[Clinical observational study of Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer].

Objective: To investigate the clinical efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. Methods: A total of 65 patients with locally advanced cervical cancer treated with Nimotuzumab combined with concurrent chemoradiotherapy in Tianjin Medical University Cancer Institute and Hospital were selected from January 2015 to November 2018. Intensity-modulated radiotherapy and intracavitary post-packaging were used for radiation therapy. Platinum and paclitaxel were used for chemotherapy. Nimotuzumab were 400 mg/week. The clinical efficacy, the changes of serum tumor markers and the occurrence of adverse events were observed for 2 years, and the evaluation was performed once for every 3 months. Results: Sixty-one cases could be evaluated by imaging during the follow-up. The best curative effect evaluation showed that complete remission (CR) was 43 (70.5%), partial remission (PR) was 9 (14.8%), stable disease (SD) was 6 (9.8%) and objective response rate (CR+PR) was 85.3%, disease control rate (CR+PR+SD) was 95.1%. Survival analysis showed that one-year overall survival rate was 93.9% and two-year overall survival rate was 79.6%. After 3 months of treatment, the serum tumor markers SCC, CA125, CEA, and HE4 were significantly lower than those before treatment (P<0.05). Safety assessments showed that the main adverse events were hematochezia, abdominal pain, diarrhea, fever and dizziness, and 37 cases of them were grades Ⅰ-Ⅱ. Conclusion: Nimotuzumab combined with concurrent chemoradiotherapy has a good clinical effect in the treatment of locally advanced cervical cancer, significantly reduces serum tumor marker levels after treatment, and is safe and tolerable in clinical use.

[Advances in basic and clinical research on hepatocellular carcinoma in 2016].

Hepatocellular carcinoma (HCC) is still one of common malignant cancers worldwide, with increasing incidence and mortality rates. Early diagnosis and effective treatment for HCC remain to be explored. This article introduces the research advances in the early specific diagnosis and effective therapies for HCC in 2016, such as molecular markers in the specific diagnosis and targeted therapy for HCC, main therapeutic regimens, robot-assisted liver resection, and no-touch radiofrequency ablation.

Effect of rosuvastatin on high glucose-induced endoplasmic reticulum stress in human umbilical vein endothelial cells.

It is well established that endothelial injury plays an essential role in atherosclerotic plaque formation. Accumulating evidence has shown that high glucose levels may detrimentally affect cultured endothelial cells through endoplasmic reticulum (ER) stress. In this study, we investigated the effect of rosuvastatin on high glucose-induced ER stress in human umbilical vein endothelial cells (HUVECs). HUVECs treated with 30 mM glucose were used to simulate high-glucose conditions, and rosuvastatin concentrations ranging from 0.1 to 10 nM were used. Cell viability was analyzed by thiazolyl blue tetrazolium bromide assay, and apoptosis rate was measured using flow cytometry. Expression of GRP78, IRE1α, XBP1s, and CHOP was quantified using western blot and real-time polymerase chain reaction. Compared to cells treated with high glucose alone, cell viability increased and apoptosis rate decreased significantly in the rosuvastatin + high-glucose groups. Furthermore, GRP78, IRE1α, XBP1s, and CHOP expression was downregulated as a result of rosuvastatin administration. These results suggest that rosuvastatin may protect HUVECs from injury induced by high glucose levels, through alleviation of ER stress.

[Clinical outcome of totally thoracoscopic cardiac surgery for mitral valve replacement: a series of 634 cases].

OBJECTIVE: To summarize the clinical outcome of totally thoracoscopic cardiac surgery for mitral valve replacement. METHODS: Clinical data of 634 cases undergoing totally thoracoscopic cardiac surgery for mitral valve replacement from May 2004 to February 2016 in Department of Thoracoscopic Cardiacsurgery, Shanghai Yodak Cardiothoracic Hospital was analyzed retrospectively. There were 292 male and 342 female patients, aged from 17 to 68 years with a mean of (45±13) years. All the 634 patients had moderate-severe mitral valve stenosis and (or) incompetence, 263 patients had moderate-severe tricuspid valve incompetence, 356 patients had atrial fibrillation, 46 patients had left atrium thrombosis. Cardiopulmonary bypass was established with right femoral artery and a single 2 stage venus cannula in the right atrium. The ascending aorta was cross-clamped and the myocardium was protected by coronary perfusion with cold crystalloid cardioplegia. Totally thoracoscopic mitral valve replacement were performed. RESULTS: Thirteen cases had incision expanded and 8 cases had conversions to sternotomy. Cardiopulmonary bypass and aortic cross-clamp time were (89±18) minutes and (51±12) minutes, respectively. Operation time was (3.1±1.2) hours. Mechanical ventilation time and intensive care unit stay were (17±6) hours and (27±8) hours, respectively. Postoperation drainage quantity was (390±70) ml. The hospital days was (9.2±2.1) days. There were 5 cases in-hospital deaths. Postoperative complications occurred in 42 cases (6.6%), including 18 cases of right hemoneumothorax, 12 cases of reoperation for bleeding, 3 cases of perivalvular leakage (reoperation was done in 1 patient), 3 cases of low cardiac output syndrome, 2 cases of acute renal failure, 2 cases of inferior vena cava injury, 1 case of right femoral artery thrombosis and liver injury, respectively. The mean duration of follow-up was (58±9) months in 608 cases, with a follow-up rate of 96.7% (608/629). Three patients had died during the period of follow-up caused by congestive heart failure (2 patients) and stroke (1 patient). Late complication among 605 survivors were 37 cases, including 32 cases of moderate tricuspid valve insufficiency, 3 cases of stroke, 1 case of perivalvular leakage and infective endocarditis, respectively.There was no reoperation during the period of follow-up. CONCLUSION: Totally thoracoscopic cardiac surgery for mitral valve replacement is safe and effective, with unique superiority and clinical feasible.

Effects of probucol on cultured human umbilical vein endothelial cells injured by hypoxia/reoxygenation.

There is increasing evidence suggesting that endoplasmic reticulum stress (ERS) plays an important role in the initiation and development of atherosclerosis. This study was designed to examine the effect of probucol on cultured human umbilical vein endothelial cells (HUVECs) injured by hypoxia/reoxygenation (H/R) and the potential mechanisms involving ERS. Injured HUVECs induced by Na2S2O4 served as an H/R model in vitro. The concentration of probucol in this study ranged from 3 to 27 µM. Cell viability was analyzed using MTT and a lactate dehydrogenase (LDH) assay. The expression of GRP78, X-box-binding protein (XBP)-1, and CHOP (c/EBP-hemologous protein) were quantified using western blot. Compared to cells with H/R injury alone, the results showed that the cell viability increased significantly with probucol, while the LDH leakage rate was significantly lower as analyzed by the LDH assay. Furthermore, the expression levels of GRP78, XBP-1, and CHOP were significantly downregulated. These results indicated that probucol effectively protected HUVEC from injury induced by H/R and that the mechanism might be related to attenuation of ERS.

Molecular characterization, tissue expression profile and SNP analysis of porcine GLP2R.

Glucagon-like peptide-2 receptor (GLP2R), a member of the G-protein-coupled receptor family, plays an important role in intramuscular fat formation. Little is known, however, about porcine GLP2R. In the present study, GLP2R was cloned, and its expression in pig muscle characterized. By rapid amplification of cDNA ends, gene sequence was obtained from Shaziling pigs. Full-length cDNA was 1868 bp, including an open reading frame 1665 bp in length, encoding 554 amino acids, and 203 bp at the 3' end. The GLP2R homology between porcine and other species was performed using bioinformatics techniques to construct a phylogenetic tree. Porcine GLP2R was most closely related to those from Orcinus orca and Ovis aries, and most distantly related to those from Chrysemys picta, Taeniopygia guttata, and Falco peregrinus. Real-time PCR analysis showed expression of porcine GLP2R in 10 different tissues from 25-day-old Yorkshire and Shaziling piglets, with expression levels being highest in the longissimus dorsi muscle and lowest in kidney. For each pig breed, expression level in longissimus dorsi muscle was highest among ten tissues (P < 0.05). Between the two breeds, GLP2R expression levels were significant in pancreas, the crureus and longissimus dorsi muscles (P < 0.05). A single SNP of porcine GLP2R, A343G, was identified, and genotypes were determined by PCR-RFLP. This study provides an insight into the function of GLP2R in swine.

Comparison of methods for the microbiological identification and typing of Cronobacter species in infant formula.

Cronobacter species represent an emerging opportunistic foodborne pathogen associated with meningitis and necrotizing enterocolitis in infants. Current evidence indicates that powdered infant formula (PIF) is the main source of Cronobacter contamination. A total of 75 strains of Cronobacter spp. from different geographic regions, as well as from PIF processing environments, were identified and typed with different methods, including biochemical profiling by the API 20E system (bioMérieux, Marcy l'Etoile, France), protein profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and genotypic profiling by ribotype. Analysis by MALDI-TOF MS and biochemical identification was more accurate compared with ribotype analysis. However, MALDI-TOF MS typing and ribotype analysis showed more discriminatory ability compared with biochemical phenotyping. In conclusion, MALDI-TOF MS is a rapid and reliable tool to identify Cronobacter spp. in PIF and has the potential to trace dissemination of Chronobacter along the production chain.

Treatment of experimental staphylococcal endocarditis due to a strain with reduced susceptibility in vitro to vancomycin: efficacy of ampicillin-sulbactam.

We evaluated several 3-day antimicrobial regimens in the treatment of experimental endocarditis caused by an oxacillin-resistant Staphylococcus aureus strain exhibiting intermediate susceptibility in vitro to vancomycin (VISA). Neither vancomycin alone nor trovafloxacin exhibited in vivo efficacy; addition of amikacin to vancomycin yielded a modest in vivo effect. In contrast, the combination of ampicillin and sulbactam was highly effective in vivo, causing a mean decrease in VISA vegetation densities of >5 log(10) CFU/g versus those of untreated controls.

The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter.

Inherited mutations in the breast and ovarian cancer susceptibility gene BRCA1 are associated with high risk for developing breast and ovarian cancers. Several studies link BRCA1 to transcriptional regulation, DNA repair, apoptosis and growth/tumor suppression. BRCA1 associates with p53 and stimulates transcription in both p53 dependent and p53-independent manners. BRCA1 splice variants BRCA1a (p110) and BRCA1b (p100) associates with CBP/p300 co-activators. Here we show that BRCA1a and BRCA1b proteins stimulate p53-dependent transcription from the p21WAF1/CIP1 promoter. In addition, the C-terminal second BRCA1 (BRCT) domain is sufficient for p53 mediated transactivation of the p21 promoter. Previous studies emphasized the importance of the BRCT domain, which shows homology with p53 binding protein (53BP1), in transcriptional activation, growth inhibition and tumor suppression. Our findings demonstrate an additional function for this domain in protein-protein interaction and co-activation of p53. We also found that BRCA1a and BRCA1b proteins interact with p53 in vitro and in vivo. The p53 interaction domain of BRCA1a/1b maps, in vitro, to the second BRCT domain (aa 1760-1863). The BRCT domain binds to the central domain of p53 which is required for sequence specific DNA binding. These results demonstrate for the first time the presence of a second p53 interaction domain in BRCA1 proteins and suggests that BRCA1a and BRCA1b proteins, like BRCA1, function as p53 co-activators. This BRCT domain also binds in vitro to CBP. These results suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP/p300 associated HAT/FAT activity for acetylation of p53 to specific promoters resulting in transcriptional activation.

Induction of apoptosis by the tumor suppressor protein BRCA1.

The breast and ovarian cancer susceptibility gene BRCA1, is a nuclear phosphoprotein which functions as a tumor suppressor. To investigate the role of BRCA1 in apoptosis, we have developed mouse fibroblast cell lines and human breast cancer cell lines expressing BRCA1. The expression of BRCA1 protein in the BRCA1 transfectants were analysed by immunofluorescence and immunohistochemistry. The BRCA1 transfectants showed a flattened morphology compared to the parental cells. We show that serum deprivation or calcium ionophore treatment of BRCA1 transfectants resulted in programmed cell death. These results indicate that BRCA1 genes may play a critical role in the regulation of apoptosis. Thus, since a wide variety of human malignancies like breast and ovarian cancers have a decreased ability to undergo apoptosis, this could be due to lack/decreased levels of functional BRCA1 proteins. Treatments that are aimed at increasing the apoptotic threshold by BRCA1 gene therapy may have the potential to prevent the progression of these malignancies.