The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
Humans ; Lung Neoplasms/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Chromatin Assembly Factor-1/metabolism* ; Animals ; Mice ; Male ; Female

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

ObjectiveTo observe the effects of Tongluo Baoshen prescription （TLBS）-containing serum on the rat podocyte injury induced by lipopolysaccharide （LPS） and explore the potential mechanisms. MethodsSD rats were used to prepare the blank serum， losartan potassium-containing serum， and low-， medium-， and high-dose TLBS-containing sera. Rat podocytes were cultured in vitro， and the effects of drug-containing sera on podocyte viability were detected by the cell counting kit-8 （CKK-8） method. The optimal intervention volume fraction of drug-containing sera and the optimal concentration of LPS for inducing the podocyte injury were determined. Rat podocytes were grouped as follows： normal control （NC， 10% blank serum）， model control （MC， 20.00 mg·L^-1 LPS+10% black serum）， losartan potassium （LP， 20.00 mg·L^-1 LPS+10% losartan potassium-containing serum）， low-dose TLBS （TLBS-L， 20.00 mg·L^-1 LPS+10% low-dose TLBS-containing serum）， medium-dose TLBS （TLBS-M， 20.00 mg·L^-1 LPS+10% medium-dose TLBS-containing serum）， and high-dose TLBS （TLBS-H， 20.00 mg·L^-1 LPS+10% high-dose TLBS-containing serum）， and the interventions lasted for 48 h. The ultrastructure of podocytes was observed under a transmission electron microscope. The podocyte apoptosis was detected by the terminal deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL） kit. Immunofluorescence was used to detect the expression of gasdermin D N-terminal fragment （GSDMD-NT） in podocytes. The mRNA and protein levels of G protein-coupled receptor family C group 5 member B （GPRC5B）， nuclear factor-κB （NF-κB） p50， NF-κB p52， NF-κB p65， Rel B， c-Rel， NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， GSDMD-NT， interleukin （IL）-1β， IL-18， nephrin， integrin α₃， and integrin β₁ in podocytes were determined by real-time quaritiative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultsCompared with the NC group， the MC group showed reduced podocyte protrusions and organelles， segmental missing of cell membranes， increased and swollen mitochondria， irregular nuclear membranes， light chromatin， increased TUNEL fluorescence-positive nuclei （P<0.01）， obviously enhanced fluorescence intensity of GSDMD-NT， up-regulated mRNA and protein levels of GPRC5B， NF-κB p50， NF-κB p52， NF-κB p65， Rel B， c-Rel， NLRP3， caspase-1， GSDMD-NT， IL-1β， and IL-18 （P<0.01）， and down-regulated mRNA and protein levels of nephrin， integrin α₃， and integrin β₁ （P<0.01） in podocytes. Compared with the MC group， the LP， TLBS-M， and TLBS-H groups showed improved ultrastructure of podocytes with increased protrusions， intact cell membranes， reduced organelles， and alleviated mitochondrial swelling， decreased TUNEL fluorescence-positive nuclei （P<0.01）， weakened fluorescence intensity of GSDMD-NT， down-regulated mRNA and protein levels of GPRC5B， NF-κB p50， NF-κB p52， NF-κB p65， Rel B， c-Rel， NLRP3， caspase-1， GSDMD-NT， IL-1β， and IL-18 （P<0.01）， and up-regulated mRNA and protein levels of nephrin， integrin α₃， and integrin β₁ （P<0.05， P<0.01）. Moreover， the changes above were the most obvious in the TLBS-H group. ConclusionThe TLBS-containing serum can regulate the GPRC5B/NF-κB/NLRP3 pathway to inhibit pyroptosis， thereby ameliorating the podocyte injury induced by LPS.

Objective Develop a risk prediction model for patients with bacterial liver abscess complicated by sepsis, and validate its predictive performance. Methods Clinical data were collected from 233 patients with bacterial liver abscesses admitted to our hospital between January 2019 and October 2024. Based on the occurrence of sepsis, the patients were categorized into a sepsis group (n=29) and a non-sepsis group (n=204). After conducting univariate analysis and subsequently multivariate Logistic regression analysis, the influencing factors were identified for the construction of a nomogram prediction model. The discrimination of the model was evaluated by the AUC of the ROC curve. The calibration of the model was assessed using the calibration curve and the Hosmer-Lemeshow test. The clinical utility of the model was evaluated through decision curve analysis. Results Age, history of hepatobiliary invasive procedures within three months, coexistence of malignancy, abscess location, blood culture results, and PCT levels are independent factors influencing the development of sepsis in patients with PLA (P < 0.05). The AUC of the model was 0.942, with a sensitivity of 92.6% and a specificity of 89.7%. Both calibration curves and the Hosmer-Lemeshow goodness-of-fit test for the model indicate good model calibration. The decision curves for model indicate that the model yields a favorable net benefit when applied to patients falling within the specified range of predicted probabilities. Conclusion The nomogram prediction model constructed in this study for sepsis in patients with PLA demonstrates good predictive value and can provide a reference for early identification of sepsis in PLA patients.

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.

IgA nephropathy is the most common primary glomerular disease in China. Its clinical manifestations are mainly proteinuria， hematuria， hypertension， edema， hyperuricemia， etc. Most patients have hidden onset. 30%-40% of patients develop into end stage renal disease 10-20 years after diagnosis and rely on dialysis or kidney transplantation to maintain their lives， which is extremely harmful. Proteinuria is a common clinical manifestation of this disease， and most patients have small-to-moderate amounts of proteinuria， while 10%-24% of patients have large amounts of proteinuria. Proteinuria is the main risk factor affecting the progression of renal function in IgA nephropathy. Podocytes are the terminal part of the glomerular filtration barrier， and various factors can affect the fusion and detachment of podocyte processes that occur after podocyte injury. They are common histological lesions in IgA nephropathy and are key factors leading to proteinuria and the continuous progression of the disease. At present， Western medicine lacks targeted treatment for podocyte injury， with limited intervention methods. Drugs such as glucocorticoids are often used for treatment， and there are many adverse reactions. Based on the physiological function of podocytes， pathological and physiological changes after injury， and histological morphology of this disease， it is believed that it is closely related to traditional Chinese medicine's "Xuanfu Theory" "Kidney Collateral Syndrome" "Collateral Disease Theory"， and "Dry Blood Theory". More and more studies have shown that traditional Chinese medicine， which has the characteristics of multiple links， pathways， and targets， has a significant therapeutic effect on podocyte injury in IgA nephropathy. It can protect podocytes and reduce proteinuria and has good application and research prospects. This article systematically summarizes the mechanism and morphological changes of podocyte injury in IgA nephropathy， the understanding of podocyte injury in traditional Chinese medicine theory， and the research progress in traditional Chinese medicine treatment of podocyte injury in IgA nephropathy， so as to provide a reference for further research and application of traditional Chinese medicine intervention in podocyte injury in IgA nephropathy.

IgA nephropathy is recognized as the most common primary glomerular disease， with up to 20%-40% of patients developing end-stage kidney disease within 20 years of onset. The deposition of IgA1-containing immune complexes targeting glycosylation defects in the mesangial region and the subsequent inflammation caused by T lymphocyte activation are considered as the main causes of IgA nephropathy， and innate immunity is also involved in the pathogenesis. Nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） is a newly discovered pattern recognition receptor expressed in renal intrinsic cells such as renal tubular epithelial cells， mesangial cells， and podocytes. Activated by external stimuli， NLRP3 can form NLRP3 inflammasomes with apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC）. The NLRP3 inflammasome can activate cysteine aspartate-specific protease-1 （Caspase-1）， causing the maturation and release of interleukin-18 （IL-18） and interleukin-1β （IL-1β） involved in inflammation. Increasing evidence has suggested that NLRP3 inflammasomes are involved in the pathogenesis and progression of IgA nephropathy and associated with the damage of renal intrinsic cells such as podocytes， mesangial cells， endothelial cells， and renal tubular epithelial cells. Chinese medicine can regulate inflammatory cytokines and their signaling pathways by acting on NLRP3 inflammasomes and related molecules， exerting therapeutic effects on IgA nephropathy. This article introduces the role of NLRP3 inflammasomes in IgA nephropathy and reviews the clinical and experimental research progress of Chinese medicine intervention in IgA nephropathy via NLRP3 inflammasomes， aiming to provide a reference for further research and application of Chinese medicine intervention in the NLRP3 inflammasome as a new therapeutic target.

Objective To explore the prognostic value of serum gap connexin 43(Cx43)and galectin-9(Gal-9)levels in elderly patients with acute cerebral infarction(ACI)after ultra-early intravenous thrombo-lytic therapy.Methods A total of 106 elderly patients with ACI who received ultra-early intravenous throm-bolytic therapy in the hospital from September 2020 to September 2022 were selected as the study group,and 100 healthy subjects who came to the hospital for physical examination during the same period were selected as the health group.The levels of Cx43 and Gal-9 in serum of all subjects were detected by enzyme-linked im-munosorbent assay(ELISA).After 2 weeks of treatment,106 elderly ACI patients were divided into good prognosis group(81 cases)and poor prognosis group(25 cases)according to the National Institutes of Health Stroke Scale(NIHSS)score.Receiver operating characteristic(ROC)curve was used to analyze the evaluation value of serum Cx43 and Gal-9 in the prognosis of ultra-early intravenous thrombolytic therapy in elderly ACI patients.Multivariate Logistic regression analysis was used to explore the influencing factors of poor prognosis of ultra-early intravenous thrombolytic therapy in elderly ACI patients.Results The levels of Cx43 and Gal-9 in the study group were higher than those in the health group(P＜0.05).The levels of Cx43 and Gal-9 in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).The area under the curve(AUC)of serum Cx43 and Gal-9 for predicting the poor prognosis in elderly ACI patients was 0.721(95％CI:0.673-0.758)and 0.837(95％CI:0.787-0.886),respectively,and the AUC of combined detection of CX43 and GAL-9 was 0.901(95％CI:0.857-0.946).The proportion of hypertension in the poor progno-sis group was higher than that in the good prognosis group(P＜0.05).Hypertension(OR=3.487,95％CI:1.564-7.773),serum Cx43≥106.53 pg/mL(OR=4.586,95％CI:1.982-10.611),serum Gal-9≥11.84 ng/mL(OR=4.345,95％CI:1.957-9.648)were risk factors for poor prognosis in elderly patients with ACI after ultra-early intravenous thrombolysis(P＜0.05).Conclusion Serum Cx43 and Gal-9 are highly expressed in elderly ACI patients,which could be used to evaluate the prognosis of elderly ACI patients after ultra-early intravenous thrombolysis therapy,and their combined detection has higher evaluation value.

Objective:To explore the association of hemoglobin(HGB) levels with bone mineral density(BMD) and osteoporosis in patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional study was conducted in 364 patients with T2DM who were hospitalized in the Department of Endocrinology and Geriatrics of the Affiliated Huaian No. 1 People′s Hospital of Nanjing Medical University from September 2019 to September 2020. Participants were stratified into tertiles(lower, middle, and upper) according to femoral BMD determined by dual-energy X-ray absorptiometry. Demographic characteristics, medical history, chronic diabetes complications, and comorbid conditions were compared among the 3 groups. The association between hemoglobin levels and BMD/osteoporosis was examined using multivariable logistic regression analyses. Interaction and stratified analyses were conducted according to age, body mass index(BMI), duration of diabetes, estimated glomerular filtration rate(eGFR), glycosylated hemoglobin(HbA 1C), total cholesterol(TC), triglycerides(TG), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C) and uric acid(UA). Results:After adjusting for age, BMI, and duration of diabetes, there were no significant differences observed in the association between hemoglobin levels and BMD or osteoporosis among postmenopausal women with T2DM(all P>0.05). After adjusting for age, BMI, duration of diabetes, and eGFR, men aged≥50 years with hemoglobin≥130 g/L showed a positive association between hemoglobin level and femoral neck BMD compared to those with hemoglobin<130 g/L( β=0.057, 95% CI 0.014-0.100, P=0.011). However, no significant associations were observed between hemoglobin level and BMDs at the total hip or lumbar spine(L1-L4), nor the risk of osteoporosis(all P>0.05). Stratified analyses revealed no significant differences in the subgroups classified based on age, BMI, diabetes duration, eGFR, HbA 1C, TC, TG, HDL-C, LDL-C, and UA(all interaction P>0.05). Conclusion:In males aged 50 and above with T2DM, elevated hemoglobin levels may be a protective factor for femoral neck bone density.

OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.