Traditional Chinese Medicine Treats Hepatic Fibrosis via NF-κB Signaling Pathway： A Review / 中国实验方剂学杂志

Hepatic fibrosis is a common complication of chronic liver disease， seriously affecting patients' quality of life and leading to severe consequences such as cirrhosis and liver cancer. Modern medicine has made progress in the treatment of hepatic fibrosis， while it still faces certain challenges and limitations. Therefore， seeking new therapeutic strategies is of great clinical significance. The nuclear factor-κB （NF-κB） signaling pathway plays a role in regulating inflammation and immune responses. Recent studies have shown that the NF-κB signaling pathway plays a key role in the occurrence and development of hepatic fibrosis. The abnormal activation of the NF-κB signaling pathway leads to the overexpression of genes related to liver inflammation and fibrosis， thereby promoting the development of hepatic fibrosis. Traditional Chinese medicine （TCM） is a traditional treatment method with unique advantages and potential. In recent years， increasing studies have proved that TCM can treat hepatic fibrosis by regulating the NF-κB signaling pathway. The active ingredients in Chinese herbal medicines can intervene in the activation of the NF-κB signaling pathway to inhibit inflammatory responses， thereby reducing the severity of hepatic fibrosis. This article reviews the mechanisms of TCM in treating hepatic fibrosis via the NF-κB signaling pathway and evaluates the efficacy and discusses the clinical application prospects of relevant Chinese herbs and formulae， aiming to provide references for further research and clinical practice.

The use of portal vein embolization combined with lenvatinib and a PD-1 inhibitor to treat patients with initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.

Perioperative immunotherapy for hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) greatly threatens the life and health of Chinese people. Most patients with HCC are already in the advanced stage when attending the hospital and are not eligible for radical treatment, and patients in the early stage of HCC who are eligible for radical treatment still face a high risk of recurrence after surgery. In recent years, immunotherapy based on immune checkpoint inhibitors (ICIs) has made great progress in the treatment of advanced HCC, and perioperative immunotherapy for HCC is attracting more and more attention. Immunotherapy in the perioperative period of HCC can improve the feasibility of hepatectomy, reduce the recurrence rate after hepatectomy, and prolong the survival of patients. This article discusses the application of ICIs-based immunotherapy in the perioperative period of HCC and the issues that need to be considered, so as to provide new ideas for perioperative immunotherapy for HCC.

Clinical efficacy of combination therapy with lenvatinib and programmed death-1 antibodies in unresectable or advanced hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1 (PD-1) antibodies in unresectable or advanced hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected. There were 54 males and 5 females, aged from 25 to 73 years, with a median age of 52 years. All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy. Observation indicators: (1) clinical efficacy; (2) adverse drug reactions and treatment; (3) follow-up and survival. Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion, overall survival and progression free survival of patients up to December 2020. Measurement data with skewed distribution were expressed as M ( P25,P75) or M (range). Count data were represented as absolute numbers and (or) percentages. The Kaplan-Meier method was used to calculate the median duration of response (DoR), median overall survival time, median progression free survival time, survival rates and draw survival curves. Results:(1) Clinical efficacy: the objective response rate (ORR), complete response rate (CR), partial response rate (PR), stable disease rate (SD), progression disease rate (PD), time to response (TTR) and median DoR of 59 HCC patients were 37.3%(22/59), 11.9%(7/59), 25.4%(15/59), 37.3%(22/59), 25.4%(15/59), 2.6 months(2.1 months, 4.0 months), 6.3 months[95% confidence interval ( CI) as 2.2 to 10.5 months], respectively. The ORR, CR, PR, SD, PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43), 16.3%(7/43), 25.6%(11/43), 37.2%(16/43),20.9%(9/43), 2.2 months(2.0 months, 3.5 months), respectively. The median DoR of 43 patients undergoing first-line therapy was not reached. The ORR, CR, PR, SD, PD, TTR and median DoR of 16 HCC patients undergoing second-line therapy were 4/16, 0, 4/16, 6/16, 6/16, 3.8 months (3.6 months, 4.1 months), 4.2 months(95% CI as 2.0 to 6.3 months), respectively. Six of 59 HCC patients underwent R 0 resection due to tumor converting to resectable HCC with the conversion and resection rate of 10.2%(6/59). Among the 6 patients, 5 cases undergoing first-line treatment had the conversion and resection rates of 11.6% (5/43) and 1 case undergoing second-line treatment had the conversion and resection rates of 1/16, respectively. (2) Adverse drug reactions and treatment: 25 of 59 HCC patients underwent 3 to 4 grade adverse drug reactions with the incidence of 42.4%(25/59). Among the 25 patients, 10 cases including 5 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of gamma glutamyltransferase >5×upper limit of normal (ULN), 9 cases including 4 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of aspartate aminotransferase >5×ULN, 5 cases including 4 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred gastrointestinal hemorrhage, 4 cases undergoing first-line therapy had the level of white blood cell count <2.0×10 9/L, 4 cases including 1 case undergoing first-line therapy and 3 cases under-going second-line therapy had the level of total bilirubin >3×ULN, 3 cases undergoing first-line therapy had the level of neutrophil count <1.0×10 9/L, 3 cases including 2 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred ascites, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy had the level of platelet count <50.0×10 9/L, 2 cases undergoing first-line therapy had the level of alanine aminotransferase >5×ULN, 2 cases undergoing first-line therapy occurred hyponatremia, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred pulmonary infection, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred type 1 diabetes, 1 case undergoing first-line therapy occurred hypokalemia, 1 case undergoing first-line therapy occurred myocarditis, 1 case undergoing first-line therapy occurred hypophysistis, 1 case undergoing first-line therapy occurred bullous dermatitis, 1 case undergoing first-line therapy occurred hypertension. Three of 59 HCC patients underwent 5 grade adverse drug reactions ,with the incidence of 5.1%(3/59), including 1 case undergoing first-line therapy with immune hepatitis, 1 case undergoing second-line therapy with immune pneumonia and 1 case undergoing second-line therapy with immune enteritis. Some of patients underwent multiple adverse drug reactions at the same time. Twenty five patients undergoing 3 to 4 grade adverse drug reactions were relieved with the treatment of drug reduction, drug withdrawal, symptomatic treatment or hormone therapy. Three patients undergoing 5 grade adverse drug reactions died after being treated with high-dose hormone shock and hepatoprotective treatment. (3) Follow-up and survival: all 59 patients were followed up for 1.5 to 25.2 months, with a median follow-up time of 13.3 months. Of them, patients undergoing first-line therapy were followed up for 1.9 to 25.2 months, with a median follow-up time of 13.5 months. During follow-up,20 cases undergoing first-line therapy died with the fatality rate of 46.5%(20/43). Patients undergoing second-line therapy were followed up for 1.5 to 24.4 months, with a median follow-up time of 10.8 months. During follow-up, 10 cases undergoing second-line therapy died with the fatality rate of 10/16. Up to the latest follow-up, the tumor diameter of the target lesion in all 59 patients, in patients undergoing first-line therapy and in patients undergoing second-line therapy was 75 mm(38 mm, 125 mm), 74 mm(36 mm, 116 mm), 84 mm(48 mm,150 mm), respectively. The ratio of tumor diameter of the target lesion at latest follow-up to tumor diameter of the target lesion at baseline were -9.05%(-27.3%, 19.7%), -16.1%(-28.8%, 13.6%), 13.2%(-24.7%, 23.5%) for all 59 patients, patients undergoing first-line therapy and patients undergoing second-line therapy, respectively. The median overall survival time and median progression free survival time of patients undergoing first-line therapy and patients undergoing second-line therapy were 17.1 months(95% CI as 11.0 to 23.2 months), 10.8 months(95% CI as 5.0 to 16.6 months) and 10.8 months(95% CI as 9.2 to 12.4 months), 3.0 months(95% CI as 1.6 to 4.4 months), respectively. Conclusion:For unresectable or advanced HCC, combination therapy with lenvatinib and PD-1 antibodies can obtain effective antitumor activity and less incidence of adverse drug reactions.

Effect of traditional Chinese medicine syndrome differentiation and standard bundle therapy in patients with septic shock / 中华危重病急救医学

Objective To evaluate an effective and feasible quantitative evaluation table of traditional Chinese medicine (TCM) syndrome differentiation, and to observe the effect of combination of TCM syndrome differentiation and standard bundle therapy in patients with septic shock. Methods A prospective randomized controlled trial was conducted. The septic shock patients with acute deficiency syndrome admitted to department of critical care medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 1st, 2016 to December 31st, 2017 were enrolled. The patients were randomly divided into control group and Shenfu group. The patients in both groups received early application of standardized bundle therapy; those in Shenfu group received 60 mL Shenfu injection infusion in addition for 7 days. The TCM syndrome score was evaluated by classification and scoring method of TCM symptoms. The circulation and tissue perfusion, severity of disease, organ function, inflammation response, adjuvant treatment and 28-day mortality were compared between the two groups. Results A total of 50 patients with septic shock were enrolled in the analysis, 25 in control group and 25 in Shenfu group. The markedly effective rate of TCM symptoms score in Shenfu group was significantly higher than that in control group [60.0% (15/25) vs. 16.0% (4/25), P < 0.01]. There was no significant difference in all parameters before treatment between the two groups. After treatment, the observation indexes of both groups were improved. Compared with control group, the mean arterial pressure (MAP) in Shenfu group increased more significantly [mmHg (1 mmHg = 0.133 kPa): 13.0 (2.5, 28.5) vs. 6.0 (0, 13.5)], the lactate (Lac) and procalcitonin (PCT) decreased more significantly [Lac (mmol/L): 0.8 (0.1, 3.7) vs. 0.5 (-0.6, 1.7), PCT (μg/L): 2.0 (0.7, 32.3) vs. 0 (-1.8, 3.8)], activated partial thromboplastin time (APTT) was shortened more significantly [s: 8.5 (0, 12.9) vs. 0 (-7.2, 10.0)], and interleukins (IL-2 receptor and IL-6) levels decreased more significantly [IL-2 receptor (ng/L):1 031.0 (533.0, 1 840.0) vs. 525.5 (186.0, 1 166.8), IL-6 (ng/L): 153.1 (21.4, 406.8) vs. 35.1 (16.3, 110.1)] with significant differences (all P < 0.05). There was no significant difference in the use time of vasoactive drugs, duration of mechanical ventilation, severity of the disease or 28-day mortality between the two groups. However, the use time of vasoactive drugs in Shenfu group was shorter than that in control group (days: 5.48±4.81 vs. 8.28±7.83), and the 28-day mortality was decreased [8.0% (2/25) vs. 20.0% (5/25)]. Conclusions TCM syndrome score is helpful to evaluate the effect of TCM syndrome differentiation and treatment, and it is effective and feasible in clinical application. Septic shock patients treated with TCM syndrome differentiation and treatment combined with standard bundle therapy were significantly improved in circulation, tissue perfusion, coagulation function and inflammation reaction.

Correlation between follicular fluid sRAGE level and ovarian responsiveness in non-PCOS patients undergoing controlled ovarian hyperstimulation / 南方医科大学学报

OBJECTIVE@#To investigate the correlation between soluble receptor for advanced glycation end products (sRAGE) level in the follicular fluid and ovarian responsiveness in non-PCOS patients undergoing controlled ovarian hyperstimulation.@*METHODS@#Ninety non-PCOS patients underwent IVF/ICSI using a short-acting long protocol for ovarian stimulation with a GnRH agonist. For each patient, the level of sRAGE in the follicular fluid was measured by enzyme linked immunosorbent assay (ELISA), and the data including the clinical baseline state, hormone level, number of oocytes obtained and the fertilization rate were collected.@*RESULTS@#Follicular fluid sRAGE level showed significant negative correlations with basal FSH level (=0.0036) and Gn dose ( 15) than in cases with oocytes obtained within the range of the target numbers (7-15) and below the target number (< 7) ( < 0.0001 and =0.0012, respectively).@*CONCLUSIONS@#Follicular fluid sRAGE level can reflect ovarian reserve function in non-PCOS patients, the number of oocytes obtained and the fertilization rate, and can thus predict ovarian responsiveness during controlled hyperstimulation in nonPCOS patients.

Assessment of liver function using T1 mapping on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI / 中华放射学杂志

Objective To investigate the effectiveness of T1 mapping on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA-enhanced) MRI for the assessment of liver function.Methods One hundred and twenty six patients with clinically suspected focal liver lesions and chronic viral hepatitis B underwent MRI were prospectively enrolled.Patients were divided into four subgroups as follows: chronic viral hepatitis B (n=22), liver cirrhosis with Child-Pugh A (n=52), Child-Pugh B(n=41),Child-Pugh C(n=11).Twenty three healthy volunteers with normal liver function were enrolled as control group.Non-enhanced and Gd-EOB-DTPA enhanced MRI of liver were performed in all subjects.Look-Locker sequences with exactly the same scan parameters and geometry position(the level of porta hepatis) were performed pre and post-contrast separately at 5, 10, 15 and 20 minutes after Gd-EOB-DTPA administration.T1 relaxation times and reduction rates of T1 relaxation times[ΔT1(%)]of the liver parenchyma were measured and calculated.One-way ANOVA was used to compare T1 relaxation times and ΔT1(%) for control group, chronic viral hepatitis B group, liver cirrhosis with Child-Pugh A group, Child-Pugh B group,and Child-Pugh C group.ROC curve analysis was performed to compare the diagnostic performance of T1 relaxation times and ΔT1(%) values in discriminating control group + chronic viral hepatitis B group + liver cirrhosis with Child-Pugh A group from Child-Pugh B + C group. Results T1 relaxation times and ΔT1(%)showed significant difference(P<0.05)among control group and different liver function groups. T1 relaxation times and ΔT1(%) of both liver cirrhosis with Child-Pugh B group and Child-Pugh C group were significantly different(P<0.05)in comparison with those of control group,chronic viral hepatitis B group and liver cirrhosis with Child-Pugh A group at all time points.T1 relaxation times of the control group,chronic viral hepatitis B group,liver cirrhosis with Child-Pugh A group and Child-Pugh B group reduced with the scanning time increase,ΔT1(%)raised with the scanning time increase.T1 relaxation times progressively increased from control group to Child-Pugh C group at every time point.ΔT1(%)showed a constant decrease from control group to Child-Pugh C group at all time points.The areas under ROC curve of T1 relaxation time pre and post-contrast at 5,10,15 and 20 minutes for assessment of liver function were 0.817,0.952,0.950,0.946,and 0.949 respectively.The areas under ROC curve of ΔT1(%)post-contrast at 5, 10, 15 and 20 minutes for evaluation of liver function were 0.873, 0.876, 0.885, and 0.898, respectively. Conclusion Gd-EOB-DTPA-enhanced T1 mapping MRI is useful for the evaluation of liver function, and helpful for distinguishing patients with moderate and severe liver damage from normal and mild liver damage.

The different types and stages of folate receptor alpha expression in endometrial carcinoma and assessment on its diagnostic performance / 实用医学杂志

Objective To explore the folate receptor alpha(FRA)expression in different types and stages of in endometrial carcinoma(EC). The sensitivity and specificity of FRA testing were compared with CA125 to evaluate its diagnostic performance.Methods Serum from 50 cases of EC patients and 30 cases of normal patients was collected.Tissue from 83 cases of typeⅠEC and 30 cases of normal endometrium and typeⅡEC were collected. The expression of serum FRA was detected by ELISA.The expression ofserum CA125 was detected by electrochemi-luminescence.The expression of FRA and CA125 in tissues was detected by immunohistochemistry. Results The rate of elevated FRA expression of in typeⅠEC tissue was higher than that in typeⅡEC(P < 0.05). The rate of elevated FRA expression in type I EC was higher than that in the early stage(P < 0.05). The ROC curve showed that the sensitivity and specificity of FRA was higher than these of CA125′s. Further,they are higher in the com-bined serum FRA and CA125.Conclusions This study shows that the FRA expression level in endometrial carci-noma varies in different subtypes,indicating the potential different pathogeneses. The rate of elevated FRA expression in type I endometrial carcinoma was higher than that in the early stage. This provides the possibility for the application of FRA targeted fluorescent developer in advanced endometrial carcinoma meticulous surgery. Combination of FRA and CA125 have better diagnostic value in detecting EC.

Study on relationship between the level LP-PLA2 in serum and type H-hypertension ischemic stroke / 国际检验医学杂志

Objective To observe the change of results of lipoprotein-associated phospholipase A2 (Lp-PLA2) ,homocysteine (Hcy ) ,high-sensitivity C-reactive protein (hs-CRP ) ,lipids and other indicators in the patients with normal group ,primary hypertension group ,type H hypertension group and type H hypertension ischemic stroke group ,and search the relationship between LP-PLA2 and type H-hypertension ischemic stroke .Methods From January 2015 to June 2017 ,continuous selected 103 patients with type H hypertension ischemic stroke group ,124 patients with type H hypertension group ,80 patients with primary hypertension group and 50 patients with healthy controls as normal group .Analyzed level of Lp-PLA2 ,Hcy ,hs-CRP and lipids in serum ,compared the difference with each group .A binary Logistic regression analysis was used to an-alyze its correlation with ischemic stroke .Results The serum concentration of total cholesterol(TC) ,low-den-sity lipoproteincholesterol(LDL-C) ,LP-PLA2 in type H hypertension group and type H hypertension ischemic stroke group was higher than primary hypertension group and normal group ,the difference was statistically significant(P＜0 .05) .The serum concentration of triglyceride (TG) in type H hypertension ischemic stroke group was higher than primary hypertension group and normal group ,the difference was statistically signifi- cant(P＜0 .05) .The serum concentration of Hcy in primary hypertension group ,type H hypertension group and type H hypertension ischemic stroke group was higher than normal group ,the difference was statistically significant(P＜0 .05) ;The serum concentration of Hcy in type H hypertension group and type H hypertension ischemic stroke group was higher than primary hypertension group ,the difference was statistically significant (P＜ 0 .05) ;The serum concentration of Hcy ,LP-PLA2 in type H hypertension ischemic stroke group was higher than type H hypertension group ,the difference was statistically significant (P＜0 .05) .The serum con-centration of hs-CRP in type H hypertension group was higher than primary hypertension group and normal group ,the difference was statistically significant (P＜0 .05) ;The serum concentration of hs-CRP in type H hy-pertension ischemic stroke group was higher than type H hypertension group ,primary hypertension group and normal group ,the difference was statistically significant (P＜0 .05) .Two element Logistic regression analysis , Lp-PLA2 were significantly related to type H hypertension ischemic stroke ( SE ＝ 0 .013 ,P ＜ 0 .05 ) . Conclusion LP-PLA2 is an inflammatory biomarker and it is closely related to the occurrence and develop-ment of type H hypertension ischemic stroke .

Over expression of TMEM66 attenuatesthe intima proliferation of carotid artery after balloon injury in rats / 基础医学与临床

Objective To clarify the role of transmembrane protein 66(TMEM66) in intima proliferation of carotid artery induced by balloon injury in rats.Methods SD rats were randomly divided into three groups (n=10), including control group, the left carotid artery balloon injury group and injury group added with lentiviruses, respectively.Accordingly, the intima proliferation of carotid artery were detected by H/E staining;the expressions of TMEM66 in carotid artery injuried by balloon were determined by Western blot,q-PCR and immunohistochemistry, and the migration and proliferation of VSMCs were measured by scratch test and CCK8 respectively.Results Compared with control group, the expression of TMEM66 in carotid artery was obviously decreased after balloon injury (P<0.05).Most importantly, the intima proliferation of carotid artery was significantly reversed by overexpression of TMEM66 via specific lentiviruses (P<0.05).Conclusions TMEM66 is able to attenuate the intima proliferation of carotid artery after balloon injury.It could be that upregulation of TMEM66 can alleviate the migration and proliferation of VSMCs by PDGF.

The inhibitory effect of endostar combined with radiotheraphy on gastric transplantation tumorinmice / 中华放射医学与防护杂志

Objective To observe the effect of endostatin(Endostar) combined with radiotheraphy on the growth,microvessel density (MVD),the expressions of regulators of G-protein signaling 5 (RGSS),vascular endothelial growth factor (VEGF) and hypoxia-induced factor-1 α (HIF-1 α) ingastric transplantation tumor,and to explore underlying mechanism.Methods Thirty-two tumor-bearing mice were randomly divided into four groups including control group,ES group,RT group and ES + RT group.Then the tumor-bearing mice survival and tumor volume alterations were observed.After treatments of drug and RT,the inhibition rate of tumor growth and tumor MVD were measured.Immunohistochemical staining method was used to detect the expressions of RGS5,VEGF and HIF-1α.Results Compared with the ES group and control group,the ES + RT and RT treatment had effective anti-tumor effect(t=7.4,5.6,P ＜ 0.05),where as the ES + RT was more obvious in anti-tumor with the lowest value of MVD in tumor.Compared with the control group,the expression of HIF-1α in ES group,RT group,and especially ES + RT group was significantly reduced (t =6.5,8.2,13.1,P ＜ 0.05).The expression levels of VEGF and RGS5 wereincreased in RT group but was reduced in ES group and ES + RT group,and the expressions of VEGF and RGS5 in ES group and ES + RT group had no significant difference (P ＞ 0.05).Rank correlation analysis showed the expression of HIF-1α and the expressions of VEGF and RGS5 were positively correlated (r =0.57,0.71,P ＜ 0.05).Conclusions A possible mechanism of Endostar combined with radiotherapy on tumor growth inhibition may due to the inhibition of HIF-1α and its downstream VEGF and RGS5,and then inhibit tumor angiogenesis that results in the recovery of tumor blood vessels and tumor oxygen supplement.

Expression of folate receptor alpha and CA125 and its clinical significance in endometrial carcinoma / 实用医学杂志

Objective To explore the expression and the pathomechanism of folate receptor alpha(FRα) and CA125 in the development and progression of endometrial carcinoma.Methods Sixty samples of endometrial carcinoma tissues,46 samples of endometrial hyperplasia tissues and 10 normal endometrial tissues were collected in the study.Immunohistochemical methods were used to detect the expression of Frαand CA125 in all tissues.The expressions of FRα and CA125 and their correlation with clinicopathological characteristics were analyzed.Results FRα was positively expressed in 93.9％ of the endometrial carcinoma tissues,with a strongly positive rate of 65.0％,which was significantly higher than that in endometrial hyperplasia tissues and normal endometrial tissues (P ＜ 0.05).The highly expressed FRαin endometrial carcinoma tissues was associated with age,FIGO stage and histologic types (P ＜ 0.05),while no statistical significance was found between the high expression of FRαand myometrial invasion.The expression of FRα in endometrial atypical hyperplasia was higher than that in other hyperplasia subgroups.The expression of CA125 in endometrial carcinoma tissues and endometrial hyperplasia tissues were both higher than that in normal endometrial tissues (P ＜ 0.05).Conclusion FRα may play an important role in the carcinogenesis and progression of endometrial carcinoma,and act as a target of therapy and a kind of assessment for prognosis in endometrial carcinoma.CA125 may be involved in the development of endometrial lesions and further researches are needed to confirm a physiological mechanism between FRA and CA125 in carcinogenesis of endometrial carcinoma.

Distribution and antibiotic resistance profile of the pathogenic isolates in a gynecology and obstetrics hospital during 2009-2014 / 中国感染与化疗杂志

Objective To analyze the distribution and antimicrobial susceptibility of the pathogenic isolates during 2009-2014 for rational use of clinical antibiotics.Methods The clinical data were reviewed and analyzed retrospectively to examine the distribution and resistance profile of the pathogenic isolates.Strain identification and antimicrobial susceptibility test were conducted by BioMerieux VITEK-2 automatic microbiology analyzer and the associated identification cards.All results were interpreted according to CLSI standards.Results A total of 6 393 strains of pathogenic bacteria were isolated during the six-year period.The top three pathogens were Escherichia coli (33.6 ％),Enterococcus faecalis (19.4 ％),and Streptococcus agalactiae (13.7 ％).In addition,8,1,and 10 strains ofListeria spp.were isolated in 2009,2010,2014,respectively.A total of 40 strains of anaerobic bacteria had been isolated since 2012.The isolates were mainly from genital tract (53.7 ％) and uterine cavity (21.3 ％),followed by blood stream (8.2 ％),including venous blood samples (6.1％) and umbilical cord blood samples (2.2 ％).There were 165 (2.6 ％) cases of surgical site infections.Escherichia,Enterococcus,and Streptococcus were the top three bacteria isolated from both uterine cavity and venous blood samples.The top three bacteria isolated from surgical sites were Escherichia,Enterococcus,and Staphylococcus.The bacteria isolated from umbilical cord blood samples were mostly Streptococcus,Escherichia,and Enterococcus.Anaerobic bacteria were mainly isolated from blood samples,which accounted for 82.5 ％ of all anaerobic bacteria.Listeria monocytogenes isolates were mainly from venous blood samples or uterine cavity.Overall,the antimicrobial susceptibility profile of the pathogenic isolates was relatively stable during the period from 2009 to 2014.Most antibiotics showed good activity against these isolates.Conclusions The pathogens isolated from this gynecology and obstetrics hospital during 2009-2014 period are mainly Escherichia coli,Enterococcusfaecalis,and Streptococcus agalactiae.Most isolates were susceptible to the commonly used antimicrobial agents.In addition to a few MRSA strains,ESBLs-producing Escherichia coli isolates were the main multidrug resistant organisms.

Optimal concentration of superparamagnetic iron oxide-short hairpin RNA dual functional molecular probe transfected into ovarian cancer cells in vitro / 北京大学学报(医学版)

Objective:To explore the effects of superparamagnetic iron oxide-short hairpin RNA ( SPIO-ShRNA) dual functional molecular probes of different concentrations on morphology and biological beha -vior of ovarian cancer SKOV3 cells in vitro.Methods:The dual functional molecular probes at an iron concentration of 5, 15, 30, 45, 75, and 100 mg/L were transfected into SKOV3 cells.The transfection rate of the probe was observed by fluorescence microscope .The distribution and content of iron particles in SKOV3 cells were determined by Prussian blue staining , atomic adsorption spectrometer and electron microscopy .Cell viability was observed by cell counting kit-8 ( CCK-8 ) .The apoptosis was detected by flow cytometry .The expression of protein within the cells was detected by Western blot .The changes of the signal intensity were measured by magnetic resonance imaging (MRI).Results: The SPIO-ShRNA dual functional molecular probe was uptaken in aconcentration-dependence manner within a certain range (5-30 mg/L) .When the concentration of the probe was 45 mg/L, the labeling rate of the cell was close to 100%;With the increase of the concentration of probe , the cell survival rate decreased gradual-ly.The cell survival rate of each experimental group were 94.626%±1.050%, 93.373%±1.180%, 91.700%±3.122%, 75.100%±4.362%, 72.983%±3.233%, 71.010%±2.910%,5, 15, 30mg/L cell survival rate was not significantly decreased , the difference was not statistically significant (P=0.226, P=0.068, P=0.475);When the concentration of the probe was greater than or equal to 45 mg/L,the survival rate decreased obviously ( P<0.001);Group of 45 mg/L protein expression rate was 68.905%± 3.510%, When the concentration of the probe was greater than or equal to 45 mg/L, the inhibition rate of the protein expression level of epidermal growth factor receptor was obviously higher than those of 5, 15, and 30 mg/L groups, the difference was statistically significant (P<0.001, P=0.001, P=0.003, all P<0.01);the MRI displayed that the signal intensity was decreased with increasing concentrations of the probe.The signal intensity of 45 mg/L group was 165.55 ±4.92, compared with the blank control group (same volume of phosphate buffer saline ), normal group(unlabeled ovarian cancer SKOV3 cells), 5, 15, and 30 mg/L groups , the signal intensity of 45 mg/L group decreased significantly (all P<0.001).Con-clusion:The dual functional molecular probe can effectively transfect and specifically inhibit the expression of SKOV3 cell lines at the iron concentration of 45 mg/L, and can also be detected by MRI .The role of diagnosis and treatment of the dual functional molecular probe has been initially confirmed .

Expression and significance of folate receptor alpha in serum of patients with endometrial carcinoma / 实用医学杂志

Objective To detect serum concentration of folate receptor alpha and to investigate its significance in the clinical application of patients with endometrial carcinoma. Methods Thirty-seven patients with endometrial carcinoma, 33 patients with endometrial hyperplasia and 10 healthy women were enrolled in this study. Sera were used to detect the the folate receptor alpha using an Enzyme-linked Immunosorbent Assay (ELISA) technique.The expression level of serum folate receptor alpha in different groups was analyzed. The correlation between the expression level of serum folate receptor alpha and age of patients, menopause, tumor morphology, myometrial invasion and clinical stage was was also analyzed in patients with endometrial carcinoma. Results Level of folate receptor alpha was successfully detected in serum of healthy women and patients with endometrial diseases. Level of folate receptor alpha in patients with endometrial carcinoma was much higher than that in patients with endometrial hyperplasia. Level of folate receptor alpha in patients with endometrial hyperplasia was also higher than that in the healthy controls, with significant difference (P 0.05). Conclusion The Serum level of folate receptor alpha can be detected, and its expression will contribute to the diagnosis, treatment and predicting the prognosis of patients with endometrial carcinoma.

Anti-apopttoic effect of resveratrol on free fatty acid-i nduced human hepatic L02 cells and its mechanisms / 医学研究生学报

Objective Resveratrol can improve nonalcoholic fatty liver disease , but its action mechanisms remain unclear . This study aimed to investigate the protective effect of resveratrol against the free fatty acid ( FFA)-induced apoptosis of human hepatic L02 cells and its possible mechanisms . Methods Human hepatic L02 cells were incubated with FFA and resveratrol for 24 hours.The prepared cells were divided into a blank control , an FFA ( 2 mmol/L) , and a resveratrol group ( 50 μmol/L resveratrol +2 mmol L/FFA).After treatment, we measured the triglyceride (TG), glutathi-one (GSH), and malonaldchyde (MDA) contents and caspase3 ac-tivity in the hepatocytes , determined the apoptosis of the cells by flow cytometry , and detected the protein expression of silent information regulator 1 (SIRT1) by Western blot as well as the mRNA expressions of catalase (CAT), Mn superoxide dismucase (MnSOD), Bcl-2, and Bax by qRT-PCR. Results The TG content and caspase 3 activity in the hepatocytes were significantly increased in the FFA ([3518.±64.2] μmol/L and [5.97 ±0.78] U/g) and the resveratrol group ([201.1 ±60.1] μmol/L and [3.60 ±0.73] U/g) as compared with those of the blank control ([40.2 ±7.4] μmol/L and [2.56 ±0.49] U/g) (both P<0.05), but the caspase3 ac-tivity was markedly decreased in the resveratrol group in comparison with that of the FFA group (P<0.05).Both early and late apop-tosis rates of the hepatocytes were remarkably higher in the FFA ([6.75 ±0.81]%and [8.52 ±0.54]%) and the resveratrol group ([4.94 ±0.44]%and [6.52 ±0.61]%) than those in the blank control ([3.38 ±0.33]% and [2.72 ±0.19]%) ( both P<0.05), with statistically significant differences between the former two groups (P<0.05).The resveratrol group showed significant differences in the GSH content ([100.2 ±8.8] nmol/g), the MDA level ([2.36 ±0.82] mg/g), and the relative expression of SIRT1 (0.84 ±0.04) from the FFA group ([73.8 ±13.1] nmol/g, [3.77 ±0.92] mg/g, and 0.61 ±0.07) and the control ([113.7 ±13.8] nmol/g, [1.85 ±0.41] mg/g, and 0.90 ±0.02) (all P<0.05).The resveratrol group also exhibited statistically significant differences in the relative expressions of the MnSOD , CAT, and Bax genes from the FFA and control groups (P<0.05). Conclusion Resveratrol attenuates FFA-induced apoptosis of human hepatic L 02 cells by activating SIRT1 and reducing the oxidative stress of hepatocytes .

Pharmacokinetics and MR imaging of SPIO-shRNA dual functional molecular probe in vivo / 药学学报

In this study, we investigated the pharmacokinetics parameters of SPIO-shRNA dual functional molecular probe and observed the main organ distribution by MRI in vivo. Eighteen New Zealand white rabbits were randomly divided into three groups and injected intravenously with different doses of SPIO-shRNA molecular probe, respectively. The blood samples were collected to analyze the pharmacokinetic parameters by measuring the iron content at 30 minutes before and after the injection. Twenty-four Kun Ming (KM) mice were randomly divided into 4 groups: the control group was injected intravenously with physiological saline 200 µL per mouse via the tail vein, the other 3 groups were injected intravenously with different doses of SPIO-shRNA molecular probe. MRI observation was performed in 24 hours, and the liver, spleen, kidney, brain and muscle were collected for iron quantification with Prussian blue staining to determine distribution of the SPIO-shRNA molecular probe in the main organ in vivo. Our results suggest that the molecular probe blood half-life is more than 3 hours. The data of MRI suggest the probe was distributed in liver and spleen, and the MRI signal was reduced with the increase in probe's doses (P < 0.05). The results of Prussian blue staining confirmed the results of MRI. Most of the probe could escape the phagocytosis of mononuclear phagocyte system. Our data provide the pharmacokinetic and distribution of SPIO-shRNA molecular probe in organs. Meanwhile, it suggests the choice of the time and dose of probe for MR imaging of tumor in vivo.

The effects of serum glycodelin-A on pregnancy outcome in women receiving intrauterine insemination / 医学研究生学报

Objective Glycodelin-A is one of glycoproteins secreted from endometrial epithelial cells , and it plays an im-portant role in embryo implantation , inhibition of reject reaction and pregnancy maintenance .Glycodelin-A will become an important potential marker in evaluating the endometrial receptivity and predicting the pregnancy outcome .The aim of this study was to investigate the correlation of glycodelin-A detected on the day of HCG and endometrial receptivity and the effects of glycodelin -A on the pregnancy outcome in the intrauterine insemination (IUI) period. Methods One hundred and seven woman patients with bilateral unobstruct-ed tubes and without endometrial lesions , endometrial polyps or intrauterine adhesions from Oct 2012 to Feb 2014 in our hospital were recruited in this study .Serum glycodelin-A in women receiving IUI on the day of HCG was measured by ELISA .Serum estradiol (E2), progesterone (P), and corpus luteum (LH) levels were measured by immunochemiluminometric assays .The condition of the endometrium was examined by transvaginalultrasonography . Results The serum glycodelin-A level on the day of HCG was higher in pregnant group [(1.47 ±0.38)ng/mL] than that in nonpregnant group ([0.62 ±0.13]ng/mL).The serum glycodelin-A level on the day of HCG was higher in endometrial thickness ≥7 mm group ([1.53 ±0.49]ng/mL) than endometrial thickness <7 mm group ([0.51 ±0.17]ng/mL). Conclusion The serum glycodelin-A level on the day of HCG may reflect endometrial receptivity to a cer-tain extent , which might have prognosis value for pregnancy following IUI .

Effect of prenatal and postnatal exposure to bisphenol A on body weight of immature mice / 安徽医科大学学报

Objective To investigate the effect of maternal exposure to bisphenol A(BPA) via drinking water on body weight of immature offspring during pregnancy and lactation. Methods The pregnant female ICR mice were exposed to BPA groups(2. 282 9,22. 829 0,228. 290 0 μg/L) by drinking water from gestational day(GD)0 till postnatal day (PND)21,water and dimethyl sulfoxide(0. 01%) were served as blank and vehicle control. Maternal body weight was recorded every three days during pregnancy. Weight of pups per litter was measured every three days during lactation. Body weight of offspring was taken notes every week till PND 42 after delactation. ResultsThere was no significant difference in pregnant maternal body weight, average numbers and body weight of pups per litter preweaning among all groups. The offspring weight of the high-dose group at PND 42 was increased compared with control groups(P<0.05). The weight of female offspring was not significantly different among all groups at PND 28~42. The male offspring weight of the middle/high group at PND 35 and all groups at PND 42 significantly was elevated(P<0.05,P<0.01),and the high group was most significant. Conclusion Body weight of immature offspring is affected,especially male offspring after delectation by pregnant and lactational BPA exposure.

Detection and Genotyping of Treponema pallidum by a Nested PCR / 中华皮肤科杂志

Objective To develop a nested PCR for the detection of early syphilis and genotyping of Treponema pallidum (TP), and to investigate the distribution of genotypes of TP in Guangzhou. Methods Specimens were consecutively collected from genital ulcers of patients with suspected chancre during 2002-2004, and were detected by dark-field microscopy and nested PCR. The acidic repeat protein (arp) gene and the T. pallidum repeat (tpr) gene family were amplified with the positive specimens above. The number of repeats presented in the arp gene and the restriction fragment length polymorphism by Mse I in the tpr gene were analyzed by electrophoresis. The strains were genotyped according to Pillay's criteria. Results Out of 62 patients with suspected chancre, 33 cases (53.2%) were positive by dark-field microscopy and 54 cases (87.1%) by nested PCR. Of 47 TP-positive specimens genotyped by arp gene, 36 (76.6%) were type 14, while of 49 cases genotyped by tpr gene 39 (79.6%) were type d. By combining genotypes of arp and tpr genes, 7 genotypes were found, including 14d (31, 66.0%), 13d (5, 10.6%), 14b (4, 8.5%), 12b (3, 6.4%), 12d (2, 4.3%), 15d(l, 2.2%) and 14i (1, 2.2%). Conclusions Nested PCR shows a high sensitivity in early detection of TP. Genotype 14d seems the predominant type of TP in Guangzhou.