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.

Objective:To investigate the effect of ginsenoside octanoate(Rh2-O)on inducing immunogenic cell death in hepa-tocellular carcinoma cells and its molecular mechanism.Methods:Effects of ginsenoside caprylate(Rh2-O)and autophagy inhibitor 3-MA on the activity of hepatocellular carcinoma cells were detected by CCK-8 assay.The effect of Rh2-O on CRT membrane eversion in Hepa1-6 cells were detected by immunofluorescence assay.Rh2-O treated mouse hepatocellular carcinoma cells were used to pre-pare a tumor vaccine for in vivo vaccination experiments in mice.Extracellular ATP levels were detected in real-time.The expression of autophagy-related genes and proteins were measured by real-time fluorescence PCR and Western blot,and the mitochondrial morphol-ogy and co-localization with autophagy proteins were observed by laser confocal microscopy.Results:Rh2-O showed strong cytotoxicity to Hepa1-6 cells[cell viability:(58.54±3.56)%]at a concentration of 150 μmol/L,and a large amount of CRT was observed on the surface of the cell membrane.The tumor emergence rate was 36.36%in the vaccinated group and 100%in the control group.The tumor vaccine prepared by Rh2-O effectively protected mice from the same type of tumor attack;Rh2-O induced an increase in the level of cellular secreted ATP(P<0.05),the mRNA of autophagy-related genes ATG3,p62,LC3 expression levels and autophagy-associated proteins LC3A and LC3B expression levels were increased(P<0.05),and co-localization of mitochondria with autophagy proteins was significantly increased(P<0.05).In addition,Rh2-O action on 3-MA pretreated hepatocellular carcinoma cells resulted in a signifi-cant decrease in extracellular ATP levels(P<0.001).Conclusion:Rh2-O may induce immunogenic cell death by inducing autophagy in hepatocellular carcinoma cells.

Objective To investigate the clinical effect of hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of mixed hemorrhoids with annular prolapse.Methods A retrospective analysis was conducted to select 80 patients with annular prolapse mixed hemorrhoids admitted to the anorectal Department of our hospital from January 2022 to April 2023.According to different treatment plans,they were divided into control group(n=40 cases)who received external stripping and internal ligation combined with tape ligation,and study group(n=40 cases)who received hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligation and suspension.The operative effect,operative status,postoperative anal pain,anal edema,stool blood score and quality of life were evaluated.Results The effective rate of the study group was 97.50％,which was higher than that of the control group(77.50％)(P＜0.05).The operation time,intraoperative blood loss,hospital stay and wound healing time of the research group were(25.03±10.00)minutes,(10.00±5.32)ml,(7.25±1.54)days and(12.21±2.00)days respectively.[is better than that of control group(29.85±14.00)minutes,ml(17.85±10.25),(11.87±2.35),(18.89±4.85)days],two groups of comparison,the difference was statistically significant(P＜0.05).The VAS scores of anal pain in the study group on 1 day,3 days and 7 days after the operation were(4.25±0.85)points,(2.89±0.54)points and(2.00±0.30)points,respectively.The scores of perianal edema were(1.87±0.36)points,(1.41±0.30)points,and(1.00±0.20)points,respectively.The hematochezia scores were(1.85±0.21)points,(1.34±0.18)points,and(0.85±0.13)points,respectively.Which were better than that of control group[(7.56±1.10),(6.54±1.03),(4.87±1.00)][(2.40±0.58),(2.03±0.49),(1.87±0.45)][(2.45±0.55),(2.03±0.47),(1.88±0.25)],and the differences were statistically significant(P＜0.05).The recurrence rate was 2.50％in the study group and 17.50％in the control group(P＜0.05).The scores of SF,MH,PF and GH of the Modified Health Survey Summary Form(SF-36)in the study group were(88.54±10.22,87.87±10.58,88.97±10.00,89.95±10.05)higher than those of the control group(67.52±10.00,70.10±11.25,71.10±9.85,70.00±10.00)(P＜0.05).Conclusion Hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of patients with annular prolapse mixed hemorrhoids has ideal surgical effect and little trauma,which is beneficial to promoting postoperative rehabilitation,alleviating anal pain,improving anal edema and hematostoecium,and improving quality of life.

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

Objective:This study aims to investigate the predictive performance of serum levels of white blood cell count(WBC),D-dimer(D-D)and N-terminal pro-brain natriuretic peptide(NT-proBNP)for major adverse cardiovascular events(MACE)in elderly patients with acute ST-segment elevation myocardial infarction(ASTE-MI).Methods:A total of 70 elderly patients with ASTEMI treated in Bozhou People's Hospital between April 2020 and May 2023 were prospectively selected as observation group.Incidence of MACE during 1-year follow-up were recorded,another 50 patients with unstable angina pectoris treated in our hospital simultaneously were selected as control group.Serum levels of WBC,D-D and NT-proBNP were compared among above groups.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum WBC,D-D and NT-proBNP for MACE in elderly patients with ASTEMI.A nomogram was established,and calibration curve and deci-sion curve analysis(DCA)were used to evaluate the performance of model.Results:A total of 40 cases(59.70％)experienced MACE during one-year follow-up.Compared to those in control group,patients in observation group had significant higher serum WBC[(11.43±1.98)×109/Lvs.(6.30±1.99)× 109/L],D-D[(0.91±0.20)mg/L vs.(0.47±0.18)mg/L]andNT-proBNP[(192.31±63.19)pg/ml vs.(114.05±22.79)pg/ml](P＜0.001 all).Compared to participants without MACE,those with MACE had significantly higher serum WBC[(13.33±1.90)× 109/L vs.(10.27±0.98)× 109/L],D-D[(1.11±0.25)mg/L vs.(0.87±0.21)mg/L]and NT-proBNP[(238.73±50.22)pg/ml vs.(150.70±39.16)pg/ml](P＜0.001 all).ROC analysis showed that the ar-ea under the curve(AUC)of the combined detection of serum WBC(AUC=0.791,95％CI 0.677～0.879),D-D(AUC=0.767,95％CI 0.650～0.859)and NT-proBNP(AUC=0.733,95％CI 0.614～0.832)was 0.916(95％CI 0.825～0.969),which was significantly higher than those of single detections(Z=2.386,4.953,3.190,P=0.017,0.004,＜0.001).The total score of the nomogram model constructed based on the levels of WBC,D-D and NT-proBNP ranged from 70 to 126 points.The predicted incidence was basically consistent with the actual in-cidence.For the internal verification of the model,the AUC of ROC curve of the training set and the validation set was 0.863 and 0.926 respectively.The DCA curve was located above the critical curve,indicating that the model had a net benefit and good clinical effectiveness.Conclusion:Serum WBC,D-D and NT-proBNP significantly el-evated in elderly patients with ASTEMI.The combined detection of serum WBC,D-D and NT-proBNP levels has good predictive value for MACE in these patients.

Objective:To evaluate the clinical efficacy of"Shibao Decoction"in the management of late-onset hypogonadism(LOH)caused by deficiency of kidney essence.Methods:Sixty male patients with late-onset hypogonadism of kidney essence defi-ciency type were randomly assigned to the treatment group and the control group,each with 30 cases.The patients in treatment group were treated with oral Shibao Decoction,while the control group was treated with oral Testosterone Undecanoate Capsules.The patients in both groups were treated for 12 weeks.The PADAM symptom score,TCM syndrome score,serum total testosterone(TT),serum free testosterone(FT),sex hormone binding globulin(SHBG),body mass index(BMI),total skeletal muscle mass index(SMI),appendicular skeletal muscle mass index(ASMI),FBG,FINS,and insulin resistance index(HOMA-IR)levels were compared be-tween the two groups.Results:After treatment,PADAM scores for each item and TCM symptoms score decreased,TT and FT in-creased in both groups,all with statistically significant differences from those of pre-treatment(P＜0.05).The level of SHBG in the control group decreased(P＜0.05),which had not changed significantly in the treatment group(P＞0.05).After treatment,SMI and ASMI increased in both groups significantly(P＜0.05).BMI decreased in the control group(P＜0.05),which had not changed significantly in the treatment group(P＞0.05).The level of FINS decreased in the control group(P＜0.05),which had not changed significantly in the treatment group(P＞0.05).FPG had not changed significantly in both groups(P＞0.05),and the insulin resist-ance index(HOMA-IR)had significantly improved in both groups,all with statistically significant differences from those of pre-treat-ment(P＜0.05).After treatment,the total effective rates of PADAM score and TCM syndrome score in the treatment group were 73.3％and 86.6％respectively,and the total effective rates in the control group were 66.7％and 76.6％respectively.The total ef-fective rates of the two scores in the treatment group were slightly higher than those in the control group(P＞0.05).There was no sig-nificant difference in the indicators between the two groups after treatment,and the treatment group is generally comparable with the control group in the therapeutic effects(P＞0.05).And no adverse reactions occurred during treatment in both groups.Conclu-sion:The"Shibao Decoction"has a remarkable therapeutic effect on late-onset hypogonadism caused by deficiency of kidney essence and has good safety.It can be used as an alternative to testosterone undecanoate and is worthy of clinical promotion and application.

Objective To investigate the clinical effect of hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of mixed hemorrhoids with annular prolapse.Methods A retrospective analysis was conducted to select 80 patients with annular prolapse mixed hemorrhoids admitted to the anorectal Department of our hospital from January 2022 to April 2023.According to different treatment plans,they were divided into control group(n=40 cases)who received external stripping and internal ligation combined with tape ligation,and study group(n=40 cases)who received hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligation and suspension.The operative effect,operative status,postoperative anal pain,anal edema,stool blood score and quality of life were evaluated.Results The effective rate of the study group was 97.50％,which was higher than that of the control group(77.50％)(P＜0.05).The operation time,intraoperative blood loss,hospital stay and wound healing time of the research group were(25.03±10.00)minutes,(10.00±5.32)ml,(7.25±1.54)days and(12.21±2.00)days respectively.[is better than that of control group(29.85±14.00)minutes,ml(17.85±10.25),(11.87±2.35),(18.89±4.85)days],two groups of comparison,the difference was statistically significant(P＜0.05).The VAS scores of anal pain in the study group on 1 day,3 days and 7 days after the operation were(4.25±0.85)points,(2.89±0.54)points and(2.00±0.30)points,respectively.The scores of perianal edema were(1.87±0.36)points,(1.41±0.30)points,and(1.00±0.20)points,respectively.The hematochezia scores were(1.85±0.21)points,(1.34±0.18)points,and(0.85±0.13)points,respectively.Which were better than that of control group[(7.56±1.10),(6.54±1.03),(4.87±1.00)][(2.40±0.58),(2.03±0.49),(1.87±0.45)][(2.45±0.55),(2.03±0.47),(1.88±0.25)],and the differences were statistically significant(P＜0.05).The recurrence rate was 2.50％in the study group and 17.50％in the control group(P＜0.05).The scores of SF,MH,PF and GH of the Modified Health Survey Summary Form(SF-36)in the study group were(88.54±10.22,87.87±10.58,88.97±10.00,89.95±10.05)higher than those of the control group(67.52±10.00,70.10±11.25,71.10±9.85,70.00±10.00)(P＜0.05).Conclusion Hemorrhoidal artery ligation combined with ultrasonic knife resection,suture,ligature and suspension in the treatment of patients with annular prolapse mixed hemorrhoids has ideal surgical effect and little trauma,which is beneficial to promoting postoperative rehabilitation,alleviating anal pain,improving anal edema and hematostoecium,and improving quality of life.

Objective:To investigate the efficacy of endoscopic sclerotherapy for internal hemorrhoids and its effects on patients' bowel function.Methods:A total of 111 patients who received endoscopic sclerotherapy at Xi'an No. 3 Hospital from September 2019 to August 2020 were retrospectively included in this study. Clinical efficacy, postoperative complications, perianal discomfort, and abnormal defecation were compared among patients with grade Ⅰ, Ⅱ, and Ⅲ internal hemorrhoids at 1, 4, 8, 12 weeks, and 6 months after surgery.Results:After 6 months of follow-up, the overall response rate was 77.48% (86/111), and the cure rate was 77.17% (79/111). The response rate and cure rate for rectal bleeding were 83.75% (67/80) and 80.00% (64/80), respectively. The response rate and cure rate for prolapse were 82.46% (47/57) and 75.44% (43/57), respectively. There were no statistically significant differences in the response rates and cure rates for rectal bleeding and prolapse symptoms among patients with grade Ⅰ, Ⅱ, and Ⅲ internal hemorrhoids at each follow-up time point (all P>0.05). Among the 111 patients, 27.93% (31/111) experienced perianal discomfort, and 40.54% (45/111) reported abnormal defecation. The incidences of perianal discomfort and abnormal defecation were not statistically significant among patients with grade Ⅰ, Ⅱ, and Ⅲ internal hemorrhoids (both P>0.05). In patients with gradeⅠ and Ⅱ internal hemorrhoids, perianal discomfort symptoms began to improve 4 weeks after surgery, while symptoms of abnormal defecation started to improve 1 week after surgery. Conclusions:Endoscopic sclerotherapy has a good clinical efficacy for rectal bleeding and prolapse symptoms in patients with grade Ⅰ, Ⅱ, and Ⅲ internal hemorrhoids. Additionally, it improves perianal discomfort and abnormal defecation by identifying the anal canal transition zone in patients with internal hemorrhoids.

Objective To investigate the effect of epifriedelanol(Epi)on gene expression of P-glycoprotein(P-gp)in human colorectal adenocarcinoma cell line LS174T and its mechanism.Methods LS174T cells were divided into control group and experimental-L,-M,-H groups.Experimental-L,-M,-H groups were treated with 5,10,20 μmol·L-1 Epi,respectively.Control group was treated with 0.1％dimethyl sulfoxide.Polymerase chain reaction was used to detect the mRNA expression level of P-gp.Theeffect of Epi on multidrug resistance protein 1(MDR1/P-gp)luciferase activity was investigated by pregnane X receptor(PXR)-MDR1/P-gp dual luciferase reporter gene assay.In addition,Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB(NF-κB)pathway related proteins.Results The relative expression levels of P-gp mRNA in experimental-M,-H groups and control group were 52.24±5.19,23.00±3.52 and 100.00±9.00;the relative expression levels of P-gp protein were 86.37±9.96,74.85±15.92 and 100.00±12.91;the relative activities P-gp luciferase were 230.19±41.32,203.10±52.84 and 279.67±19.20;the relative expression levels of p65(RelA/p65)in nucleus were 132.36±23.93,145.96±25.15 and 100.00±10.88;the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β(p-IKKα/β)in cytoplasm were 184.00±54.82,290.10±49.59 and 100.00±15.34;the relative expression levels of phosphorylated NF-κB inhibitory protein α(p-IκBα)in cytoplasm were 125.73±18.77,133.69±20.25 and 100.00±8.12;the relative expression levels of IκBα in cytoplasm were 78.36±14.83,70.44±14.57 and 100.00±22.82,respectively.The above indexes of experimental-M and experimental-H groups were compared with control group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T,and the mechanism may be related to activation of NF-κB and suppression of PXR.