ObjectiveTo investigate the effect of different exercise interventions on metabolism and liver parameters in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide evidence-based recommendations for clinical exercise rehabilitation. MethodsThis study was conducted according to the PRISMA guidelines， and the protocol was registered on the PROSPERO platform， with a registration number of CRD42025641717. PubMed， Web of Science， Scopus， Wiley Online Library， CNKI， Wanfang Data， and VIP were searched for related articles published up to September 2024. The Cochrane tool for assessing risk of bias was used to assess the quality of articles， and Stata MP 17.0 was used to perform the network meta-analysis. ResultsA total of 57 articles were included， involving 2 648 patients. The results showed that aerobic exercise combined with resistance exercise had the best effect in improving body mass index （mean difference ［WMD］=-0.97， 95% confidence interval ［CI］： -1.66 to -0.28］， P<0.05， surface under the cumulative ranking curve ［SUCRA］=85.4） and triglycerides （WMD=-29.6， 95%CI： -46.66 to 12.54， P<0.05， SUCRA=87.3）； resistance exercise was the optimal intervention method for improving total cholesterol （WMD=-15.99， 95%CI： -24.19 to -7.79， P<0.05， SUCRA=79.9） and glutamine transaminase （WMD=-8.08， 95%CI： -12.13 to -4.02， P<0.05， SUCRA=87.3）； low-intensity aerobic exercise had the best effect in improving aspartate aminotransferase （WMD=-4.3， 95%CI： -8.45 to -0.15， P<0.05， SUCRA=73.5）， gamma-glutamyl transpeptidase （GGT） （WMD=-3.26， 95%CI： -7.79 to 1.27， P>0.05， SUCRA=82.3）， and glycated hemoglobin （HbA1c） （WMD=-0.6， 95%CI： -2.02 to 0.82， P>0.05， SUCRA=78.8）； moderate-intensity aerobic exercise was the optimal intervention modality to improve Homeostasis Model Assessment of Insulin Resistance （WMD=-0.92， 95%CI： -1.51 to -0.33， P<0.05， SUCRA=69.4）. It should be noted that there were no significant differences in HbA1c and GGT across different exercise interventions （all P>0.05）， suggesting that there was currently no sufficient statistical evidence to support that exercise could improve these two indicators. ConclusionBased on the comprehensive league table and cumulative probability ranking， aerobic exercise combined with resistance exercise， resistance exercise， and low- and moderate-intensity aerobic exercise may be the best exercise modality for improving key indicators in MAFLD patients， and targeted exercise modalities should be selected for intervention against different indicators； however， due to limitations of the original studies， further studies are needed for validation and exploration.

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.

Objective:To assess the association between temperature and risk of animal injury, and identifying vulnerable populations.Methods:Based on a time-stratified case-crossover design, the number of animal injuries monitored in hospitals of Guangdong Provincial Injury Surveillance System in 2011 and 2015-2016 was included, and the daily meteorological data were derived from the fifth generation of European ReAnalysis-Land, which was produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression combined with a distributed lagged nonlinear model was applied to analyze the association of temperature and animal-specific injuries. We also conducted stratified analysis by region, sex, age, occupation, and location of injury occurrence.Results:There was an almost linear relationship between temperature and the occurrence of animal injury. The excess risk ( ER) of animal injury was 2.65% (95% CI: 2.27%-3.04%) for a 1 ℃ rise in temperature with much higher risk of occurrence ( ER=9.34%, 95% CI: 7.57%-11.13%) for non-mammalian injury than that for mammalian injuries ( ER=2.30%, 95% CI: 1.90%-2.70%). Stratified analysis revealed that the occurrence of animal injury was more susceptible to temperature influences in urban ( ER=2.78%, 95% CI: 2.35%-3.21%), female ( ER=2.71%, 95% CI: 2.16%-3.27%), the elderly aged 60 years and above ( ER=3.05%, 95% CI: 1.65%- 4.47%), farmer ( ER=4.66%, 95% CI: 3.03%-6.32%) and agricultural area ( ER=10.63%, 95% CI: 7.57%-13.79%) than their correspondents. In terms of mammalian injury, dog bites showed the highest risk ( ER=2.71%, 95% CI: 2.12%-3.30%). In terms of non-mammalian,snake injuries were highly influenced by temperature ( ER=16.74%, 95% CI: 11.33%-22.40%). Conclusions:The ambient temperature rises could increase the risk of animal injury with much higher risk for non-mammalian than that for mammalian injuries. Our findings suggest that global warming may increase the risk and disease burden from animal injuries.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.