ObjectiveTo dynamically observe and evaluate the damage to the pulmonary air-blood barrier in mice during the inflammatory cancer transformation process of ulcerative colitis （UC） based on the "lung-intestine correlation" theory. MethodsSixty-five C57BL/6 mice were divided into a normal group （n=25） and a model group （n=40） using a random number table. Azoxymethane/dextran sodium sulfate （DSS） method was used to establish a mouse model of UC inflammation cancer transformation in the modeling group. According to the tissue collection time points at 5， 8， 11， 13， and 15 weeks， the normal group mice were randomly divided into the normal 5w， 8w， 11w， 13w， and 15w groups. The model group mice， 10 mice of which died after the first cycle of DSS administration， were randomly divided into model 5w， 8w， 11w， 13w， and 15w groups. During the experiment， the general condition of the mice was observed daily， and their body weight was measured weekly. At the corresponding tissue collection time points， the colon length of each group was measured. Histopathology of mouse lung and colon tissues was examined using HE staining. Immunofluorescence was used to detect changes in the positive expression of tight junction protein （ZO-1）， vascular endothelial cadherin （VE-cadherin）， and cytoskeletal protein （F-actin） in lung and colon tissues. RT-PCR was used to detect the mRNA expression of apoptosis regulatory proteins B-cell lymphoma-2 （Bcl-2）， BCL2-associated X protein （Bax）， and Cysteine aspartic acid protease-3 （Caspase-3） in lung tissues. Western Blot was employed to measure protein levels of ZO-1， VE-cadherin， and F-actin in lung tissues. ResultsCompared to the normal group at the same time point， the mice in the model group at each time point generally had poorer conditions， with weight loss and shortened colon length （P＜0.05 or P＜0.01）. In the model 5w group， there was significant inflammatory cell infiltration in the colon tissue； in the model 8w group， there was mild atypical hyperplasia； in the model 11w group， the crypt structure was disordered， and moderate to severe atypical hyperplasia occurred； in the model 13w and 15w groups， tumors appeared. Pulmonary interstitial lesions， inflammation， vasculitis， and fibrosis were observed at all stages of UC inflammation cancer transformation. The protein levels of ZO-1， VE-cadherin， and F-actin， as well as Bcl-2 mRNA expression in lung tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period， while the expressions of Bax and Caspase-3 mRNA increased； the expressions of ZO-1， VE-cadherin， and F-actin proteins in colon tissue decreased during the acute inflammatory recovery period， atypical hyperplasia period， and canceration period （P＜0.01 or P＜0.05）. Compared to the model 5w group， the ZO-1 and F-actin protein levels and Bcl-2 mRNA expression in lung tissue in the other model groups increased in the atypical hyperplasia period and canceration period， while the expressions of Bax and Caspase-3 mRNA decreased； the expression of ZO-1 protein in colon tissue increased in the canceration period， and the expression of VE-cadherin protein decreased in the atypical hyperplasia period （P＜0.01 or P＜0.05）. ConclusionIn the process of "inflammatory response-atypical hyperplasia-carcinogenesis" in UC inflammatory cancer transformation mice， there were damage to air-blood barrier.

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 To evaluate and improve missing data imputation methods to enhance the performance of binary classification prediction model.Methods By simulating data missing scenes,the effects of direct elimination,mean imputation,random forest(RF)imputation algorithm,and multiple imputation-random forest(MI-RF)on the performance of the prediction model were jointly evaluated by receiver operating characteristic area under curve(AUC)and root mean square error(RMSE).Bayesian Network was introduced for the random forest imputation algorithm to optimize the imputation method using the correlations between variables.Results Under different missing proportions,both AUC and RMSE indicated that Bayesian network optimized random forest(BN-RF)imputation algorithm was better.In addition,when the missing proportion was 10％-20％,various imputation methods had roughly the same improvement effect for the prediction model;when the proportion of missing data was 30％-40％,compared to the mean imputation,except for the BN-RF,RF was more effective and its effect was slightly better than MI-RF;however,when the proportion of missing data was close to 50％,even if the model performance was still appropriate,the imputation data gradually deviated from the true data features,resulting in a decrease in the usability of the model.Conclusion The overall effect of BN-RF is satisfactory,and it should be chosen when random missing was 30％-40％.

Objective:To explore the mechanism of modified Shaoyao Decoction with Astragali Radix and Houttuynize Herba in regulating PI3K/Akt/NF-κB pathway against intestinal mucosal barrier injury in ulcerative colitis (UC) rats.Methods:Totally 72 Wistar rats were randomly divided into a blank control group, a model group, a mesalazine group, and modified Shaoyao Decoction high-, medium-, and low-dose groups using a random number table method. After successful modeling, the mesalazine group was given 0.2 g/kg of mesalazine suspension by gavage, while modified Shaoyao Decoction high-, medium-, and low-dose groups were given 44.5, 22.3, and 11.1 g/kg of modified Shaoyao Decoction by gavage, once a day, for a total of 4 weeks. The pathological changes of colon tissue were observed using HE staining; immunofluorescence assay was used to detect the expressions of tight junction protein (ZO-1), cytoskeletal protein (F-actin), and vascular endothelial cadherin (VE cadherin) in colon tissue; Western blot was used to detect the protein expressions of PI3K, Akt, NF-κB, VEGF, and cyclooxygenase (COX-2) in colon tissue; QRT PCR was used to detect the expressions of PI3K and Akt mRNA in colon tissue; ELISA method was used to detect the levels of serum TNF-α and endothelin (ET).Results:Compared with the model group, the DAI scores of the mesalazine group and modified Shaoyao Decoction high-dosage group decreased significantly on the 7th, 14th, 21st and 28th day after modeling ( P<0.05 or P<0.01). In mesalazine group and modified Shaoyao Decoction high-, medium-, and low-dose groups, the pathological injury score of colon tissue decreased ( P<0.01), the immunofluorescence intensity of ZO-1, F-actin and VE-cadherin protein expression in colon tissue increased ( P<0.05 or P<0.01), and the expressions of PI3K, Akt, NF-κB and VEGF protein decreased ( P<0.01). The expression of COX-2 protein and the levels of PI3K mRNA and Akt mRNA decreased in the mesalazine group and modified Shaoyao Decoction high- and medium groups ( P<0.05 or P<0.01). Conclusion:Modified Shaoyao Decoction can antagonize the intestinal barrier injury of UC by inhibiting PI3K/Akt/NF-κB pathway and promote the healing of intestinal mucosal ulcer.

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.

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.