The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Objective: To analyze the epidemiological characteristics and changing trends of non suicidal self injury (NSSI) behaviors among middle school students in Jiading District of Shanghai, from 2015 to 2023, so as to provide a basis for the development of NSSI prevention and control measures among students. Methods: Using a stratified cluster random sampling method, a total of five times for Shanghai Adolescent Health Risk Behavior Surveys were conducted for every two years in Jiading District of Shanghai from 2015 to 2023. A total of 5 231 middle school students from junior high schools and senior high schools were selected for questionnaire surveys. Intergroup comparisons were performed using the x 2 test or the χ 2 trend test, and the JointPoint 5.0 software was used to analyze the changing trends, with the annual percent change (APC) used for evaluation. A binary Logistic regression model was employed to analyze the related factors of NSSI behavior among middle school students. Results: In 2023, the reported NSSI rate among middle school students in Jiading District was 14.2%. The rate was significantly higher among junior high school students (17.1%) than that among senior high school students (11.1%), and higher among females (19.2%) than that among males (10.0%) ( χ 2=10.04, 23.21, both P <0.01). From 2015 to 2023, the overall reported NSSI rate showed an increasing trend, rising from 8.6% in 2015 to 14.2% in 2023 ( χ 2 trend =22.25), with an APC of 6.64% ( t =3.49), and the APC for girls was 9.79 % ( t =3.20) (all P <0.05). Among students reporting NSSI, the proportion experiencing ≥6 episodes increased from 10.8% in 2015 to 19.2% in 2023 ( χ 2 trend =6.57, P <0.05). Multivariate Logistic regression analysis indicated that girls, junior high school students, those with insomnia, depressive emotion and drinkers had higher risks of NSSI, compared to boys, senior high school students, those without insomnia, non depressive emotion students and non drinkers ( OR =1.71, 1.96, 3.44, 4.76, 1.77, all P < 0.05 ). Conclusions The reported rate of NSSI among middle school students in Jiading District of Shanghai, increased annually from 2015 to 2023, and the proportion of repeated NSSI also showed an upward trend. Early intervention measures targeting middle school students, especially junior high school students and females, should be implemented to prevent and control its occurrence and development.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

Objective To systematically evaluate the psychological characteristics of adolescent inflammatory bowel disease(IBD)patients during the transition period and provide evidence-based guidance for healthcare professionals in developing transition management strategies.Methods A systematic search was conducted across The Cochrane Library,PubMed,Web of Science,CINAHL,Embase,SinoMed,CNKI,Wanfang,and VIP databases for qualitative studies on adolescent IBD patients during transition,from database inception to May 2024.Eligible studies were critically appraised,and themes were synthesized using the meta-aggregation approach of meta-synthesis.Results Twelve studies were included,yielding 13 findings that were synthesized into five categories:self-development challenges,healthcare system transition barriers,family support conflicts,social adaptation difficulties,and lack of societal support systems.Conclusion Adolescents with IBD experience complex psychological challenges during transition,characterized by excessive psychological burdens,inadequate healthcare support,and insufficient societal recognition.Targeted interventions are needed to improve psychological outcomes during this critical phase.

Objective To construct a prediction model for atrial fibrillation(AF)after pacemaker implantation based on clinical features and plasma atrial natriuretic peptide(ANP)and brain na-triuretic peptide(BNP).Methods A retrospective analysis was conducted on 242 patients under-going pacemaker implantation in our department from January 2020 to October 2023.According to the occurrence of postoperative AF or not,they were divided into an AF group(61 cases)and a non-AF group(181 cases).The risk factors of AF after pacemaker implantation were analyzed,and a risk prediction model of AF after pacemaker implantation was constructed based on clinical features and plasma ANP and BNP levels.Results The AF group had significantly advanced age,larger proportions of hypertension and coronary heart disease,larger left ventricular diameter,and higher ANP,BNP,IL-6 and IL-8 levels,but lower proportion of using calcium antagonists when compared with the non-AF group(P＜0.01).Binary logistic regression analysis showed that hy-pertension,coronary heart disease,ANP,BNP and IL-6 were risk factors(P＜0.05,P＜0.01),and taking calcium antagonists was protective factor for AF after pacemaker implantation(P＜0.05).Hosmer Lemeshow fitting test indicated the model had a good fitness(x2=7.264,P=0.508).ROC curve analysis showed that the area under curve(AUC)value of the risk model for AF after pacemaker implantation in the training set was 0.826(95％CI:0.768-0.884),with an accuracy of 79.3％(192/242),and the AUC value of the model in the validation set was 0.835(95％CI:0.733-0.938).Conclusion Our AF prediction model based on clinical features and plasma ANP and BNP had good performance,and can provide auxiliary reference in predicting AF in patients undergoing pacemaker implantation.

Objective:This study aims to clarify the role of family and community health environments in improving the health status of elderly patients with chronic diseases,and provide recommendations and references for optimizing and enhancing chronic disease management capabilities.Methods:Based on data from the 2018 China Health and Retirement Longitudinal Study(CHARLS),this study analyzes a sample of 9,388 elderly patients with chronic diseases.A hierarchical linear model(HLM)is employed to examine the effects of family and community health environments on chronic disease management outcomes,as well as their variations across urban-rural settings and disease types.Results:The findings indicate that a supportive family health environment significantly improves both self-rated health(β=0.097,P<0.001)and disease control outcomes(β=0.033,P<0.05)among elderly patients with chronic diseases.In contrast,community health environments contribute positively only to self-rated health(β=0.062,P<0.001)but do not significantly affect disease control outcomes.Moreover,no moderating effect of community health environments was observed on the relationship between family health environments and either self-rated health or disease control.The effects of family and community health environment on self-rated health and control results were different between urban and rural areas,while the effects of family health environment on control results were different in disease types.Conclusion:The explanatory power of the family health environment on the health status of elderly patients with chronic diseases is higher than that of the community health environment.However,the two have not been effectively integrated.It is recommended to incorporate the health needs of elderly patients with chronic diseases into the optimization of healthy family construction and to establish a four-in-one comprehensive chronic disease management system involving"patients,families,communities,and primary healthcare institutions."new models for chronic disease management should be explored and innovated.

Objective To construct a prediction model for atrial fibrillation(AF)after pacemaker implantation based on clinical features and plasma atrial natriuretic peptide(ANP)and brain na-triuretic peptide(BNP).Methods A retrospective analysis was conducted on 242 patients under-going pacemaker implantation in our department from January 2020 to October 2023.According to the occurrence of postoperative AF or not,they were divided into an AF group(61 cases)and a non-AF group(181 cases).The risk factors of AF after pacemaker implantation were analyzed,and a risk prediction model of AF after pacemaker implantation was constructed based on clinical features and plasma ANP and BNP levels.Results The AF group had significantly advanced age,larger proportions of hypertension and coronary heart disease,larger left ventricular diameter,and higher ANP,BNP,IL-6 and IL-8 levels,but lower proportion of using calcium antagonists when compared with the non-AF group(P＜0.01).Binary logistic regression analysis showed that hy-pertension,coronary heart disease,ANP,BNP and IL-6 were risk factors(P＜0.05,P＜0.01),and taking calcium antagonists was protective factor for AF after pacemaker implantation(P＜0.05).Hosmer Lemeshow fitting test indicated the model had a good fitness(x2=7.264,P=0.508).ROC curve analysis showed that the area under curve(AUC)value of the risk model for AF after pacemaker implantation in the training set was 0.826(95％CI:0.768-0.884),with an accuracy of 79.3％(192/242),and the AUC value of the model in the validation set was 0.835(95％CI:0.733-0.938).Conclusion Our AF prediction model based on clinical features and plasma ANP and BNP had good performance,and can provide auxiliary reference in predicting AF in patients undergoing pacemaker implantation.