Objective:To investigate the effect of flexible visiting policies in ICUs by comparing with restrictive visiting policies.Methods:English database (Pubmed, embase, Cochrane library, scopus, OvidSP, Wiley Online library, Google scholar and web of science) and Chinese database (CNKI, VIP, CBM and Wanfang) are retrieved, the search time is up to February 2020. The included literatures were evaluated quantitatively and qualitatively.Results:The flexible visiting policies can reduce the risk of delirium in ICU patients [RR=0.59, 95%CI=(0.36,0.96)], shorten the length of stay [MD=-0.21, 95%CI=(-0.35,-0.06)], improve patients' anxiety symptoms [MD=-2.2, 95%CI=(-3.8,-0.61)], reduce the incidence of anxiety and depression and improve the nursing satisfaction of patients and their families, without increasing the risk of ICU acquired infection [RR= 0.77, 95% CI= (0.51, 1.16)] and patient mortality (RR= 0.82, 95% CI= (0.53, 1.26)]. Sensitivity analysis suggested that the results were stable.Conclusions:Compared with the current restrictive visitation policies, the flexible visitation system can reduce the risk of delirium, improve anxiety symptoms and depression, and obtain more satisfaction from family members and patients, and It can be tried further.

Objective To compare of clinical effect between radiotherapy and chemoradiotherapy and investigate the prognostic factors in elderly patients with esophageal squamous cell cancer.Methods 229 elderly patients with esophageal squamous cell cancer who received radiotherapy and chemoradiotherapy from January 2009 to December 2013 were retrospective analyzed.The Local control rate and survival rate were calculated by Kaplan-Meier method,and the short effect and long term effect between radiotherapy and chemoradiotherapy were compared.Cox regression model was used for invariant analysis and multivariate analysis.Results The follow up time was 15.3months.The short effect of radiotherapy group was not better than that of chemoradiotherapy group,with CR 35.6％ vs 45.8％,RR 61.0％ vs 53.0％,SD 2.7％ vs 0 and PD 0.7％ vs 1.2％ (P=0.211).The 1-,2-,3-year local control rates of radiotherapy group were significantly poorer than that of chemoradiotherapy group,with 82.8 ％,60.5 ％ and 52.7％ vs 89.5％,85.4％ vs 80.9％,respectively (P=0.009).However,there were no significance difference between the 1-,2-,3-year survival rates of radiotherapy group and chemoradiotherapy group,with 66.4％,29.5％,17.1％ vs.65.9％,40.3 ％,30.8 ％,respectively (P =0.071).In invariant analysis,T stage,N stage,clinical stage and radiotherapy dose (＜ 60 Gy,60 ～66 Gy,＞66 Gy) were related with the prognosis of esophageal carcinoma.The COX regression model showed that T stage,N stage and radiotherapy dose were independent prognostic factors that effected survival rate.Conclusion In elderly patients with esophageal squamous cell cancer,chemoradiotherapy can improve the local control rates,but not benefit the survival rate.T stage,N stage and radiotherapy dose were independent prognostic factors that effected survival rate,which could provided evidence for prognosis judgement and clinical practice.

Objective To improve the non?surgical N staging system for esophageal carcinoma ( EC) . Methods A retrospective analysis was performed in 501 patients newly diagnosed with esophageal squamous cell carcinoma who received radiotherapy in our hospital from 2009 to 2013. The impacts of the supraclavicular lymph nodes and mediastinal lymph nodes on the overall survival ( OS) rate were analyzed. The original non?surgical N staging system was improved and the proposed N staging system was evaluated. The OS rates were calculated using the Kaplan?Meier method and analyzed using the log?rank test. The univariate and multivariate analyses were performed using the log?rank test and Cox regression model, respectively. Results The 3?and 5?year sample sizes were 404 and 205, respectively. In all patients, the 1?, 3?, and 5?year OS rates were 64?9%, 26?5%, and 18?3%, respectively;the 1?, 3?, and 5?year distant metastasis?free ( DMF) rates were 86?2%, 68?9%, and 67?3%, respectively;the 1?, 3?, and 5?year local control rates were 72?7%, 53?1%, and 43?6%, respectively. The univariate analysis showed that the incidence, 3?year OS rate, and 3?year DMF rate of supraclavicular lymph node metastases in patients with cervical and upper?thoracic EC were significantly higher than those in patients with middle?thoracic and lower?thoracic EC ( 25?7% vs. 14?2%, P=0?034;24?2% vs. 11?5%, P=0?016;84?8% vs. 69?2%, P=0?007) . The multivariate analysis also showed that the number of metastatic lymph nodes was an independent prognostic factor for the OS and DMF rates in patients ( P= 0?000;P= 0?007 ) . Conclusions It is reasonable to classify upper?thoracic EC with supraclavicular lymph node metastasis into stage N1 diseases. The proposed N staging system with the factor of the number of metastatic lymph nodes is more scientific and objective than the original N staging system.

OBJECTIVETo investigate the effect of celecoxib in enhancing the chemosensitivity of oral cancer cells and the correlation of this effect with cell cycle arrest.

METHODSKB/VCR cell line was treated with celecoxib (10, 20, 40, and 80 µmol/L) and/or VCR (0.375, 0.75, 1.5, and 3 µmol/L), and the growth inhibition rates of KB/VCR cells were assessed with MTT assay. Flow cytometry was employed to analyze the distribution of cell cycle. Western blotting was performed to detect the expression of P-glycoprotein (P-gp) and the cell cycle related proteins Cyclin D1 and p21(WAF1/CIP1).

RESULTSLow concentrations of celecoxib (<20 µmol/L) produced no obvious effect on the proliferation of the cells. But at 10 µmol/L, celecoxib significantly enhanced the toxicity of VCR in a time-dependent manner, and the combined treatments for 24, 48, and 72 h caused growth inhibition rates of (37.53∓2.05)%, (46.67∓3.17)% and (54.02∓1.53)%, respectively, significantly higher than those following treatments with celecoxib or VCR alone (P<0.01). Compared with the cells treated with VCR alone , the cells with combined treatments showed a significantly increased cell percentage in G0/G1 phase [(56.08∓0.46)%] with decrease percentages in S phase [(22.83∓0.20)%] and G2/M phase [(21.09%∓0.66)%]. The combined treatment also significantly down-regulated cyclin D1, up-regulated p21(WAF1/CIP1), and reduced P-gp expressions in the cells.

CONCLUSIONSCelecoxib enhances the chemosensitivity of KB/VCR cells by down-regulating P-gp expression, which is partially mediated by modification of cyclin D1 and p21(WAF1/CIP1) to result in cell cycle arrest.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Celecoxib ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Humans ; KB Cells ; Mouth Neoplasms ; drug therapy ; metabolism ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology

Background: Mature oocytes at the metaphase II status (MII-stage oocytes) played an important role in assisted reproductive technology in non-human primates. Objectives: In order to improve the proportion of MII-stage oocytes retrieval, three different superovulation protocols were performed on 24 female cynomolgus monkeys. Methods: All the monkeys received once-daily injection of follicle-stimulating hormone (25 international unit [IU]) on day 3 of the menstruation, 3-day intervals, twice daily for 8–12 days until the time of human chorionic gonadotropin (1,500 IU) injection, on the 14–17th day of menstruation collecting oocytes. The difference between protocol I and protocol II was that 0.1 mg the gonadotropin-releasing hormone agonist was injected on day 1 of the menstruation, while the difference between personalized superovulation protocol and protocol II was that oocytes could be collected on the 14–17th day of menstrual cycle according to the length of each monkey. Results: The total number of oocytes harvested using the personalized superovulation protocol was much higher than that using protocol I (p < 0.05), and the proportion of MII-stage oocytes was significantly greater than that from either superovulation protocol I or II(p < 0.001 and p < 0.01 respectively), while the proportion of immature oocytes at the germinal vesicle was less than that from superovulation protocol I (p < 0.05). Conclusions The personalized superovulation protocol could increase the rate of MII-stage oocytes acquired, and successfully develop into embryos after intracytoplasmic sperm injection, and eventually generated fetus.

Objective:To construct a service index system suitable for palliative care institutions at all levels, and provide reference for medical institutions to carry out programmed palliative care services.Methods:From April 2020 to June 2021, using expert focus group method, combined with domestic and foreign literature review and pilot work experience, the flow chart of hospice care service was preliminarily drawn, and the service indicators were formulated. Delphi expert letter consultation method was used to conduct two rounds of consultation among 16 experts, and finally the palliative care service index system was formed.Results:The positive coefficient of experts in the two rounds of Delphi expert letter consultation were 16/20 and 16/16, the authority coefficient was 0.828, 0.831, and the Kendall harmony coefficient was 0.236, 0.389, respectively. Finally, the palliative care service index system consisted of 8 indicators for primary level, 18 indicators for secondary level and 40 indicators for tertiary level.Conclusions:The established palliative care service index system is scientific and reliable, which can provide reference for all levels of hospice care institutions to carry out programmed services.

Objective:To explore if protective effects of dapagliflozin (Dapa) administration on attenuating DOX-induced myocardial injury in rats.Methods:A total of 30 specific pathogens free grade 8 week old male Sprague Dawley rats. Rats were randomly divided into three groups. Control group (Con group, n = 5), rats received intraperitoneal saline (1.25 ml/kg) injection once per week plus saline (8 mg/kg) daily via gavage for 6 weeks. Dox group ( n = 15) rats received intraperitoneal Dox (2.5 mg/kg) injection once per week plus saline (8 mg/kg) daily via gavage for 6 weeks. Dox + Dapa group ( n = 10), rats received intraperitoneal Dox (2.5 mg/kg) injection once per week plus Dapagliflozin (4 mg/kg) daily via gavage for 6 weeks, observed to week 10. Survival status, echocardiography, pathology, and expression of Bcl-2, Bax gene and protein were observed. Results:The survival rate of ats in Con, Dox, and Dapa+Dox groups was 100.0%, 66.7% and 90.0% respectively. The echocardiography were performed in Con, Dox, and Dapa+Dox groups left ventricular ejection fraction was (95.40 ± 2.51)%, (83.09 ± 4.92)% and (91.71 ± 3.45)%, respectively; left ventricular fraction shortening was (66.80 ± 7.43)%, (47.27 ± 5.10)% and (59.43 ± 6.92)%, respectively; Both indexes in Dapa+Dox group was higher than that in Dox group, but lower than that in Con group, all P<0.05; Left ventricular end-diastolic diameter was (4.80 ± 0.83) mm, (5.90 ± 0.83) mm and (4.85 ± 0.69) mm respectively; left ventricular end-systolic diameterwas (1.80 ± 0.44) mm, (2.90 ± 0.53) mm and (2.00 ± 0.57) mm in Con, Dox, and Dapa + Dox groups, respectively; Both indexes in Dapa + Dox group was decreased than that in Dox group, but Dapa + Dox group was increased than that in Con group, all P<0.05. Pathologic changes have been shown that myocardial fibers arranged neatly in the Con group under HE staining, while those broken myocardial fibers disordered arranged in the Dox group, and those changes in the Dapa + Dox group were slightly relieved than that in Dox group. The collagen volume fraction of rats in Con, Dox and Dapa+Dox groups were (2.64 ± 1.04)%, (16.85 ± 1.70)% and (6.75 ± 1.89)% under sirius red staining, Dapa+Dox group was lower than that in Dox group but higher than that in Con group, all P<0.05. Pathologic changes under transmission electron microscope have been shown that a few of normal structure mitochondria in the Con group. A large number of swollen mitochondria with disappeared mitochondrial crest in the Dox group; but neatly arranged with mitochondrial crest blurred in the Dapa+Dox group. The quantitative real-time PCR was used to detected Bcl-2 and Bax, there were 0.93 ± 0.09, 0.35 ± 0.30 and 0.89 ± 0.25 in Bcl-2, 0.99 ± 0.10, 3.10 ± 0.10 and 0.86 ± 0.04) in Bax, while Bcl-2/Bax 0.94 ± 0.17, 0.11 ± 0.06 and 1.03 ± 0.27, respectively. The westernblot was used to detected Bcl-2 and Bax, there were 1.00 ± 0.18, 0.32 ± 0.20 and 1.30 ± 0.41 in Bcl-2, 0.66 ± 0.11, 2.44 ± 0.66 and 0.90 ± 0.61 in Bax, while Bcl-2/Bax: 1.50 ± 0.18, 0.12 ± 0.05 and 1.80 ± 0.82, respectively; the above results shown that both myocardial Bax mRNA and protein expression in Dox group were higher than that in Dapa + Dox group and Con group, both P<0.05, and there was no difference in the two later groups, P>0.05; both the myocardial Bcl-2 mRNA and protein expression in Dox group were lower than that in Dapa+Dox group and Con group, both P<0.05, and there was no difference between two later groups, P>0.05; Bcl-2/Bax in Dox group was significantly lower thanthat in Dapa+Dox groupand Con group, both P<0.05, and there was no difference between Dapa+Dox group and Con group, P>0.05. Conclusions:Simultaneous dapagliflozin treatment significantly attenuated DOX-induced cardiotoxicity, which might be related to prevent myocardial apoptosis.

Objective There is a Few studies explored the association between vitamin intake and meta-bolic dysfunction-associated fatty liver disease(MAFLD),while the existing results were still contradictory.This study aimed to investigate the association between dietary vitamins and all-cause mortality as well as fibrosis risk in patients with MAFLD.Methods The data were extracted from the third National Health and Nutrition Examination Surveys 1988-1994.Dietary vitamins was assessed using a 24 h diet recall,including vitamin A,vitamin B6,vitamin B12,vitamin C,vitamin D,thiamin,riboflavin,folic acid and α-tocopherol.The non-alcoholic fatty liver disease fibrosis score(NFS)<-1.455 was considered as non-advanced fibrosis,while NFS≥-1.455 was considered as advanced fibrosis.Results A total of 3844 MAFLD participants were included in this study.The median time of follow-up was 310 months.1739 participants(45.3%)were deceased during the follow-up.The intake of thiamin,riboflavin,α-tocopherol,VB6,and VB12 were significantly higher in patients with NFS-determined non-advanced fibrosis(P<0.05).After adjusting,a significantly lower risk of fibrosis was found in patients with the highest quartile(>11.5 mg/d)of α-tocopherol intake compared to the lowest intake group(P = 0.031).Compared to the lowest quartile group,the risk of mortality was reduced by 0.34 folds in the group consuming the highest quartile amount(>130 mg/d)of VC(HRs:0.66,95%CI:0.51～0.85,P = 0.001).Conclusions More α-tocopherol intake reduced fibrosis grade in MAFLD patients.VC intake may reduce all-cause mortality in patients with MAFLD.

Objective: To investigate IMRT planning process using the combined application of failure modes and effects analysis (FMEA) and fault tree analysis (FTA) by reference to the report of Task Group 100 of the AAPM, and stablish and optimize the quality. Methods: A multidisciplinary team detailed the process mapping of IMRT planning using Eclipse TPS. The team evaluated the potential failure modes (FMs) of every process step. The evaluation was divided into two groups according to whether quality management (QM) was considered. For every FM, occurrence (O), severity (S) and detectability (D) by consensus were evaluated, and the product of O, S and D yielded the risk priority number (RPN), which permitted the ranking of the FMs. Finally, FTA was used to determine the root factors contributing to the riskiest failure modes. Results: The IMRT plan process consisted of 10 major sub-processes and 33 steps, which amounted to 47 failure modes. For the group without quality management, the RPN of FMs was between 13.2-271.8, 27 of which had RPN≥80, and 18 FMs had S≥8. For the group with quality management, the RPN of FMs was between 11.2-158.4, 11 of which had RPN≥80. The difference of RPN between the two groups was statistically significant (RPN of the group without QM=101.17±66.34, RPN of the group with QM=59.54±35.64, t=8.501, P<0.05). Finally, FTA was used to determine the root factors contributing to the FMs, i. e., prescription dose definition and importing images. Conclusions The FMEA and FTA methods are operable and practical, which can systematically and comprehensively analyze the potential failures and risks existing in the process of IMRT plan. And the FMEA and FTA can contribute to establish and optimize the quality management program in radiotherapy.

Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide. Metastasis is a marker of cancer deterioration in patients with liver cancer and a major cause of death. In order to develop effective therapeutic strategies, it is urgent to study the molecular basis of liver cancer metastasis. Methods: Immunohistochemistry was used to detect the expression of fatty acid synthase (FASN) in HCC. Wound healing and transwell cell invasion assays was used to confirm the role of FASN in liver cancer migration and invasion. Proteins that interacted with FASN were identified using iTRAQ (isobaric tag for relative and absolute quantification). Co-immunoprecipitation (Co-IP) and cellular immunofluorescence analysis were used to assess the interaction between FASN and signal transduction and transcription activator 3 (STAT3). The expression of STAT3, p-STAT3, matrix metalloproteinase (MMP)-2 and MMP-9 was detected after FASN knockdown using Western blot method. Statistical analysis was performed using the t-test. Results: Immunohistochemistry showed that the expression of FASN in HCC tissue was higher than that in adjacent tissues. iTRAQ, Co-IP and immunofluorescence analysis revealed that FASN interacted with STAT3. Western blot analysis showed that the expression of p-STAT3, MMP-2 and MMP-9 decreased after FASN knockdown. Conclusion FASN may promote the metastasis of liver cancer by interacting with STAT3 and affecting the expression of MMP-2/MMP-9.