Objective To explore the efficacy of calmodulin antagonist berbamine(BBM)on multidrug resistance(MDR)reversal and its mechanism. Methods Human breast cancer cell line MCF7 and its adriamycin-resistant counterpart MCF7/ADR were used in the study.The cells were cultured with ADR and different concentration of BBM. MTT assay was used to analyze the effect of BBM on cell growth inhibition.According to the MTT assay,the 50% inhibitory concentration(IC 50 ),the multiples of drug resistance and increased sensitivity of ADR were calculated.The concentration of intracellular ADR and expression level of P-glycoprotein(P-gp)were detected by flowcytometry(FCM).The mRNA expression level of mdr1 gene was detected by semi-quantitative reverse transcriptase polymerase chain reaction(RT-PCR)with ?-actin as internal reference. Results The IC 50 of ADR in MCF7 and MCF7/ADR cells were(0.98?0.06)?mol/L and(101.20?5.72)?mol/L,respectively.The resistant multiple of MCF/ADR cells to ADR was 103 folds higher than that of MCF7 cells.BBM increased the chemo-sensitivity of ADR in MCF7/ADR cells with dose-dependent relationship,i.e.when 5*!?mol/L ,10*!?mol/L and 20*!?mol/L BBM was added into the culture the chemo-sensitivity of ADR was increased to 2.76,5.88,and 28.26 folds(P

Tanshinones are the bioactive components of the Chinese medicinal herb Salvia miltiorrhiza, while its biosynthetic pathway remains to be characterized. Rapid identification and characterization of the genes correlated to tanshinones biosynthesis is very important. As one of the intermediates of tanshinones biosynthesis, the ferruginol content is relative low in both root and engineered bacteria. It is urgent to construct an efficient system for conversion of miltiradiene to ferruginol to obtain large amount of ferruginol as the substrates for further identifying other downstream genes involved in tanshinones biosynthesis. In this study, we constructed the whole-cell yeast biocatalysts co-expressing miltiradiene oxidase CYP76AH1 and cytochrome P450 reductases (SmCPR1) from Salvia miltiorrhiza, and then characterized it with RT-PCR. After permeabilization, the yeast whole-cell could catalyze turnover of miltiradiene to ferruginol efficiently through single-step biotransformation with a conversion efficiency up to 69.9%. The yeast whole-cell biocatalyst described here not only provide an efficient platform for producing ferruginol in recombinant yeast but also an alternative strategy for identifying other CYP genes involved in tanshinones biosynthesis.

The paper described the professional approach of Shanghai Hospital Development Center(SHDC)in developing a professional team of public hospital directors by such means as operation and management-autonomy,fixed tenures system,performance appraisal,part-time job control and income distribution. Recommendations raised include an organic unity of management functions of investors and power of management of the directors to motivate them in their management;building a comprehensive investor management system and strict cadre management mechanism to enhance supervision of the directors.

Objective:To evaluate the changes in the systemic circulation and microcirculation in the patients undergoing gastrointestinal surgery under general anesthesia in Xining area.Methods:A total of 27 patients, aged 18-60 yr, underwent gastrointestinal surgery under general anesthesia in Xining area (2 260 m), of long lived (more than two generations) Han nationality, with no alternating life between plateau and plain, with no cardiopulmonary abnormalities, were enrolled.Anesthesia was induced with midazolam, sufentanil, etomidate, and cisatracurium and maintained with propofol, remifentanil and cisatracurium.At 5 min before induction of anesthesia (T 1), 10 min after induction of anesthesia (T 2), 1 h after start of operation (T 3), immediately after the end of operation (T 4), and 30 min after recovery from anesthesia (T 5), systemic circulation indexes including cardiac output (CO), stroke volume (SV), stroke volume variability (SVV), systemic vascular resistance index (SVRI), and mean arterial pressure (MAP) and heart rate (HR) were recorded, and sublingual microcirculation indexes including total vascular density (TVD), perfused vessel density (PVD), portion of perfused vessels (PPV), and microvascular flow index (MFI) were determined by sidestream dark field imaging. Results:Systemic circulation Compared with the baseline at T 1, CO and HR were significantly decreased at T 2-4, SVV was decreased at T 5, SVRI was increased at T 3 and T 4, and MAP was decreased at T 2 ( P<0.05). Compared with those at T 2, CO and SV were significantly increased at T 5, SVV was decreased at T 5, SVRI was increased at T 3 and T 4, and MAP was increased at T 4 and T 5 ( P<0.05). Compared with those at T 3, SV was significantly decreased at T 4, CO was increased at T 5, and SVV and SVRI were decreased at T 5 ( P<0.05); Compared with those at T 4, CO, SV and HR were significantly increased at T 5, and SVV and SVRI were decreased at T 5 ( P<0.05). Microcirculation Compared with those at T 1, TVD, PVD, PPV and MFI were significantly decreased at T 2-4, and PPV and MFI were decreased at T 5 ( P<0.05). Compared with those at T 2, TVD was significantly increased at T 5, PVD was increased at T 4 and T 5, and PPV was increased at T 3 and T 4 ( P<0.05). TVD was significantly higher at T 5 than at T 3( P<0.05). TVD was significantly higher at T 5 than at T 4 ( P<0.05). Conclusions:The density of microcirculation and blood flow rate are decreased after induction of general anesthesia and during anesthesia operation, which are most significant at the initial stage after induction, and decoupling between systemic circulation and microcirculation occurs during operation and anesthesia resuscitation in the patients at high altitude.

Objective To explore the diagnostic value of contrast-enhanced ultrasound combined with tumor markers in benign and malignant ovarian tumors.Methods The clinical data of 100 patients with ovarian tumors treated in our hospital from May 2016 to May 2017 were analyzed retrospectively.The parameters of contrast-enhanced ultrasonography (CEUS) for benign and malignant ovarian tumors were analyzed.The levels of tumor markers were measured and the ultrasound imaging was analyzed.Analysis of the detection rate of benign and malignant ovarian tumors by contrast-enhanced ultrasound alone or in combination with tumor markers.Results Compared with benign ovarian tumors,ovarian malignant tumors have the characteristics of uneven enhancement,early onset and peak time of contrast enhancement,and higher rate of enhancement (P ＜ 0.05);compared with benign ovarian tumors,serum CA125 and CA199 levels in patients with ovarian malignant tumors were higher,with significant difference (P ＜ 0.05).The detection rates of contrast-enhanced ultrasound combined with tumor markers were higher than those of ultrasound or tumor markers alone,and were in accordance with pathological criteria.Conclusions The application of combined contrast-enhanced ultrasound and tumor markers in the diagnosis of ovarian benign and malignant tumors has a high detection rate,can significantly improve the accuracy of clinical detection,and provide a strong basis for treatment.

OBJECTIVETo explore the differences in the clinical therapeutic effects on xerophthalmia of and deficiency between the needling technique (the combined reinforcing technique to induce warm sensation) and the reinforcing needing technique achieved by rotating needle.

METHODSA total of 54 patients of xerophthalmia were randomized into an observation group (28 cases) and a control group (26 cases). In both of the groups, the main acupoints included Cuanzu (BL 2), Sizhukong (TE 23), Taiyang (EX-HN 5) and Fengchi (GB 20); the combined acupoints were Danzhong (CV 17), Sanyinjiao (SP 6), Taixi (KI 3) and Taichong (LR 3). In the observation group, the needling technique was used and in the control group, the reinforcing needing technique achieved by rotating needle was adopted. The treatment was given once every day. 10 treatments made one course and 2 courses were required. Before and after treatment, the score of eye symptoms, tear secretion and the breakup time of tear film were observed in the two groups. The clinical therapeutic effects were compared between the two groups after treatment and in 4-week follow-up after treatment separately.

RESULTSAfter treatment, the total effective rate was 92.9% (26/28) in the observation group and was 80.8% (21/26) in the control group, without significant difference in comparison (>0.05). In 4-week follow-up after treatment, the total effective rate was 85.7% (24/28) in the observation group and was 61.5% (16/26) in the control group, indicating the significant difference in comparison (<0.05). After treatment, the differences were significant in the score of eye symptoms, tear secretion and the breakup time of tear film as compared with those before treatment in the two groups (all <0.01). After treatment, the improvements of the score of eye symptoms, tear secretion and the breakup time of tear film in the observation group were better remarkably than those in the control group, indicating the significant differences (all <0.05).

CONCLUSIONThe needling technique achieves the significant therapeutic effects on xerophthalmia of and deficiency and the recurrence rate of the disease is low.

Objective:To investigate the predictive value of stress hyperglycemia for the functional outcomes in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the Affiliated Hospital of Lianyungang, Xuzhou Medical University from September 1, 2019 to December 31, 2020 were enrolled prospectively. The glucose to glycated hemoglobin ratio (GAR) was used to express stress hyperglycemia. The functional outcome was evaluated by the modified Rankin Scale at 3 month after discharge, 0-2 was defined as a good outcome and >2 as a poor outcome. Multivariate logistic regression analysis was used to determine the independent related factors of functional outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of GAR for poor functional outcome. Results:A total of 1 286 patients with AIS were included. Their median age was 67 years old, and 762 were males (59.3%). The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 2. The median fasting blood glucose level was 5.48 mmol/L, the median glycosylated hemoglobin was 6.00%, and the median GAR was 0.92. Eight hundred and twelve patients (63.1%) had good outcomes and 474 (36.9%) had poor outcomes. The GAR in the good outcome group was significantly lower than that in the poor outcome group (0.86 vs. 1.03; P<0.001). All patients were divided into 4 groups (GAR1, GAR2, GAR3, and GAR4) according to the GAR quartile from low to high. Multivariate logistic regression analysis showed that after adjusting for relevant confounding factors, GAR4 (taking the GAR1 as a reference, odds ratio [ OR] 8.896, 95% confidence interval [ CI] 5.775-13.702; P<0.001), age ( OR 1.041, 95% CI 1.027-1.055; P<0.001) and baseline NIHSS score classification ( OR 25.898, 95% CI 14.221-47.163; P<0.001) were closely associated with the poor outcomes at 3 months. Further subgroup analysis showed that the higher level of GAR was significantly and independently correlated with the poor functional outcome, regardless of whether the patients had diabetes or not. The ROC curve analysis showed that the area under the curve of GAR predicting poor outcome at 3 months was 0.705 (95% CI 0.675-0.735; P<0.001), and the predictive value was significantly higher than that of glycosylated hemoglobin and fasting blood glucose. When the cut-off value of GAR was 0.97, the Yoden index was the largest, which was 0.370. The sensitivity and specificity of its predicting the poor outcome at 3 months were 61.6% and 75.4%. Conclusion:Whether or not diabetes is present, GAR is an independent predictor of the poor outcomes in patients with AIS.