ObjectiveTo investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsAnimal experiments were conducted with 50 female SD rats， which were randomized into a sham operation group （10 rats） and a modeling group （40 rats）. An autologous endometrial transplantation method was used for the modeling of EMs. The 36 successfully modeled rats were randomly allocated into four groups （n=9 each）： The model group， the low-dose （7.87 g·kg^-1） Luoshi Neiyi prescription group， the high-dose （15.74 g·kg^-1） Luoshi Neiyi prescription group， and the dienogest （0.20 mg·kg^-1） group. The physiological status and ectopic lesion volumes of rats in each group were observed. Hematoxylin-eosin （HE） staining was used to observe the morphology of the eutopic endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory factors including interleukin-1β （IL-1β） and prostaglandin E₂ （PGE₂） in the serum of EMs rats. Immunohistochemistry was used to detect the expression of matrix metalloproteinase-9 （MMP-9） and vascular endothelial growth factor A （VEGFA） in the eutopic endometrial tissue. Western blot was adopted to determine the protein levels of TLR4， myeloid differentiation factor 88 （MyD88）， phosphorylated nuclear factor-κB （p-NF-κB）/NF-κB， MMP-9， and VEGFA in the eutopic endometrial tissue. In the cell experiments， the cell-counting kit-8 （CCK-8） assay was employed to screen the optimal concentration of Luoshi Neiyi prescription-containing serum， and a scratch assay was performed to assess the migration ability of iheESCs cells. Interventions with Luoshi Neiyi prescription-containing serum， resatorvid （TAK-242， a TLR4 inhibitor）， and lipopolysaccharides （LPS， a TLR4 agonist） were conducted， and Western blot was used to detect the expression of proteins related to the TLR4/NF-κB signaling pathway. ResultsThis experiment successfully replicated 36 EMs rat models. Compared with the sham operation group， the model group exhibited visible ectopic lesions on the abdominal wall and an increase in the writhing response score （P<0.01）. Furthermore， HE staining revealed the model group exhibited a thickened eutopic epithelium， stromal cell disarrangement， and evident infiltration of inflammatory cells. In addition， the model group showed elevated serum levels of IL-1β and PGE₂ （P<0.05， P<0.01）， increased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.01）， and up-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. Compared with the model group， all treatment groups exhibited a reduction in the ectopic lesion volume （P<0.01）. Furthermore， the writhing response scores were decreased in the high-dose Luoshi Neiyi prescription group and the dienogest group （P<0.05， P<0.01）. The pathological state of the ectopic endometrial tissue was alleviated to varying degrees in the treatment groups. Low-dose Luoshi Neiyi prescription reduced serum PGE₂ levels， and high-dose Luoshi Neiyi prescription and dienogest decreased serum IL-1β and PGE₂ levels in EMs rats （P<0.05， P<0.01）. The treatment groups showed decreased positive expression of MMP-9 and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01） and down-regulated protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA in the ectopic endometrial tissue （P<0.05， P<0.01）. The cell experiments showed that 5%， 10%， and 20% Luoshi Neiyi prescription-containing sera significantly reduced the viability and inhibited the migration of iheESCs. Compared with the control group， 5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups and the TAK-242 group showed reduced protein levels of TLR4， MyD88， p-NF-κB/NF-κB， MMP-9， and VEGFA （P<0.01）. Compared with the control group， the LPS group showed increased expression of the above proteins （P<0.01）. Compared with the LPS group， the LPS+5%， 10%， and 20% Luoshi Neiyi prescription-containing serum groups showed reduced expression of the above proteins （P<0.05， P<0.01）. ConclusionLuoshi Neiyi prescription may modulate the TLR4/NF-κB signaling pathway to reduce the inflammatory response and histopathological damage in the eutopic endometrium and suppress the adhesive， invasive， and angiogenic biological processes in the ectopic endometrial tissue， thereby exerting its therapeutic effect on EMs.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.

Objective:To establish an identical UPLC-MS/MS method for determination of related substances of 15 drugs(bezafibrate,acipimox,gliquidone,glimepiride,glipizide,glibenclamide,enalapril,captopril,irbesartan,amlodipine,felodipine,nimodipine,nitrendipine,nisoldipine,nifedipine).Methods:The chromatography was performed on Waters ACQUITY UPLCHSS T3(2.1 mm × 100 mm,1.8 μm)column,mobile phase was 0.01 mmol·L-1 Ammonium formate solution containing 0.1％formic acid and methanol with gradient elution.The flow rate was 0.3 mL·min-1,and the injection volume was 2 μL.The detection was carried out by electrospray ioniza-tion(ESI).Multiple-reaction monitoring(MRM)was employed with switching electrospray ion source polarity in positive and negative mode.Results:The 21 related substances showed good linearity(r ≥0.998 35)in the tested ranges.The precision(RS D≤3.45％)and stability(RSD≤3.48％)of the method were good for the related sub-stances.The average recoveries of the related substances were in the range of 91.81％-101.84％with relative standard deviations RSD≤4.66％.Conclusion:The method is rapid,simple,accurate and highly sensitive,and can be used as a auxiliary test method and confirmatory method for current drug standards.

Objective To describe and analyze the current status,changing trend and influencing factors of the disease burden of cervical,endometrial and ovarian cancer in China from 1990 to 2021.Methods Data on incidence,mortality,disability-adjusted life year(DALY),and other indicators for cervical,endometrial and ovarian cancer were collected from the 2021 Global Burden of Disease database.Joinpoint regression models were used to analyze time trends,and age-period-cohort(APC)models assessed their impact on incidence and mortality.Spearman correlation analysis was performed to evaluate the relationship between the sociodemographic index(SDI)and the cancer indicators.Finally,the attributable risk factors for the disease burden were analyzed.Results From 1990 to 2021,age-standardized incidence rates of cervical and endometrial cancers in China significantly increased,while ovarian cancer showed no significant change.Age-standardized mortality,DALY,and years of life lost due to premature death(YLL)decreased significantly.The disease burden was heavier in middle-aged and older groups.APC model indicated an increase in cervical cancer incidence and a decrease in mortality over time.Furthermore,the incidence risks of cervical and endometrial cancers were elevated in successive birth cohorts,whereas a lower risk was observed for ovarian cancer.Correlation analysis showed significant associations between cancer incidence and mortality with SDI.Obesity has significantly contributed to the disease burden of common gynecologic cancers in China.Conclusion Mortality rates of cervical,endometrial and ovarian cancer have declined,while the incidence of cervical and endometrial cancers has significantly increased.The trends in incidence and mortality are influenced by age,period and cohort effects.Future efforts should focus on controlling risk factors like obesity to reduce the disease burden.

Objective To explore the influencing factors of acute kidney injury in severe burn patients,and to construct a visual risk nomogram model.Methods A total of 390 patients with severe burn admitted to the Institute of Burn Frostbite and Tissue Function Reconstruction of Chinese People's Armed Police Force Specialty Medical Center from January 2018 to January 2022 were collected as an internal training data set,and 50 patients with severe burn admitted from February to December 2022 were collected as an external validation data set.The 390 patients of the internal training data set were divided into the acute kidney injury group and the non-acute kidney injury group according to the occurrence of acute kidney injury,and the baseline data of patients in the two groups were compared.Univariate and multivariate Logistic regression were used to analyze the risk factors of acute kidney injury in severe burn patients of the internal training data set,and a nomogram model was drawn.Subsequently,the model was verified both internally and externally.Kaplan-Meier analysis and Log-rank test were used to compare the 90-day survival rate of patients between the acute kidney injury group and the non-acute kidney injury group.Results The burn area(OR=1.18,95%CI:1.06 to 2.36,P=0.004),sequential organ failure assessment(SOFA)score(OR=1.81,95%CI:1.21 to 5.92,P<0.001),inhalation injury(OR=3.21,95%CI:1.23 to 6.35,P<0.001),neutrophil to lymphocyte ratio(NLR)(OR=1.22,95%CI:1.05 to 3.65,P<0.001)and albumin(ALB)(OR=0.78,95%CI:0.57 to 0.92,P=0.011)were the independent risk factors for the development of acute kidney injury in severe burn patients.The nomogram model was established by the above factors.The area under the receiver operating characteristic curve(AUC)of the internal training data set was 0.833(95%CI:0.752 to 0.935),the sensitivity was 81.2%,and the specificity was 83.2%.The AUC of the external validation data set was 0.842(95%CI:0.762 to 0.912),the sensitivity 87.2%,and the specificity was 78.7%.The 90-day survival rate of patients in the acute kidney injury group after burns was significantly lower than that in the non-acute kidney injury group(P<0.001).Conclusion Larger burn area,higher SOFA score,combined inhalation injury,increased NLR,and decreased ALB level are the risk factors for the occurrence of acute kidney injury in severe burn patients,which are related to the 90-day survival rate of patients after burns.The nomogram model based on the risk factors can provide certain reference for clinical individualized prevention and treatment of acute kidney injury in severe burn patients.

Objective:To observe the role of impulsivity in cognitive impairment in manic episodes of bipolar Ⅰ disorder(BPDTI)patients.Methods:180 cases of patients with BPDTI manic episodes admitted to our hospital from February 2024 to December 2024 were selected as the manic group,and another 180 cases of volunteers who were psychologically tested as normal during the same period were selected as the healthy group.The impulse Barratt-11 scale(BIS-11)and the MATRICS Consensus Cognitive Test(MCCB)were used to investigate and evaluate impulsivity and cognitive function,and correlation analysis and risk factor analysis were conducted.Results:In the BIS-11 scale,there was no statistically significant difference between the two groups in the unplanned factor(P＞0.05),but there were significant differences compared between the two groups in cognitive,motor factors,and total score(P＜0.05).The MCCB scores of the manic group in information processing speed,working memory,word learning,visual learning,social cognition,reasoning and problem solving,and attention vigilance were significantly lower than those of the healthy group(P＜0.05).The relationship between BIS-11 total score and cognitive impulsivity factor and MCCB total score and word learning showed there were negative correlation(P＜0.05);The exercise factor in the BIS-11 scale were negatively correlated with the MCCB total score and working memory factor(P＜0.05);The unplanned factor in the BIS-11 scale showed there were negative correlation with the MCCB total score,word learning(P＜0.05),and information processing speed.BIS-11,the number of years of education was an influencing factor for BPDTI mania(P＜0.05).Conclusion:BPDTI mania patients had high impulsivity and cognitive impairment,high impulsivity and number of years of education were influencing factors for mania,high impulsivity affected cognitive function through corresponding brain regions,aggravating the condition.

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

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