ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

Microbial infections are a prevalent challenge in the prevention and treatment of oral diseases. Antibiotic therapy faces clinical limitations due to its single-target mechanism and tendency to induce resistance with repeated use, necessitating novel antibacterial strategies. Stimuli-responsive antibacterial materials, whose antimicrobial activity can be modulated by external stimuli, offer advantages such as remote controllability, potential for localized precision treatment, and a reduced risk of inducing resistance. Among these materials, mechanical force-triggered piezoelectric materials exhibit significant antibacterial activity in the biomedical field owing to their unique piezoelectric effect, excellent stability, and good biocompatibility. Research has shown that piezoelectric materials can convert mechanical energy into electrical energy in response to external forces, which enables antibacterial effects without requiring an external power source. The underlying mechanisms primarily include direct electric field effects, generation of reactive oxygen species, and immune modulation. Preliminary applications in treating oral infections (e.g., dental caries, periodontitis, and peri-implantitis) have confirmed their stability and biocompatibility, establishing a foundation for clinical translation. However, long-term efficacy and biosafety in the complex oral microenvironment require further validation. Future research should focus on optimizing material preparation protocols to enhance antibacterial efficacy and stability, further investigating the underlying antimicrobial mechanisms, and systematically evaluating their therapeutic outcomes and safety profiles across various types of oral infections. This review summarizes the antibacterial effects, mechanisms, stability, safety, and research progress of piezoelectric materials in the stomatologic field, aiming to provide new insights for further research and application in this area.

ObjectiveTo construct and validate a clinical prediction model for inflammatory remission outcomes in rheumatoid arthritis （RA） patients with liver and kidney deficiency syndrome treated with Bushen Zhiwang Decoction （补肾治尪汤， BZD） based on metabolomics. MethodsA prospective cohort study was conducted， enrol-ling 60 RA patients with liver and kidney deficiency syndrome. All patients were treated with BZD and conventional-dose oral conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） for 12 months. Clinical data were collected， and the change in disease activity score in 28 joints （DAS28） after treatment compared with baseline （△DAS28） was used as the primary outcome and grouping criterion. Peripheral blood samples were collected before treatment to analyze plasma metabolites. Differential analysis and least absolute shrinkage and selection operator （LASSO） regression were used to preliminarily screen differential metabolites， followed by machine learning algorithms to further identify a core metabolite combination. Based on the expression levels of the core metabolite combination， a novel metabolite index， namely the metabolomics-based inflammatory remission score （Met-IRS）， was calculated using standar-dized metabolite values， and its clinical applicability was evaluated. A clinical prediction model was constructed by integrating clinical characteristics and Met-IRS， and the model performance was assessed. ResultsAmong the 60 patients， those with △DAS28 ≥ 0.27 were assigned to the high inflammatory remission group， while those with △DAS28 ＜ 0.27 were assigned to the low inflammatory remission group， with 30 cases in each group. Compared to the low inflammatory remission group， the high inflammatory remission group showed a higher frequency of methotrexate use and a lower positive rate of rheumatoid factor （RF） （P＜0.05）. Seven core metabolites were identified as the optimal combination， including mangiferic acid， fatty acid-hydroxy fatty acid ester 40∶6， fatty acid-hydroxy fatty acid ester 18∶0， fatty acid-hydroxy fatty acid ester 36∶1， glucosylceramide， lysophosphatidylcholine 22∶5， and pregnanetriol ketone. The calculated Met-IRS comprehensively reflected the characteristics of differential metabolites and demonstrated clinical applicability. Met-IRS was significantly higher in the high inflammatory remission group than in the low inflammatory remission group， and was positively correlated with high inflammatory remission outcomes （P＜0.05）. Based on the variables Met-IRS， methotrexate use， leflunomide use， and RF positivity， a clinical prediction model for inflammatory remission in RA treatment （Cj-RTRM） was constructed. Model performance evaluation demonstrated that the model had good clinical predictive ability， with an area under the receiver operating characteristic curve （AUC） of 0.880， sensitivity 0.967， specificity 0.700 and Youden's index 0.667. ConclusionThe clinical prediction model Cj-RTRM constructed based on the metabolomics-based inflammatory remission score Met-IRS can effectively predict clinical inflammatory remission outcomes in RA patients treated with BZD and accurately identify the advantageous population for this treatment. This model provides guiding evidence for dynamic inflammation monitoring， targeted management， and identification of populations with advantages in traditional Chinese medicine.

Childhood adversity is a risk factor for developing depressive symptoms or suffering from depressive disorders across the life course. However， existing evidence has focused on the analysis of the association between childhood adversity and depression from a single theoretical perspective， and there is a lack of comprehensive understanding of its multiple action pathways. By systematically summarizing the cumulative risk model， sensitive-period model， recency model， risk chain model， and the stress sensitization， stress amplification， and stress inoculation hypotheses， as well as the emerging pubertal stress recalibration hypothesis， this article attempts to construct an integrated theoretical framework to elucidate the internal logical synergy among these models. Furthermore， by reviewing relevant empirical evidence， this article analyzes the applicability and limitations of different theoretical models in illustrating the underlying psychopathological mechanisms of depression. The current evidence suggests that the impact of childhood adversity on the risk of psychopathology may be driven by a complex dynamic process involving the interaction of exposure timing， cumulative load， response boundaries of biological systems， and modification by later environments. Future research should utilize longitudinal cohorts and multimodal data within a unified analytical framework to comprehensively examine the multiple pathways through which childhood adversity affects the risk of depression. This will provide a reference for precisely identifying high-risk populations， targeting "recalibration windows" represented by adolescence， developing focused intervention strategies， and ultimately blocking the cascading effects of early life adversity as early as possible. ［Funded by the "Pioneer" and "Leading Goose" R&D program of Zhejiang Province （number， 2024C03006）］

Objective To understand the situation of corn mycotoxins contamination in Heilongjiang Province , and to analyze the causes of pollution and propose prevention and control measures. Methods Among the 473 corn samples were collected from various regions in Heilongjiang Province , and 16 mycotoxins , including aflatoxins , fumonisins, deoxynivalenol and their metabolites , zearalenone , ochratoxin A , alternariol , alternariol monomethyl ether , tentoxin , and tenuazonic acid , were detected in the corn samples. The detection and quantification were carried out using ultra-high performance liquid chromatography tandem mass spectrometry isotope internal standard method. Results All samples were detected with mycotoxins, the detection rate was 100%, and each sample was contaminated by one or more mycotoxins. The detection rate of 16 mycotoxins ranged from 0.21% to 98.31%. The average contamination level ranged from 0.67 μ g/kg-259.19 μ g/kg. Three types of toxins exceeded the standard, with exceeding rates of deoxynivalenol (2.54%, 12/473), zearalenone (4.02% ,19/473), and fumonisins (2.54%,12/473), respectively. The samples exceeding the standard were distributed in Mudanjiang, Shuangyashan, Jixi, Harbin, and Qiqihar. Conclusion Corn in Heilongjiang Province is contaminated by a combination of mycotoxins. It is necessary to strengthen monitoring from multiple links and adopt a variety of ways and control measures to reduce corn contamination.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.