ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

ObjectiveTo investigate the mechanism of Zuogui Wan （ZGW） in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells （OSCs） for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group， a model group， a low-dose ZGW group （2.7 g·kg^-1）， a high-dose ZGW group （5.4 g·kg^-1）， and an estradiol valerate group （0.15 mg·kg^-1）， with 8 mice in each group. Except the blank group， all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg^-1 to establish an ovarian aging mouse model. After successful modeling， each group was continuously administered for 4 weeks， once daily. The physiological status of the mice was observed， and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin （HE） staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and mouse interleukin-6 （IL-6） levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS， STING， p-STING， TANK-binding kinase 1 （TBK1）， p-TBK1， interferon-induced transmembrane protein 3 （Fragilis）， and Vasa homolog protein （MVH）. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues， and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 （Oct4） were calculated. ResultsCompared with the blank group， the model group showed reduced body weight， ovarian wet weight， and ovarian index （P<0.01） and a disordered estrus cycle （P<0.01）. In addition， the levels of serum follicle-stimulating hormone （FSH）， TNF-α， IL-6， and IL-1β were increased （P<0.01）， while anti-Müllerian hormone （AMH） and estradiol （E₂） levels were decreased （P<0.01）. The protein expression of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue was increased （P<0.05， P<0.01）， while that of OSCs stemness factors MVH and Fragilis was reduced （P<0.01）. Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs （P<0.01）. The mRNA expression of inflammatory factors TNF-α， IL-6， and IL-1β in ovarian tissue was increased （P<0.05， P<0.01）. Compared with the model group， the treatment groups exhibited improved body weight， ovarian wet weight， and ovarian index （P<0.05） and a reduced rate of estrus cycle disorder （P<0.05， P<0.01）. The levels of serum FSH， TNF-α， IL-6， and IL-1β were decreased （P<0.05， P<0.01）， while AMH and E₂ levels were increased （P<0.01）. The protein expression levels of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue were decreased （P<0.05）， while the protein expression of MVH and Fragilis was increased （P<0.05）， and the fluorescence intensities of MVH and Oct4 were increased （P<0.05， P<0.01）. The mRNA expression of inflammatory factors in ovarian tissue was decreased （P<0.05）. ConclusionZGW alleviate ovarian inflammatory response， regulate ovarian microenvironment homeostasis， and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway， thereby improving ovarian function and delaying ovarian aging.

Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.

ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Objective:TTo evaluate the therapeutic effect of meridian acupuncture combined with electromyographic biofeedback therapy on spastic cerebral palsy.Methods:A randomized controlled trial study was conducted. Totally 128 children with spastic cerebral palsy in our hospital from September 2022 to September 2024 were divided into two groups using a random number table method, with 64 cases in each group. The control group received routine rehabilitation training and electromyographic biofeedback therapy, while the observation group received combined meridian acupoint therapy on the basis of the control group. Both groups received 3 weeks of treatment, making a total of 3 treatment courses. The Gross Motor Function Test (GMFM) was used to evaluate the motor function of children; the Developmental Behavior Assessment (DBA) was used to assess the psychological and behavioral development status of children aged 0-6, the Fine Motor Function Assessment (FMFM) was used to assess the fine motor skills of children; the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive level of children; the Modified Ashworth Rating Scale (MAS) was used to assess the muscle strength level of children; the clinical efficacy was evaluated.Results:The total effective rate of the observation group was 92.19% (59/64), while that of the control group was 76.56% (49/64), with statistical significance ( χ2=5.93, P=0.015). The observation group had higher scores for lying down and turning over, sitting, crawling and kneeling, standing, walking, running, and jumping after treatment compared to the control group ( t-values of 2.82, 5.83, 4.97, 4.23, 4.41, respectively, P<0.01); the scores for gross motor skills, fine motor skills, adaptability, language, and social behavior were higher than thoes in the control group ( t values of 3.34, 3.73, 5.33, 3.75, 5.47, respectively, P<0.01); the FMFM and MoCA scores were higher than those in the control group ( t values of 5.23 and 4.41, respectively, P<0.01); the MAS grading level was lower than that of the control group ( t=8.46, P<0.01). Conclusion:The combination of meridian acupuncture and electromyographic biofeedback can improve the motor function, psychological and behavioral development, fine motor skills, cognitive development, and clinical efficacy of children with spastic cerebral palsy.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Recent advances in large models demonstrate significant prospects for transforming the field of medical imaging. These models, including large language models, large visual models, and multimodal large models, offer unprecedented capabilities in processing and interpreting complex medical data across various imaging modalities. By leveraging self-supervised pretraining on vast unlabeled datasets, cross-modal representation learning, and domain-specific medical knowledge adaptation through fine-tuning, large models can achieve higher diagnostic accuracy and more efficient workflows for key clinical tasks. This review summarizes the concepts, methods, and progress of large models in medical imaging, highlighting their potential in precision medicine. The article first outlines the integration of multimodal data under large model technologies, approaches for training large models with medical datasets, and the need for robust evaluation metrics. It then explores how large models can revolutionize applications in critical tasks such as image segmentation, disease diagnosis, personalized treatment strategies, and real-time interactive systems, thus pushing the boundaries of traditional imaging analysis. Despite their potential, the practical implementation of large models in medical imaging faces notable challenges, including the scarcity of high-quality medical data, the need for optimized perception of imaging phenotypes, safety considerations, and seamless integration with existing clinical workflows and equipment. As research progresses, the development of more efficient, interpretable, and generalizable models will be critical to ensuring their reliable deployment across diverse clinical environments. This review aims to provide insights into the current state of the field and provide directions for future research to facilitate the broader adoption of large models in clinical practice.
Humans ; Diagnostic Imaging/methods* ; Precision Medicine/methods* ; Image Processing, Computer-Assisted/methods*

Objective: To investigate the epidemiological characteristics and spatial-temporal clustering of scarlet fever in Wenzhou City, Zhejiang Province from 2015 to 2024, so as to provide a basis for prevention and control for scarlet fever. Methods: The data of scarlet fever cases in Wenzhou City from 2015 to 2024 were collected from the Surveillance System of China Information System for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the temporal, demographic, and regional distribution characteristics of scarlet fever. Spatial autocorrelation and spatio-temporal scanning analyses were employed to examine the spatial-temporal clustering of scarlet fever. Results: A total of 1 731 cases of scarlet fever were reported in Wenzhou City from 2015 to 2024, with an average annual reported incidence of 2.08/100 000 , showing a declining trend (AAPC=-11.037%, P<0.05). Incidence peaks occurred from April to June and from November to January of the following year, with seasonal indices all exceeding 100%. The average annual reported incidence was higher in males than in females (2.43/100 000 vs. 1.70/100 000, P<0.05). The cases were mainly children aged ≤10 years, with 1 662 cases accounting for 96.01%. Lucheng District, Ouhai District and Taishun County had the top three average annual reported incidences of scarlet fever, at 7.17/100 000, 5.18/100 000 and 4.73/100 000, respectively. Spatial autocorrelation analysis showed that, spatial clustering of scarlet fever cases in the periods 2015 to 2019 and 2021 to 2024 (Moran's I>0, all P<0.05). Spatio-temporal scanning analysis identified a primary-type clustering and a secondary-type clustering of scarlet fever in Wenzhou City from 2015 to 2024. The primary-type clustering was centered on Wutian Subdistrict in Ouhai District, covering 19 townships / subdistricts, with a clustering period from January 2015 to December 2019. The secondary-type clustering was centered on Xiaocun Town in Taishun County, covering 42 townships / subdistricts, with a clustering period from April 2018 to June 2019. Conclusions The incidence of scarlet fever in Wenzhou City from 2015 to 2024 showed an overall declining trend, with a high incidence among school-aged children and distinct spatial-temporal clustering. Peaks in cases occurred from April to June and from November to January of the following year. Focused prevention and control efforts are recommended in Lucheng District, Ouhai District, and Taishun County.

Objective:To investigate the value of the five-sectional screening method of the central nervous system（CNS）in early detection of fetal CNS abnormalities during the first trimester.Methods:The data of pregnant women who underwent nuchal translucency（NT）screening at the Affiliated Suzhou Hospital of Nanjing Medical University from September 2018 to September 2023 were retrospectively analyzed. And a five-sectional screening method of CNS was performed in all fetuses at the meantime. The five-sectional screening protocol in the first trimester consists of the mid-sagittal plane of the fetal head，trans-ventricular plane，trans-thalamus plane，axial plane of the fetal head at the posterior fossa level，and the sagittal plane of the fetal spine. All fetuses underwent ultrasound screening during the second trimester and the third trimester sequentially after NT screening. All the ultrasound findings were tracked，and all fetuses were followed up until delivery or after induction. Fetuses with CNS abnormalities found or suspected in the first trimester were reviewed by at least one senior physician，and follow-up examinations were routinely performed after 2 weeks to further confirm the diagnosis or find other abnormalities that may be present.Results:A total of 13 679 fetuses were screened，included 11 415 singleton pregnancies and 1 132 twin pregnancies. Among them，there were 289 cases of missed follow-up and unexplained fetal death，included 263 singleton pregnancies and 13 twin pregnancies. A total of 13 390 fetuses were finally included，among which，35 cases developed CNS abnormalities with 34 cases detected by prenatal ultrasound and 1 case of closed spina bifida missed in prenatal diagnosis，and the detection rate of CNS malformation by prenatal ultrasound was 97.14%（34/35）. Of the 35 fetuses with CNS abnormalities，24 were detected by the CNS five-sectional screening method in the first trimester，with a sensitivity of 68.57%，a specificity of 100%，a positive predictive value of 100%，and a negative predictive value of 99.92%. Among them，there were 2 cases of anencephaly，3 cases of exencephaly and 6 cases of encephalocele were all detected in the first trimester. In addition，6 cases of holoprosencephaly，3 cases of severe ventriculomegaly，2 cases of open spina bifida，and 2 cases of Dandy-Walker malformation were detected in the first trimester. In this study，1 case of agenesis of corpus callosum（ACC），1 case of arachnoid cyst，1 case of lissencephaly，1 case of schizencephaly，and 1 case of mega cisterna magna were not detected in early pregnancy.Conclusions:The fetal five-sectional screening method of CNS in the first trimester has high specificity，positive predictive value and negative predictive value for the detection of fetal CNS abnormalities，but the sensitivity is moderate. The five-sectional screening method for CNS in early pregnancy may be an effective method for early detection of fetal CNS abnormalities.