Objective To explore influencing factors in diagnosing stump vaginal lesions by comparing the clinical data of patients with vaginal wall resection after total hysterectomy.Methods This retrospective study included patients who underwent vaginectomy due to stump vaginal lesions[including high-grade intraepithelial lesion(HSIL)or cancer]in Obstetrics and Gynecology Hospital,Fudan University between Jan 1,2013 and Sep 30,2022.The diagnosis was confirmed based on pathology results after vaginal stump resection,then patients were categorized into HSIL group and vaginal cancer(VC)group.We analyzed the differences in clinical features between the groups and evaluated the diagnostic value of various indicators for vaginal cancer.Additionally,within the VC group,patients whose colposcopic biopsy showed HSIL while whose pathology upgraded to invasive cancer after stump colpotomy were classified as the high-grade pathologic invasive cancer group(HC group).We then compared the HSIL group and the HC group to assess the predictive value of each index for pathological escalation.Results Significant differences were observed between the HSIL and VC groups in terms of age,etiology of previous hysterectomy,proportion of clinical symptoms,proportion of abnormal physical examination findings,proportion of abnormal imaging findings,proportion of papillary lesions,proportion of vaginal roof lesions,and squamous cell carcinoma antigen(SCCA)(P<0.05).However,there were no significant differences in fertility,previous hysterectomy,or HPV infection rate.Abnormal physical examination and imaging findings demonstrated better diagnostic performance(AUC>0.7).The proportion of vaginal apex lesions was significantly higher in the HC group compared with the HSIL group(P<0.05).Conclusion Previous hysterectomy for cervical cancer,presence of clinical symptoms,abnormal physical findings,abnormal imaging manifestations,and lesions at the vaginal apex are significant influencing factors in the diagnosis of vaginal stump carcinoma.Although colposcopy remains the primary diagnostic method,vaginal resection should be considered to rule out invasive carcinoma when high-risk factors exist,even if colposcopic biopsy pathology suggests HSIL.

AIM To investigate the in vivo pharmacokinetics of chlorogenic acid,isoquercetin,ferulic acid,isorhamnetin and shionone in Asteris Radix et Rhizoma in rats.METHODS Twelve rats were randomly assigned into 2 groups and given intragastric administration of conventional dose(0.63 g/kg)and large dose(3.3 g/kg)of Asteris Radix et Rhizoma extracts,respectively,after which blood collection was made at 0.083,0.167,0.33,0.5,0.75,1,1.5,2,4,6,8,12,24 h,UPLC-MS/MS was adopted in the plasma concentration determination of various effective constituents,and main pharmacokinetic parameters were calculated.RESULTS Various effective constituents in the large dose group demonstrated prolonged t1/2,MRT0-∞ as compared with those in the conventional dose group(P＜0.05).After dose correction,Cmax of chlorogenic acid,isoquercetin,shionone in the large dose group displayed no obvious changes(P＞0.05),while Cmax of ferulic acid,isorhamnetin,and AUC0-t,AUC0-∞ of various effective constituents were higher than those in the conventional dose group(P＜0.05).CONCLUSION Various effective constituents in the high dose of Asteris Radix et Rhizoma can maintain high-concentration and long-time effects on rat bladder tissue.

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.

Objective:To investigate the association of lipid accumulation product(LAP),triglyceride glucose index(TyG)with the risk of coronary heart disease(CHD).Methods:A total of 433 patients admitted to Department of Cardiology,Cangzhou People's Hospital for chest pain between February 2021 and December 2021 were included and divided into case group(n=236)and control group(n=197)according to the results of coronary angiography.Gen-eral data,LAP,TyG and other biochemical indexes were compared between two groups.The subjects were grouped according to LAP and TyG quartiles(L1,L2,L3,L4;T1,T2,T3,T4),and different Logistic regression models were constructed to analyze the association of different LAP,TyG levels with the risk of CHD using the L1 group and the T1 group as references,respectively,and receiver operating characteristic(ROC)curve of LAP and TyG predicting risk of CHD were drawn.Results:Compared with participants in control group,those in case group had significant higher proportions of smoking(27.60％ vs.19.80％),diabetes(21.61％ vs.14.21％),hypertension(38.14％ vs.28.43％),dyslipidemia(36.86％ vs.24.87％)and body mass index(BMI)[(25.97±3.90)kg/m2 vs.(25.11±3.56)kg/m2],waist circumference[(85.44±5.39)cm vs.(83.59±5.39)cm],uric acid[325.50(270.25,378.25)μmol/L vs.300.00(245.00,365.00)μmol/L],homocysteine[13.34(10.90,16.46)μmol/L vs.12.27(10.26,15.00)μmol/L],leucocytes[(6.07±1.52)× 109/Lvs.(5.75±1.43)×109/L],LAP[39.84(30.06,59.02)vs.30.06(21.85,44.78)],and TyG[(8.86±0.57)vs.(8.56±0.60)](P＜0.05 or＜0.01).Multifactorial Logistic regression analysis showed that after adjusting for each risk factor,risk of CHD in L3 and L4 groups were significantly higher than that of L1 group,and risk of CHD in T3 and T4 groups were significantly higher than that of T1 group(P＜0.05 or＜0.01).ROC curve analysis showed that the area under curve(AUC)of LAP and TyG predicting the risk of CHD was 0.656(95％CI 0.609～0.701),0.665(95％CI 0.618～0.709)re-spectively,and the critical value was 30.21 and 8.73 respectively.Conclusion:LAP and TyG are risk factors for CHD,and with the elevation of their levels,the risk of CHD gradually increases.

Objective To explore influencing factors in diagnosing stump vaginal lesions by comparing the clinical data of patients with vaginal wall resection after total hysterectomy.Methods This retrospective study included patients who underwent vaginectomy due to stump vaginal lesions[including high-grade intraepithelial lesion(HSIL)or cancer]in Obstetrics and Gynecology Hospital,Fudan University between Jan 1,2013 and Sep 30,2022.The diagnosis was confirmed based on pathology results after vaginal stump resection,then patients were categorized into HSIL group and vaginal cancer(VC)group.We analyzed the differences in clinical features between the groups and evaluated the diagnostic value of various indicators for vaginal cancer.Additionally,within the VC group,patients whose colposcopic biopsy showed HSIL while whose pathology upgraded to invasive cancer after stump colpotomy were classified as the high-grade pathologic invasive cancer group(HC group).We then compared the HSIL group and the HC group to assess the predictive value of each index for pathological escalation.Results Significant differences were observed between the HSIL and VC groups in terms of age,etiology of previous hysterectomy,proportion of clinical symptoms,proportion of abnormal physical examination findings,proportion of abnormal imaging findings,proportion of papillary lesions,proportion of vaginal roof lesions,and squamous cell carcinoma antigen(SCCA)(P<0.05).However,there were no significant differences in fertility,previous hysterectomy,or HPV infection rate.Abnormal physical examination and imaging findings demonstrated better diagnostic performance(AUC>0.7).The proportion of vaginal apex lesions was significantly higher in the HC group compared with the HSIL group(P<0.05).Conclusion Previous hysterectomy for cervical cancer,presence of clinical symptoms,abnormal physical findings,abnormal imaging manifestations,and lesions at the vaginal apex are significant influencing factors in the diagnosis of vaginal stump carcinoma.Although colposcopy remains the primary diagnostic method,vaginal resection should be considered to rule out invasive carcinoma when high-risk factors exist,even if colposcopic biopsy pathology suggests HSIL.

AIM To prepare the oral lyophilized tablets of gastrodin-coated micropowder.METHODS Fluidized bed bottom spray method was adopted in the preparation of coated micropowder,after which the oral lyophilized tablets were further prepared.With mannitol consumption,pullulan consumption and xanthan gum consumption as influencing factors,comprehensive score for appearance traits,moisture,disintegration time and the sedimentation volume ratio as an evaluation index,the formulation was optimized by Box-Behnken method,then the taste-masking effect,appearance traits,moisture,disintegration time,content uniformity and dissolution rate were investigated.RESULTS The optimal formulation was determined to be 44.20 mg/tablet for mannitol consumption,3.70 mg/tablet for pullulan consumption,1.30 mg/tablet for xanthan gum consumption,66.67 mg/tablet for coated micropowder,and 1.5 mg/tablet for sucralose micropowder,the comprehensive score was 17.43.The obtained oral lyophilized tablets demonstrated good taste-masking effect,appearance traits and content uniformity with the disintegration time of 3-5 s,whose dissolution rates were less than 5％within 3 min in the simulated oral environment(phosphate buffer solution at pH 6.8)and more than 85％within 15 min in the simulated gastric environment(hydrochloric acid solution at pH 1.2).CONCLUSION The oral lyophilized tablets of gastrodin-coated micropowder display good taste,ease of swallowing and simple and feasible preparation process,which can provide a new idea for the taste improvement of other oral lyophilized tablets and unpleasant-smelling raw medicines.

AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P＜0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P＜0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P＜0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P＜0.05,P＜0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P＜0.05,P＜0.01);mitigated inflammation and collagen deposition(P＜0.05,P＜0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.05,P＜0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

Objective:To investigate the association of lipid accumulation product(LAP),triglyceride glucose index(TyG)with the risk of coronary heart disease(CHD).Methods:A total of 433 patients admitted to Department of Cardiology,Cangzhou People's Hospital for chest pain between February 2021 and December 2021 were included and divided into case group(n=236)and control group(n=197)according to the results of coronary angiography.Gen-eral data,LAP,TyG and other biochemical indexes were compared between two groups.The subjects were grouped according to LAP and TyG quartiles(L1,L2,L3,L4;T1,T2,T3,T4),and different Logistic regression models were constructed to analyze the association of different LAP,TyG levels with the risk of CHD using the L1 group and the T1 group as references,respectively,and receiver operating characteristic(ROC)curve of LAP and TyG predicting risk of CHD were drawn.Results:Compared with participants in control group,those in case group had significant higher proportions of smoking(27.60％ vs.19.80％),diabetes(21.61％ vs.14.21％),hypertension(38.14％ vs.28.43％),dyslipidemia(36.86％ vs.24.87％)and body mass index(BMI)[(25.97±3.90)kg/m2 vs.(25.11±3.56)kg/m2],waist circumference[(85.44±5.39)cm vs.(83.59±5.39)cm],uric acid[325.50(270.25,378.25)μmol/L vs.300.00(245.00,365.00)μmol/L],homocysteine[13.34(10.90,16.46)μmol/L vs.12.27(10.26,15.00)μmol/L],leucocytes[(6.07±1.52)× 109/Lvs.(5.75±1.43)×109/L],LAP[39.84(30.06,59.02)vs.30.06(21.85,44.78)],and TyG[(8.86±0.57)vs.(8.56±0.60)](P＜0.05 or＜0.01).Multifactorial Logistic regression analysis showed that after adjusting for each risk factor,risk of CHD in L3 and L4 groups were significantly higher than that of L1 group,and risk of CHD in T3 and T4 groups were significantly higher than that of T1 group(P＜0.05 or＜0.01).ROC curve analysis showed that the area under curve(AUC)of LAP and TyG predicting the risk of CHD was 0.656(95％CI 0.609～0.701),0.665(95％CI 0.618～0.709)re-spectively,and the critical value was 30.21 and 8.73 respectively.Conclusion:LAP and TyG are risk factors for CHD,and with the elevation of their levels,the risk of CHD gradually increases.

Objective To investigate the antitumor effects of triptolide against CT26 colon cancer and its impact on the expression of Polo-like kinase-1(PLK-1)protein.Methods Forty clean grade BALB/c mice,each mouse was implanted with 1×106 CT26 cells into the dorsal side of the right forelimb to establish a tumor-bearing mouse model.Experimental animals were randomly divided into four groups,the tumor model group(saline control),the positive drug group[oxaliplatin,5 mg/(kg·d)],the low-dose triptolide group[50 μg/(kg·/d)],and the high-dose triptolide group[100 μg/(kg·d)].The drugs were administered through intraperitoneal injection(10 times in total,once every other day).The in vitro effects of the drugs on the proliferation,migration,invasion,and mitosis of CT26 cells were also assessed.Results Triptolide significantly inhibited the proliferation,migration,and invasion of CT26 colon cancer cells,and disrupted the separation of centrosomes and the correct arrangement of chromosomes during the prophase of mitosis in tumor cells.The binding energy of triptolide and PLK-1 protein was-7.1 kcal/mol,and it could down-regulate the expression of PLK-1 in CT26 cells.Conclusion Triptolide exerts its antitumor effects against CT26 colon cancer by downregulating the expression of PLK-1.