Objective: To explore the early effects of birth weight at different gestational ages on blood pressure trajectory among primary school students, so as to provide evidence for incorporating gestational age birth weight into individualized early warning and intervention strategies for childhood hypertension. Methods: From May to November 2023, a purposeful sampling method was used to recruit 1 676 students in grade 1-3 from three primary schools in a certain urban district of Chongqing. Follow up assessments were conducted in May 2024(T1), November 2024(T2), and May 2025(T3). General demographic and birth related information were collected via self administered questionnaires, while height, weight and blood pressure were obtained through physical examinations. Linear mixed effects model was used to analyze the associations between birth weight at different gestational ages and blood pressure trajectories. Results: During the T1-T3 period, the systolic blood pressure of boys were 98.5 (93.0, 104.5 ),98.5 (93.5, 105.0), and 97.5 (92.5, 103.5)mmHg, respectively, while the diastolic blood pressure were 60.5 (56.5, 65.0), 61.5 ( 57.0 , 65.5), and 60.0 (56.0, 64.0)mmHg, respectively. For girls, the systolic blood pressure were 95.5 (90.0, 102.0),95.5 (90.5, 101.5), and 96.0 (90.5, 101.5)mmHg, respectively, and the diastolic blood pressure were 60.5 (56.0, 64.5 ),61.5 (57.5, 65.5), and 59.5 (56.0, 63.0)mmHg, respectively. Through Friedman test within both boys and girls, diostolic blood pressure were statistically significant across three measurements( χ 2=48.85，81.54，both P <0.01). The proportion of normal blood pressure increased , and the proportion of prehypertension and hypertension decreased with time( χ 2=39.72，25.62，both P < 0.01 ). Linear mixed effects model analysis revealed that after adjusting for age, sex, household income monthly, parental education, family history of hypertension and maternal pregnancy complications, large for gestational age had significantly higher trajectories of systolic ( β = 1.50) and diastolic( β =0.94) blood pressure compared to appropriate for gestational age(both P <0.01). Conclusion Large for gestational age is associated with elevated blood pressure trajectories during school age, and it may be considered as an early indicator for individualized screening and intervention for childhood hypertension.

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.

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

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Aim To investigate the regulatory effects and underlying mechanisms of 4-methoxybenzyl alcohol(4-MBA),an active ingredient of Gastrodia elata,on hepatic cholesterol metabolism.Methods Acute hy-perlipidemia mouse models were established via egg yolk emulsion induction,and hyperlipidemia rat models were constructed using a high-fat diet.Serum and he-patic total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-den-sity lipoprotein cholesterol(HDL-C)levels were quan-tified via enzymatic assays.Hepatic histopathological changes were evaluated through hematoxylin-eosin(HE)and Oil Red O staining.Interactions between 4-MBA and key cholesterol metabolism targets were sim-ulated using molecular docking.mRNA and protein ex-pression levels of LDL receptor(LDLR),proprotein convertase subtilisin/kexin type 9(PCSK9),liver X receptor α(LXRα),peroxisome proliferator-activated receptor γ(PPARγ),ATP-binding cassette transporter G1(ABCG1),and cholesterol 7α-hydroxylase(CYP7A1)were assessed using quantitative polymer-ase chain reaction(qPCR)and immunohistochemis-try.Results In acute hyperlipidemic mice,4-MBA administration significantly reduced serum TG and LDL-C levels while elevating HDL-C(P＜0.05).Hy-perlipidemic rats exhibited decreased serum TG and LDL-C,increased HDL-C(P＜0.01),reduced hepatic LDL-C(P＜0.01),and elevated hepatic HDL-C(P＜0.01).Although TC levels showed a downward trend,the difference lacked statistical significance.He-patic lipid accumulation and steatosis were alleviated.Upregulated mRNA and protein expression of LDLR,PPARγ,LXRα,and ABCG1(P＜0.01),alongside downregulated PCSK9(P＜0.05),were observed.Conclusion 4-MBA modulates cholesterol metabolism primarily via the LDLR/PCSK9 pathway to enhance cholesterol uptake and the PPARγ-LXRα-CYP7A1/ABCA1 axis to promote cholesterol utilization and ef-flux.

Objective:To evaluate preoperative high-resolution thin-layer cervical enhanced CT used to predict the venous route of the submental flap reflux vein and its relationship with adjacent structures in order to guide the anatomical understanding and protection of submental flap in pharyngeal cancer surgery.Methods:Sixty consecutive patients with pharyngeal cancer who underwent submental flap repair surgery in our department from March 2022 to December 2024, as well as 60 patients who were accepted neck dissection suffering other cancers, were selected. Before surgery, high-resolution cervical enhanced CT scans were performed, and the position of the transverse section of the facial vein in the venous phase horizontal image gradually variation tendency was focused layer by layer. The direction and adjacent relationship of the submental flap reflux veins were determined and recorded. Combined with 60 patients with other head and neck tumors who underwent neck dissection in our department during the same period (a total of 120 cases, 240 sides), the classification and management of the draining veins of Fang′s mental flap were conducted. Type Ⅰ mainly drains into the internal jugular vein; Type Ⅱ mainly drains into the external jugular vein and Type Ⅲ mainly drains into the anterior jugular vein (often accompanied by an external jugular draining branch). The status and proportion of venous drainage were analyzed.Results:Vascular predictive coincidence rate was 98.3% (59/60) among the 60 patients with pharyngeal cancer. Only one patient was predicted to have a simple return to the external jugular vein. However, during the operation, in addition to the main return to the external jugular vein, a small portion also returned to the internal jugular vein. Submental flap reflux vessels were classified into three types based on intraoperative submental flap venous return in 60 cases of laryngopharyngeal cancer, in conjunction with the analysis of venous return patterns from 240 cervical CT scans. Type Ⅰ mainly refluxed to the internal jugular vein, accounting for 42.1%. Type Ⅱ mainly refluxed to the external jugular vein (47.9%). Type Ⅲ mainly refluxed to the anterior jugular vein (10.0%). The total detection rate of CT reading of 240 venous reflux was 98.7% (237/240). Vascular predictive coincidence rate was 97.9%(235/240).Conclusion:The detailed analysis of submental venous return vessels can accurately predict the direction of reflux veins and its surrounding areas by preoperative high-resolution enhanced CT scan. This provides reliable guidance for the anatomy and protection of the submental flap reflux veins during surgery.

Objective To explore the association between mid-upper arm circumference(MUAC)and sarcopenia in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods A total of 402 middle-aged and elderly patients with T2DM admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from March 2022 to October 2024 were selected.Among them,308 patients with simple diabetes mellitus were included in non-sarcopenia group,and 94 patients with combined sarcopenia were included in sarcopenia group.Multivariate Logistic regression analysis was used to determine the association between MU AC and sarcopenia in middle-aged and elderly patients with T2DM.The predictive ability of MUAC for sarcopenia in middle-aged and elderly patients with T2DM was evaluated by using the receiver operating characteristic curve.Results There were statistically significant differences in age,body mass index,MUAC,triglycerides,direct bilirubin,alanine aminotransferase,aspartate aminotransferase,appendicular skeletal muscle mass,appendicular skeletal muscle mass index,grip strength and 6-meter walking speed between two groups of patients(P＜0.05).The results of multivariate Logistic regression showed that a smaller MUAC and increased age were both risk factors for sarcopenia in middle-aged and elderly patients with T2DM(P＜0.05).The optimal cutoff value of MUAC for diagnosing sarcopenia in middle-aged and elderly patients with T2DM:27.90cm for males and 26.95cm for females.Conclusion MUAC is associated with sarcopenia in middle-aged and elderly patients with T2DM and can be used for the early identification and diagnosis of middle-aged and elderly T2DM patients with sarcopenia.

Objective To explore the molecular mechanism of Guben Zhike Pingchuan Granules in treating cough variant asthma(CVA)through network pharmacology and molecular docking technology;To use CVA model rats for validation;To provide a basis for the basic research and clinical application of Guben Zhike Pingchuan Granules.Methods TCMSP and BATMAN-TCM databases were used to retrieve the active components and corresponding targets of Guben Zhike Pingchuan Granules,and CVA disease targets were screened using OMIM,GeneCards,DrugBank,PharmGKB databases to obtain drug disease intersection targets.Cytoscape 3.10.1 software was used to construct the drug-component-target network and screen the key components;STRING database was used to construct protein-protein interaction(PPI)network and screen core targets;GO and KEGG enrichment analysis was conducted using DAVID platform;AutoDock Vina software was used to conduct molecular docking on the core targets and key components with high degree value respectively.CVA rat model was established by smoking combined with intraperitoneal and subcutaneous multi-point injection of ovalbumin.The rats were randomly divided into blank group,model group,montelukast sodium tablets group,Guben Zhike Pingchuan Granules low-and high-dosage groups.The groups received corresponding medicine for 15 d.HE staining was used to observe the morphology of lung tissue;ELISA was used to detect the contents of serum interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α);immunohistochemistry was used to detect the positive expressions of AKT,EGFR and NFKB1 in lung tissue.Results A total of 9 996 active components and 1 119 potential targets of Guben Zhike Pingchuan Granules,2 740 CVA targets,467 drug and disease intersection targets were screened out;PPI network topology analysis showed that AKT1,STAT3,EGFR,NFKB1 and MTOR were the core targets;the results of enrichment analysis showed that Guben Zhike Pingchuan Granules played an anti-inflammatory role in the treatment of CVA mainly through the interaction of EGFR/PI3K-Akt/NF-κB signaling pathway;molecular docking showed good binding ability between the core targets and key components,with a binding energy of<-7.0 kcal/mol for EGFR and Quercetin.Animal experiment results showed that after intervention with Guben Zhike Pingchuan Granules,the alveolar walls of the lung tissue in the model rats narrowed,the size of the alveoli became uniform,lymphocyte infiltration improved significantly,bronchioles contracted,and mucus in the lumen decreased;compared with the model group,the serum contents of IL-1β and TNF-α decreased in Guben Zhike Pingchuan Granules low-and high-dosage groups and montelukast sodium tablets group,and the positive expressions of AKT,EGFR and NFKB1 in lung tissue decreased(P<0.05,P<0.01).Conclusion Guben Zhike Pingchuan Granules may mediate the inflammatory response through the EGFR/PI3K-Akt/NF-κB signaling pathway,significantly improve the structural damage of CVA lung tissue,inhibit inflammatory cell infiltration,down-regulate the expressions of inflammatory factors,and thus exert therapeutic effects on CVA.