Objective To explore the mechanism of acute liver injury induced by Cortex dictamni through network pharmacology and in vivo experiment in animal.Methods The chemical constituents and targets of Cortex dictamni were retrieved from TCMSP,TCMIP and SwissTargetPrediction databases,and the related targets of liver injury diseases were identified through GeneCards and CTD databases.The protein interaction network of the intersection targets was analyzed by STRING database and the core targets were selected.The GO function and KEGG pathway enrichment analysis were completed by DAVID database,and the multi-level association network diagram of"drug-component-target"was constructed by Cytoscape software.In the animal study,Cortex dictamni was administered to mice at a dosage of 92.7 g/(kg·d)via intragastric administration,and the biological samples were collected after 7 days.The pathological changes of liver were observed by hematoxylin-eosin(HE),Masson and Oil Red O staining.The expression levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and lactate dehydrogenase(LDH)in serum,as well as malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),and interleukin(IL)-1β in liver tissues,were quantified using enzyme-linked immunosorbent assay(ELISA).The expressions of protein kinase B1(AKT1),IL-6,TNF-α,tumor protein p53(TP53),cystatin 3(CASP3),and IL-1β mRNA in liver tissues were determined using real-time quantitative reverse transcription PCR(qRT-PCR).Molecular docking was employed to verify the binding affinity of potentially toxic components to their respective targets.Results A total of 14 chemical constituents,244 predicted targets and 202 intersection targets with liver injury were obtained.The GO biological process analysis mainly involved positive regulation of gene expression,negative regulation of apoptosis process.KEGG pathway enrichment analysis mainly included cancer pathway and PI3K-Akt,TNF,IL-17 signaling pathways.The pathological sections revealed severe hemorrhage,a considerable amount of hepatocyte necrosis,nuclear fragmentation or dissolution in the liver tissues of mouse with HE staining after the administration of Cortex dictamni.Masson staining showed evident fibrosis in the liver tissues,while Oil Red O staining indicated a substantial production of lipid droplets.Compared with the control group,the ELISA results demonstrated a significant increase in serum AST,ALT,ALP,LDH levels,as well as hepatic MDA,TNF-α,and IL-1β levels(P<0.05),and a decrease in hepatic SOD levels(P<0.05)in the treated group.The qRT-PCR results indicated a significant elevation in the expression levels of relevant mRNAs in the liver tissues of the treated mice(P<0.05).Molecular docking showed that the potentially toxic components of obacunone,dictamnine and fraxinellon had good binding affinity to AKT1,IL-6,TNF-α,TP53,CASP3 and IL-1β.Conclusion Obacunone,dictamnine,fraxinellon,and limonin might be the potential toxic components of acute liver injury induced by Cortex dictamni in mice.Cortex dictamni could act on the liver by changing the expressions of AKT1,IL-6,TNF-α,TP53,CASP3,IL-1β and other proteins,affecting energy metabolism,cell differentiation,inflammation,oxidative stress and immunity,leading to liver injury.

Dictamni cortex is the root bark of Rutaceae plants.It is the main medicinal part and the key drug of 'Zhuhuang Fengbi'.It has the effects of clearing heat and detoxifying,dispelling wind and drying dampness,and relieving itching.Dictamni cortex mainly contains 228 chemical components such as alkaloids,sesquiterpenes,limonoids,fatty acids,volatile oils,flavonoids,steroids,etw.Its pharmacological activities in vivo and in vitro include antibacterial activity,anti-inflammatory activity,hepatoprotective activity,cardiovascular protection activity,insecticidal activity,anticancer activity,anti-allergic activity,and improvement of gastrointestinal activity.It has been reported that Dictamni cortex also has potential hepatotoxicity,among which dictamnine,fraxinellone and limonin compounds are potential hepatotoxic components.In this paper,the chemical constituents,pharmacological effects and toxicity of Dictamni cortex are reviewed by consulting domestic and foreign literature,to provide theoretical support for the clinical rational application and related product development of Dictamni cortex.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective This study was aimed to investigate the effects of ω-3 polyunstaurated fatty acids (ω-3 PUFAs) on the growth of gastric cancer cells in nude mice,and to find whether the Ros homolog gene Rho-associated coiled-coil containing protein kinase 1 (RHO-ROCK1) signaling pathway is involved.Methods 16 BALB/C nude mice were injected subcutaneously with SGC7901 gastric cancer cells to establish the tumor-bearing mouse model.The mice were randomized:control group (normal saline) and intervention group (ω-3 PUFAs).The mRNA expression of Ros homolog gene family,member A (RHOA),RHOC,and ROCK1 in tumor tissue were detected by quantitative polymerase chain reaction (qPCR).Immunofluorescence and Western blot were used to detect RHOA,RHOC,and ROCK1 protein expression.Results The volume and weight of the tumors in the ω-3 PUFAs group were slightly smaller than that in the control group (P ＞ 0.05).Compared to the control group,hematoxylin and eosin staining showed multifocal tumor necrosis in the ω-3 PUFAs group,while the tumors of the control group showed abundant blood supply.qPCR and Western blot showed that the mRNA and proteins expression of RHOA and ROCK1 in the ω-3 PUFAs group was significantly lower than those in the control group (P ＜ 0.05).The immunofluorescence redults also showed that the expression of these proteins in the ω-3 PUFAs group was slightly lower than that in the control group.Conclusions These results suggested that ω-3 PUFAs may affect the growth of gastric cancer in nude mice by affecting the expression of RHOA,RHOC and ROCK1,thus inhibiting the excessive proliferation of gastric cancer cells and leading to tumor necrosis.

Objective To survey the prevalence of stress urinary incontinence(SUI)and related knowledge among postpartum women in Shanghai Melong district.Methods A questionnaire survey on the knowledge of stress urinary incontinence was conducted among 317 postpartum women who were home visited by Meilong Community Health Service Center between March 2017 and June 2017.The self-designed questionnaire included the general situation(age, height, weight, occupation, menstrual history), pregnancy and childbirth, and knowledge of SUI; the International Consultation on Incontinence Questionnaire Short form(ICIQ-SF)was also used.Total 317 questionnaires were distributed and 313 valid ones were retrieved(98.73%).Results The prevalence of SUI in the participants was 26.84%(84/313).Multivariate logistic regression showed that BMI≥24 kg/m2(OR=6.24, 95% CI: 3.41 -11.41), complicated metabolic syndrome(OR=9.84, 95% CI: 2.77 -34.96)and birth weight of previous child ≥4 kg(OR=0.09,95%CI:0.04-0.19)is independent risk factors for the development of SUI.The average SUI knowledge score was(10.39 +8.65)points, only 26.20%(82/313)of the participants knew Kegel training(score 5.99 ±1.60).The SUI knowledge level of postpartum women was associated with educational level(F=12.41),occupation(F=9.06), income(F=4.05), reproductive history(F=10.98)and presence of urinary incontinence symptom(F=22.31)(all P<0.05). Conclusion The knowledge level of maternal stress urinary incontinence in Meilong district is relatively low,and the publicity of SUI and pelvic floor rehabilitation knowledge should be enhanced for the pregnant women.

Objective To analyze the molecular characteristics and prognosis in acute myeloid leukemia patients with AML1/ETO.Methods The clinical data of 63 cases of acute myeloid leukemia (AML) patients with AML1/ETO positive were analyzed retrospectively.56 cases of AML patients with AML1/ETO negative in the same period were analyzed as control.Characteristics in morphology,immunology,cytogenetics,molecular biology and the clinical effects of treatment were studied and analyzed.Results M2a was 57.12 ％ (36/63),M2b was 33.33 ％ (21/63) in AML with AML1/ETO.The percent of initial marrow blasts was 0.46±0.16.The positive rate of CD34,CD13,CD33,CD19,CD7 and CD56 was 67.21％,52.46 ％,40.98 ％,63.93 ％,4.92 ％ and 50.82 ％,respectively.The rate of t(8;21) translocation was 82.54 ％.There was 4.76 ％ with additional chromosome abnormality,three cases with EV1 1and one case with MLL/AT9.The overall CR rate,the relapse rate,the 3-year and the 5-year overall survival rate was 71.43 ％,51.11％,(43.01±5.31) ％ and (32.79±3.81) ％,respectively.There was no significant difference compared with the control group (P ＞ 0.05).But extramedullary infiltration,the expression of CD56 and additional chromosome abnormality had statistical effects on overall survival (P ＜ 0.05).Conclusions There has unique characteristics in AML with AML1/ETO.The effects of treatment and the prognosis are affected by many factors,so the efficacy and prognosis of AML with AML1/ETO couldn' t just depend on AML1/ETO.

Purpose To investigate the clinicopathological features of adolescent mixed epithelial and stromal tumor of the kidney ( MESTK) and improve recognization of this rare disease. Methods Clinicopathological and immunohistochemical characteristics of MESTK occured in 17-year-old girl were studied. Reviewed the related literatures, clinical and pathological characteristics of adoles-cent MESTK were analysed comprehensively. Results Congenital perineal spill was the main clinical manifestations. Microscopically, the tumor showed nodules and was composed of a mixture of epithelial and stromal elements. Glands were lined with columnar or cilia-ted columnar cells. Stromal cells surrounding glands seemed like ovaries and away from glands seemed like the differentiation of smooth muscle. Immunohistochemical staining revealed that the epithelial cells were positive for CK7 and vimentin. Stromal cells expressed desmin, smooth muscle actin ( SMA) , ER and PR. It was noteworthy that stromal cells away from glands expressed desmin. Conclu-sions As a kind of rare benign neoplasm of kidney, MESTK often occurs in perimenopausal women. But MESTK can also occur in ad-olescence, and has nothing to do with the use of hormone. Therefore, the renal tumor occurred in teenagers with biphasic differentiation should be differentiated from MESTK.

Objective To compared two classical rat models of nephrotic syndrome and to provide some reference data to researchers.Methods Thirty male SD rats were randomly divided into control group,puromycin aminonucleoside-induced nephrotic syndrome (PAN) group and adriamycininduced nephrotic syndrome (ADR) group.The body weight,twenty four hour proteinuria level,serum albumin concentration,cholesterol concentration,creatinine and urea concentration were measured.The renal pathology change was evaluated.The drug toxic effects,administration methods and the costs were also compared.Results There was no significant difference in body weight and hair color between control group and PAN group.Compared to control group,the body weight of the rats significantly decreased at day 15 and day 21 in ADR group (P ＜ 0.01),accompanied by epilation and diarrhea.Compared to control group,the 24-hour urinary protein levels increased significantly at day 10 (P ＜ 0.01),day 15 (P ＜ 0.01),and reached the peak level at day 15 (P ＜ 0.01),day 21 (P ＜ 0.01) in PAN group and ADR group respectively.Compared to control group,the serum albumin concentration decreased significantly at day 10 (P＜0.01),and return to normal level at day 15.The serum cholesterol concentration was increased significantly at day 10 (P ＜ 0.01) and return to normal at day 15 in PAN group.Compared to control group,the serum albumin concentration was decreased significantly at day 15 (P＜0.05) and return to normal at day 21 in ADR group.No significant difference of serum creatinine and serum urea nitrogen levels were found among three groups.Compared to control group,the width of foot process increased significantly at day10 (P ＜ 0.01) and day 15 (P ＜ 0.05) in PAN group and ADR group respectively.To successfully induce a nephrotic rat model (per 100 g),the cost of PAN group was 3.1 times of ADR group (578.10 yuan vs 186.94 yuan).Conclusions Nephrotic syndrome can be induced by both PAN and ADR.The administration of PAN via intraperitoneal injection is more convenient as compared to ADR via tail intravenous injection.Compared to ADR,PAN can induce nephrotic syndrome model more rapidly,with more consistent detection index,and less toxic effects,but its cost is more expensive.

Objective To investigate the characteristics and risk factors of hospital infection in elderly patients with acute leukemia and provide basis for its prevention and treatment. Methods The hospital infection rate,infection sites,pathogenic bacteria and infectious factors of 116 elderly patients with acute leukemia between January 1999 and January 2008 were analyzed retrospectively,and compared with groups of non-elderly patients in the corresponding period. Results The incidence of hospital infection [62.9 %(73/116)]and death[52.1 %(38/116)]in elderly patients were higher than that of non-elderly ones (P <0.01). The most commonly infective sites were oral cavity and respiratory system. The multiple and serious infection in elderly patients was more than that of non-elderly noes. The common pathogenic bacteria were mainly grant-negative one. The results of multivariate aralysis showed that the absolute neutrophil count in peripheral blood,cycles of chemotherapy,latest infections,stages of treatment,length of hospitalization and seasons on hospitalization were found as independent risk factors for hospital infection in elderly patients with acute leukemia. Conclusion The incidence of hospital infection and death in elderly patients was high. The absolute neutrophil count in peripheral blood,cycles of chemotherapy,latest infections,stages of treatment,length of hospitalization and seasons on hospitalization are independent risk factors for elderly patients with acute leukemia.

Objective To investigate various factors influencing long-term survival of the patients with APL. Methods The clinical data of 62 cases with APL were analyzed retrospectively. Univariate and multivariate analysis of the potential factors influencing survival and prognosis were carried out with Log-Rank and Cox regression method, including sex, age, initial WBC count, initial Plt count, the level of LDH,first induction regimen, length from induction therapy to CR, and post-remission therapy. Results 62 cases were followed up for 6 to 102 months. 5-year OS and relapse-free survival (RFS) were (77.1±6.2)% and (71.4± 3.68)%, respectively.Univariate analysis revealed that initial WBC count, first induction regimen, length from induction therapy to CR and post-remission therapy were important prognostic factors for long-term survival. Multivariate analysis demonstrated that initial WBC count and post-remission therapy were associated with RFS and OS. Conclusion The post-remission therapy combining ATRA, As2O3 and chemotherapy would significantly improve the long-term survival of APL patients entering CR.