ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

OBJECTIVE To develop a nomogram model for prediction of the risk of sepsis in the patients with acute liver failure(ALF)and validate its clinical value.METHODS Totally 228 patients with ALF who were treated in the Fifth Medical Center of Chinese PLA General Hospital from Jan.2009 to Mar.2023 were recruited as the re-search subjects and were grouped according to the occurrence of sepsis,the clinical characteristics and results of laboratory tests were collected from the patients.The subjects were brought into multivariate logistic regression a-nalysis after the primary screening with univariate regression analysis,the independent predictive factors were screened out,and the nomogram model was established.The accuracy,calibration accuracy and clinical practica-bility of the model were assessed by means of receiver operating characteristic(ROC)curves,calibration curves and decision curve analysis(DCA).RESULTS Among the 228 patients with ALF,159(69.74％)were diagnosed with sepsis.Totally 6 independent predictive factors were screened out by the multivariate analysis,including age[odd ratio(OR)=1.098,95％CI:1.030 to 1.220],aspartate transaminase(OR=0.998,95％CI:0.996 to 0.999),white blood cells counts(OR=1.037,95％CI:1.020 to 1.064),hemoglobulin(OR=0.981,95％CI:0.962 to 0.998),lactic acid(OR=1.187,95％CI:1.022 to 1.426)and mechanical ventilation(OR=3.463,95％CI:2.340 to 5.125).The area under the curve(AUC)of the nomogram model was 0.864(95％CI:0.807 to 0.921)in the training set,0.817(95％CI:0.717 to 0.918)in the validation set,remarkably better than that of sequential organ failure assessment(SOFA)scores[0.710(95％CI:0.625 to 0.795)and 0.647(95％CI:0.515 to 0.779)].Hosmer-Lemeshow test(P=0.512)and the calibrated curves showed that the predication probability of the model was highly consistent with the actual risk,and DC A indicated that the net clinical benefit was brought more from the model than from SOFA score.CONCLUSION The age,hemoglobulin,aspartate transaminase,white blood cells counts,lactic acid and mechanical ventilation are the independent predictive factors for the sepsis in the ALF patients.The nomogram model established based on the factors has high predictive efficiency and clini-cal application value.

OBJECTIVE To develop a nomogram model for prediction of the risk of sepsis in the patients with acute liver failure(ALF)and validate its clinical value.METHODS Totally 228 patients with ALF who were treated in the Fifth Medical Center of Chinese PLA General Hospital from Jan.2009 to Mar.2023 were recruited as the re-search subjects and were grouped according to the occurrence of sepsis,the clinical characteristics and results of laboratory tests were collected from the patients.The subjects were brought into multivariate logistic regression a-nalysis after the primary screening with univariate regression analysis,the independent predictive factors were screened out,and the nomogram model was established.The accuracy,calibration accuracy and clinical practica-bility of the model were assessed by means of receiver operating characteristic(ROC)curves,calibration curves and decision curve analysis(DCA).RESULTS Among the 228 patients with ALF,159(69.74％)were diagnosed with sepsis.Totally 6 independent predictive factors were screened out by the multivariate analysis,including age[odd ratio(OR)=1.098,95％CI:1.030 to 1.220],aspartate transaminase(OR=0.998,95％CI:0.996 to 0.999),white blood cells counts(OR=1.037,95％CI:1.020 to 1.064),hemoglobulin(OR=0.981,95％CI:0.962 to 0.998),lactic acid(OR=1.187,95％CI:1.022 to 1.426)and mechanical ventilation(OR=3.463,95％CI:2.340 to 5.125).The area under the curve(AUC)of the nomogram model was 0.864(95％CI:0.807 to 0.921)in the training set,0.817(95％CI:0.717 to 0.918)in the validation set,remarkably better than that of sequential organ failure assessment(SOFA)scores[0.710(95％CI:0.625 to 0.795)and 0.647(95％CI:0.515 to 0.779)].Hosmer-Lemeshow test(P=0.512)and the calibrated curves showed that the predication probability of the model was highly consistent with the actual risk,and DC A indicated that the net clinical benefit was brought more from the model than from SOFA score.CONCLUSION The age,hemoglobulin,aspartate transaminase,white blood cells counts,lactic acid and mechanical ventilation are the independent predictive factors for the sepsis in the ALF patients.The nomogram model established based on the factors has high predictive efficiency and clini-cal application value.

Objective:To investigate the effect of graded rehabilitation intervention on cardiac function,self-man-agement ability,exercise tolerance,sleep quality and quality of life in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 125 patients with CHF admitted to Lu'an People's Hospital be-tween April 2020 and October 2023.Patients were divided into control group(n=62)and intervention group(n=63).Participants in the control group received routine rehabilitation intervention,while those in the intervention group received additional graded rehabilitation intervention.Both groups were intervened for 3 months.Cardiac function indexes,6min walking distance(6MWD),metabolic equivalent(METs),scores of exercise of self-care a-gency(ESCA),Pittsburgh sleep quality index(PSQI)and the MOS item short from health survey(SF-36),and in-cidence of adverse events during the intervention were compared between the two groups.Results:Compared to pa-tients in the control group,those in intervention group had significant lower left ventricular end-diastolic volume(LVEDV)[(108.19±2.96)ml vs.(129.51±3.34)ml],left ventricular end-systolic volume(LVESV)[(50.68±2.28)ml vs.(67.38±2.68)ml],score of Pittsburgh sleep quality index(PSQI)[(8.30±1.87)points vs.(13.99±2.06)points](P＜0.001 all),and significant higher left ventricular ejection fraction(LVEF)[(58.17±2.08)％vs.(50.70±1.63)％],ESCA score[(148.29±19.48)points vs.(124.68±15.93)points],6MWD[(413.58±15.11)m vs.(372.22±14.62)m],METs[(6.88±0.64)kcal·kg-1·h-1 vs.(6.13±0.62)kcal·kg-1·h-1],total SF-36 score[(128.97±6.62)points vs.(104.35±5.46)points](P＜0.001 all).The inci-dence of adverse events in the intervention group was significantly lower than that in the control group(5.00％vs.18.33％,P=0.023).Conclusion:The graded rehabilitation intervention may improve the heart function,self-management ability,exercise tolerance,sleep quality and quality of life in CHF patients,and has high safety.

Objective:To investigate the effect of graded rehabilitation intervention on cardiac function,self-man-agement ability,exercise tolerance,sleep quality and quality of life in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 125 patients with CHF admitted to Lu'an People's Hospital be-tween April 2020 and October 2023.Patients were divided into control group(n=62)and intervention group(n=63).Participants in the control group received routine rehabilitation intervention,while those in the intervention group received additional graded rehabilitation intervention.Both groups were intervened for 3 months.Cardiac function indexes,6min walking distance(6MWD),metabolic equivalent(METs),scores of exercise of self-care a-gency(ESCA),Pittsburgh sleep quality index(PSQI)and the MOS item short from health survey(SF-36),and in-cidence of adverse events during the intervention were compared between the two groups.Results:Compared to pa-tients in the control group,those in intervention group had significant lower left ventricular end-diastolic volume(LVEDV)[(108.19±2.96)ml vs.(129.51±3.34)ml],left ventricular end-systolic volume(LVESV)[(50.68±2.28)ml vs.(67.38±2.68)ml],score of Pittsburgh sleep quality index(PSQI)[(8.30±1.87)points vs.(13.99±2.06)points](P＜0.001 all),and significant higher left ventricular ejection fraction(LVEF)[(58.17±2.08)％vs.(50.70±1.63)％],ESCA score[(148.29±19.48)points vs.(124.68±15.93)points],6MWD[(413.58±15.11)m vs.(372.22±14.62)m],METs[(6.88±0.64)kcal·kg-1·h-1 vs.(6.13±0.62)kcal·kg-1·h-1],total SF-36 score[(128.97±6.62)points vs.(104.35±5.46)points](P＜0.001 all).The inci-dence of adverse events in the intervention group was significantly lower than that in the control group(5.00％vs.18.33％,P=0.023).Conclusion:The graded rehabilitation intervention may improve the heart function,self-management ability,exercise tolerance,sleep quality and quality of life in CHF patients,and has high safety.

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BACKGROUND: Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive. OBJECTIVE: This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD. SEARCH STRATEGY: Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025. INCLUSION CRITERIA: Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included. DATA EXTRACTION AND ANALYSIS: Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. RESULTS: A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = -0.57; 95% confidence interval [CI] = [-0.87, -0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = -1.00; 95% CI = [-1.18, -0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = -0.38; 95% CI = [-0.61, -0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture's relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect. CONCLUSION Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future. Please cite this article as: Kuang HJ, Yang HS, Feng YX, Tang H, Fan Q, Xu YQ, Cui S, Musil R, Luxenburger H, Zhang YX, Zhao H, Zhang YQ. Efficacy and safety of acupuncture therapies for adult patients with mild and moderate major depressive disorder: A systematic review and meta-analysis. J Integr Med. 2025; 23(5):471-491.
Humans ; Acupuncture Therapy/methods* ; Depressive Disorder, Major/therapy* ; Adult ; Antidepressive Agents/therapeutic use* ; Treatment Outcome ; Randomized Controlled Trials as Topic

This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit