Background: s/Aims: Increasing evidence indicates that metabolites play a significant role in the pathogenesis of liver cancer and have potential as biomarkers for early detection. This review summarizes the current literature on the utility of metabolomic profiling as a screening strategy for early diagnosis of liver cancer. Methods: We searched PubMed, Embase, and Web of Science for studies published between 2004 and 2024 that examined metabolite alterations in liver cancer. The metabolites differentially expressed in liver cancer versus healthy controls, cirrhosis, and hepatic B virus cases are summarized. The diagnostic performance of the metabolite-based models was also evaluated, highlighting their potential as early detection biomarkers for liver cancer. Results: A total of 96 studies were included in this review, encompassing case-only, case-control, nested case-control, and cohort designs. The analysis identified taurine and taurochenodeoxycholic acid to be consistently associated with an increased risk of liver cancer, supported by findings from both the discovery and validation cohorts. Notably, a diagnostic model incorporating 10 metabolites including taurine and taurochenodeoxycholic acid, achieved an area under the receiver operating characteristic curve of 0.86 (95% confidence interval, 0.82-0.88), indicating strong discriminatory power for early liver cancer detection. Nevertheless, heterogeneity across studies was observed, largely owing to differences in biological sample types and metabolomic platforms. Conclusions This review highlights the significant roles of taurine and taurochenodeoxycholic acid in liver cancer development. Future research should prioritize the standardization of analytical methodologies, increased sample sizes, and integration of metabolomics with other omics layers to enhance our understanding of liver cancer biology and improve biomarker accuracy and clinical utility.

ObjectiveChronic atrophic gastritis (CAG) is usually diagnosed by gastroscopy and histopathological biopsy. These procedures remain the reference standard, but their invasive nature and resource requirements may limit their use in large-scale population screening and repeated follow-up. A convenient and reproducible method for noninvasive auxiliary screening may help identify individuals who require further endoscopic assessment. Fingertip photoplethysmography (PPG) provides a noninvasive recording of peripheral pulse waves and allows harmonic features to be extracted from the signal. In this study, the so-called meridian-related variables were defined as PPG-derived harmonic parameters labelled according to meridian nomenclature, rather than as direct measurements of meridian physiology. This study aimed to compare these harmonic parameters between patients with CAG and non-CAG controls, identify parameters that remained different after age adjustment, and develop a multivariable model for noninvasive auxiliary screening and pre-endoscopic risk stratification of CAG. MethodsA total of 343 participants were included, comprising 171 patients with CAG and 172 non-CAG controls. CAG diagnosis was established using gastroscopy and histopathology as the reference standard. Fingertip PPG signals were collected using a PPG-based pulse acquisition device. Eight PPG-derived harmonic parameters labelled according to meridian nomenclature were extracted for analysis. Between-group differences were first assessed using nonparametric tests. Age-adjusted analyses were then performed to reduce potential confounding by age. The false discovery rate (FDR) method was applied for multiple-comparison correction. A multivariable logistic regression model integrating age and multiple harmonic parameters was constructed. Model performance was evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Internal validation performance was assessed using stratified five-fold cross-validation and bootstrap optimism correction. Threshold performance was examined using both a high-specificity strategy and a Youden index-based cutoff. Decision curve analysis was used to evaluate the model’s net clinical benefit across a range of threshold probabilities. ResultsAll eight harmonic parameters were non-normally distributed. In the univariate analysis, the stomach-labelled harmonic parameter (ST), bladder-labelled harmonic parameter (BL), and liver-labelled harmonic parameter (LR) differed between the CAG and non-CAG groups. After age adjustment and FDR correction, only ST and BL remained statistically significant. Compared with non-CAG controls, patients with CAG showed higher ST values and lower BL values. This finding indicates an associated differential harmonic pattern that was not fully explained by age distribution. However, the discriminative ability of a single harmonic parameter was limited. The best-performing single indicator was ST, with an AUC of 0.652 (95% CI: 0.595-0.707). The multivariable model integrating age and multiple harmonic parameters achieved an AUC of 0.791 (95% CI: 0.743-0.835), representing an improvement of 0.139 over ST alone. In internal validation, stratified five-fold cross-validation yielded a mean AUC of 0.753 (95% CI: 0.715-0.781), and the bootstrap optimism-corrected AUC was 0.748. These results suggest that the model retained moderate discriminative performance after internal validation.At a specificity of at least 95%, the model achieved a sensitivity of only 40.4% (95% CI: 25.7%-49.7%). This high-specificity cutoff may be suboptimal as the preferred threshold for an initial screening setting because of the potential risk of missed CAG cases. The Youden index-based optimal cutoff was 0.419, corresponding to a sensitivity of 80.7% and a specificity of 62.8%. This threshold may better match the practical aim of noninvasive auxiliary screening, where sensitivity is usually prioritized to reduce missed cases. Decision curve analysis showed that, within a threshold probability range of 10%-55%, the model provided higher net clinical benefit than the reference strategies of recommending gastroscopy for all participants or for none. ConclusionPatients with CAG showed associated harmonic differences in fingertip PPG-derived features, mainly characterized by higher ST and lower BL values after age adjustment and FDR correction. Compared with a single harmonic parameter, the multivariable model showed better overall discrimination and retained moderate internal validation performance. These findings suggest that PPG-derived harmonic parameters labelled according to meridian nomenclature may provide auxiliary information for noninvasive auxiliary screening and front-line triage before gastroscopic confirmation in CAG. The present results support further validation rather than immediate clinical implementation. External validation in independent, multicenter, and preferably prospective screening cohorts is needed to assess the model’s generalizability, screening performance, and potential clinical utility.

ObjectiveChronic atrophic gastritis (CAG) is usually diagnosed by gastroscopy and histopathological biopsy. These procedures remain the reference standard, but their invasive nature and resource requirements may limit their use in large-scale population screening and repeated follow-up. A convenient and reproducible method for noninvasive auxiliary screening may help identify individuals who require further endoscopic assessment. Fingertip photoplethysmography (PPG) provides a noninvasive recording of peripheral pulse waves and allows harmonic features to be extracted from the signal. In this study, the so-called meridian-related variables were defined as PPG-derived harmonic parameters labelled according to meridian nomenclature, rather than as direct measurements of meridian physiology. This study aimed to compare these harmonic parameters between patients with CAG and non-CAG controls, identify parameters that remained different after age adjustment, and develop a multivariable model for noninvasive auxiliary screening and pre-endoscopic risk stratification of CAG. MethodsA total of 343 participants were included, comprising 171 patients with CAG and 172 non-CAG controls. CAG diagnosis was established using gastroscopy and histopathology as the reference standard. Fingertip PPG signals were collected using a PPG-based pulse acquisition device. Eight PPG-derived harmonic parameters labelled according to meridian nomenclature were extracted for analysis. Between-group differences were first assessed using nonparametric tests. Age-adjusted analyses were then performed to reduce potential confounding by age. The false discovery rate (FDR) method was applied for multiple-comparison correction. A multivariable logistic regression model integrating age and multiple harmonic parameters was constructed. Model performance was evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Internal validation performance was assessed using stratified five-fold cross-validation and bootstrap optimism correction. Threshold performance was examined using both a high-specificity strategy and a Youden index-based cutoff. Decision curve analysis was used to evaluate the model’s net clinical benefit across a range of threshold probabilities. ResultsAll eight harmonic parameters were non-normally distributed. In the univariate analysis, the stomach-labelled harmonic parameter (ST), bladder-labelled harmonic parameter (BL), and liver-labelled harmonic parameter (LR) differed between the CAG and non-CAG groups. After age adjustment and FDR correction, only ST and BL remained statistically significant. Compared with non-CAG controls, patients with CAG showed higher ST values and lower BL values. This finding indicates an associated differential harmonic pattern that was not fully explained by age distribution. However, the discriminative ability of a single harmonic parameter was limited. The best-performing single indicator was ST, with an AUC of 0.652 (95% CI: 0.595-0.707). The multivariable model integrating age and multiple harmonic parameters achieved an AUC of 0.791 (95% CI: 0.743-0.835), representing an improvement of 0.139 over ST alone. In internal validation, stratified five-fold cross-validation yielded a mean AUC of 0.753 (95% CI: 0.715-0.781), and the bootstrap optimism-corrected AUC was 0.748. These results suggest that the model retained moderate discriminative performance after internal validation.At a specificity of at least 95%, the model achieved a sensitivity of only 40.4% (95% CI: 25.7%-49.7%). This high-specificity cutoff may be suboptimal as the preferred threshold for an initial screening setting because of the potential risk of missed CAG cases. The Youden index-based optimal cutoff was 0.419, corresponding to a sensitivity of 80.7% and a specificity of 62.8%. This threshold may better match the practical aim of noninvasive auxiliary screening, where sensitivity is usually prioritized to reduce missed cases. Decision curve analysis showed that, within a threshold probability range of 10%-55%, the model provided higher net clinical benefit than the reference strategies of recommending gastroscopy for all participants or for none. ConclusionPatients with CAG showed associated harmonic differences in fingertip PPG-derived features, mainly characterized by higher ST and lower BL values after age adjustment and FDR correction. Compared with a single harmonic parameter, the multivariable model showed better overall discrimination and retained moderate internal validation performance. These findings suggest that PPG-derived harmonic parameters labelled according to meridian nomenclature may provide auxiliary information for noninvasive auxiliary screening and front-line triage before gastroscopic confirmation in CAG. The present results support further validation rather than immediate clinical implementation. External validation in independent, multicenter, and preferably prospective screening cohorts is needed to assess the model’s generalizability, screening performance, and potential clinical utility.

Dong Nai province in southern Viet Nam was among the hardest hit in a measles outbreak in 2024–2025 with over 7000 cases. Our analysis outlines major takeaways for measles control in recommending the need for strengthened surveillance, digital communication and intersectoral collaboration to address immunization gaps and build health system resilience in Viet Nam.

Objective: To evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

The circadian clock is an endogenous time-keeping system that maintains physiological homeostasis by integrating environmental and genetic interactions. Heart failure is a complex clinical syndrome characterized by structural abnormalities and/or functional impairment of the heart. Growing evidence suggests that core circadian components, such as BMAL1 and REV-ERBα, play important roles in modulating myocardial energy metabolism, inflammatory responses, and oxidative stress, contributing to myocardial structural and metabolic remodeling during heart failure progression. Notably, circadian disruption is closely associated with heart failure, with aberrant blood pressure rhythms and disturbances in the sleep-wake cycle in patients. The time-dependent efficacy of heart failure medications further supports the potential of chronotherapy-based strategies to improve clinical outcomes. Here, we summarize the multifaceted regulatory roles of the circadian clock, particularly core clock genes, in heart failure pathogenesis, providing a theoretical framework for developing personalized chronotherapeutic strategies for heart failure management.
Humans ; Heart Failure/physiopathology* ; Circadian Rhythm/physiology* ; Circadian Clocks/physiology* ; ARNTL Transcription Factors/physiology* ; Nuclear Receptor Subfamily 1, Group D, Member 1/physiology* ; Oxidative Stress ; Energy Metabolism ; Animals

BACKGROUND: Spinal cord injury (SCI) survivors often experience constipation, which contributes to a reduced sense of well-being and a lower quality of life. Acupressure offers a non-pharmacological and non-invasive alternative therapy for treating constipation. OBJECTIVE: This study examined the effects of home-based acupressure on constipation and subjective well-being among SCI survivors. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This randomized controlled trial randomly assigned 80 adults from Hong Kong with SCI to two study groups. Using a video demonstration filmed by a registered traditional Chinese medicine practitioner, the intervention group performed home-based acupressure (self-administered or caregiver-assisted) twice daily, 15 min/session, for 10 consecutive days. The control group performed manual light touching of the abdomen with the same frequency and duration as the intervention group. Both groups received defecation education through a structured booklet. MAIN OUTCOMES MEASURES: The primary outcome was constipation severity. Secondary outcomes included bowel habits, psychological well-being, and quality of life. Focus group interviews were conducted after the intervention to collect subjective feedback from participants. RESULTS: Significant group-by-time interaction effects on constipation severity (P = 0.005) and quality of life (P = 0.001) revealed that home-based acupressure produced better results than the control. These treatment effects persisted at the one-month follow-up and continued to have a large effect size (Cohen's d > 0.8). Compared to the control group, the acupressure group also had improvements in anxiety (Cohen's d = 0.69) and depression (Cohen's d = 0.72) at the end of the intervention period. Three qualitative categories were identified from the focus group interviews: improvements in bowel function and management; reduced psychological distress following relief from constipation; and acceptability of home-based acupressure. CONCLUSION: Acupressure effectively relieves constipation, enhances psychological well-being, and improves quality of life in people with SCI. These data provide novel evidence supporting the use of home-based acupressure as an acceptable and effective therapy for treating constipation after SCI. TRIAL REGISTRATION ClinicalTrials.gov (NCT05558657). Please cite this article as: Li MQ, Li Y, Lam W, Yeung WF, Ho YS, Li JY, Sun TC, Yuen S, Hu YL, Yorke J. Home-based acupressure for managing constipation and subjective well-being in spinal cord injury survivors: A randomized controlled trial. J Integr Med. 2025; 23(6):660-669.
Humans ; Acupressure/methods* ; Constipation/psychology* ; Male ; Female ; Spinal Cord Injuries/complications* ; Middle Aged ; Adult ; Quality of Life ; Aged

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To investigate the epidemiological characteristics of Mycoplasma pneumoniae(MP)infection among pediatric inpatients with respiratory tract infections(RTIs)at Children's Hospital of Hebei Province,providing evidence for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024.Nasopharyngeal aspirates or deep sputum samples were collected,and polymerase chain reaction(PCR)was used to detect nucleic acids of 13 respiratory pathogens,including MP and adenovirus.The epidemiological trends across different years,seasons,genders,and age groups were analyzed.Results Among the 79 546 enrolled cases(male:47 437,59.6%;female:32 109,40.4%),the MP-positive rate was 17.7%(14 106/79 546),peaking in 2023(28.8%)and reaching the lowest in 2021(7.0%).Except for the period from July 2020 to March 2021 with exceptionally low MP positivity,epidemic peaks consistently occurred between August and February or March of the following year.Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring(P<0.001).Female children exhibited a higher MP-positive rate(20.1%,6444/32 109)than males(16.2%,7662/47 437)(P<0.001).The MP-positive rate increased with age:infancy(3.2%,849/26 741),toddlerhood(9.3%,1935/20 763),preschool(21.2%,3918/18 448),and school-age(54.5%,7404/13 594)(P<0.001).Co-infections with other respiratory pathogens were observed in 37.3%(5264/14 106)of MP-positive cases,with human rhinovirus(HRV)being the most frequent co-pathogen(43.3%,2279/5264 of mixed infections).Conclusion MP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province.Infections occur year-round but predominantly in autumn,with higher susceptibility in females and school-age children.Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.