of 15 Hz, and the current of 3 to 10 mA, depending on patients' tolerance. The needles were retained for 20 min. The treatment was delivered once every other day, 3 interventions a week and 12 interventions as 1 course. Both patients reported the micturition desire after 1 intervention with acupuncture and the catheter was removed on the same day. The urination was ameliorated without dysuresia after 1-2 courses of treatment, and the agitated behavior was alleviated. It can be the reference for the clinical treatment of urinary retention in patients with Alzheimer's disease with agitation.
Humans ; Alzheimer Disease/psychology* ; Acupuncture Therapy ; Urinary Retention/etiology* ; Male ; Female ; Aged ; Acupuncture Points ; Psychomotor Agitation/complications*

BACKGROUND: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective Cervical disc herniation(CDH)is one of the common orthopaedic diseases.With the in-depth study of it and the development of cervical implants,the establishment of cervical fusion animal models has become an indispensable part.Notably however,studies of the establishment and evaluation of cervical fusion animal models in China are currently lacking.This study aimed to provide a suitable animal model and evaluation scheme for implants for cervical spine-related research.Methods Small-tailed Han sheep were chosen for anterior cervical discectomy fusion(ACDF)after modified surgery,and a polyetheretherketone(PEEK)interbody fusion cage(Cage)(control group),3D-printed Ti6Al4V Cage(group 1),and new method Ti6Al4V Cage(group 2)were implanted in different cervical segments(C2/3～C4/5)in each sheep,respectively.Hematology and histopathological analyses were carried out after surgery to evaluate recovery of sheep and the biosafety of the materials.Bone in-growth and bone fusion were assessed by X-ray,computed tomography(CT),Micro-CT and quantitative analysis,hard tissue section staining,and biomechanical tests.Results The modified ACDF ovine model was established successfully.There were no significant differences in important hematology indexes(P＞0.05)and histopathological analysis showed no pathological changes,such as inflammatory cell infiltration.The implants had good biosafety.Furthermore,X-ray and CT examinations showed that the position of internal fixation and the interbody fusion were good.Micro-CT and quantitative analysis at 3 and 6 months after operation showed that compared with PEEK Cage group,the bone volume/total volume and trabecular number were significantly increased(P＜0.01)while the trabecular spacing was significantly decreased in the new method Ti6Al4V and 3D-printed Ti6Al4V groups compared with the PEEK Cage group(P＜0.01).Moreover,the new method new method Ti6Al4V Cage group had more bone growth(P＜0.01).Hard tissue section staining demonstrated that the pores of the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had obvious bone growth and relatively dense pores in the new method Ti6Al4V and 3D-printed Ti6Al4V groups,and the combination was slightly better than that of PEEK Cage.Biomechanical evaluation indicated that the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage reduced the range of cervical flexion-extension,lateral bending,and axial rotation(P＜0.05)compared with the PEEK cage,as well as enhancing the stability of the cervical vertebra,and the new method Ti6Al4 V Cage was more advantageous(P＜0.05).Conclusions After the establishment of the modified ACDF ovine model,reasonable and effective assessment method were used to demonstrate the suitability and effectiveness of the model and the good biosecurity of all three Cage materials.Compared with the PEEK Cage,the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cages showed better performances in terms of bone growth and bone fusion,which could enhance the stability of the cervical vertebrae.The new method Ti6Al4V Cage was particularly advantageous.

ObjectiveThe natural history of chronic HBV infection often involves a histologically defined immune tolerance state， and once such immune tolerance state is broken， antiviral therapy should be initiated immediately. This study aims to investigate the correlation between immune-mediated liver injury and virological indicators for HBV and precisely identify the patients with a histologically defined immune tolerance state. MethodsThis study was conducted among 577 HBeAg-positive chronic hepatitis B （CHB） patients with HBV DNA >2×10⁶ IU/mL who did not receive antiviral therapy in The Fifth Medical Center of PLA General Hospital， Tianjin Second People’s Hospital， Shanghai Ruijin Hospital， and Taizhou Hospital of Zhejiang Province from January 2010 to December 2022. Liver biopsy was performed to determine the extent of liver injury， and the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and virological indicators were measured. The proportion of patients with a histologically defined immune tolerance state was analyzed based on the cut-off values of noninvasive indicators recommended in various guidelines， especially HBV load. In addition， a diagnostic model was established for the histologically defined immune tolerance state based on serum HBV DNA at the time when its correlation with liver immunopathological injury disappeared as the new threshold in combination with multiple indicators. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. The binary Logistic regression analysis was used to establish a multivariate diagnostic model； the area under the receiver operating characteristic curve （AUC） was used to investigate the diagnostic efficiency of different models， and the Z test was used for comparison of AUC. ResultsAmong the patients with an immune tolerance state defined by the noninvasive indicators in the Chinese guidelines （2022 edition）， the EASL guidelines （2017 edition）， the AASLD guidelines （2018 edition）， and the APASL guidelines （2015 edition） for the prevention and treatment of CHB， the patients with a histologically defined immune tolerance state who met the definition in this article （HBV DNA>2×10⁶ IU/mL） accounted for 47.0%， 38.5%， 36.0%， and 44.6%， respectively， which did not exceed 50%. When the threshold of serum HBV DNA increased to >2×10⁸ IU/mL， although the correlation between immune-mediated liver injury and HBV DNA disappeared （r=-0.029， P=0.704）， the patients with a histologically defined immune tolerance state reached only 52.0%. In the cohort of 251 HBeAg-positive patients with serum HBV DNA >1×10⁸ IU/mL， there were significant differences in the levels of HBsAg， HBeAg， HBV DNA， ALT， and AST between the significant liver injury group with 140 children and the non-significant liver injury group with 111 patients （all P<0.05）， and the multivariate binary Logistic regression analysis showed that AST， HBV DNA， and HBeAg were influencing factors for histologically defined immune tolerance state in patients （all P<0.05）. Based on the above indicators and related clinical data， a predictive model was established as logit（P）=1.424－0.028×AST， with an AUC of 0.730， an optimal cut-off value of 30.5 U/L， a sensitivity of 52.8%， and a specificity of 84.1%. A total of 238 adult patients with chronic HBV infection who underwent liver biopsy in Taizhou Hospital of Zhejiang Province were enrolled as the validation cohort， and the analysis showed that the predictive model established in this study had a better efficiency than AST/ALT， FIB-4， and APRI， with an AUC of 0.698， 0.555， 0.518， and 0.373， respectively （all P<0.05）. ConclusionFor HBeAg-positive patients with chronic HBV infection and HBV DNA>2×10⁸ IU/mL， an AST level of >30.5 U/L might indicate the “breakdown” of histologically defined immune tolerance state.

Objective: To understand the current situation of mental health education in primary and secondary schools in Beijing, so as to provide the data support and policy suggestions for mental health work in Beijing. Methods: From April to May 2024, a multi stage random sampling method was used to select 399 primary and secondary schools in Beijing to conduct a questionnaire survey. Chi square test was used to compare the differences resource allocation of mental health education, current status of mental health education by regions and educational stages. Results: There were significant differences in reporting rates for the allocation of professional and part time psychological teachers in different regions and educational stages (professional: χ 2=17.86, 20.74 , part time: χ 2=13.56, 25.63, P <0.05). There was significant differences the implementation of mental health education courses for students in different educational stages ( χ 2=12.83, P <0.05). There was significant differences the implementation of mental health education training for staff in different regions ( χ 2=17.79, P <0.05). Professional psychology teachers were well equipped in urban schools (84.13%) and 9 year or 12 year schools (85.33%),and part time psychology teachers were well equipped in suburban schools (68.49%) and primary schools (71.35%). Schools in the outer suburbs (96.88%) had the best implementation of mental health education training for staff, and the 9 year or 12 year schools (100.00%) had the best implementation of mental health education courses for students. Totally 93.98% of schools carried out mental health education activities, 90.23% of schools established mental health consultation rooms, and 88.97% of schools integrated mental health education into other courses. Conclusions The development of mental health education in primary and secondary schools in Beijing is good. It is suggested that the quality of mental health education in primary and secondary schools in Beijing should be improved by implementing the requirements of psychological teacher allocation, the coordination among family, school and community, and paying attention to teachers mental health level.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.

This study investigated the primary pathogenesis and syndrome evolution of different heart failure with preserved ejection fraction(HFpEF)stages based on the classical and clinical experience of traditional Chinese medicine(TCM),combined with the clinical characteristics of pre-heart failure,symptomatic heart failure,and advanced heart failure.This study summarizes and refines the three core syndrome factors:water,deficiency and blood stasis.Water-fluid retention was observed throughout these three stages,from the beginning to the end.With the advancement of the disease,the heart yang changes from stagnation to deficiency,water-fluid retention gradually increases,blood stasis becomes increasingly prominent,and the disease location develops dynamically from the upper to the middle and lower jiao.This study proposes three methods of treating HFpEF.The main pathogenesis of pre-heart failure is lung qi dysfunction-induced water retention,which can be treated by dispersing lung qi and transforming water retention using Fuling Xingren Gancao Decoction.The primary pathogenesis of symptomatic heart failure is yang and qi deficiency-induced water retention,which can be treated with tonifying yang,supplementing qi,and transforming water retention using Shengxian Decoction combined with Linggui Zhugan Decoction.The primary pathogenesis of advanced heart failure is yang deficiency with blood stasis and water retention affecting the heart,which can be treated with tonifying yang,circulating blood,and expelling water retention using Zhenwu Tingli Decoction.Chinese medicine can be flexibly added or subtracted according to the patients'concurrent patterns.However,the daily care of patients should be considered.This study explores the staging treatment of HFpEF from water,deficiency and blood stasis to provide a TCM clinical reference for treating HFpEF.