Metabolic associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， and its progression is closely associated with the development of liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. However， there is still a lack of effective therapies for MAFLD in clinical practice. Telomere is the protective structure at the end of chromosomes， and telomere shortening and functional impairment have been identified as one of the key factors regulating the pathological progression of MAFLD. This article systematically reviews the core mechanism of action of telomere regulation in MAFLD， including its molecular functions in nucleotide metabolism， oxidative stress， and epigenetic regulation， as well as its pathological effect in hepatocytes and hepatic stellate cells. In addition， this article explores the clinical prospects of telomeres as biomarkers and therapeutic targets for MAFLD， in order to provide a theoretical reference for improving the precise diagnosis and treatment system of MAFLD.

Objective:To investigate the effect of curcumin on phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway on the autophagy of Bacille Calmette-Guérin (BCG)-infected macrophages.Methods:The infection model was established by infecting THP-1-derived macrophages with BCG. Five groups were involved in this study, which were control group, BCG group, BCG+ curcumin group, BCG+ curcumin+ IGF-1(PI3K agonist) group, and BCG+ curcumin+ LY294002 (PI3K inhibitor) group. The fluorescence intensity of autophagosomes was observed under fluorescence microscope using the fluorescent dye monodansylcadaverine (MDC staining). The expression of PI3K, Akt, mTOR, phospho-PI3K (p-PI3K), phospho-Akt (p-Akt), phospho-mTOR (p-mTOR), microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ), and Beclin-1 at protein level were detected by Western blot. Colony forming unit was used to detect macrophage load. Multiple independent, normal, and homogeneous data were compared using one-way analysis of variance, and pairwise comparisons were conducted using LSD test.Results:BCG infection significantly decreased the fluorescence intensity of autophagosomes, and the expression of autophagy marker proteins LC3-Ⅱ and Beclin-1 ( P<0.05), but increased the expression of p-PI3K, p-Akt, and p-mTOR ( P<0.05). Curcumin increased the fluorescence intensity of autophagosomes and enhanced the expression of LC3-Ⅱ and Beclin-1 proteins in a concentration-dependent manner ( P<0.05). Besides, curcumin inhibited the expression of p-PI3K, p-Akt, and p-mTOR ( P<0.05). The PI3K agonist IGF-1 reversed the above effects of curcumin. Compared with the BCG+ curcumin group, the fluorescence intensity of autophagosomes and the expression of LC3-Ⅱ and Beclin-1 proteins were further increased ( P<0.05), while the expression of p-PI3K, p-Akt and p-mTOR was further decreased ( P<0.05) in the BCG+ curcumin+ LY294002 group. Compared with the BCG group, the bacterial loads in the BCG+ curcumin group and the BCG+ curcumin+ LY294002 group decreased significantly ( P<0.05), while the bacterial load in the BCG+ curcumin+ IGF-1 group increased significantly ( P<0.05). Conclusions:Curcumin can promote the autophagy of BCG-infected macrophages, which contributes to the clearance of Mycobacterium tuberculosis by macrophages. Part of the mechanism may be related to the inhibition of PI3K/Akt/mTOR pathway.

Objective To explore the efficacy of endoscopic therapy for esophageal and gastric variceal bleeding(EGVB),investigate the risk factors for rebleeding within 1 year,and establish a predictive model accordingly.Methods A retrospective study was conducted using the clinical and follow-up data of 120 EGVB patients who underwent endoscopy at our hospital between January 2021 and December 2022.The efficacy of endoscopic therapy was analyzed,and the patients were divided into a bleeding group and a non-bleeding group based on whether rebleeding occurred within 1 year after treatment.The factors influencing rebleeding within 1 year after treatment were analyzed,and a predictive model was established using logistic regression analysis.The model's goodness of fit was evaluated using the Hosmer-Lemeshow test,and its clinical value was analyzed using the receiver operating characteristic(ROC)curve.Results The hemostasis success rate within 72 hours after endoscopic therapy was 100％in all 120 patients.Four weeks after endoscopic treatment,endoscopic reexamination showed that the complete and partial disappearance rate of varices was 75.83％(91/120),with rebleeding occurring in 10 cases(8.33％).There were 34 cases(28.33％)of cumulative rebleeding at 6 months and 63 cases(52.50％)at 1 year after endoscopic therapy.Nine patients(7.50％)died within 1 year after endoscopic therapy,all of whom were rebleeding cases.A total of 63 patients with rebleeding were included in the bleeding group,and 57 patients without rebleeding were included in the non-bleeding group.Serum sodium＜135 mmol/L(odds ratio[OR]=3.837,95％confidence interval[CI]:1.095-13.445),Child-Pugh grade C(OR=3.835,95％CI:1.137-12.935),esophageal varices degree G3(OR=5.113,95％CI:1.565-16.707),and main portal vein diameter＞12 mm(OR=5.964,95％CI:2.295-15.497)were identified as risk factors of rebleeding within 1 year after endoscopic therapy in EGVB patients(P＜0.05).The risk prediction model for rebleeding within 1 year after endoscopic therapy in EGVB patients was shown as P=1/{1+e[-(-3.815+1.345×serum sodium+1.344×Child-Pugh grade+1.786×main portal vein diameter+1.632×esophageal varices degree)]}.The Hosmer-Lemeshow x2 was 3.158(P=0.856).The area under the curve(AUC)for predicting rebleeding within 1 year after endoscopic therapy in EGVB patients was 0.815,indicating good predictive performance.Clinical validation showed that the model had an accuracy of 82.30％,with sensitivity and specificity being 81.03％and 83.63％,respectively.Conclusion Endoscopic therapy for EGVB achieves a high rate of acute bleeding control,but patients remain at risk of rebleeding.Rebleeding is associated with serum sodium＜135 mmol/L,Child-Pugh grade C,main portal vein diameter＞12 mm,and esophageal varices degree G3.The logistic regression model can effectively predict the probability of rebleeding within 1 year after endoscopic therapy.

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

Objective The identification of TCM constitution plays an important role in"treating and preventing diseases"of TCM.At present,the identification of damp-heat constitution and balanced constitution is mostly determined by questionnaire,and subjective factors have a great influence.Aiming at the identification of damp-heat constitution and balanced constitution in TCM,this paper utilizes voice signal to automatically realize the constitution identification task,in order to provide assistance for the clinical identification of TCM constitution.Methods Based on deep learning Transformer and transfer learning,a pure attentional mechanism model was designed for the identification of constitution in TCM sound diagnosis.We collected 700 voices from 34 subjects,pre-processed the voice data to obtain the corresponding Mayer spectrum diagram,and used the Transformer model pre-trained based on the public data set to improve the performance of the model for audio classification.Results The accuracy of the experimental results was 83.33%,the AUC was 92.16%,the sensitivity was 80.25%,and the specificity was 87.03%.Compared with the Convolutional Neural Network(CNN),the performance of the deep learning model was better.Conclusion In this paper,the damp-heat constitution and balanced constitution identification model Transformer has achieved better identification effect,indicating that it can improve the efficiency of TCM acoustic diagnosis of constitution identification,and promote the objective and intelligent development of constitution identification.

OBJECTIVE To study the chemical constituents in the root bark of Schisandra sphenanthera and their cytotoxic activ-ities.METHODS The compounds were isolated and purified by silica,Sephadex LH-20 and semi preparative-HPLC and the chem-ical structures were identified by 1 H-NMR,13 C-NMR and MS data analysis.The cytotoxic activities of the compounds were deter-mined by MTT method.RESULTS Twenty lignans were isolated and deduced as:Matairesinol(1),2-Hydroxy-2-(3′,4′-di-hydroxyphenyl)methyl-3-(3″,4″-dimethoxyphenyl)methyl-gamma-butyrolactone(2),(+)-Nortrachelogenin(3),2-Hydroxy-2-(4′-O-β-D-glucopyranosyl-3′-hydroxyphenyl)methyl-3-(3″,4″-dimethoxyphenyl)methyl-γ-butyrolactone(4),Nortracheloside(5),Burselignan(6),(+)-Cycloolivil(7),5-Methoxy-(+)-isolariciresinol(8),(-)-Isolariciresinol 3α-O-β-D-glucopyranoside(9),(+)-9-O-β-D-Glucopyranosyl lyoniresinol(10),(-)-Secoisolariciresinol(11),Licarin A(12),Cedrusin(13),Mataires-inol 4′-O-β-D-glucopyranoside(14),Pregomisin(15),Meso-dihydroguaiaretic acid(16),7S,8R-Erythro-4,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-7-O-β-D-glucopyranoside(17),Gomisin M2(18),Gomisin M3(19),Pinoresinol(20).Com-pounds 1-3,12,15,16,18 and 19 showed cytotoxic activity against A549,HCT116 and SW620 cell lines with IC50 values ranging from 1.4 to 22.9 μmol·L-1.CONCLUSION Compounds 1-4,6-12,14,17-19 are isolated from the plant for the first time,com-pounds 1-3,12,15,16,18 and 19 exhibit cytotoxic activities.

Purpose To analyze the expression of SNAP23 in esophageal squamous cell carcinoma(ESCC)and its influence on invasion of ESCC cells.Methods A total of 41 cases of ESCC and paired normal adjacent tissue(NAT)were collected.The expression and localization of SNAP23 were detected by immunohistochemical EnVision method.The differences of SNAP23 expression levels between ESCC tissues and NAT tissues were compared to analyze the relationship between SNAP23 expression and clinicopathological characteristics.The expression level of SNAP23 in human immortalized esophageal epithelial cells SHEE and ESCC cell lines TE-1,TE-13 and KYSE150 were detected by Western blot.Lentiviral vector transfection technique was used to construct stable transfection cell lines with knock-down and overexpression of SNAP23 gene.The effect of SNAP23 on invasion of ESCC cell line TE-13 was evaluated by cell invasion experiment.Results The expression of SNAP23 in ESCC was significantly higher(53.7％,22/41)than that in the NAT group(19.5％,8/41),the difference was statistically significant(x2=10.303,P＜0.01).The expression level of SNAP23 in ESCC tissues was significantly correlated with maximum tumor diameter(x2=4.193,P＜0.05)and invasion depth(x2=7.264,P＜0.05),but was not correlated with patient gender,age,tumor site,tumor type,pathologic grade,vascular embolus,nerve invasion and lymph node metastasis(P＞0.05).Compared with human immortalized esophageal epithelial cells SHEE,SNAP23 was highly expressed in ESCC cell lines(P＜0.000 1).Compared with the sh-NT group,the invasion of ESCC cell line TE-13 was inhibited when SNAP23 expression was knocked down(P＜0.000 1);compared with the Vector group,the invasion of ESCC cell line TE-13 was enhanced after overexpression of SNAP23(P＜0.000 1).Conclusion SNAP23 is highly expressed in ESCC tis-sue and cell lines,and its expression level in ESCC tissues is positively correlated with tumor maximum diameter and invasion depth;SNAP23 promotes the invasion of ESCC cells.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Thyroid-associated ophthalmopathy(TAO)is a progressive eye disease characterized by immune-mediated inflammation of the extraocular muscles and orbital connective tissue.TAO tends to have complex and diverse symptoms and signs,with the features of diversity and concealment,which seriously affect the quality of life of patients.The pathogenesis of TAO is closely associated with thyroid autoimmunity.This article reviews the pathogenesis,clinical features,and treatment of TAO.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.