Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

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.

Objective:To analyze the epidemiological characteristics, spatial clustering, and correlation between dental fluorosis detection rates and meteorological factors in children aged 8 - 12 years old in 37 counties (cities, districts, hereinafter referred to as counties) affected by coal-burning-borne endemic fluorosis in Guizhou Province, and to provide a scientific basis for prevention and control of the disease.Methods:Monitoring data on dental fluorosis in children aged 8 - 12 years old from 2019 to 2022 were collected from the National Health Security Information System for Endemic Diseases. Meteorological data, including annual average temperature, annual average precipitation, annual sunshine hours, and annual average relative humidity, were obtained from the Guizhou Provincial Bureau of Statistics. Descriptive epidemiology, analytical epidemiology, and spatial correlation analysis methods were used to analyze the data. Visual maps were created based on the clustering levels of annual dental fluorosis detection rates (high-high, low-low, high-low, low-high). Spatial autocorrelation and meteorological factors were used to analyze the epidemiological characteristics, spatial clustering, and the impact of meteorological factors on dental fluorosis.Results:From 2019 to 2022, a total of 3 649 161 children aged 8 - 12 in the counties affected by coal-burning-borne endemic fluorosis were monitored, and 115 793 children were diagnosed with dental fluorosis, with a detection rate of 3.17%. The detection rates were 4.73% (45 093/954 338) in 2019, 3.35% (31 424/938 445) in 2020, 2.86% (21 727/760 195) in 2021, and 1.76% (17 549/996 183) in 2022, respectively. The dental fluorosis indices were 0.09, 0.07, 0.06, and 0.03, respectively. The number of counties with detection rates > 6% was 7, 5, 5, and 0 in 2019 - 2022, respectively. Dafang County consistently had the highest detection rates, with rates of 10.06% (6 783/67 408), 10.07% (1 955/19 421), 13.54% (4 017/29 667), and 4.83% (3 284/76 206) in 2019 - 2022, respectively. The Moran's I indices for dental fluorosis detection rates were 0.45, 0.53, 0.53, and 0.53 in 2019 - 2022, with Z = 4.29, 5.07, 5.31, and 5.10, respectively ( P < 0.05), indicating global spatial autocorrelation (positive) and spatial clustering of dental fluorosis detection rates. The number of counties with "high-high" clustering of detection rates was 7, 7, 6, and 7 in 2019 - 2022, mainly concentrated in the northwestern region, including Qixingguan District, Nayong County, Dafang County, Zhijin County, and Jinsha County of Bijie City. "Low-high" clustering areas were distributed in Zhongshan District of Liupanshui City in 2019, 2020, and 2022. The detection rate of dental fluorosis was associated with local annual average temperature (°C) and annual precipitation (mm) ( r = - 0.393, - 0.337, P = 0.016, 0.041). Conclusions:From 2019 to 2022, the detection rate of dental fluorosis in children aged 8 - 12 in coal-burning-borne endemic fluorosis areas in Guizhou Province has been decreasing year by year, and it shows spatial clustering. The high clustering area is in the northwest of Guizhou Province, which should be regarded as a key prevention and control area for coal-burning-borne fluorosis in the future. At the same time, areas with lower temperatures and precipitation should also strengthen prevention and control efforts.

Objective:To analyze the epidemiological characteristics, spatial clustering, and correlation between dental fluorosis detection rates and meteorological factors in children aged 8 - 12 years old in 37 counties (cities, districts, hereinafter referred to as counties) affected by coal-burning-borne endemic fluorosis in Guizhou Province, and to provide a scientific basis for prevention and control of the disease.Methods:Monitoring data on dental fluorosis in children aged 8 - 12 years old from 2019 to 2022 were collected from the National Health Security Information System for Endemic Diseases. Meteorological data, including annual average temperature, annual average precipitation, annual sunshine hours, and annual average relative humidity, were obtained from the Guizhou Provincial Bureau of Statistics. Descriptive epidemiology, analytical epidemiology, and spatial correlation analysis methods were used to analyze the data. Visual maps were created based on the clustering levels of annual dental fluorosis detection rates (high-high, low-low, high-low, low-high). Spatial autocorrelation and meteorological factors were used to analyze the epidemiological characteristics, spatial clustering, and the impact of meteorological factors on dental fluorosis.Results:From 2019 to 2022, a total of 3 649 161 children aged 8 - 12 in the counties affected by coal-burning-borne endemic fluorosis were monitored, and 115 793 children were diagnosed with dental fluorosis, with a detection rate of 3.17%. The detection rates were 4.73% (45 093/954 338) in 2019, 3.35% (31 424/938 445) in 2020, 2.86% (21 727/760 195) in 2021, and 1.76% (17 549/996 183) in 2022, respectively. The dental fluorosis indices were 0.09, 0.07, 0.06, and 0.03, respectively. The number of counties with detection rates > 6% was 7, 5, 5, and 0 in 2019 - 2022, respectively. Dafang County consistently had the highest detection rates, with rates of 10.06% (6 783/67 408), 10.07% (1 955/19 421), 13.54% (4 017/29 667), and 4.83% (3 284/76 206) in 2019 - 2022, respectively. The Moran's I indices for dental fluorosis detection rates were 0.45, 0.53, 0.53, and 0.53 in 2019 - 2022, with Z = 4.29, 5.07, 5.31, and 5.10, respectively ( P < 0.05), indicating global spatial autocorrelation (positive) and spatial clustering of dental fluorosis detection rates. The number of counties with "high-high" clustering of detection rates was 7, 7, 6, and 7 in 2019 - 2022, mainly concentrated in the northwestern region, including Qixingguan District, Nayong County, Dafang County, Zhijin County, and Jinsha County of Bijie City. "Low-high" clustering areas were distributed in Zhongshan District of Liupanshui City in 2019, 2020, and 2022. The detection rate of dental fluorosis was associated with local annual average temperature (°C) and annual precipitation (mm) ( r = - 0.393, - 0.337, P = 0.016, 0.041). Conclusions:From 2019 to 2022, the detection rate of dental fluorosis in children aged 8 - 12 in coal-burning-borne endemic fluorosis areas in Guizhou Province has been decreasing year by year, and it shows spatial clustering. The high clustering area is in the northwest of Guizhou Province, which should be regarded as a key prevention and control area for coal-burning-borne fluorosis in the future. At the same time, areas with lower temperatures and precipitation should also strengthen prevention and control efforts.

Objective To investigate the association between triglyceride-glucose(TyG)index and the prevalence of gallstones in women,and to assess whether it can be used as a convenient indicator for the epidemiological survey of gallstones in women.Methods A total of 22 979 adult women who underwent physical examination in Subei People's Hospital of Jiangsu from January 2021 to June 2023 were enrolled,and according to the results of abdominal color Doppler ultrasound,they were divided into gallstone group with 1 763 women and non-gallstone group with 21 216 women.The independent samples t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.The multivariate logistic regression analysis,the restricted cubic spline analysis,the subgroup analysis,and mediating effect were used to investigate the association between TyG index and the risk of gallstones in women.Results The overall prevalence rate of gallstones was 7.7％in women.Compared with the non-gallstone group,the gallstone group had significantly higher age,BMI,FPG,TG,TyG index,TC,Hb,BUN,UA,SCr,TC,and LDL-C(all P<0.05),and the women with diabetes,fatty liver,hypertension,and hyperuricemia were more likely to have gallstones(all P<0.05).The multivariate logistic regression analysis showed that based on the quartiles of TyG index,the risk of gallstones in the Q3(8.97-9.38)group was 1.38(95％confidence interval[CI]:1.15-1.62,P<0.001)times that in the Q1(<8.63)group,and the risk of gallstones in the Q4(≥9.38)group was 1.39(95％CI:1.16-1.68,P<0.001)times that in the Q1 group.After adjustment for all covariates,TyG index,as a continuous variable,showed an independent positive correlation with the risk of gallstones(odds ratio[OR]=1.24,95％CI:1.11-1.39,P=0.004).The restricted cubic spline curve revealed a significant nonlinear association between TyG index and the risk of gallstones(P for non linear=0.008),and the threshold analysis showed statistical significance in the effect of TyG index below the inflection point of 8.95(OR=1.34,95％CI:1.15-1.97,P=0.042).The subgroup analysis showed that TyG index was significantly positively correlated with gallstones in women with a BMI of<25 kg/m2,an age of<50 years,an age of≥50 years,the absence of diabetes or fatty liver,total cholesterol<5.72 mmol/L,total bilirubin<21 μmol/L,a hemoglobin level of 110-150 g/L,and blood urea nitrogen<7.5 μmol/L(all P<0.05).A mediating analysis was performed for the subgroups with a statistically significant P value for interaction,and the results showed that BMI accounted for 23.0％of the mediating effect in the influence of TyG index on gallstones,and fatty liver and diabetes accounted for 15.7％and 21.0％,respectively.Conclusion In women,a higher TyG index indicates a higher risk of gallstones.Lowering TyG index may reduce the risk of gallstones by improving insulin sensitivity.

Objective To investigate the effect of exogenous luteinizing hormone (LH) on vitrification granulosa cells and its mecha-nisms. Methods The granulosa cells of 4-week-old preadolescent mice were selected and divided into the fresh group (without vitrification procedure),the vitrification group (treated according to vitrification procedure) and the LH group (treated with 0.3 IU/L of LH intervention on the basis of the vitrification group). Granulocyte count was performed,and Realtime PCR and Western blot were used to detect the expression changes of Foxl2,PI3K,AKT and mTOR mRNAs and proteins in each group. Results Compared with the vitrification group,the total number of granulosa cells in the LH group was significantly increased (P<0.05),and the expression of Foxl2,PI3K,AKT and mTOR mRNAs and proteins were elevated (P<0.05). Conclusion The intevention of exogenous LH is beneficial for the survival of vitrifi-cation granulosa cells,and the mechanism may be related to the activation of PI3K/AKT/mTOR pathway.

Nutritional support therapy is one of the extremely important treatment methods for patients in the intensive care unit. Timely and effective nutritional support regimens can improve patients' immune function, reduce complications, and optimize clinical outcomes. Energy expenditure is influenced by multiple factors, including patients' baseline characteristics (such as physical condition, gender, age) and dynamic changes in indicators (such as body temperature, nutritional support regimens, and therapeutic interventions). The currently recognized "gold standard" for accurately assessing energy metabolism in clinical practice is the indirect calorimetry system, also known as the metabolic cart. This device monitors carbon dioxide production and oxygen consumption in real time and uses specific algorithms to estimate the metabolic proportions of the three major nutrients (carbohydrates, fats, and proteins) in energy expenditure. An appropriate nutrient ratio helps maintain the balance between supply and demand in the body's nutritional metabolism. In the management of critically ill patients, the application of the metabolic cart enables personalized nutritional therapy, avoiding over- or under-supply of energy and optimizing the use of medical resources. Furthermore, with real-time, quantitative data support from the energy metabolism monitoring system, clinicians can develop more precise nutritional intervention strategies, thereby improving patient prognosis. This article provides a systematic review of the technical features of the metabolic cart and its application value in various critical care scenarios, aiming to offer a reference for indirect calorimetry in clinical practice.
Humans ; Critical Illness/therapy* ; Nutritional Support ; Energy Metabolism ; Calorimetry, Indirect