ObjectiveTo investigate the therapeutic effects and mechanisms of modified Huangqi Jianzhong decoction （HQJZ） on gastric precancerous conditions （GPC）. MethodsIn the cell experiment， human gastric mucosal epithelial cells underwent malignant transformation induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPC （MC cells）. The cells were allocated into four groups： control ， model， low-dose HQJZ （HQJZ-L）， and high-dose HQJZ （HQJZ-H）. The control and model groups were cultured with the complete medium， while HQJZ-L and HQJZ-H groups received additional interventions with HQJZ at low （0.5 g·L^-1） and high （1.0 g·L^-1） doses， respectively. Cell counting kit-8 （CCK-8） assay was used to evaluate cytotoxicity， Transwell assay to assess cell invasion， Annexin V-FITC/PI staining to detect apoptosis， immunofluorescence assay to analyze reactive oxygen species （ROS） expression and mitochondrial autophagy， and Western blot to verify expression of proteins in key pathways. In the animal experiment， the GPC model was established in healthy BALB/c mice through MNNG induction. Twenty-four mice were allocated into four groups： control， model， HQJZ-L， and HQJZ-H. Control and model groups received normal saline （10 mL·kg^-1·d^-1） orally， while HQJZ-L and HQJZ-H groups were administrated with low-dose （6.24 g·kg^-1·d^-1） and high-dose （12.48 g·kg^-1·d^-1） HQJZ， respectively. After treatment， hematoxylin‑eosin （HE） staining and AB-PAS staining were performed to observe histopathological changes in the gastric tissue. Immunofluorescence assay was used to detect reactive oxygen species （ROS） and microtubule-associated protein 1 light chain 3 （LC3） levels in the gastric mucosa， TdT-mediated dUTP nick-end labeling （TUNEL） staining to assess apoptosis rates， and Western blotting and immunohistochemistry （IHC） to analyze the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， and foxhead box O3 （FoxO3）. ResultsCell viability assays showed that HQJZ dose-dependently reduced MC cell viability compared with the control group （P<0.05， P<0.01）. Transwell assays revealed that the model group exhibited enhanced cell invasion compared with the control group （P<0.05）. Compared with the model group， HQJZ treatment attenuated the cell invasion （P<0.05）. Gastric mucosal pathology in mice demonstrated that compared with the control group， the model group showed elevated HE and AB-PAS pathological scores （P<0.05）， while HQJZ treatment reduced these scores （P<0.05）. Transmission electron microscopy revealed increased mitochondrial number and volume in the model group compared with the control group. HQJZ treatment resulted in abnormal mitochondrial structure and significant alterations in rough endoplasmic reticulum morphology and distribution， presenting as dilated and hollow forms. Mitochondrial and apoptosis assessments indicated that compared with the control group， the model group exhibited enhanced Mito Tracker Green fluorescence （P<0.05）， no significant change in DCFH-DA fluorescence， Mito Tracker Red CMXRos fluorescence， ROS immunofluorescence， or malondialdehyde （MDA） level， increased GSH level （P<0.05）， enhanced LC3 fluorescence （P<0.05）， no significant change in apoptosis rate， and elevated ATP content in cells and mouse serum （P<0.05）. Compared with the model group， HQJZ treatment reduced Mito Tracker Green fluorescence （P<0.05）， increased DCFH-DA fluorescence， Mito Tracker Red fluorescence， MDA level， LC3 fluorescence， and apoptosis rate （P<0.05）， and decreased cellular ATP content （P<0.05）. The HQJZ-L group showed no significant change in ROS immunofluorescence or GSH level， whereas the HQJZ-H group demonstrated enhanced ROS immunofluorescence and glutathione （GSH） level （P<0.05）. Immunohistochemistry and Western blotting revealed that compared with the control group， the model group exhibited increased numbers of PCNA- and Ki67-positive cells （P<0.05） and elevated protein levels of FoxO3， sirtuin 1 （SIRT1）， and B-cell lymphoma 6 （Bcl-6） （P<0.05）. HQJZ treatment reduced the numbers of PCNA- and Ki67-positive cells （P<0.05） and lowered the protein levels of FoxO3， SIRT1， and Bcl-6 （P<0.05）. ConclusionHQJZ alleviates the progression of gastric precancerous lesions by regulating mitochondrial function via the FoxO3/ROS pathway and promoting apoptosis of GPC-malignant cells.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective: To explore the influencing factors of incident caries at age 5 among caries-free 3-year-old children in Beijing, construct a machine learning prediction model based on oral health behavioral data, and provide a scientific basis and practical tool for early risk identification, stratified prevention and control, and home-kindergarten-medical collaborative intervention of incident dental caries in preschool children. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and written informed consent was obtained from the guardians of the study participants and their guardians. Children with complete baseline data at age 3 and follow-up data at age 5 from Beijing public oral health programs were included. Oral examinations were conducted according to World Health Organization diagnostic criteria, and questionnaires were completed by guardians. Risk factors were screened by Logistic regression. The total sample was randomly divided into a test set (20%) and a validation set (80%). Five-fold cross-validation was performed on the validation set for model training and tuning, and the final model performance was evaluated on the test set. Four machine learning models—decision tree, random forest, Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM)—were constructed. Model performance was evaluated using the area under the curve (AUC), accuracy, and specificity. Shapley Additive Explanations (SHAP) was used for model interpretation. Results: The incidence of incident caries for 3 372 5-year-old children in Beijing was 50.96%. Multivariate logistic regression showed that parental caries, sleeping with milk, frequent feeding at night, no postprandial cleaning, high sugar intake, insufficient bedtime tooth brushing, and non-fluoride toothpaste use were significant risk factors (P < 0.05). Although all four machine learning models performed well, the XGBoost model performed the best (AUC = 0.806). Feature importance and SHAP analysis indicated that the frequency of bedtime tooth brushing, the frequency of candy consumption, and parental caries status were the top three predictors. Conclusion The XGBoost model based on oral health behaviors at age 3 can accurately predict the risk of incident caries in 5-year-old children in Beijing. Bedtime tooth brushing, sugar control, and parental oral health management are key points for caries prevention in preschool children.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Abstract The World Health Organization (WHO) emphasizes that tuberculosis preventive treatment is a key measure for ending the tuberculosis epidemic. In 2023, Huzhou City initiated the construction of Zero Tuberculosis City based on the pilot program of Zero Tuberculosis Communities in Zhejiang Province, and established a three-level tuberculosis preventive treatment system for latent tuberculosis infection (LTBI) at the municipal, county (district), and township (subdistrict) levels. Strategies including formulating standards and norms, promoting preventive treatment clinics at all levels, improving staffing and clarifying work responsibilities were implemented to strengthen active intervention and management of LTBI and improve the standardization of preventive treatment. From 2023 to 2024, a total of 27 535 individuals tested positive for Mycobacterium tuberculosis (MTB) in Huzhou City. The acceptance rate of preventive treatment was 34.82%, and the completion rate was 57.89%. During follow-up, the incidence density of active pulmonary tuberculosis among MTB-positive individuals who did not receive preventive treatment was 393.83/105 person-years, while that among individuals who received preventive treatment but interrupted treatment was 293.83/105 person-years, and that among individuals who received and completed preventive treatment was 46.08/105 person-years. Practices have shown that the LTBI preventive treatment system constructed in Huzhou City features strong accessibility and high operability, which has effectively expanded the coverage of interventions for high-risk groups, significantly reduced the risk of active pulmonary tuberculosis among MTB-positive individuals, and provided a replicable and promotable practical paradigm for LTBI prevention and control nationwide. In the future, Huzhou City will continue to rely on the primary medical and health network to optimize the whole-process standardized management of LTBI, leverage smart prevention and control technologies, optimize diagnosis and treatment services and cross-regional linkage mechanisms, continuously consolidate the achievements of the Zero Tuberculosis City initiative, steadily reduce the regional tuberculosis epidemic, and contribute to the achievement of the strategic goal of ending the tuberculosis epidemic.

ObjectiveTo explore the effectiveness of health information dissemination and its influencing factors using the "Shanghai CDC" WeChat public account as a case study, providing references for public health institutions to optimize the use of official new media platforms for effective publicity. MethodsA total of 1 030 headline articles published on the "Shanghai CDC" WeChat public account between 2016 and 2019 were analyzed using content analysis and non-parametric tests to examine the impact of factors such as titles and content categories. ResultsFrom 2016 to 2019, the number of WeChat public account followers increased by 280 000, with the articles accumulating over 8.8 million views. The median (P₂₅, P₇₅) open rate of articles was 5.90% (3.69%, 10.31%), and the median (P₂₅, P₇₅) sharing and forwarding rate was 6.60% (4.25%, 9.17%). Factors such as the use of first- and second-person pronouns, degree adverbs, negative adverbs, explicit viewpoints, and title length all significantly affected the open rate of articles, with OR (95%CI) values of 0.175 (0.041‒0.756), 32.606 (2.350‒452.432), 4.079 (1.093‒15.230), 0.106 (0.028‒0.409), and 1.184 (1.063‒1.319),respectively (all P<0.05). In terms of content, statistical significant differences in dissemination effectiveness were observed across article categories and themes (P<0.05). In terms of article categories, articles related to news hotspots and service information had higher open rates of 9.58% and 14.00%, respectively. These two types of articles also obtained higher sharing and forwarding rates of 7.65% and 9.16%, respectively. In terms of article topics, compared with healthy life and health products, among the top four topics in terms of publication volume, the open rates of articles about infectious diseases and disease-causing biology and immunization programs were higher, accounting for 7.88% and 6.88%, respectively, with no significant difference in sharing and forwarding rates. ConclusionThe "Shanghai CDC" WeChat public account demonstrated good dissemination effectiveness. Enhancing article titles by increasing informational content and degree adverbs (e.g., "highly," "most," and "extremely") and negative adverbs (e.g., "no") can improve dissemination reach. Public health WeChat accounts should incorporate news hotspots or service information in their articles. While maintaining their strengths in disseminating knowledge on infectious diseases and immunization programs, they should also enhance public education in other professional fields within their scope of responsibility to improve the overall dissemination impact of health information.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

ObjectiveTo investigate the effects of ethoxysanguinarine （ETH） on angiotensin Ⅱ （Ang Ⅱ）-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 （IRE1）/regulated IRE1-dependent decay （RIDD） signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation， which was identified as a cardiomyocyte apoptosis model. Subsequently， the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 （CCK-8） to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group， a model group （Ang Ⅱ， 1 mmol·L^-1）， and low-， medium-， and high-dose ETH groups （1.25， 2.5， and 5 mmol·L^-1）. Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling （TUNEL） staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins， endoplasmic reticulum stress， and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip， p-IRE1， and Bid in H9c2 cells （P<0.05， P<0.01）， indicating the induction of endoplasmic reticulum stress， activation of the IRE1/RIDD signaling pathway， and initiation of the apoptosis process. Compared with the blank group， the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes， as well as in both early and late apoptosis rates （P<0.01）. The expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 proteins were significantly increased， while the expression level of Bcl-2 protein was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group （P<0.05）. The expression levels of Bid， Bax， and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group （P<0.05， P<0.01）. The high-dose ETH group significantly reduced the expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 （P<0.05， P<0.01） and significantly increased the expression level of Bcl-2 （P<0.05）. The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins in the high-dose ETH group were significantly decreased （P<0.05， P<0.01）. ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

ObjectiveTo investigate the effects of ethoxysanguinarine （ETH） on angiotensin Ⅱ （Ang Ⅱ）-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 （IRE1）/regulated IRE1-dependent decay （RIDD） signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation， which was identified as a cardiomyocyte apoptosis model. Subsequently， the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 （CCK-8） to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group， a model group （Ang Ⅱ， 1 mmol·L^-1）， and low-， medium-， and high-dose ETH groups （1.25， 2.5， and 5 mmol·L^-1）. Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling （TUNEL） staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins， endoplasmic reticulum stress， and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip， p-IRE1， and Bid in H9c2 cells （P<0.05， P<0.01）， indicating the induction of endoplasmic reticulum stress， activation of the IRE1/RIDD signaling pathway， and initiation of the apoptosis process. Compared with the blank group， the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes， as well as in both early and late apoptosis rates （P<0.01）. The expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 proteins were significantly increased， while the expression level of Bcl-2 protein was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group （P<0.05）. The expression levels of Bid， Bax， and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group （P<0.05， P<0.01）. The high-dose ETH group significantly reduced the expression levels of Bid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 （P<0.05， P<0.01） and significantly increased the expression level of Bcl-2 （P<0.05）. The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased （P<0.01）. The expression levels of Bip， p-IRE1， and p-RIDD proteins in the high-dose ETH group were significantly decreased （P<0.05， P<0.01）. ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.