Objective To investigate the effect of AG490 on the apoptosis of pancreatic acinar cells and expression of apoptosis gene FasL and Bcl-2 in rat model of severe acute pancreatitis (SAP). Methods Seventy-two healthy Wistar rats were randomly divided into control group (n=24), SAP group (n=24) and AG490 group (n=24). Heart blood samples were taken to detect serum amylase at 6 h, 12 h and 24 h after operation in three groups. Pancreatic tissue were observed under light microscope to analyze pathological changes and pathological scores. The index of pancreatic acinar cell apoptosis was detected by TUNEL. The expressions of FasL and Bcl-2 mRNA in pancreatic tissue was detected by RT-PCR. Results Compared with control group, the damage of pancreatic tissue was gradually increased, the serum level of amylase significantly increased (P＜0.01), the index of pancreatic acinar cell apoptosis increased, the expression of FasL mRNA was significantly increased, the expression of Bcl-2 mRNA was significantly decreased (P＜0.05 or P＜0.01) in SAP group. Compared with SAP group, the pancreatic injury was improved significantly, the serum amylase significantly decreased ( P＜0.01), the apoptosis index rate of pancreatic acinar cells was increased, the expression of FasL mRNA was significantly increased, and the expression of Bcl-2 mRNA was significantly decreased (P＜0.05 or P＜0.01) in AG490 group. Conclusion The inhibition of the JAK/STAT3 signaling pathway may regulate the apoptosis-related gene to increase the apoptosis of pancreatic acinar cells, thereby reducing the reaction and pathological damages of acute pancreatitis.

Objective To better understand the knowledge, attitude, practice status of sexual dysfunction (SD) in medical staffs in field of reproductive health in Tianjin. Methods Using random, stratified and clustered sampling ap-proach, we selected 507 medical staffs in field of reproductive healthcare in Tianjin. Self-administered questionnaire on sex-ual dysfunction KAP was employed to survey the general condition, to understand SD knowledge and their attitude to SD, to perceive SD prevalence of the medical staffs and their demand to sexual dysfunction training. Results The people who re-spond to our survey had high awareness to SD, but they are lack of knowlege in mechanism on sexual behavior and female SD related knowledge. Multiple-factor analysis indicated that young age group respondants(β=-0.827,P=0.018)and medical staffs from high-tier medical institutions (β=-0.223, P=0.048) showed higher awareness. When they suffered SD, 49.28%re-spondants would see doctor immediately, 36.85% informants chosen temporary observation, and 9.73% informants shown negative altitude. Minority (17.14%) of medical staff are able to confirmed SD to themselves and 90.48% of medical staff de-mand training on SD related knowledge. Conclusion It’s necessary to perform continuing education to medical staffs via different intervention, so as to improve their cognitive level and attitude to SD, and these can help them providing better ser-vice to their patients and the public.

Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment ( P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.

OBJECTIVETo explore the biological function of BMAL1 in human acute myeloid leukemia by means of the HL-60 cell line in whica circadian gene BMAL1 was konocked-out by the CRISPR/Cas9 technology.

METHODSTwo sgRNAs for BMAL1 were designed and the PX459 knockout vectors containing the sgRNA were constructed. The activity of 2 sgRNAs was detected by T7 endonuclease I. the BMAL1 knocked out HL-60 cells were prepared by transient transfection of the target vectors into the cells. Western blot was used to detect the expression of BMAL1 protein. The apoptosis of the targeted cells was detected by flow cytometry. The proliferation status of the cells was assessed by the CCK-8 assay.

RESULTSThe PX459-sgRNA vectors were successfully constructed and screened to assure the activity of the targeting vector. It was found that the expression of BMAL1 protein was not detected in BMAL1-knocked out HL- 60 cells. Further, it was shown that BMAL1 knockdout could promote the apoptosis of HL-60 cells and inhibit the cell proliferation ability.

CONCLUSIONBMAL1 knocked out HL-60 cells have bean successfully established using the CRISPR/Cas9 gene editing technique, and BMAL1 knockout can promote the HL-60 cell apoptosis and inhibit its proliferation.These result reveal the biological role of the BMAL1 circadian gene in acute myeloid leukemia.

Apoptosis ; Cell Proliferation ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; Transfection

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome