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.

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 develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

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 develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

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 mediating effect of thyroid stimulating hormone(TSH)levels on the risk of osteoporosis(OP)in patients with T2DM and menopause.Methods A total of 179 menopausal T2DM patients who were admitted to our hospital from January 2020 to January 2023 were enrolled in this study.All the participants were divided into diabetes without complication group(T2DM group,n=95)and diabetes with complication group(Com group,n=84)according to the co-existence of complications.Logistic regression analysis was used to analyze the influencing factors for T2DM complications.According to the co-existence of OP,all the patients were divided into OP group(n=86)and Non-OP group(n=93).And the influencing factors for OP occurrence are analyzed using random forest algorithm.Logistic regression analysis was used to investigate the relationship between TSH and T2DM complications and OP.The Bootstrap method was used to analyze the mediating effect of TSH between T2DM complications and OP.Results DM duration,HbA1c,free triiodothyronine,free thyroxine,and TSH were independent influencing factors for T2DM complications(P＜0.05),while P1NP,TSH,vitamin D,and DM duration were influencing factors for the occurrence of OP.After adjusting for confounding factors,there was a negative correlation between TSH and the risk of T2DM complications(P＜0.05),and a negative correlation between TSH and OP(P＜0.05).Mediation effect analysis showed that TSH played a mediating role between T2DM complications and OP.Conclusions TSH is negatively correlated with the risk of T2DM complications and OP,and plays a mediating role between T2DM complications and OP,partially mediating the impact of T2DM complications on OP.

Objective: To construct a hypertension risk prediction model for residents aged 18-79 years, so as to provide an assessment tool for early screening and prevention of hypertension in high-risk groups. Methods: The permanent residents aged 18-79 years from 6 townships (streets) in Fangshan District of Beijing Municipality were selected as the study subjects using a multi-stage stratified random sampling method from March to June 2023. Demographic information, lifestyle, body mass index (BMI), blood pressure, fasting blood glucose, and blood lipid were collected through questionnaire survey, physical examination, and laboratory tests. Subjects were randomly divided into training and validation sets at a 7∶3 ratio. The logistic regression model was used to screen the risk factors of hypertension, and a hypertension risk prediction nomogram was constructed. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis were used to verify the discrimination, fit, and clinical application value of the model. Results: A total of 4 438 subjects were included, including 2 365 males (53.29%) and 2 073 females (46.71%), with a mean age of (44.99±14.90) years. The prevalence of hypertension was 35.29% (1 566 cases), and the standardized prevalence was 24.74%. The logistic regression model screened out 9 influencing factors of hypertension. The nomogram was established as ln[p/ (1-p)]= -2.873 + 0.935×40-<50 years + 1.463×50-<60 years + 1.908×60-<70 years + 2.346×70-79 years + 0.298×male-0.675×college degree or above + 0.384×smoking + 0.227×drinking + 0.572×overweight + 1.449×obesity + 0.557×heart rate ≥80 beats/min + 0.428×diabetes + 0.484×dyslipidemia. The area under the ROC curve of the validation set was 0.821 (95%CI: 0.798-0.843), and the calibration curve results showed that the calibration curve fitted the actual curve well. Decision curve analysis showed that the threshold probability was in the range of 0.10 to 0.70, and the model had good predictive value and clinical application value. Conclusion The nomogram based on age, gender, educational level, smoking, drinking, body mass index, heart rate, diabetes, and dyslipidemia can be used to predict the risk of hypertension among residents aged 18-79 years.