Objective: To understand the current status and associated factors of sleep problems among preschool children in Hainan Province, so as to provide scientific evidence for improving sleep health in this population. Methods: From January 2021 to June 2022, a total of 4 105 preschool children aged 3-6 years from 62 kindergartens in Hainan Province were selected using stratified cluster random sampling method. Demographic information and lifestyle habits were collected through the Hainan Province Child Growth and Development Survey Questionnaire. The Children s Sleep Habits Questionnaire (CSHQ) was employed to assess sleep status. Unconditional binary Logistic regression model was applied to investigate the associated factors of sleep problems among preschool children. Results: The overall CSHQ score for children was 58.03±18.84, with 80.95% of preschool children exhibiting sleep related issues. The top three most prevalent sleep problem domains were bedtime resistance (72.42%), sleep anxiety ( 54.88 %), and parasomnias (38.86%). Logistic regression analysis revealed that higher family annual income ( OR=0.60, 95%CI = 0.45-0.79), higher maternal education level ( OR=0.53, 95%CI =0.32-0.89), regular or daily vitamin D supplementation ( OR=0.77, 95%CI =0.60-0.99), and fully self initiated eating behavior ( OR=0.71, 95%CI =0.59-0.85) were negatively related with children s sleep problems; in addition, screen exposure ( OR=1.27, 95%CI =1.06-1.51) and picky eating ( OR= 1.47 , 95%CI =1.21-1.78) were positively related to children s sleep problems (all P <0.05). Conclusion The high detection rate of sleep problems among preschool children in Hainan Province is multifactorially associated with family environment, dietary habits, and lifestyle behaviors.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Despite therapeutic advancements over recent decades, the prognosis for patients with metastatic CRC (mCRC) remains poor. Approximately 2%-4% of mCRC cases exhibit human epidermal growth factor receptor 2 (HER2) amplification or overexpression, defining a distinct molecular subtype. This HER2-positive status is strongly associated with primary resistance to anti-epidermal growth factor receptor (EGFR) therapies, which are the standard of care for patients with RAS wild-type tumors. Beyond its well-established role in breast and gastric cancers, HER2 has emerged as a pivotal biomarker and actionable therapeutic target in mCRC. However, selecting appropriate treatment strategies remains challenging due to patient heterogeneity and diverse molecular subtypes. This review systematically summarizes the molecular biology, diagnostic strategies, and advances in targeted therapies for HER2-positive mCRC. On the diagnostic front, we discuss the applications of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.

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.

Objective To analyze the epidemiological characteristics of poisonous mushroom-related foodborne disease incidents in Chongqing from 2010 to 2024, and to provide a scientific basis for effective prevention and control of mushroom-related foodborne diseases. Methods Data of poisonous mushroom related foodborne disease incidents reported by the CDCs of 39 districts and counties in Chongqing from 2010 to 2024 were collected, and their epidemic characteristics were analyzed. Results A total of 264 poisonous mushroom poisoning outbreaks were reported in Chongqing from 2010 to 2024, resulting in 1 046 cases of illness, 543 hospitalizations, and 15 deaths, with a mortality rate of 1.43%. The peak of poisoning incidents was from June to October, accounting for 89.02% of the total number of incidents. The top three high-incidence areas were Pengshui Miao Tujia Autonomous County, Dianjiang County, and Nanchuan District. Poisonous mushroom poisoning incidents occurring in household settings, accidental picking and ingestion, and cases involving unidentified mushroom species accounted for 89.02%, 83.33%, and 90.15% of all foodborne disease outbreak incidents, respectively. Conclusion Foodborne disease incidents related to poisonous mushrooms in Chongqing City show an upward trend, and the effectiveness of prevention and control needs to be improved. Based on their seasonal, regional and household clustering characteristics, efforts should be made before the peak season of mushroom poisoning in high-risk areas, targeting key populations with health education, monitoring and early warning, food safety supervision, and medical treatment.

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Alcoholic liver disease(ALD), a major cause of chronic liver disease worldwide, poses a serious threat to human health. Despite the availability of various drugs for treating ALD, their efficacy is often uncertain, necessitating the search for new therapeutic approaches. Traditional Chinese medicine polysaccharides have garnered increasing attention in recent years due to their versatility, high efficiency, and low side effects, and they have demonstrated significant potential in preventing and treating ALD. Emerging studies have suggested that these polysaccharides exert their therapeutic effects through multiple mechanisms, including the inhibition of oxidative stress and the regulation of lipid metabolism, gut microbiota, and programmed cell death. This review summarizes the recent research progress in the pharmacological effects and regulatory mechanisms of traditional Chinese medicine polysaccharides in treating ALD, aiming to provide a scientific basis and theoretical support for their application in the prevention and treatment of ALD.
Humans ; Liver Diseases, Alcoholic/metabolism* ; Polysaccharides/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Oxidative Stress/drug effects* ; Medicine, Chinese Traditional ; Gastrointestinal Microbiome/drug effects* ; Lipid Metabolism/drug effects*