Treatment with ß-elemene combined with paclitaxel inhibits growth, migration, and invasion and induces apoptosis of ovarian cancer cells by activation of STAT-NF-κB pathway

In this study, we aimed to analyze the anti-cancer effects of β-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of β-elemene and paclitaxel. The in vitro results showed that β-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or β-elemene treatment alone. Results demonstrated that β-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of β-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with β-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that β-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.

Study on relationship between cervical microecology and cervical squamous intraepithelial lesions / 中华检验医学杂志

Objective:To explore the relationship between cervical microecology and cervical squamous intraepithelial lesions (SIL).Methods:All subjects were recruited from the health care center or gynecology of the Affiliated Wuxi No.2 People′s Hospital of Nanjing Medical University from March to May of 2019, including 12 subjects normal cervix with 37-47 years old, 21 low-grade squamous intraepithelial lesion (LSIL) subjects with 39-48 years old, 5 high-grade squamous intraepithelial lesion (HSIL) subjects with 38-45 years old and 3 cervical squamous cell carcinoma subjects with 42-43 years old. All subjects were required to fill in a questionnaire, and performed cervical examination. Meanwhile, the microecology of cervical secretions was analyzed by the next generation sequencing (NGS) and the NGS results were analyzed by bioinformatics. Subjects were divided into human papilloma virus (HPV)-negative groups, low-risk HPV (lrHPV), 16/18 high-risk HPV (hrHPV) and other hrHPV infection groups based on HPV test results of NGS. The Venn diagram of data, microecology diversity, the relative abundance and co-occurrence of species, and the receiver operating characteristic (ROC) curve were analyzed.Results:A total of 909 species at the species level were obtained from the cervical secretions of all the subjects, and there was overlap among the groups. There was no significant difference in total HPV infection rate, 16/18 hrHPV infection rate and other hrHPV infection rates among subjects with different cervical lesions (all of P>0.05). Grouped by HPV infection, the 16/18 hrHPV-infected and other hrHPV-infected subjects had increased cervical microecology diversity ( U=39.00 and 43.00, all of P<0.05), and the relative abundance of Lactobacillus crispatus (L.crispatus) had no differences among the groups ( H=4.37, P=0.213 6). Grouped by cervical conditions, the cervical microecology diversity of the subjects with cervical lesions increased ( H=14.60, P=0.002 2), while the L.crispatus relative abundance decreased ( H=13.98, P=0.000 8). Among all the detected species, Mycoplasma, Chlamydia and Streptococcus B had a co-occurrence, while Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia had a co-occurrence. As the SIL diagnostic index, the area under the ROC curve (AUC) of the relative L.crispatus relative abundance was 0.874 [95% confidence interval ( CI):0.732-0.957]. L.crispatus combined with Lactobacillus jensenii (L.jensenii) and Mycoplasma had an AUC of 0.943 [95 %CI: 0.822-0.991] in the SIL diagnosis. Conclusions:The decreased L.crispatus relative abundance and the increased cervical microecology diversity may be related to HPV infection and cervical lesions; simplified NGS data may be helpful to the SIL diagnosis.

Prospective association of childhood BMI trajectory and polygenic genetic risk with puberty timing / 中国学校卫生

Objective@#To examine pubertal timing across body mass index (BMI) trajectory under polygenic susceptibility in boys and girls,and to provide a reference basis for children’s adolescent development deviation form early intervention strategies.@*Methods@#All the participants were recruited from 1 to 3 grade in 2016 from 2 Bengbu primary school and were followed up for 3 consecutive years. The study comprised 997 children (418 boys) with available data for height, weight, BMI, breast Tanner stages and testicular volume annually. The polygenic risk score (PRS) was computed based on 17 SNPs derived from published genome-wide association studies for early pubertal timing. Group-based trajectory model (GBTM) was used to identified BMI trajectory in children. Accelerated failure time model (AFT) was used to examine associations of different BMI trajectory and polygenic risk with pubertal development in boys and girls.@*Results@#Classes of BMI trajectory were persistently healthy weight, persistently overweight and persistently obesity. Adjusted concomitant variables, boys with persistently obesity exhibited 6.10-mo delay of testicular volume in low polygenic risk group (adjusted TR=1.05，P=0.04). Compared with the girls in persistently healthy weight group, the girls with low PRS were persistently overweight or obesity, which was associated with thelarche age 3.42 and 6.84-mo earlier, respectively (adjusted TR=0.97，0.94,P<0.01). Persistently overweight or obesity in girls with moderate PRS was associated with an earlier age of thelarche timing of 6.72 and 8.96-mo, respectively (adjusted TR=0.94，0.92, P<0.01). At high PRS groups, the persistently obese girls were found to have a more advanced age (10.80 and 12.96-mo, respectively) of thelarche (adjusted TR=0.90，0.88, P<0.01).@*Conclusion@#Persistently overweight and obesity is associated with early thelarche in girls, but persistently obesity may increase delayed puberty risk in boys with low polygenic risk.

Application evaluation of failure mode and effect analysis in optimization of vascular recanalization process / 中华危重病急救医学

Objective@#To investigate the clinical application and effect evaluation of failure mode and effect analysis (FMEA) in the optimization of vascular recanalization in patients with ST-segment elevation myocardial infarction (STEMI).@*Methods@#A total of 389 STEMI patients admitted to the emergency department of the Fifth Central Hospital in Tianjin from January 2014 to January 2015 were served as the control group, and 398 STEMI patients admitted to the chest pain center of the Fifth Central Hospital in Tianjin from January 2016 to October 2017 were served as the experimental group. In the control group, routine emergency treatment was used. At the same time, the intervention room was 24-hour prepared for emergency vascular recanalization. The experimental group used FMEA. Through the usage of FMEA, the main factors those caused the delay in revascularization treatment were determined, and the revascularization process was optimized for these influencing factors, thereby shortening the "criminal" blood vessel opening time of patients. The door-to-balloon dilatation time (D-to-B time), troponin testing time, placement time of the catheterization room, initiation of the catheterization room to balloon dilatation time, and preoperative and 1 week postoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, heart function parameters [left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD)] within 1 week, 3 months and 6 months after intervention, and the incidence of main cardiovascular adverse events within 1 month after intervention, hospital mortality, the length of hospital stay, and readmission within 1 year in the patients of two groups were recorded.@*Results@#D-to-B time (minutes: 70.6±3.6 vs. 79.4±8.7), troponin testing time (minutes: 17.1±2.3 vs. 65.2±6.5), placement time of the catheterization room (minutes: 28.9±9.8 vs. 52.3±12.2) and activation of the catheterization room to balloon expansion time (minutes: 47.3±9.3 vs. 65.1±7.2) in the experimental group were significantly shorter than those in the control group (all P < 0.01). The NT-proBNP levels at 1 week after intervention in the two groups were lower than the preoperative levels, slightly lower in the experimental group, but the difference was not statistically significant. There was no significant difference in cardiac function at 1 week and 3 months after intervention between the two groups. The LVEF and FS at 6 months after intervention in the experimental group were significantly higher than those in the control group [LVEF: 0.622±0.054 vs. 0.584±0.076, FS: (38.1±4.3)% vs. (35.4±6.2)%, both P < 0.01], and LVESD and LVEDD were decreased significantly [LVESD (mm): 31.2±3.8 vs. 34.7±4.2, LVEDD (mm): 49.2±5.3 vs. 52.4±5.6, all P < 0.01]. The length of hospital stay in the experimental group was significantly shorter than that in the control group (days: 8.3±3.2 vs. 13.2±6.8, P < 0.01), the incidence of major cardiovascular adverse events within 1 month after intervention [13.6% (54/398) vs. 19.8% (77/389)], hospital mortality [1.8% (7/398) vs. 4.9% (19/389)], and readmission rate within 1 year [9.5% (38/398) vs. 14.5% (56/389)] in the experimental group were significantly lower than those in the control group (all P < 0.05).@*Conclusion@#The usage of FMEA to optimize the vascular recanalization procedure can shorten the emergency treatment time of STEMI patients, reduce the occurrence of adverse events, and improve the prognosis.

Application evaluation of failure mode and effect analysis in optimization of vascular recanalization process / 中华危重病急救医学

OBJECTIVE@#To investigate the clinical application and effect evaluation of failure mode and effect analysis (FMEA) in the optimization of vascular recanalization in patients with ST-segment elevation myocardial infarction (STEMI).@*METHODS@#A total of 389 STEMI patients admitted to the emergency department of the Fifth Central Hospital in Tianjin from January 2014 to January 2015 were served as the control group, and 398 STEMI patients admitted to the chest pain center of the Fifth Central Hospital in Tianjin from January 2016 to October 2017 were served as the experimental group. In the control group, routine emergency treatment was used. At the same time, the intervention room was 24-hour prepared for emergency vascular recanalization. The experimental group used FMEA. Through the usage of FMEA, the main factors those caused the delay in revascularization treatment were determined, and the revascularization process was optimized for these influencing factors, thereby shortening the "criminal" blood vessel opening time of patients. The door-to-balloon dilatation time (D-to-B time), troponin testing time, placement time of the catheterization room, initiation of the catheterization room to balloon dilatation time, and preoperative and 1 week postoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, heart function parameters [left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD)] within 1 week, 3 months and 6 months after intervention, and the incidence of main cardiovascular adverse events within 1 month after intervention, hospital mortality, the length of hospital stay, and readmission within 1 year in the patients of two groups were recorded.@*RESULTS@#D-to-B time (minutes: 70.6±3.6 vs. 79.4±8.7), troponin testing time (minutes: 17.1±2.3 vs. 65.2±6.5), placement time of the catheterization room (minutes: 28.9±9.8 vs. 52.3±12.2) and activation of the catheterization room to balloon expansion time (minutes: 47.3±9.3 vs. 65.1±7.2) in the experimental group were significantly shorter than those in the control group (all P < 0.01). The NT-proBNP levels at 1 week after intervention in the two groups were lower than the preoperative levels, slightly lower in the experimental group, but the difference was not statistically significant. There was no significant difference in cardiac function at 1 week and 3 months after intervention between the two groups. The LVEF and FS at 6 months after intervention in the experimental group were significantly higher than those in the control group [LVEF: 0.622±0.054 vs. 0.584±0.076, FS: (38.1±4.3)% vs. (35.4±6.2)%, both P < 0.01], and LVESD and LVEDD were decreased significantly [LVESD (mm): 31.2±3.8 vs. 34.7±4.2, LVEDD (mm): 49.2±5.3 vs. 52.4±5.6, all P < 0.01]. The length of hospital stay in the experimental group was significantly shorter than that in the control group (days: 8.3±3.2 vs. 13.2±6.8, P < 0.01), the incidence of major cardiovascular adverse events within 1 month after intervention [13.6% (54/398) vs. 19.8% (77/389)], hospital mortality [1.8% (7/398) vs. 4.9% (19/389)], and readmission rate within 1 year [9.5% (38/398) vs. 14.5% (56/389)] in the experimental group were significantly lower than those in the control group (all P < 0.05).@*CONCLUSIONS@#The usage of FMEA to optimize the vascular recanalization procedure can shorten the emergency treatment time of STEMI patients, reduce the occurrence of adverse events, and improve the prognosis.

Effect of atorvastatin calcium combined with sitagliptin phosphate onβ2-MG and UA in type 2 diabetes / 中国生化药物杂志

Objective To investigate the effect of atorvastatin calcium combined with sitagliptin phosphate on β2-microglobulin (β2-MG ) in peripheral blood and serum uric acid ( UA) levels in patients with type 2 diabetes.Methods A total of 78 patients with type 2 diabetes in endocrinology department from Hangzhou Xiasha Hospital were collected and randomly divided into the control group and the experimental group, with 39 cases in each group.The two groups of patients were treated by conventional treatment, life intervention, the control group were treated by metformin hydrochloride sustained-release tablet and sitagliptin phosphate, the experimental group were treated on the basis of control group with atorvastatin calcium.Both groups were treated for 3 cycles, one cycle for 7 days.The clinical curative effect,β2-MG in peripheral blood and urine, serum UA levels and adverse reactions were compared between two groups after treatment.Results After treatment, compared with control group, the clinical total effective rate in experimental group was higher (P<0.05).The serum IgG,β2-MG, urineβ2-MG and UAlb, serum UA levels were lower in two groups post-treatment compared with pre-treatment(P<0.05).Compared with control group, serum IgG, β2-MG, urine β2-MG and UAlb, serum UA levels were lower (P<0.05).There was no significant difference between two groups.Conclusion The atorvastatin calcium combined with sitagliptin phosphate has a significant efficacy in the treatment of patients with type 2 diabetes, it could down-regulate β2-MG in peripheral blood and urine and serum UA levels, improve immunity and prevent patients from cardiovascular complications.

Expression of glucose-regulated protein 78 in ovarian cancer tissues and its clinical significance / 中国医师进修杂志

Objective To explore the expression of glucose-regulated protein (Grp) 78 in ovarian cancer tissues and its clinical significance.Methods The expression of Grp78 in 60 cases of ovarian cancer tissue,15 cases of ovarian borderline tumor tissue,10 cases of normal ovarian tissue,10 cases of ovarian cyst tissue,was detected by immunohistochemistry,and analyzed the relationship between its expression and clinicopathological features of ovarian cancer.Results The expression of Grp78 in ovarian borderline tumor and ovarian cancer tissue was significantly higher than that in normal ovarian and ovarian cyst tissue[7/15 and 68.3％ (41/60) vs.1/10 and 1/10] (P ＜0.05).The expression of Grp78 was positively correlated with clinicopathological staging and lymphatic metastasis of ovarian cancer (P ＜ 0.05),negatively correlated with histological differentiation (P ＜ 0.05).No correlation with age and ascites (P ＞ 0.05).Conclusions The levels of Grp78 are elevated in ovarian cancer specimens; high expression of Grp78 maybe participate in the occurrence,development,and prognosis of ovarian cancer.Increased expression of Grp78 might be a useful marker for predicting the carcinogenesis and progression of ovarian cancer.