[Combinational Overexpression of Foxa3 and Hnf4α Enhance the Proliferation and Prolong the Functional Maintenance of Primary Hepatocytes].

In an in vitro culture system, primary hepatocytes usually display a low proliferation capacity, accompanied with a decrease of viability and a loss of hepatocyte-specific functions. Previous studies have demonstrated that the combination introductions of certain hepatocyte-specific transcription factors are able to convert fibroblasts into functional hepatocyte-like cells. However, such combinational usage of transcription factors in primary hepatocytes culture has not yet sufficiently studied. The forkhead box protein A3 (FoxA3) and hepatocyte nuclear factor 4α (Hnf4α) are liver-enriched transcription factors that play vital roles in the differentiation, and maintenance of hepatocytes. Thus, we simultaneously overexpressed the two genes, Foxa3 and Hnf4α, in rat hepatocytes and observed that the combinational augmentation of these two transcription factors have enhanced the proliferation and stabilized the hepatocyte-specific functions of primary hepatocytes over a long-term culture period.

[Global incidence and mortality of renal cell carcinoma in 2020].

Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.

[Spatiotemporal changes of COVID-19 outbreak in Shanghai].

Objective: To clarify the epidemiological characteristics and spatiotemporal clustering dynamics of COVID-19 in Shanghai in 2022. Methods: The COVID-19 data presented on the official websites of Municipal Health Commissions of Shanghai during March 1, 2022 and May 31, 2022 were collected for a spatial autocorrelation analysis by GeoDa software. A logistic growth model was used to fit the epidemic situation and make a comparison with the actual infection situation. Results: Pudong district had the highest number of symptomatic and asymptomatic infectants, accounting for 29.30% and 35.58% of the total infectants. Differences in cumulative attack rates and infection rates among 16 districts (P<0.001) were significant. The rates were significantly higher in Huangpu district than in other districts. The attack rate of COVID-19 from March 1, 2022 to May 31, 2022 had a global spatial positive correlation (P<0.05). Spatial distribution of COVID-19 attack rate was different at different periods. The global autocorrelation coefficient from March 16 to March 29, April 6 to April 12 and May 18 to May 24 had no statistical significance (P>0.05). Our local autocorrelation analysis showed that 22 high-high clustering areas were detected in eight periods.The high-risk hot-spot areas have experienced a "less-more-less" change process. The growth model fitting results were consistent with the actual infection situation. Conclusion: There was a clear spatiotemporal correlation in the distribution of COVID-19 in Shanghai. The comprehensive prevention and control measures of COVID-19 epidemic in Shanghai have effectively prohibited the growth of the epidemic, not only curbing the spatially spread of high-risk epidemic areas, but also reducing the risk of transmission to other cities.

Tuning Dzyaloshinskii-Moriya interaction via an electric field at the Co/h-BN interface.

The Dzyaloshinsky-Moriya interaction (DMI) at the Co/h-BN interface can emerge and be enhanced by applying a downward electric field. The height of the Co atom relative to the h-BN layer with the electric field determines the variation of DMI. One half reduction of J1 is beneficial to generate skyrmions. Tuning the DMI by an electric field sheds new light for research on skyrmions.

[Impact of obstructive sleep apnea on the long-term cardiovascular outcomes in patients with acute coronary syndrome].

Objective: To investigate the impact of obstructive sleep apnea (OSA) on long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Methods: This is a single-center, prospective cohort study. Between June 2015 to January 2020, consecutive ACS patients hospitalized at Beijing Anzhen Hospital, Capital Medical University were enrolled. All patients underwent portable sleep breathing monitoring, and they were then divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 events/hour) and no/mild OSA group (AHI<15 events/hour). The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, ischemia-driven revascularization and hospital admission for unstable angina or heart failure. MACCE were compared yearly by the log-rank test. Multivariable Cox regression analyses were performed to determine the independent predictors of MACCE. Results: A total of 1 927 patients with ACS were enrolled, including 1 629 males (84.5%), aged (56.4±10.5) years. Moderate/severe OSA was present in 1 014 (52.6%) patients. Compared with no/mild OSA group, moderate/severe OSA group exhibited a higher body mass index (P<0.05). Hypertension, prior PCI were more prevalent in moderate/severe OSA group (both P<0.05). The difference of ACS category between the two groups was statistically significant (P=0.021). The rate of patients who underwent PCI and the number of stents were higher in the moderate/severe OSA group. During a 5-year follow-up (median 2.9 years (IQR 1.5-3.6 years)), the cumulative incidence of MACCE was significantly higher in the moderate/severe OSA group than in the no/mild OSA group (34.0% vs. 24.0%, HR=1.346, 95%CI 1.100-1.646, log-rank P=0.004). The cumulative incidence of MACCE remained statistically higher at 4 and 5 year in the moderate/severe OSA group as compared to the no/mild OSA group (33.3% vs. 22.9%, HR=1.397, 95%CI 1.141-1.710, log-rank P=0.001; 34.0% vs. 24.0%, HR=1.341, 95%CI 1.096-1.640, log-rank P=0.004, respectively). Multivariate analysis showed that moderate/severe OSA (HR=1.312, 95%CI 1.054-1.631, P=0.015) was an independent predictor of long-term MACCE in ACS patients. Conclusions: Moderate/severe OSA is observed in more than 52% ACS patients. Moderate/severe OSA is an independent predictor of long-term MACCE.

[Biocompatibility of extracellular matrix hydrogel with human iPSCs differentiated cardiomyocytes].

Objective: To observe the biocompatibility of porcine omental derived extracellular matrix (ECM) hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the feasibility of ECM hydrogel as a delivery vector of cell transplantation. Methods: A series of chemical, physical and enzymatic methods were applied to acellularize the porcine omentum. Subsequently, the extracted ECM was prepared into thermosensitive hydrogel. The biochemical composition of the hydrogel was identified by histological staining. The microstructure was observed by scanning electron microscopy. The hydrogel was then injected into the myocardium of mice to observe its in situ gelation ability. Differentiation of human induced pluripotent stem cells into cardiomyocytes was achieved by small molecule induction, and then the obtained hiPSC-CMs were cultured. hiPSC-CMs cultured onto the prepared hydrogel were defined as the hydrogel group, while conventionally cultured hiPSC-CMs were defined as the control group. Cardiomyocyte viability and growth patterns were detected using live/dead staining, CCK-8 and phalloidin staining. Immunofluorescence staining and Western blot of cardiomyocytes were used to determine the survival and phenotypic maintenance markers of cardiomyocytes in materials. Results: The results of HE staining, oil red O staining and DAPI fluorescence staining showed that there was no significant cell debris, nucleus and lipid residue in the prepared ECM hydrogel. The Sirius red staining and Alcian blue staining showed that the hydrogel retained collagen and glycolaminoglycan, which were the main components of ECM. The prepared hydrogel behaves as a viscous liquid at 4 ℃ and as a gel state at 37 ℃. Scanning electron microscope results showed that the microstructure of the hydrogel was composed of irregular fibers and pores of different sizes. Under the guidance of ultrasound, the prepared ECM hydrogel could be successfully injected into the myocardium of mice. Immediately after the injection, the hyperechoic signal could be observed under ultrasound, suggesting that the hydrogel remained in the myocardium. HE staining of myocardial tissue evidenced that there was lump of gel in the injection area. The differentiated hiPSC-CMs were co-cultured with the prepared ECM hydrogel, and the results of live/dead staining showed that most of the hiPSC-CMs in the hydrogel group and the control group were alive, dead cells were scanty. The results of CCK-8 test showed that the absorbance values of the two groups were similar (P>0.05). The results of phalloidin staining showed that hiPSC-CMs could extend normally when co-cultured with ECM hydrogel. The cell morphology of the hydrogel group was similar with that of the control group, and there was no statistically significant difference in the F-actin coverage area per cell between the two groups (P>0.05). Immunofluorescence staining of cardiomyocyte markers showed that there was no significant difference in the coverage area of α-actinin and connexin-43 (Cx-43) per field between the hydrogel group and the control group (both P>0.05), the quantitative results of DAPI staining showed that there was no statistically significant difference in the number of cells between the two groups (P>0.05). Meanwhile, the results of Western blot showed that the expression levels of α-actinin and Cx-43 in cardiomyocytes in the hydrogel group were similar as those in the control group (both P>0.05). Conclusions: These results show that preparation of the ECM hydrogel from porcine omentum is successful. The hydrogel has good biocompatibility and no obvious cytotoxicity. Besides, the hydrogel can support the survival of hiPSC-CMs in vitro and maintain its phenotype. These properties make it a promising injectable cardiac tissue engineering material.

[CD44 regulates biological behavior and Ras signaling pathway in nasopharyngeal carcinoma stem cells].

Objective: To study the biological behavior of nasopharyngeal carcinoma stem cells and to explore the activation of Ras signaling pathway regulated by CD44. Methods: CNE2-SC and 5-8F-SC were nasopharyngeal carcinoma stem cells and obtained by serum-free suspension culture. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, cell adhesion array were used to investigate the growth, proliferation, migration and adhesion of nasopharyngeal carcinoma stem cells. Western blot test was used to detect the expressions of Ras signaling pathway related proteins and siRNA-mediated interference was used to determine the activation of Ras signaling pathway regulated by CD44. Results: The growth rates of CNE2-SC and 5-8F-SC cells were significantly lower than those of nasopharyngeal carcinoma cells at 24, 48 and 72 hours after inoculation (P<0.05). After 14 days of implantation, the colony formation rates of CNE2-SC (44.5±1.9)% and 5-8F-SC (47.4±1.8)% were higher than those of CNE2 (34.9±1.5)% and 5-8F (37.2±1.7)%, respectively(P<0.01). The migration cell number of CNE2-SC was (87.6±7.8), 3.97 times higher than that of CNE2 (P<0.01). The migration cell number of 5-8F-SC was (67.2±5.7), 3.07 times higher than 5-8F (P<0.01). The adhesion rates of CNE2-SC and CNE2 cells were (42.1±7.6)% and (8.9±2.0)%, respectively at 3 hours after inoculation and were (82.4±5.0)% and (12.1±2.2)% at 6 hours after inoculation, respectively. The adhesion rate of CNE2-SC cells was higher than that of CNE2 cells (all P<0.01). The adhesion rates of 5-8F-SC and 5-8F cells were (53.6±6.1)% and (7.3±1.5)% at 3 hours after inoculation, and (90.7±3.6)% and (11.0±1.2)% at 6 hours after inoculation, respectively. The adhesion rate of 5-8F-SC cells was higher than that of 5-8F cells (P<0.01). The expression levels of CD44, Ras and N-cadherin were significantly higher, while phosphatase and tensin homolog deleted on chromosome 10 (PTEN), E-cadherin in nasopharyngeal carcinoma stem cells were lower than those of the nasopharyngeal carcinoma cells. Furthermore, the levels of phosphorylated mitogen extracellular kinase1/2 (p-MEK1/2) and phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2)were significantly increased in nasopharyngeal carcinoma stem cells (P<0.01). Correlation analysis showed that the protein expression levels of CD44 was highly positively correlated with RAS in nasopharyngeal carcinoma stem cells(r=0.985, P=0.002; r=0.962, P=0.038). Deletion of CD44 in CNE2-SC decreased the expression levels of HER-2, Ras and p-ERK1/2, p-Akt and phosphorylated protein kinase C-δ(p-PKCδ) (P<0.01). Conclusions: Despite compare to the nasopharyngeal carcinoma cell, nasopharyngeal carcinoma stem cells grows at a relatively slow rate, the capacities of clone formation, migration, adhesion are promoted. This may be related to the CD44-regulated abnormal activation of Ras signaling pathway.

[Relationship between waist-hip ratio and sleep-disordered breathing in patients with acute coronary syndrome and its effect on long-term prognosis].

Objective: To investigate the relationship between different waist-hip ratios and sleep-disordered breathing (SDB) in patients with acute coronary syndrome (ACS) and its effect on patients' long-term prognosis. Methods: A total of 725 patients who were diagnosed with ACS in the emergency ward of Beijing An Zhen Hospital from June 2015 to May 2017 were included, and all the patients were monitored for sleep and breathing. Patients were divided into four groups according to their waist-hip ratios. The differences of SDB-related indicators among the four groups were compared, and the correlation between different waist-hip ratios and SDB was analyzed using multiple logistic regression. COX regression analysis and Kaplan-Meier curve were used to compare the prognostic differences among the four groups. Results: As the waist-hip ratio increased, the apnea hypopnea index (AHI) (P=0.004) and the proportion of sleep apnea hypopnea syndrome (OSAHS) increased (39.3% vs 46.0% vs 53.2% vs 60.0%, P=0.004). Meanwhile, the number of hypoventilation increased, and the mean and minimum arterial oxygen saturation (SaO(2)) decreased (all P<0.001). Logistic regression analysis showed that high waist-hip ratio was significantly related with OSAHS (OR=2.579, 95%CI 1.521-4.373, P<0.001). The survival curves showed the highest incidence of major cardio-cerebral vascular events (MACCE) occurred in the high waist-hip ratio group (Log Rank P=0.036). COX regression analysis showed that high waist-hip ratio was an independent risk factor for MACCE in ACS patients (HR=2.855, 95%CI 1.375-5.929, P=0.005). Conclusions: In ACS patients, central obesity is related with SDB. Patients with high waist-hip ratio have a poor prognosis. Elevated waist-hip ratio and SDB jointly impact the prognosis of ACS patients.

[Predictors for perioperative blood loss in pediatric patients with congenital scoliosis].

Objective: To identify predictors of massive blood loss after posterior hemivertebra resection for patients with congenital scoliosis. Methods: The data of 106 children with congenital scoliosis were collected from June 2017 to June 2019 in Beijing Children's Hospital. All the cases received posterior hemivertebra resection and internal fixation. The blood volume was estimated by weight and height. The visible blood loss was recorded according to medical record, and the hidden blood loss was calculated by OSTHEO formula. Perioperative information including age, gender, height, weight, Cobb and kyphosis angle, level fused, number of screws, operative time, and laboratory examinations was collected. Then multivariable linear regression was performed to determine the independent risk factors of blood loss. Results: All the surgeries were completed successfully. The mean age of the children was (7.3±2.3) years and the operative time was (162±56) min. The mean fused levels were 3 and the correction rate for deformity was 78.4%. The amount of blood loss was (568±208) ml which accounted for 42.3% of total blood volume. The visible and hidden blood loss was (334±193) ml and (234±199) ml, respectively, and which accounted for 58.8% and 41.2% of total blood loss. Multivariable linear regression analysis indicated that age, preoperative Cobb angle, the time of surgery and the number of fused levels were independent risk factors of total blood loss. Preoperative Cobb angle ≥40°, spinal fusion ≥4 levels and operative duration ≥140 min indicated more blood loss (all P<0.05). Conclusions: The perioperative blood loss of congenital scoliosis is massive with a high percentage of hidden blood loss. The patients with severe deformity, more fused levels and increased operative time brings higher risk of massive blood loss.

[Comparison of clinical efficacy between proximal gastrectomy with double tract reconstruction and total gastrectomy with Roux-en-Y reconstruction for proximal gastric cancer].

Objective: To compare the clinical efficacy of proximal gastrectomy with double tract reconstruction (PG-DT) and total gastrectomy with Roux-en-Y reconstruction (TG-RY) for proximal gastric cancer. Methods: The retrospective study was conducted. Clinicopathological data of 132 patients with proximal gastric cancer confirmed by pathology who underwent PG-DT (n=51) or TG-RY (n=81) by the same surgeon team in Southwest Hospital of Army Military Medical University between January 2006 and December 2016 were collected. Patients with preoperative neoadjuvant therapy, non-R0 resection and non-adenocarcinoma confirmed by pathology were excluded. Observation indicators included intraoperative (operation time and blood loss); postoperative (time to flatus, hospital stay, total complications, metastasis of lymph nodes around distal side of stomach from cases undergoing TG-RY), follow-up (long-term hemoglobin level, incidence of anemia, and survival) parameters. Survival analysis was conducted using the Kaplan-Meier method, and Log-rank test was used to compare survival difference between two groups. Results: No statistically significant differences were found between two groups in the baseline data, including age, gender, BMI, hemoglobin level before operation, postoperative TNM stage, tumor size and histological differentiation between two groups (all P>0.05). There were no significant differences between PG-DT and TG-RY in intraoperative blood loss [200 (200) ml vs. 200 (195) ml, Z=-1.860, P=0.063], time to flatus [(2.7±1.0) days vs. (2.6±1.1) days, t=0.225, P=0.823], postoperative hospital stay [10(3) days vs. 10 (4) days, Z=-0.449, P=0.654] and morbidity of perioperative complications [5.9% (3/51) vs. 8.6% (7/81), χ(2)=0.081, P=0.775]. Compared with the TG-RY group, PG-DT group had longer total operative time [294 (97) minutes vs. 255 (71) minutes, Z=-3.148, P=0.002]. The hemoglobin data of 42 patients with PG-DT and 56 patients with TG-RY were collected 1 year after operation. The incidence of anemia in PG-DT group was lower than that of TG-RY group [64.2%(27/42) vs. 82.1% (46/56), χ(2)=4.072, P=0.045], and PG-DT group had higher level of hemoglobin than TG-RY group [(114.4±16.3) g/L vs. (106.6±15.0) g/L, t=2.435, P=0.017]. There were 4 cases (4/81, 4.9%) with metastasis of lymph nodes around distal side of stomach in TG-RY group. All of these 4 tumors were T4 in depth and were more than 5 cm in diameter. The median follow-up period was 26 (1 to 110) months. One-year, 3-year and 5-year survival rates were 93.2%, 65.3% and 55.0% in PG-DT group, and 85.8%, 63.8% and 47.2% in TG-RY group, respectively without significant difference (χ(2)=0.890, P=0.345). Conclusions: Compared with TG-RY, PG-DT has the same safety and feasibility for proximal gastric cancer. Although the operative time is a little longer than TG-RY, PG-DT has advantages in improving the postoperative hemoglobin level.

[Effect of moderate or severe obstructive sleep apnea on cardiac structure and function in patients with acute coronary syndrome].

Objective: To investigate the effect of obstructive sleep apnea (OSA) on cardiac structure and function in patients with acute coronary syndrome (ACS). Methods: A total of 767 patients with ACS consecutively hospitalized at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017 were enrolled in this study. There were 637 males and 130 females. Patients who met the inclusion criteria according to the sleep apnea hypopnea index (AHI) were examined with portable sleep respiration monitoring. Patients were divided into moderate or severe OSA group (AHI≥15,n=389) and non or mild OSA group (AHI<15, n=78). The general information and echocar diographic results were analyzed. The data fitted normal distribution were compared between the groups with independent sample t test. Results: The body mass index [(27.8±3.6) vs (25.8±3.4) kg/m(2), t=-7.854, P<0.01], neck circumference [(41.1±4.2) vs (39.3±3.2) cm, t=-6.717, P<0.01] and waist-to-hip ratio (0.99±0.54 vs 0.97±0.53, t=-4.735, P<0.01) at admission were significantly higher in moderate or severe OSA group than those in non or mild OSA group. The left ventricular end-diastolic diameter, inter-ventricular septum thickness, left atrial diameter,right atrial diameter were all significantly higher, and the E/A peak ratio was remarkably lower in the moderate or severe OSA group (t=-2.130, 0.278, -3.045, -2.241, 2.260, all P<0.05). Conclusion: Moderate or severe OSA may aggravate cardiac remodeling and diastolic function in ACS patients.

[Comparative study on clinical efficacy of two surgical methods for gastric gastrointestinal stromal tumors at unfavorable position].

Objective: To investigate the safety and feasibility of laparoscopic operation in thetreatment of gastric gastrointestinal stromal tumor (GIST) at unfavorable positions. Methods: A retrospective cohort study was conducted to analyze the clinical data of patients with gastric GIST at unfavorable positions confirmed by pathology after surgery (laparoscopy or laparotomy) at the Southwest Hospital of the Army Medical University and the Minda Hospital of Hubei Minzu University from June 2008 to June 2018. The unfavorable positions of stomach are defined as the esophagogastric junction, the proximal cardia of gastric lesser curvature, the pylorus of stomach, the posterior wall of stomach and the antrum of stomach.Exclusion criteria:(1) preoperative chemotherapy or imatinib therapy; (2) diameter of tumor > 10 cm; (3) tumor metastasis or concurrence of other malignant tumors. A total of 244 patients (238 in Southwest Hospital and 6 in Minda Hospital) were enrolled, including 122 males and 122 females with age of 41-70years. Operative methods should be adopted according to patients' wishes. There were 146 cases in the laparoscopic surgery group and98 cases in the open surgery group. The intraoperative blood loss, operative time, postoperative first flatus time, postoperative firstfeeding time,average hospital stay, morbidity of postoperative complication,1-,3-,and 5-year recurrence free survival(RFS) and overall survival (OS)rate were compared between the two groups. Results: There were no significant differences in sex, age, tumor size, tumor risk grade or growth pattern between the laparoscopic and the open surgery groups (all P>0.05),and these two groups were comparable. Compared with open group, laparoscopic group had less intraoperative blood loss [(31.4±2.3) ml vs. (143.9±3.7) ml, t=292.800, P<0.001], shorter postoperative first flatus time [(2.1±0.7) days vs.(3.8±0.8) days, t=17.550,P<0.001], shorter postoperative first feeding time [(2.1±0.5) days vs.(2.3±1.7) days, t=1.339,P=0.020], shorter hospital stay [(8.6±2.6) days vs. (13.6±3.2) days, t=13.410, P<0.001], and lower morbidity of postoperative complication [16(11.0%) vs. 21(21.4%),χ2=4.996,P=0.025], whose differences were statistically significant. While the operation time was similar in two groups [(124.7±15.8) minutes vs. (120.9±14.5) minutes, t=1.903,P=0.058]. The median follow-up of all the patients was 43 (1 to 119) months.In laparoscopic group and open group, the 1-, 3- and 5-year RFS were 94.5% vs. 93.9%, 91.1% vs. 90.8%,and 82.2% vs. 81.6%, respectively, and 1-, 3- and 5-year OS were 98.6% vs. 95.9%, 95.9% vs. 94.9%,and 91.1% vs. 88.8%, respectively, whose differences were not statistically significant (all P>0.05). Conclusion: In the experienced gastrointestinal surgery center, laparoscopic resection of gastric GIST at unfavorable position is safe and feasible, achieving the same efficacy of open surgery.

[Prospective cohort study on the impact of moderate/severe obstructive sleep apnea on the prognosis of patients with acute myocardial infarction].

Objective: To investigate the impact of moderate/severe obstructive sleep apnea (OSA) on the prognosis of acute myocardial infarction. Methods: We prospectively selected patients with acute myocardial infarction (AMI) who were hospitalized at the Emergency Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. Patients who met the inclusion criteria were examined with portable sleep respiration monitoring. Patients were divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 beats/hour) and no/mild OSA group (AHI<15 beats/hour) according to sleep AHI. The incidence of major adverse cerebrovascular events (MACCE) after discharge was compared between the two groups, and the independent risk factors of MACCE were analyzed. Results: A total of 432 patients were enrolled in this study, including 211 moderate/severe OSA patients (48.8%). Compared with no/mild OSA group,patients with moderate/severe OSA had higher body mass index ((27.17±3.22) kg/m(2) vs. (25.55±3.44) kg/m(2), t=-5.033,P<0.001), higher proportion of history of percutaneous coronary intervention (PCI) (18.5%(39/211) vs. 8.6%(19/221), χ(2)=9.076,P=0.003), and higher proportion of 3-vessel disease (31.3%(66/211) vs. 24.9%(55/221), χ(2)=10.196,P=0.017). The median follow-up time was 1.0 (0.7, 1.7) years. The incidence of MACCE in the moderate/severe OSA and no/mild group was 19.9%(42/211) and 11.3%(25/221), respectively. Kaplan-Meier analysis showed a higher cumulative risk of MACCE in patients with moderate/severe OSA (log-rank test,χ(2)=5.467, P=0.019). Multivariate Cox regression analysis showed that moderate/severe OSA (HR=1.915, 95%CI 1.016-3.611, P=0.045) and diabetes mellitus (HR=1.819, 95%CI 1.022-3.238, P=0.042) were independent risk factors for MACCE at 1 year post discharge in patients with AMI. Conclusions: Nearly half of AMI patients are complicated with moderate/severe OSA in this patient cohort. Coronary artery disease is more severe in AMI patients complicating with moderate/severe OSA. Moderate/severe OSA is an independent risk factor for MACCE at 1 year after discharge in patients with AMI. Whether the prognosis of AMI can be improved by intervention of OSA remains to be investigated. Trial Registration: Clinical Trial.gov, NCT03362385.

[Association between hypothyroidism and sleep breathing disorders in patients with coronary heart disease].

Objective: To explore the association between hypothyroidism and sleep breathing disorders in patients with coronary heart disease (CHD). Methods: A total of 784 patients with CHD were consecutively enrolled at the Emergency & Critical Care Center of Beijing Anzhen Hospital from June 2015 to May 2017. According to thyroid function test results, patients were divided into hypothyroidism group (79 cases) and non-hypothyroidism group (705 cases). All patients had undergone sleep monitoring. The sleep apnea status was compared between the two groups. Multivariate logistic regression and linear regression models were used to analyze the association between hypothyroidism and sleep breathing disorders in patients with CHD. Results: The proportion of females, mean body weight and body mass index in the hypothyroidism group were higher than those in the non-hypothyroidism group [26.6% vs.16.2%, (78.6±11.6) kg vs. (75.7±12.0) kg, (27.7±3.2) kg/m(2) vs. (26.6±3.5) kg/m(2), all P<0.05]. Patients in hypothyroidism group had a decreased average oxygen saturation (SaO(2)) compared with patients in non-hypothyroidism group [ (93.2±2.9) % vs. (93.9±2.0) %, P=0.030]. In addition, events of hypoventilation in hypothyroidism group were significantly higher than those in non-hypothyroidism group[92.5 (45.8, 758.3) times vs. 68.0 (33.0, 125.0) times, P=0.013]. There were no significant differences in apnea hypopnea index, diagnosis of obstructive sleep apnea and other sleep breathing parameters between the two groups (P>0.05). A multiple linear regression analysis found that in patients with CHD, the correlation between hypothyroidism and average sleep SaO(2) was significant (ß=-0.508, 95%CI -0.989--0.026, P=0.039). Conclusions: CHD patients with hypothyroidism had a lower sleep average SaO(2), and a higher sleep hypopnea events. There is a correlation between hypothyroidism and sleep hypoxia in patients with CHD. Clinical trial registration: clinicalTrials.gov, NCT03362385.

[Impact of concomitant use of P2Y12 inhibitors and proton pump inhibitors on ischemia events in patients with acute coronary syndrome in real world].

Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% (n=5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs.

Anti-apoptotic function of herpes simplex virus -2 latency-associated transcript RL1 sequence and screening of its encoded microRNAs.

BACKGROUND: The latency-associated transcript (LAT) gene of herpes simplex virus (HSV)-2 is the only detectable viral gene expressed during latent infection in neurons. LAT inhibits apoptosis and maintains latency by promoting the survival of infected neurons. However, whether LAT functions during HSV-2 infection via its encoded RNAs or via its encoded proteins remain unknown. Increasing evidence has indicated that LAT is likely to functionally promote the establishment of latent infection via LAT-encoded microRNAs (miRNAs). AIM: To explore whether the RL1 fragment of the five adjacent miRNAs has an effect on cell apoptosis, then provide supporting evidence to elucidate the potential role of these miRNAs and to aid screening of their cellular targets. METHODS: A number of techniques, including MTT assay, flow cytometry and DNA ladder analysis, were used to verify the role of the RL1 fragment and the contribution of the individual miRNAs to the anti-apoptotic effect. RESULTS: Five miRNAs (miR-H3, miR-H4-3p, miR-H4-5p, miR-H24 and miR-H19) were detected by quantitative PCR in PC12 cells stably expressing RL1 after pEGFP-RL1 plasmid transfection in vitro. The data indicated that expression of HSV-2 LAT RL1 seems to provide protection against apoptosis of PC12 cells induced by ActD. Antisense miRNAs specifically inhibiting these five miRNAs could efficiently reduce their expression. Transfection of antisense-miR-H3, antisense-miR-H4-5p and antisense-miR-H19 into PC12 cells stably expressing RL1 were able to partly reverse the anti-apoptotic effect of these miRNAs. CONCLUSIONS: These findings indicate that the apoptotic role of the RL1 fragment is likely to be related to overexpression of miR-H3, miR-H4-5p and miR-H19 in PC12 cells.

Factors associated with syphilis infection: a comprehensive analysis based on a case-control study.

This study aimed to comprehensively evaluate factors that influence the likelihood of syphilis infection from risk-taking behaviours and medical conditions. A retrospective case-control study was conducted by enrolling 664 syphilis inpatients (excluding 11 congenital syphilis patients) and 800 sex- and age-matched controls. Medical histories, clinical data and patient interview data were collected and subjected to logistic regression analyses. The prevalence of syphilis in the study population was 3·9% (675/17,304). By univariate analysis, syphilis infection was associated with migration between cities, marital status, smoking, reproductive history, hypertension, elevated blood urea nitrogen (BUN) and infection with hepatitis B virus (HBV) (P < 0·05). A high rate of syphilis-HBV co-infection was observed in HIV-negative patients and further research revealed an association between syphilis and specific HBV serological reactivity. Syphilis was also associated with the frequency, duration and status of tobacco use. Multivariate analysis indicated that syphilis infection was independently associated with migration between cities [adjusted odds ratio (aOR) 1·368, 95% confidence interval (CI) 1·048-1·785], current smoking (aOR 1·607, 95% CI 1·177-2·195), elevated BUN (aOR 1·782, 95% CI 1·188-2·673) and some serological patterns of HBV infection. To prevent the spread of infectious diseases, inpatients and blood donors should be tested for HIV, syphilis, HBV and HCV simultaneously.

Eight paths of ERK1/2 signalling pathway regulating hepatocyte proliferation in rat liver regeneration.

Although it is known that hormones, growth factors and integrin promote hepatocyte proliferation in liver regeneration (LR) through ERK1/2 signalling pathway, reports about regulating processes of its intracellular paths in hepatocytes of LR are limited. This study aims at exploring which paths of ERK1/2 signalling pathway participate in the regulation of rat LR, especially in hepatocyte proliferation, and how they do so. In all, 14 paths and 165 genes are known to be involved in ERK1/2 signalling pathway. Of them, 161 genes are included in Rat Genome 230 2.0 Array. This array was used to detect expression changes of genes related to ERK1/2 signalling pathway in isolated hepatocytes of rat LR, showing that 60 genes were related to hepatocytes of LR. In addition, bioinformatics and systems biology methods were used to analyse the roles of 14 above paths in regenerating hepatocytes. We found that three paths, RTK→SHC→GRB2/SOS→RAS→RAF, IntegrinΒ→FAK→RAC→PAK→RAF and GΒγ→PI3KΒγ→RAC→PAK→RAF, promoted the G1 phase progression of hepatocytes by activating ERK1/2. A further four paths, Gq→PLCΒ→PKC→SRC/PYK2→GRB2/SOS→RAS→RAF, RTK→PLCγ→PKC→SRC/PYK2→GRB2/SOS→RAS→RAF, IntegrinΒ→FAK/SRC→GRB2/SOS→RAS→RAF and IntegrinΒ→FAK→RAC→PAK→RAF, advanced the cell progression of S phase and G(2)/M checkpoint by activating ERK1/2, and so did PP1/2→Mek1/2 by decreasing the negative influence on ERK1/2. At the late phase of LR, Gαs→AC→EPAC→Rap1→Raf blocked hepatocyte proliferation by decreasing the activity of ERK1/2 and so did PP1/2→Mek1/2. In summary, 60 genes and 8 paths of ERK1/2 signalling pathway regulated hepatocyte proliferation in rat LR.

Cryptococcosis and tuberculosis co-infection at a university hospital in Taiwan, 1993-2006.

BACKGROUND: The human immunodeficiency virus (HIV) epidemic and increasing use of immunosuppressive agents have increased the prevalence of both cryptococcosis and tuberculosis (TB). However, the status of co-infection with both pathogens remains unknown. METHODS: This study retrospectively reviewed patient records of cryptococcosis and TB co-infection from 1993 to 2006. The temporal sequence of co-infection was defined as either concurrent or sequential. Data collected included patient demographics, HIV status, co-morbidities, clinical manifestations, treatment strategies, and outcome at 1-year follow-up. RESULTS: There were 23 patients with cryptococcosis and TB co-infection, representing 5.4% of cryptococcosis or 0.6% of TB cases. Eleven (48%) patients were HIV-infected, and no underlying disease or immunocompromised state could be identified in six (26%) patients. Twelve (52%) patients presented with concurrent infection, but diagnosis of co-infection could be achieved simultaneously in only three (13%). Constitutional symptoms, particularly fever and weight loss, were the most common presenting symptoms, developing in more than two-thirds of the patients. The majority (83%) of the patients made a good recovery following dual antifungal and anti-TB therapy. There were three mortalities at the 1-year follow-up, which might be attributable to a delay in diagnosis and treatment of co-infection. The outcomes of HIV-infected and non-HIV-infected patients were not significantly different. CONCLUSIONS: Cryptococcosis and TB co-infection, although rare, develops in both immunocompromised and healthy individuals. Early diagnosis and treatment may improve patient prognosis. There should be a high index of suspicion in order to achieve a timely diagnosis in a TB endemic area.