Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Both cathartic colon （CC） and cathartic-dependent constipation （CDC） are caused by the abuse of stimulant laxatives， while their concepts are not completely the same.Starting from the disease name of CC， this article traced the origin and evolution of the concept of CC， summarizes and compared the similarities and differences between CC， CDC， and slow transit constipation （STC）， and called for strict differentiation among the three.Furthermore， this article explored the specific contents of Western medicine clinical subtypes and traditional Chinese medicine （TCM） syndrome differentiation of CDC and delved into the TCM pathogenesis of CDC according to both literature and clinical practice.The relationship between clinical subtypes and TCM syndromes was established， and the syndrome characteristics of CDC of different clinical subtypes and TCM syndromes were summarized.The recommended prescriptions for corresponding syndromes were listed.A systematic CDC diagnosis and treatment approach of "clinical subtypes-syndrome differentiation-syndrome characteristics-recommended prescriptions" was thus formed.Additionally， the paper provides an overview of current research on CDC in both Western medicine and TCM contexts， identifies future research directions， and suggests research pathways for refining and advancing CDC studies.

Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Pigeon circovirus(PiCV)is globally widespread and is considered a potential cause of young pigeon sickness syndrome(YPDS),which leads to severe immunosuppression and high mortality.Due to the inability of PiCV to be cultured in cells,the development of traditional vac-cines is severely limited,and no effective vaccines is currently available.To develop a novel PiCV DNA candidate vaccine,we cloned the △Cap gene lacking a nuclear localization signal(NLS),and fused it at its C-terminus with the transmembrane and cytoplasmic regions of the Newcastle dis-ease virus(NDV)F protein(△Cap-TMCT).Two DNA vaccine candidates were constructed:pCAGG-△Cap,targeting intracellular expression,and pCAGG-△Capt,for cell surface expression,respectively.The results of indirect immunofluorescence and Western blot analyses confirmed suc-cessful expression of both recombinant plasmids in DF1 cells.Immunization studies in mice re-vealed that pCAGG-△Capt induced significantly higher levels of specific IgG antibodies,T-cell re-sponses,and cytokine secretion compared to pCAGG-△Cap,as assessed by ELISA,flow cytome-try,and ELISpot assays.These findings suggest that targeting △Cap-TMCT fusion protein to the cell surface can effectively enhance its immunogenicity,highlighting its potential as a PiCV DNA vaccine candidate.This study provides new strategies and theoretical foundations for the design and development of PiCV DNA vaccines.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.

Objective:To compare the performance differences of domestic and imported CD3/CD28 activation beads for manufacturing CAR-T cells,providing a backup or alternative for domestic CAR-T cell research and manufacture.Methods:A mature protocol using imported CD3/CD28 activation beads with a 1∶1 ratio for CD3+T cells was implemented as research control.Domestic beads were used with gradient ratios of 1∶2,1∶1,and 2∶1 to activate T cells.72 h after T cell activation,CAR-T cells were manufactured by CAR lentiviral infection and cell proliferation was monitored at 2-,4-,and 7-days post-infection.Flow Cytometry was used to detect CAR-T cell positivity 5 days after infection and to detectCD4/CD8 phenotype of CAR-T cells and PD1+TIM3+cell exhaustion ratio 8 days after infection.Results:CAR-T cells manufactured by domestic CD3/CD28 activation beads exhibited similar phenotype compared with those manufactured by imported CD4/CD8 beads.The positive rate of CAR-T cells prepared with domestic beads was slightly lower than that of imported beads(53.7%vs 57.9%).However,the proliferation of CAR-T cells manufactured by domestic beads was about twice that of cells manufactured by imported beads,and the exhaustion level was only half that of imported beads(4.21%vs 7.91%).Moreover,the use of domestic magnetic beads was lower than that of imported magnetic beads,which was advantageous for cutting the costs of CAR-T cells research and manufacture.Conclusion:Domestic CD3/CD28 activation beads used for CAR-T cells manufacturing demonstrate comparable overall performance to their imported counterparts,showing potential as a backup or alternative for imported beads.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.

Objective To explore the application value of microwave ablation under ultrasound-magnetic resonance imaging(US-MRI)in the treatment of small liver cancer.Methods A total of 94 patients with small liver cancer were selected and randomly divided into observation group and control group using a random number table method,with 47 patients in each group.The observation group underwent microwave ablation under US-MRI,while the control group received surgical resection.The tumor control rate,periopera-tive indicators,liver function indicators[total bilirubin(TBIL),albumin(ALB),aspartate aminotransferase(AST),and alanine amin-otransferase(ALT)],postoperative complications,and 6-month follow-up status were compared between the two groups.Results There was no significant difference in tumor control rate between the two groups(P>0.05).In the observation group,the proportion of patients with smaller intraoperative blood loss,shorter operative time and postoperative performance status(PS)score of 0-1 was higher than those in the control group(P<0.05).After treatment,the levels of TBIL,AST and ALT were lower and the level of ALB was higher,and the incidence of complications was lower in the observation group(P<0.05).There were no significant differences between the two groups in residual lesion and recurrence(P>0.05).Conclusion The short-term efficacy of microwave ablation under US-MRI in the treatment of small liver cancer is similar to that of surgical treatment,and the microwave ablation under US-MRI can also reduce liver function injury,reduce intraoperative blood loss and shorten operation time.

Objective Observe the impact of Qang Gu Kang Wei extraction(KW)on skeletal muscle atrophy in simulated weightlessness rats by regulating endoplasmic reticulum stress and mitochondrial fusion.Methods SD rats were randomy divided the control group(Control),the simulated weightlessness group(TS),and the KW group(TS+KW).Rats were treated with KW with or without tail suspension(TS)for 28 days,and the cross-sectional areas of the gastrocnemius muscle were compared with a control group.The expression levels of endoplasmic reticulum stress(ERS)and key proteins involved in mitochondrial fusion were also analyzed.Results KW treatment reduced the loss of muscle cross-sectional area caused by TS.TS increased the protein expression of glucose-regulated Protein 78(GRP78)and components of the ERS signaling pathways,while KW treatment reduced this increase.TS also inhibited the expression of mitofusin 2(MFN2),which was increased by KW treatment.Additionally,KW treatment promoted the interaction between GRP78 and the endoplasmic reticulum protein sigma-1 receptor(Sig-1R).Conclusion KW may attenuate muscle atrophy caused by simulated weightlessness by regulating ERS and mitochondrial fusion fusion.

Objective To investigate the mechanisms of 6-hydroxygenistein(6-OHG)in the treatment of high-altitude hypoxia-induced lung injury.Methods The intersection targets of 6-OHG and high-altitude hypoxia-induced lung injury were identified using databases,including Swiss Target Prediction,SuperPred,GeneCards,and OMIM.The STRING database and Cytoscape software were used to construct a protein interaction network for the intersection targets of drugs and diseases,and targets with degree values greater than the median were identified as key targets.GO and KEGG enrichment analyses of key targets were performed using the DAVID database to identify relevant signaling pathways.The Maestro 13.7 software was used for molecular docking validation.A large hypobaric hypoxic chamber was used to establish a high-altitude lung injury model in mice.A total of 42 male BALB/c mice were randomly assigned to 3 groups(n=14 in each group),including a normal control group,which was exposed to the environmental conditions at the altitude of 1400 m and received a single intraperitoneal injection of normal saline,a model group,which received a single intraperitoneal injection of normal saline,and a 6-OHG group,which received a single intraperitoneal injection of 6-OHG at 100 mg/kg.Then,1 h after drug administration,mice in the model and 6-OHG groups were placed in a large hypobaric hypoxic simulation chamber for animal experiments.Then,they ascended to an altitude of 8 000 m at a speed of 10 m/s,remained in that environment for 24 h,and then descended to an altitude of 3500 m.Mice in the three groups were sacrificed,and their lung tissues were extracted to measure the water content in the lungs.Pathological changes were observed using HE staining,and the levels of malondialdehyde(MDA),H2O2,total superoxide dismutase(T-SOD),and glutathione(GSH)were measured.Western blot was performed to determine the expression levles of p-PI3K/PI3K,p-AKT/AKT,hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF)proteins.Results Key targets such as serine/threonine protein kinase 1(AKT1),HIF-1α,epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9),and peroxisome proliferator-activated receptor A(PPARA)were identified.GO and KEGG enrichment analyses showed that the targets of 6-OHG in the treatment of high altitude hypoxia-induced lung injury were mainly involved in PI3K/AKT,HIF-1α/VEGF,tumor necrosis factor(TNF),and other signaling pathways.The results of animal experiments demonstrated that compared with the model group,the 6-OHG group showed significant improvement in the pathological damage of lung tissues induced by high altitude hypoxia,presenting statistically significant differences in the levels of MDA,H2O2,GSH,and T-SOD(P＜0.01).The results of Western blot assay revealed statistically significant differences in the p-PI3K/PI3K,p-AKT/AKT,HIF-1α,and VEGF levels in the lung tissues of the 6-OHG group compared with those of the model group(P＜0.01).The molecular docking results showed that 6-OHG could form stable binding with PI3K,AKT,HIF-1α,and VEGF.Conclusion 6-OHG may alleviate lung injury induced by high altitude hypoxia in mice by activating the PI3K/AKT signaling pathway and inhibiting the HIF/VEGF signaling pathway.