Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

OBJECTIVE To acquire the real-world incidence of ceftazidime-avibactam sodium(CAZ)-related ad-verse reactions of blood system among a large sample of drug medication patients based on the active monitoring system so as to provide reference for safe clinical use of drugs.METHOD With the help of'Adverse Drug Event Active Surveillance and Assessment System-Ⅱ'(ADE-ASAS-Ⅱ),the use of CAZ of the patients who were hospi-talized in Chinese PLA General Hospital from Jan.1,2020 to Dec.31,2023 were retrospectively and automatical-ly monitored,the patients who were alarmed by system were evaluated by two persons,the incidence rates of CAZ-related thrombocytopenia,hemoglobin decreased and leucopenia were calculated,and the related influencing factors were analyzed.RESULTS Among the 278 case-times(191 cases)of patients who were treated with drugs and were enrolled in the study,there were 3(1.08％)case-times of thrombocytopenia,8(2.88％)case-times of hemoglobin decreased and 19(6.83％)case-times of leucopenia;the total incidence of adverse reactions of blood system was 10.79％.Logistic regression analysis showed that age and duration of drug administration were the in-fluencing factors for the CAZ-related adverse reactions of blood system.CONCLUSIONS It is common for the CAZ-related adverse reactions of blood system.The middle-aged and elderly patients who take drug therapy for a long time period are more likely to have the blood system-related adverse reactions.It is necessary to focus on the monitoring of renal function of the patients and adjust the dosage of administration in a timely manner so as to re-duce the incidence of adverse reactions of the blood system.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective:To explore the symptom improvement effect of a self-made eczema and dermatitis conditioning formula combined with Qingpeng ointment on damp heat type eczema.Methods:A prospective study was conducted on 70 patients with damp heat type eczema ffrom June 2023 to August 2024.Random number table method was used to divide them into two groups.Among them,35 cases were in the single group and treated with Qingpeng plaster alone,while the remaining 35 cases were in the combination group and treated with a self-made eczema and dermatitis conditioning formula orally combined with Qingpeng plaster.After one month of treatment,the clinical efficacy,TCM syndrome scores before and Post-treatment,disappearance time of main symptoms,and the long-term recurrence rate was also compared.Results:The total effective rate of the combined group was 91.43％,which was higher than that of the single group(71.43％,P＜0.05);Before treatment,there was no significant difference in the scores of TCM syndromes between the two groups(P＞0.05).Post-treatment,the scores of TCM syndromes related to the main symptoms(skin erythema,papules,blisters,obvious exudation,severe itching,and burning sensation in the skin lesions)and secondary symptoms(dry mouth,bitter mouth,yellow and red urine,sticky stool or constipation)in both groups decreased,and the combined group was lower than the single group(P＜0.05);The disappearance time of skin burning sensation,exudation,erythema,itching,and skin lesion related symptoms in the combined group was shorter than that in the single group(P＜0.05);Two groups of patients were followed up for six months Post-treatment,and there were no lost cases during the follow-up period.There was no difference between the combined group and the single group(x2=3.214,P=0.073).Conclusion:The combination of self-made eczema and dermatitis conditioning formula and Qingpeng ointment can improve the clinical efficacy of damp heat type eczema,reduce its TCM syndrome score,shorten the duration of main symptoms,and lower the long-term recurrence rate of patients.The mechanism may be related to the regulation of T lymphocyte subsets in eczema patients by the self-made eczema and dermatitis conditioning formula,and the reduction of the body's inflammatory response.

Objective:Explore the effect of modified position on correction of breech presentation and the ma-ternal and infant outcomes in primiparas at 30-34 weeks of gestation in the midwifery clinic.Methods:From Jan-uary to December2024,274 primiparas at30-34 weeks of gestation who visited the midwifery clinic of The Gener-al Hospital of Northern Theater Command were selected.They were randomly divided into two groups according to the coin-tossing method.Through the inclusion exclusion,and elimination criteria,the selected pregnant women were finally categorized into the knee-chest position group(control group,n=126)and the modified position group(observation group,n=140).The success rate of breech presentation correction,delivery mode,duration of labor,1-minute and 5-minute Apgar scores of vaginally delivered infants,umbilical artery blood gas,postpartum re-covery,and postpartum depression incidence were compared between the two groups.Results:The success rate of breech presentation correction in the observation group was significantly higher than that in the control group(77.9%vs 58.7%,P<0.05).After breech presentation correction,the vaginal delivery rate was higher in the ob-servation group than in the control group(80.7%vs 66.2%,P<0.05).Among women who achieved vaginal de-livery,the intrapartum complication rate was significantly lower in the observation group than in the control group(22.7%vs.46.9%,P<0.05).The duration of the first stage of labor(557.7±195.5 min vs.629.6±208.2 min)and the second stage of labor(67.7±11.4 min vs.79.6±10.3 min)was significantly shorter in the observation group than in the control group(P<0.05).The pH of umbilical artery blood gas of newborns in the observation group delivered vaginally was significantly higher than that in the control group(7.367±0.028 vs.7.322±0.027,P<0.05).There were no statistically significant differences in the1-minute and5-minute Apgar scores of vaginally delivered infants,base excess,and lactate between the two groups(P>0.05).The initial time of lactation(21.7±4.4 h vs.23.5±4.1 h),time to ambulation(8.2±1.2 d vs.9.2±1.4 d),time for lochia to subside(29.6±4.8 d vs.34.1±4.8 d),and postpartum hemorrhage(298.1±56.1 ml vs.362.9±42.6 ml)in the observation group were significantly lower than those in the control group(P<0.05).There were no statistically significant differ-ences in the depression scores(EPDS)at 1 week and 6 weeks postpartum between the two groups of women with vaginal delivery(P>0.05).Conclusions:The modified position in the midwifery clinic significantly improves the success rate of breech presentation correction for primiparas at 30-34 weeks of gestation,good maternal and infant outcomes,and could be widely applied in clinical practice.

Objective:To analyze the gene chip related to dermatomyositis based on bioinformatics,to explore the immune in-filtration mechanism of key genes in dermatomyositis by CIBERSORT deconvolution algorithm,and to predict the therapeutic targets of dermatomyositis by network pharmacology.Methods:The gene microarray of dermatomyositis was searched in GEO database,and the differentially coexpressed genes were screened and analyzed.The differentially coexpressed genes were analyzed by GO analysis,KEGG analysis,protein interaction network construction(PPI)by R software package.Verify the expression levels of key genes,and the correlation of immune cell infiltration was analyzed by CIBERSORT deconvolution method.Through the medical ontology informa-tion retrieval platform Coremine medical database,the traditional Chinese medicine treatment targets of dermatomyositis were screened and summarized.Results:A total of 196 differentially expressed genes were screened.GO enrichment analysis showed that these differentially expressed genes were mainly concentrated in defense response to virus,blood particles,double-stranded RNA binding,polypeptide antigen binding,and so on.KEGG enrichment analysis showed that it was enriched in RIG-Ⅰ-like receptor sig-nal pathway,Toll-like receptor signal pathway and other signal pathways related to the pathogenesis of dermatomyositis.Finally,four key genes of dermatomyositis,STAT1,ISG15,IRF7 and IRF9 were obtained.Through CIBERSORT algorithm,M1 macrophages,M2 macrophages and CD8+T cells were the three kinds of cells with the highest average proportion and the most obvious immune infil-tration,and there was a significant positive correlation between activated natural killer cells and activated dendritic cells,while there was a significant negative correlation between resting mast cells and activated mast cells.The therapeutic targets of traditional Chinese medicine such as fish brain stone were predicted based on Coremine medical database;through channel analysis,it could be found that these traditional Chinese medicines are mainly attributed to liver meridian,lung meridian,spleen meridian;efficacy analysis is mainly focused on clearing heat,detoxification,promoting blood circulation and removing blood stasis,relieving cough and resolving phlegm and so on.Conclusion:Four key genes and some key signal pathways of dermatomyositis,STAT1,ISG15,IRF7 and IRF9 were obtained by bioinformatics method,the immune infiltration mechanism was analyzed by CIBERSORT algorithm,and the thera-peutic potential targets of traditional Chinese medicine were screened out to provide direction for the pathogenesis and treatment of der-matomyositis.

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 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 investigate the dynamic characteristics of human papillomavirus (HPV) genomic integration during cervical lesion progression and the clinical value of HPV integration detection in stratify HPV-positive women, and to explore its molecular mechanisms in cervical carcinogenesis.Methods:A prospective cohort study was designed to enroll high-risk HPV (HR-HPV) positive women who underwent cervical cancer screening in Drum Tower Hospital Affiliated to Nanjing University Medical School and Nanjing Maternity and Child Health Care Hospital from July 2022 to July 2024. Cervical exfoliated cells samples were collected, and HPV whole genome targeted capture and high-throughput sequencing technology were used. The HPV integration patterns, host gene functional region distribution and pathway enrichment characteristics of 157 samples with different cervical lesions grades were analyzed, including 31 cases of normal cervix, 40 cases of cervical intraepithelial neoplasia (CIN) Ⅰ, 32 cases of CIN Ⅱ, 42 cases of CIN Ⅲ, and 12 cases of cervical cancer.Results:HR-HPV integration was detected in 80.2% (126/157) of the 157 HR-HPV positive samples. The incidence of HR-HPV integration in cervical cancer patients was 12/12, which was higher than that in normal women (77%, 24/31). The incidence of HPV16 integration was significantly higher in high-grade lesions, and the incidence of HPV16 integration was 43% (18/42) in CIN Ⅲ patients and 8/12 in cervical cancer patients ( P<0.001). A total of 14 438 integration events were detected in 126 samples with HPV integration. The integration sites were mainly distributed in the host intergenic region (51.0%, 7 359/14 438) and intronic region (38.1%, 5 494/14 438), and the integration frequency of viral L1 gene was the highest (28.4%, 4 498/16 781). Functional enrichment analysis showed that HPV integration-related host genes were significantly enriched in transport of small molecules,cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway, and purine ribonucleotide biosynthetic process, which synergistically drove carcinogenesis through multiple mechanisms. Conclusions:HPV integration events are significantly associated with the progression of cervical lesions. HPV integrated detection based on cervical exfoliated cells is expected to optimize the current screening strategy, reduce excessive intervention of HPV positive women and facilitate their accurate triage management.

Objective To investigate the feasibility and safety of transoral transgastric natural orifice transluminal endoscopic surgery(TG-NOTES)cholecystectomy in miniature pigs.Methods A total of 11 miniature pigs were selected as the experimental subjects and underwent TG-NOTES cholecystectomy.These pigs were divided into the Group A and Group B according to the surgical procedures.Among them,7 miniature pigs in the Group A underwent endoscopic cholecystectomy without dissecting the gallbladder triangle,while 4 miniature pigs in the Group B underwent endoscopic cholecystectomy after dissecting the gallbladder triangle.The success rate of surgery,the time of each stage of surgery,the incidence of complications,the success rate of cholecystectomy and the survival rate of miniature pigs in the two groups were counted.One miniature pig in the Group A and 4 miniature pigs in the Group B were selected for survival experiments.After surviving for 1 week,they were killed and dissected to observe the healing of incision and incidence of complications.Results The surgical survival rate of experimental animals was 100%,and the success rate of cholecystectomy was 100%.There was no significant difference in the surgical time,time of cut the stomach into the abdomen,time of gallbladder exploration or time of gallbladder removal of miniature pigs between the two groups(P>0.05).The time of ligating gallbladder artery of miniature pigs in the Group B was longer than that in the Group A,and the time of isdating gallbladder was shorter than that in the Group A,with statistically significant differences(P<0.05).There was no significant difference in the average number of complications of miniature pigs between the two groups(P>0.05).The dissection of animals after survival experiments revealed that the incisions healed well without serious complications.Conclusion This study successfully establishes the surgical model of TG-NOTES cholecystectomy,and confirms the safety and feasibility of TG-NOTES cholecystectomy.