ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

This paper systematically reviews the current status of integrated traditional Chinese and western medicine in the treatment of Helicobacter pylori （Hp） infection， as well as recent progress in clinical and basic research both in China and internationally. It summarizes the advantages of traditional Chinese medicine （TCM） in Hp infection management， including improving Hp eradication rates， enhancing antibiotic sensitivity， reducing antimicrobial resistance， decreasing drug-related adverse effects， and ameliorating gastric mucosal lesions. These advantages are particularly evident in patients who are intolerant to bismuth-containing regimens， those with refractory Hp infection， and individuals with precancerous gastric lesions. An integrated， whole-process management approach and individualized， staged comprehensive treatment strategies combining TCM and western medicine are proposed for Hp infection. Future prevention and control of Hp infection should adopt an integrative Chinese-western medical strategy， emphasizing prevention， strengthening primary care， implementing proactive long-term monitoring， optimizing screening strategies， and advancing the development of novel technologies and mechanistic studies of Chinese herbal interventions. These efforts aim to provide a theoretical basis and practical pathways for the establishment and improvement of Hp infection prevention and control systems.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective:To observe therapeutic effect of catalpol on Sj?gren's syndrome(SS)model mice and explore further mechanism through vitro experiments.Methods:Eight-week-old NOD mice were given catalpol 100 mg/kg by gavage for 8 weeks.Serum levels of IFN-γ and IL-17 were measured.Pathological of salivary glands were observed.lnc-NONHSAT071210 shRNA trans-fected salivary gland epithelial cell lines were treated with 50 μmol/L catalpol,and expression of lnc-NONHSAT071210 was detected.Cells were intervented by 10 ng/ml IFN-γ,lnc-NONHSAT071210 shRNA and catalpol treatment for 72 h,cell proliferation and expressions of IL-17 and IFN-γ were detected.Results:Compared with control group,expressions of IFN-γ and IL-17 were decreased(P<0.05),pathology of salivary gland showed that infiltration of lymphocytes was reduced and destruction of gland structure was significantly reduced in catalpol group.Compared with IFN-γ intervention group,catalpol treatment significantly increased prolifera-tion of salivary gland epithelial cells,and decreased expressions of IFN-γ and IL-17(P<0.05).After catalpol treatment,expression of lnc-NONHSAT071210 was decreased(P<0.05).Moreover,IFN-γ and IL-17 expressions were decreased by catalpol and lnc-NONH-SAT071210 shRNA co-treatment(P<0.01).Conclusion:Catalpol can inhibit expressions of inflammatory cytokines in serum and infiltration of lymphocyte in salivary gland of SS model mice,and inhibit salivary gland ductal fine epithelial inflammatory response and progression of SS by regulating lnc-NONHSAT071210.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.

Objective:To investigate the temporal and spatial distribution characteristics of fluoride in drinking water in rural areas of Shaanxi Province.Methods:From April 2019 to September 2023, rural drinking water monitoring sites were set up in all 108 agriculture-related counties (cities and districts) in Shaanxi Province. The ex-factory water and tap water were collected annually in dry season and wet season for water fluoride determination and water fluoride exceeding standard evaluation, and the exceedance rates of water fluoride were compared according to different years, regions, water period types, water sample types, water source types, and water treatment methods.Results:A total of 31 221 water samples were collected in Shaanxi Province from 2019 to 2023, and the median water fluoride was 0.370 mg/L, ranging from 0.001 to 6.220 mg/L. The exceedance rates of water fluoride in each year were 5.93% (370/6 236), 3.21% (200/6 232), 3.05% (191/6 260), 3.64% (228/6 256), and 2.36% (147/6 237), respectively. The differences between different years were statistically significant (χ 2 = 132.31, P < 0.001). The exceedance rates of water fluoride in Guanzhong, Northern Shaanxi, and Southern Shaanxi were 5.10% (563/11 044), 5.93% (376/6 339), and 1.42% (197/13 838), respectively, with statistically significant differences between different regions (χ 2 = 355.76, P < 0.001). The exceedance rates of water fluoride during the dry season and wet season were 3.68% (574/15 615) and 3.60% (562/15 606), respectively, with no statistically significant difference between the two water periods (χ 2 = 0.12, P = 0.724). The fluoride exceedance rates of ex-factory water and tap water were 3.15% (442/14 024) and 4.04% (694/17 197), respectively. The fluoride exceedance rate of tap water was higher than that of ex-factory water, and the difference was statistically significant (χ 2 = 17.21, P < 0.001). The fluoride exceedance rates of surface water and groundwater were 0.37% (39/10 588) and 5.32% (1 097/20 633), respectively. The fluoride exceedance rate of groundwater was higher than that of surface water, and the difference was statistically significant (χ 2 = 488.68, P < 0.001). The fluoride exceedance rates of conventional treatment, sedimentation and filtration, disinfection only, and untreated water samples were 1.21% (111/9 174), 2.82% (130/4 604), 3.56% (309/8 686), and 6.69% (586/8 757), respectively. There was a statistically significant difference between different water treatment methods (χ 2 = 396.04, P < 0.001). Conclusions:The fluoride exceedance rate of drinking water in rural areas of Shaanxi Province has decreased from 2019 to 2023, and the exceedance water samples are mainly concentrated in Northern Shaanxi and Guanzhong regions. There are differences in the fluoride exceedance rate of water samples in different years, regions, water sample types, water source types, and water treatment methods.

Objective:To explore the application efficacy of the continuous oral care program led by dental nurses in adolescent patients with fixed orthodontics and to provide a reference for continuous care to enhance the oral health level of patients.Methods:A randomized controlled trial was carried out in the Orthodontic Department of Shanghai Stomatological Hospital from June to December 2022. A total of 132 adolescent patients with fixed orthodontics were selected through the convenience sampling method and divided into the experimental group and the control group by the random number table method, with 66 patients in each group. The experimental group was provided with the continuous oral care program led by dental specialist nurses, while the control group received routine care. The intervention lasted for 12 months. The Oral Health Impact Scale, the Oral Health Self-Management Ability Questionnaire, and the plaque index were utilized to assess the intervention effect before and after the intervention.Results:A total of 65 participants in the experimental group completed the study, with an age of (14.41 ± 1.60) years, comprising 32 males and 33 females. In the control group, 64 participants completed the study, with an age of (14.15 ± 1.69) years, including 28 males and 36 females. Prior to intervention, there were no statistically significant differences in scores for oral health self-management ability, Oral Health Impact Profile-14, or total plaque index between the experimental and control groups (all P>0.05). Following intervention, the score for oral health self-management ability in the experimental group was (77.42 ± 11.70) points, significantly higher than (70.47 ± 17.49) points of the control group ( t = 2.65, P<0.05). Additionally, the score on the Oral Health Impact Profile-14 for the experimental group was (16.40 ± 3.45) points and their total plaque index was measured at 1.68 ± 0.55 both significantly lower than those recorded in the control group at (18.16 ± 3.79) points and a total plaque index of 1.92 ± 0.47 respectively ( t = - 2.75, - 2.55, both P<0.05). Conclusions:The implementation of the continuous oral care program led by dental specialist nurses is conducive to improving the oral health self-management ability of adolescent patients with fixed orthodontics, reducing dental plaque, improving oral cleanliness, and improving the oral health-related quality of life of patients.

Objective:To observe therapeutic effect of catalpol on Sj?gren's syndrome(SS)model mice and explore further mechanism through vitro experiments.Methods:Eight-week-old NOD mice were given catalpol 100 mg/kg by gavage for 8 weeks.Serum levels of IFN-γ and IL-17 were measured.Pathological of salivary glands were observed.lnc-NONHSAT071210 shRNA trans-fected salivary gland epithelial cell lines were treated with 50 μmol/L catalpol,and expression of lnc-NONHSAT071210 was detected.Cells were intervented by 10 ng/ml IFN-γ,lnc-NONHSAT071210 shRNA and catalpol treatment for 72 h,cell proliferation and expressions of IL-17 and IFN-γ were detected.Results:Compared with control group,expressions of IFN-γ and IL-17 were decreased(P<0.05),pathology of salivary gland showed that infiltration of lymphocytes was reduced and destruction of gland structure was significantly reduced in catalpol group.Compared with IFN-γ intervention group,catalpol treatment significantly increased prolifera-tion of salivary gland epithelial cells,and decreased expressions of IFN-γ and IL-17(P<0.05).After catalpol treatment,expression of lnc-NONHSAT071210 was decreased(P<0.05).Moreover,IFN-γ and IL-17 expressions were decreased by catalpol and lnc-NONH-SAT071210 shRNA co-treatment(P<0.01).Conclusion:Catalpol can inhibit expressions of inflammatory cytokines in serum and infiltration of lymphocyte in salivary gland of SS model mice,and inhibit salivary gland ductal fine epithelial inflammatory response and progression of SS by regulating lnc-NONHSAT071210.

Objective:To investigate the temporal and spatial distribution characteristics of fluoride in drinking water in rural areas of Shaanxi Province.Methods:From April 2019 to September 2023, rural drinking water monitoring sites were set up in all 108 agriculture-related counties (cities and districts) in Shaanxi Province. The ex-factory water and tap water were collected annually in dry season and wet season for water fluoride determination and water fluoride exceeding standard evaluation, and the exceedance rates of water fluoride were compared according to different years, regions, water period types, water sample types, water source types, and water treatment methods.Results:A total of 31 221 water samples were collected in Shaanxi Province from 2019 to 2023, and the median water fluoride was 0.370 mg/L, ranging from 0.001 to 6.220 mg/L. The exceedance rates of water fluoride in each year were 5.93% (370/6 236), 3.21% (200/6 232), 3.05% (191/6 260), 3.64% (228/6 256), and 2.36% (147/6 237), respectively. The differences between different years were statistically significant (χ 2 = 132.31, P < 0.001). The exceedance rates of water fluoride in Guanzhong, Northern Shaanxi, and Southern Shaanxi were 5.10% (563/11 044), 5.93% (376/6 339), and 1.42% (197/13 838), respectively, with statistically significant differences between different regions (χ 2 = 355.76, P < 0.001). The exceedance rates of water fluoride during the dry season and wet season were 3.68% (574/15 615) and 3.60% (562/15 606), respectively, with no statistically significant difference between the two water periods (χ 2 = 0.12, P = 0.724). The fluoride exceedance rates of ex-factory water and tap water were 3.15% (442/14 024) and 4.04% (694/17 197), respectively. The fluoride exceedance rate of tap water was higher than that of ex-factory water, and the difference was statistically significant (χ 2 = 17.21, P < 0.001). The fluoride exceedance rates of surface water and groundwater were 0.37% (39/10 588) and 5.32% (1 097/20 633), respectively. The fluoride exceedance rate of groundwater was higher than that of surface water, and the difference was statistically significant (χ 2 = 488.68, P < 0.001). The fluoride exceedance rates of conventional treatment, sedimentation and filtration, disinfection only, and untreated water samples were 1.21% (111/9 174), 2.82% (130/4 604), 3.56% (309/8 686), and 6.69% (586/8 757), respectively. There was a statistically significant difference between different water treatment methods (χ 2 = 396.04, P < 0.001). Conclusions:The fluoride exceedance rate of drinking water in rural areas of Shaanxi Province has decreased from 2019 to 2023, and the exceedance water samples are mainly concentrated in Northern Shaanxi and Guanzhong regions. There are differences in the fluoride exceedance rate of water samples in different years, regions, water sample types, water source types, and water treatment methods.