Acute respiratory distress syndrome (ARDS) is an important cause of death in critically ill patients. Prone ventilation is one of the effective treatment methods for ARDS, but the current clinical implementation rate is not high, which is mainly due to the occurrence of serious complications such as tracheal tube and venous pipeline disconnection, pressure sores, hemodynamic instability and so on, and requires adequate personal and cooperation. The medical staff of the department of critical care medicine of Beijing Shijitan Hospital Affiliated to Capital Medical University designed a kind of support bracket for human body carrying and turning over which can help the critically ill patients to easily complete the position conversion during prone position ventilation, and has obtained the national utility model patent (Patent Number: ZL 2017 2 1847759.9). The support bracket is simple in design, composed of stent, rotating shaft and bandage. It is reliable and easy to operate. It can significantly reduce the difficulty of prone position ventilation, avoid the occurrence of related complications, reduce the labor load of medical staff, and improve the treatment quality of patients.

Objective:To determine the risk factors of extubation failure and its effect on the prognosis of patients who had successfully passed a spontaneous breathing trial (SBT).Methods:The clinical data of patients with mechanical ventilation more than 24 hours who passed SBT admitted to department of intensive care unit (ICU) of First Hospital of Qinhuangdao from November 2018 to November 2019 were retrospectively analyzed. According to the outcome of weaning within 48 hours after weaning, patients were divided into weaning success group and weaning failure group. The baseline data, the presence of basic cardiopulmonary diseases, B-type natriuretic peptide (BNP), fluid balance, albumin and hemoglobin within 24 hours before weaning, the time of mechanical ventilation before weaning, rapid shallow breathing index (RSBI) during SBT, oxygenation index, cough peak flow at the end of SBT, and prognostic indicators were collected. The outcome of weaning was taken as the dependent variable, and the observation factors were taken as the independent variable for univariate analysis. The factors with statistical significance in univariate analysis were analyzed by binary Logistic regression to determine the influencing factors of weaning failure.Results:Of the 204 patients, 167 (81.9%) were successfully weaned, and 37 (18.1%) failed. Compared with the weaning success group, the total duration of mechanical ventilation and the length of ICU stay in the weaning failure group were significantly longer [days: 13.0 (7.5, 23.5) vs. 5.0 (3.0, 8.0), 17.0 (12.5, 31.0) vs. 10.0 (6.0, 15.0), both P < 0.01], and the tracheotomy rate and mortality were significantly higher (32.4% vs. 0%, 51.4% vs. 0%, both P < 0.01). Univariate analysis showed that there were significant differences in age, proportion of patients with cardiopulmonary diseases, BNP and cough peak flow between weaning failure group and weaning success group [age (years old): 70.65±15.78 vs. 62.69±15.82, cardiopulmonary diseases: 62.2% vs. 24.6%, BNP (ng/L): 416.87 (32.70, 1 225.80) vs. 45.36 (10.00, 273.60), cough peak flow (L/min): 59.89±9.06 vs. 83.84±16.52, all P < 0.01]. However, there were no significant differences in gender, acute physiology and chronic health evaluationⅡ (APACHEⅡ) at admission, mechanical ventilation time before weaning, albumin, hemoglobin, oxygenation index, RSBI and fluid balance 24 hours before weaning between weaning failure group and weaning success group [male: 51.4% vs. 68.3%, APACHEⅡ: 16.70±6.65 vs. 15.67±6.28, mechanical ventilation time before weaning (days): 6.0 (2.5, 11.0) vs. 5.0 (3.0, 8.0), albumin (g/L): 27.78±4.15 vs. 27.76±4.46, hemoglobin (g/L): 102.43±15.80 vs. 100.61±17.19, oxygenation index (mmHg, 1 mmHg = 0.133 kPa): 359.33±79.83 vs. 365.75±78.23, RSBI (times·L -1·min -1): 50.73±24.97 vs. 46.76±15.53, positive fluid balance: 70.3% vs. 69.5%, all P > 0.05]. The results of binary Logistic regression analysis showed that age ≥ 75 years old [odds ratio ( OR) = 3.099, 95% confidence interval (95% CI) was 1.003-9.574, P = 0.049], presence of cardiopulmonary diseases ( OR = 3.599, 95% CI was 1.126-11.498, P = 0.031), BNP within 24 hours before weaning ( OR = 1.002, 95% CI was 1.000-1.003, P = 0.005) were the risk factors of extubation failure, while cough peak flow at the end of SBT was the protective factor ( OR = 0.869, 95% CI was 0.823-0.917, P = 0.000). Conclusions:For patients who had successfully passed SBT, age ≥ 75 years old, the presence of cardiopulmonary diseases and an increased level of BNP within 24 hours were the risk factors of extubation failure. In addition, the higher the cough peak flow at the end of SBT, the lower the risk of weaning failure will be.

Objective To compare the efficacy, safety, and the life quality of patients with early gastric cancer ( EGC) between endoscopic submucosal dissection ( ESD) and surgical treatment. Methods A total of 460 cases with EGC receiving endoscopic therapy or surgical treatment were collected from October 2009 to January 2015 in the Cancer Hospital, Chinese Academy of Medical Sciences. The clinical efficacy and life quality of ESD and surgical treatment for EGC patients were retrospectively analyzed. Results There were 434 cases collected in the study, including 208 cases ( 229 lesions) in the ESD group and 226 cases in the surgery group. For the short-term clinical outcomes of the ESD group, the hospitalization time ( 7. 85 ± 3. 18 d VS 16. 68±5. 89 d, P<0. 001), hospitalization cost (3782. 30±1898. 84 CNY VS 9685. 60± 3643. 97 CNY, P<0. 001 ) and complications [ 0 ( 0/208 ) VS 6. 2% ( 14/226 ) , P<0. 001 ] were statistically different compared with those of the surgery group. For the long-term clinical outcomes, there was no statistical significance on recurrence rate[0. 4%(1/229) VS 0. 9% (2/226), P=0. 622] between the two groups. The cumulative multiple hazard probability curve showed that the ESD group had a significantly higher risk of multiple primary lesions than the surgery group ( P=0. 004) after the same follow-up period. In order to exclude the influence of confounding factors, COX regression model was used to control the age and other factors, and multiple primary risks of the two groups were also statistically significant ( P=0. 013) . The health score of self-evaluation and life quality between the two groups were statistically significant ( P<0. 001) . Conclusion For the short-term clinical outcomes, the ESD group was better than the surgery group. For the long-term clinical outcomes, multiple primary risks were higher in the ESD group than those in the surgery group, but most of the multiple primary cases were successfully treated with a second ESD. The health score of self-evaluation and life quality were better in the ESD group than those in the surgery group.

Objective To quantitatively estimate the deaths and life expectancy losses attributable to diet high in sodium in China,and examine the gains and shifts under different control scenarios of sodium consumption.Methods Based on data from the cause-of-death through the National Mortality Surveillance System,and 24 hours urinary sodium values from Global Burden of Disease study on Chinese's estimates,population attributable fractions with the framework of comparative risk assessment were used to analyze the deaths and life expectancy losses due to diet high in sodium.The same methods were followed to examine the gains and shifts under different control scenarios of sodium consumption.Results In 2013,1 430 (940 for men and 490 for women)thousand deaths were attributable to diet high in sodium,accounting for 15.6％ (17.4％ for men and 13.0％ for women) of all-cause deaths in China,which causing 2.17 (2.49 for men and 1.71 for women) years of life expectancy loss.Diet with high sodium in 2013 caused 1 200,50 and 180 thousand deaths from cardiovascular disease,chronic kidney disease and stomach cancer respectively,accounting for 31.5％,30.8％ and 64.8％ of those specific causes.Comparing to the baseline in 2013,if the targets of 10％ decrease of sodium consumption by 2020 and 15％ by 2030 for Chinese chronic disease prevention and treatment planning,and 30％ decrease by 2030 for WHO non-communicable disease monitoring framework are achieved,220,340 and 730 thousand deaths will be averted,which may gain 0.30,0.45 and 0.95 years of life expectancy,respectively.Conclusions As one of the leading risk factors,diet high in sodium had caused heavy burden of disease from cardiovascular disease,chronic kidney disease and stomach cancer on Chinese residents.Intervention programs on sodium-reductionare urgently needed in China and related cost-effectiveness is highly expected.

The contents of general practice discipline construction comprise of orientation, team development, personnel training, scientific research, teaching base establishment and management of the discipline, etc. At present, the weakness in above aspects of general practice discipline construction is still the major challenges in most of the primary healthcare institutions. Our experiences in last 10 years shows that the application of Leicester Assessment Package can effectively promote the general practice discipline development for primary care institutions.

Objective: To understand the in vitro growth characteristics of Cryptococcus gattii VGⅠ and VGⅡ isolated in China and the diversity in their virulence to Galleria mellonella. Methods: Based on the results of multilocus sequence typing for eight strains of Cryptococcus gattii isolated in China, the strains were cultured in vitro to draw growth curves, observe the melanin production and measure the capsule thickness. The median lethal time (LT₅₀) and median lethal dose (LC₅₀) at 48 h of Cryptococcus gattii were calculated using Galleria mellonella infection test. Fourteen strains of Cryptococcus neoformans were studied for comparison. Results: The eight Cryptococcus gattii strains were six VGⅠ and two VGⅡ. The growth curves of Cryptococcus gattii VGⅠ and VGⅡ were similar to that of Cryptococcus neoformans when culture at 30℃. The total number for each of them could reach 10⁸ CFU/ml at 96 h under 30℃. However, the total number at any time point at 37℃ was less than that at 30℃. There was no significant difference in the amount of melanin produced by Cryptococcus neoformans under 30℃ and 37℃, but both VGⅠand VGⅡ types of Cryptococcus gattii could produce more amount of melanin under 37℃ than under 30℃. The ratio of capsule/cell wall diameter of Cryptococcus gattii VGⅠwas greater at 37℃ than that at 30℃ with statistical significance (P<0.001). Cryptococcus neoformans showed the longest LT₅₀, followed by VGⅠand VGⅡ types of Cryptococcus gattii. The LT₅₀ of Cryptococcus gattii VGⅡ at the concentration of 1×10⁶ CFU/ml was 72 h, and its LC₅₀ at 48 h was 1×10⁸ CFU/ml. Conclusions Like Cryptococcus neoformans, Cryptococcus gattii VGⅠ and VGⅡ grew faster under 30℃ than under 37℃, but more melanin was produced and thicker capsule was formed under 37℃ than under 30℃. Among Cryptococcus neoformans and VGⅠ and VGⅡ types of Cryptococcus gattii, Cryptococcus gattii VGⅡ showed the shortest LT₅₀ and the strongest virulence to Galleria mellonella.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).