Objective To explore the clinical factors influencing complete response in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Methods Clinical data of LARC patients treated in the Department of Radiation Oncology at Beijing Shijitan Hospital between January 2013 and December 2024 were retrospectively collected. All patients received nCRT, after which surgery or a watch-and-wait approach was adopted based on treatment response. Univariable and multivariable logistic regression analyses were performed to identify prognostic factors influencing complete response. A clinical prediction model was constructed based on the multivariable analysis results, and its predictive performance was evaluated using the receiver operating characteristic curve. Results A total of 113 eligible patients were included. After nCRT, 19 patients (16.8%) achieved complete response, including 3 with clinical complete response and 16 with pathological complete response. Univariable analysis indicated that pretreatment clinical N stage, extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen were associated with complete response after nCRT (P<0.05). Multivariable logistic regression analysis identified pretreatment extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen as independent influencing factors for complete response (P<0.05). A prediction model incorporating these independent factors yielded an area under the receiver operating characteristic curve of 0.813 (95% confidence interval: 0.713-0.913), with a sensitivity of 89.5% and a specificity of 60.6%, demonstrating good predictive performance. Conclusion Pretreatment extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen are independent factors influencing complete response after nCRT in LARC patients. The prediction model combining these factors may assist in evaluating treatment efficacy following nCRT in LARC patients.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Objective To investigate the efficacy and safety of dual antiplatelet therapy within 72hours of onset in patients with small artery occlusion(SAO)who do not carry the cytochrome P450 2C19(CYP2C19)loss-of-function(LOF)allele,under the precise guidance of rapid testing for the CYP2C19gene.Methods A retrospective study was conducted to collect patients with stroke of SAO who presented within 72hours of onset and did not carry the CYP2C19 LOF allele,attending the Department of Neurology,Xuzhou Central Hospital between January and December 2023.Patients were divided into two groups:the control group and the experimental group,the control group received aspirin monotherapy,and the experimental group received dual antiplatelet therapy with aspirin and clopidogrel.Baseline characteristics of both groups were collected,and the modified Rankin scale(mRS)scores and National Institutes of Health Stroke Scale(NIHSS)scores were recorded on the 1st,7th,21st and 90th days of treatment.Additionally,the occurrence of adverse e-vents was documented.The primary efficacy outcome was the incidence of new stroke within 90 days,while the primary safety outcome was the occurrence of moderate-to-severe bleeding within 90days.Results A total of 130 patients were enrolled in the study,with 61 patients in the control group,and 69 patients in the experimental group.Within the experimental group,patients with stroke onset within 24 hours accounted for 11.6％,those with onset between 24 and 48 hours accounted for 47.8％,and those with onset between 48 and 72 hours accounted for 40.6％.There were no statistically significant differences in baseline characteristics between the two groups(P＞0.05).Regarding new strokes within 90days,there were 9 cases(14.8％)in the control group,and 3 cases(4.3％)in the experimen-tal group,with a statistically significant difference(x2=4.185,P＜0.05).For moderate-to-severe bleeding within 90days,there were 0 cases in the control group,and 1 case(1.4％)in the experimental group,there was no statistically significant difference between the two groups(P＞0.05).Conclusion For patients with stroke of SAO who are non-carriers of CYP2C19 LOF allele and have onset within 72 hours,dual antiplatelet therapy with aspirin combined with clopidogrel can effectively reduce the recurrence of stroke.Addition-ally,the two drugs demonstrate consistent safety profiles,with no observed increase in adverse events such as bleeding associated with the combination therapy.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Objective:To explore the effects of essential tremor(ET)on the mitochondrial morphology of GABAer-gic and glutamatergic neurons in the inferior olive(IO).Methods:The ET mouse model was established via intraper-itoneal injection of harmaline.Twelve 8-week-old male C57BL/6J mice were randomly divided into saline control group and harmaline treatment group(HA).Behavioral tests,including open field test,rotarod test,balance beam test,and tremor scoring,were conducted to assess the behavior of mice.Using genetic engineering technology and the CRISPR/Cas9 system,we designed and generated 6 male GAD2-Mito-GFP mice and 6 male VGLUT2-Mito-GFP mice,all being 8-week-old.The mice of each transgenic line were randomly divided into Control and HA group.Immunofluorescence staining was used to analyze the expression of c-FOS positive cells in the IO of both the Control and HA groups,and to classify different types of neurons.Mitochondrial network analysis(MiNA)was performed to quantitatively analyze the area,mean aspect ratio,branch length,and other of mitochondria in different types of neurons in the IO under ET con-ditions.Results:Compared to the Control group,the HA group exhibited motor abnormalities and significant tremors.Immunofluorescence results showed a significant increase in the number of c-FOS positive cells in the IO,primarily in GABAergic neurons.MiNA results revealed that the mitochondria of GABAergic neurons showed increased area,branch length diameter,demonstrating irregular morphology.Conclusion:ET induces activation of GABAergic neurons in the IO and leads to more prominent mitochondrial morphological changes.This provides a new perspective for further inves-tigation of the pathogenesis of essential tremor and its relationship with mitochondrial.

This paper interprets the 2025 edition of the national health industry standard WS/T 512,"Regulation for cleaning and disinfection management of environmental surface in healthcare".The promulgation of the 2016 e-dition marked the entry of healthcare environmental hygiene(HEH)in China into a phase of standardized and reg-ulated management.The first comprehensive revision of the WS/T 512 standard after eight years of implementa-tion not only summarizes past practical experience but also heralds new requirements for healthcare environmental hygiene.This paper discusses the rbackground for revision of the standard,the solicitation of suggestions and the revised contents and interpretation.It also analyzes the revisions and highlights of the 2025 edition in the context of domestic and international research progress in environmental infection control,aiming to assist healthcare institu-tions in better understanding and implementing the standard,thereby improving the quality and efficiency of HEH in China.

Objective:To explore the effects of essential tremor(ET)on the mitochondrial morphology of GABAer-gic and glutamatergic neurons in the inferior olive(IO).Methods:The ET mouse model was established via intraper-itoneal injection of harmaline.Twelve 8-week-old male C57BL/6J mice were randomly divided into saline control group and harmaline treatment group(HA).Behavioral tests,including open field test,rotarod test,balance beam test,and tremor scoring,were conducted to assess the behavior of mice.Using genetic engineering technology and the CRISPR/Cas9 system,we designed and generated 6 male GAD2-Mito-GFP mice and 6 male VGLUT2-Mito-GFP mice,all being 8-week-old.The mice of each transgenic line were randomly divided into Control and HA group.Immunofluorescence staining was used to analyze the expression of c-FOS positive cells in the IO of both the Control and HA groups,and to classify different types of neurons.Mitochondrial network analysis(MiNA)was performed to quantitatively analyze the area,mean aspect ratio,branch length,and other of mitochondria in different types of neurons in the IO under ET con-ditions.Results:Compared to the Control group,the HA group exhibited motor abnormalities and significant tremors.Immunofluorescence results showed a significant increase in the number of c-FOS positive cells in the IO,primarily in GABAergic neurons.MiNA results revealed that the mitochondria of GABAergic neurons showed increased area,branch length diameter,demonstrating irregular morphology.Conclusion:ET induces activation of GABAergic neurons in the IO and leads to more prominent mitochondrial morphological changes.This provides a new perspective for further inves-tigation of the pathogenesis of essential tremor and its relationship with mitochondrial.

AIM To investigate the clinical effects of Supplemented Gegen Qinlian Decoction combined with acupuncture on patients with ulcerative colitis of Large Intestinal Dampness-heat Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 1-month administration of Pefikang Capsules and Mesalazine Sustained Release Granules,and observation group(60 cases)for 1-month administration of Supplemented Gegen Qinlian Decoction,acupuncture,Pefikang Capsules and Mesalazine Sustained Release Granules.The changes in clinical effects,symptom remission time,TCM syndrome scores,Geboes index,lesion activity index,Baron score,inflammatory factors(IL-6,IL-8,TNF-α),immune function indices(IgA,IgG,IgM),IBDQ score and recurrence rate were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05),along with shorter symptom remission time(P＜0.05)and lower recurrence rate(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,Geboes index,lesion activity index,Baron score,inflammatory factors,IgG,IgM(P＜0.05),and increased IBDQ score(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients with ulcerative colitis of Large Intestinal Dampness-heat Pattern,Gegen Qinlian Decoction combined with acupuncture can improve clinical symptoms,promote disease recovery,enhance immune functions and life quality,and reduce recurrence rate.