Objective: To investigate the impact of RHAG 808A variant, commonly identified in the Chinese population, on RhAG protein, RhD and RhCE antigens expression through in vivo and in vitro expression analysis. Methods: A missense mutation of RHAG gene (c. 808G>A, p. Val270Ile) with high frequency was found in KMxD database. Bioinformatics analysis was performed using Polyphen-2 and Provean software. High resolution melting (HRM) method was utilized to screen for the variant carriers in the blood donors. The expression of RhAG protein, RhD and RhCE antigens on the surface of red cells of variant carriers were detected via flow cytometry. Wild-type and mutant vectors of RHAG were constructed and transfected into HEK 293T cells for in vitro expression analysis. Then, the expression of RhAG protein, RhD and RhCE antigens were analyzed by flow cytometry. Results: Polyphen-2 and Provean software suggested that the amino acid change (p. Val270Ile) of RhAG protein may be harmful or neutral respectively. Among the 999 blood donors from Guangzhou Blood Center, 4 homozygous carriers and 99 heterozygous carriers of RHAG 808A mutant allele were identified. The frequency of this allele was 5.4% (107/1 998). No significant differences in RhAG protein, RhD and RhCE antigens expression level was identified between the homozygous carriers, heterozygous carriers of RHAG 808A variant allele and the wild-type individuals. In vitro analysis for antigen expression study obtained the similar results. Conclusion: The RHAG 808A variant allele commonly identified in the Chinese population has no effect on the expression of RhAG protein, RhD and RhCE antigens, so the variant should be a population polymorphism site.

Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.

Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.
Diabetes Mellitus, Type 2/drug therapy* ; Glucagon-Like Peptide-1 Receptor/therapeutic use* ; Glucagon-Like Peptides ; Humans ; Hypoglycemic Agents/therapeutic use* ; Motivation ; Obesity/drug therapy*

To investigate the clinical features and influencing factors for new-onset atrial fibrillation (AF) early after coronary artery bypass grafting. Methods    The clinical data of 339 patients undergoing coronary artery bypass grafting in our hospital from January 2012 to January 2019 were retrospectively analyzed. There were 267 males and 72 females with an average age of 37-83 (58.03±8.90) years. The clinical features and influencing factors for new-onset AF after surgery were investigated. Results    There were 234 patients of off-pump coronary artery bypass grafting (OPCABG), with 36 (15.4%) new-onset AF patients after operation, among whom 16.1% were males and 12.5% were females. There were 105 patients of on-pump coronary artery bypass grafting (CABG), with 39 (37.1%) new-onset AF patients, among whom 40.7% were males and 25.0% were females. The incidence was higher after the CABG surgery than that after the OPCABG surgery (37.1% vs. 15.4%, P<0.05). There was no statistical difference in the incidence rate between males and females (P>0.05). The incidence of new-onset AF after surgery was higher in ≥60 years patients for both  operations (18.9% and 45.8%), which was significantly higher than that in <45 years patients (P<0.05). For both operations, the incidence of new-onset AF after surgery was high on the second day (24-48 h) after surgery, and most of the AF lasted for 1 day (P<0.05). The hypertension (OR=4.983, P=0.036), frequent premature atrial contraction or atrial tachycardia (OR=17.682, P=0.002), postoperative creatine kinase isoenzyme MB (CKMB) (OR=0.152, P=0.042), left anterior and posterior diameters (OR=17.614, P<0.001) and preoperative ejection fraction (OR=7.094, P=0.011) were influencing factors for new-onset AF after OPCABG. Diabetes (OR=11.631, P=0.020), other cardiac malformations (OR=29.023, P=0.002), frequent premature ventricular contraction or ventricular tachycardia (OR=0.047, P=0.001), and postoperative CKMB (OR=3.672, P=0.040) were influencing factors for new-onset AF after CABG. Conclusion    The incidence of new-onset AF after CABG is higher than that after OPCABG, and it increases with age increasing. There is no difference in the incidence between males and females. The influencing factors for the two operations are different.

Objective:To analyze the clinical characteristics and prognostic factors in patients with new-onset acute heart failure (AHF) and acutely decompensated chronic heart failure (ADCHF).Methods:Patients with heart failure (HF) admitted to Beijing Hospital during January 2009 to December 2017 with follow-up records were retrospectively enrolled. According to the duration of heart failure, the patients were divided into new-onset AHF group (duration of HF<1 month) and ADCHF group (duration of HF ≥1 month). Clinical data were collected and endpoint events (all-cause death and cardiovascular death) were recorded. The Kaplan-Meier survival curve and the log-rank method was used to compare survival between different groups. The multivariate Cox regression model was used to analyze the independent risk factors for the end-point events in patients with new-onset AHF and ADCHF.Results:The study enrolled 562 patients,292 (52.0%) with new-onset AHF and 270 (48.0%) with ADCHF. Patients with new-onset AHF were more likely to have coronary heart disease, acute myocardial infarction, higher diastolic blood pressure and higher troponin I levels(χ2=12.999,15.018, t=-2.088, Z=-2.727; all P<0.05). Patients with ADCHF were more likely to have poor cardiac function, atrial fibrillation, larger left ventricle and left atrium diameter, higher proportion of patients with pulmonary hypertension(χ2=16.565, 15.688, t=2.714, 5.029, χ2=15.274; all P<0.05). There were 205 (36.5%) all-cause deaths and 132 (23.5%) cardiovascular deaths during 28 (14, 60) months of follow-up. All-cause mortality rate [33.2%(97/292) vs. 40.0%(108/270), log-rank P=0.010] and cardiovascular mortality rate [18.8%(55/292) vs. 28.5%(77/270), log-rank P=0.001]were significantly lower in patients with new-onset AHF than those in ADCHF group. Multivariate Cox regression analysis showed that low body mass index (BMI), reduced hemoglobin, reduced resting heart rate, enlarged left atrium, and segmental wall motion abnormalities were independent risk factors for poor prognosis in new-onset AHF patients. It was different with ADCHF patients. Conclusion:Patients with new-onset AHF are more likely to have coronary heart disease; and lower BMI, reduced hemoglobin, acute coronary disease are associated with poor prognosis of patients. It is necessary to identify the underlying diseases early and actively standardize treatment to avoid the deterioration of cardiac function and readmission.

Objective To study effects of different types of high-impact exercises on the increment of bone mineral density (BMD) and bone mineral content (BMC) . Methods Thirty-nine male volunteers, including 13 hoopsters, 13 paratroopers, and 13 common college students as the control, were recruited and divided into two subgroups (subgroup 1:20-22 years old; subgroup 2:23-25 years old). Their BMDs and BMCs on calcaneus, first through fifth metatarsus, hip, and lumbar spine (L1-4) were evaluated. Results The BMC of calcaneus, the first and second metatarsals, total lumbar spine, and total hip in the hoopster group was significantly higher than that in the control group and paratrooper group. The hoopster group obtained statistically higher BMD at the lumbar spine, hip, and femoral neck than the other two groups. However, the BMCs and BMDs of the paratrooper group and control group had no significant differences at almost all measured anatomical locations. Conclusions BMC and BMD are not always in positive correlation with vertical ground reaction forces during normal exercises. Compared with parachuting training, playing basketball as a kind of variable load exercise can effectively increase BMC and BMD, and is more beneficial for reducing the risk of osteoporotic fracture.

OBJECTIVE: To investigate the risk factors and clinical outcome for carbapenems-resistant Pseudomonas aeruginosa (CRPA) infection, and to provide reference for the prevention and treatment of CRPA infection.METHODS: In retrospective investigation, medical records of CRPA and carbapenems-sensitive Pseudomonas aeruginosa (CSPA) infection were collected from our hospital during 2013-2016. CRPA infection risk factors were judged by single factor analysis. The relationship of CRPA risk factors and death was judged by multivariate Logistic regression analysis. RESULTS: A total of 556 cases of P. aeruginosa infection were collected, including 96 cases of CRPA injection, accounting for 17. 3％. Multivariate Logistic regression analysis of related factors of CRPA infection showed that independent risk factors of CRPA infection included admission to ICU for more than 3 days before the isolation of P. aeruginosa [OR= 2. 691, 95％ CI (1. 348, 5. 373), P=0. 005], the use of third-generation or fourth-generation cephalosporin [OR= 0. 386, 95％ CI (0. 200, 0. 742), P=0. 004], complicated with other pathogenic bacteria infection [OR= 1. 892, 95％ CI (1. 132, 3. 164), P=0. 015], combined with 2 kinds of antibiotics or above [OR=5. 631, 95％ CI (2. 556, 12. 407), P=0. 000]. Clinical outcome analysis, mortality rate of CRPA infection were 12. 5％, significantly higher than CSPA infection (2. 8％), Logistic regression analysis, there is a correlation between death rate [OR=5. 003, 95％CI (1. 975, 12. 675), P=0. 001] and CRPA infection. CONCLUSIONS: For the prevention of CRPA nosocomial infection, it is necessary to reduce the time of ICU stay and rationally select antibiotics according to pathogenic bacteria so as to reduce the occurrence of CRPA infection.

Objective To explore the association of nocturnal serum cortisol levels with diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus. Methods Serum cortisol levels of 316 overweight or obese type 2 diabetic patients were tested at midnight by the method of chemiluminescence. Diabetic microvascular complications were compared among various groups according to nocturnal serum cortisol levels. All the patients with nocturnal serum cortisol level > 50 nmol/L were asked to undergo overnight low-dose dexamethasone suppression test to rule out the possibility of subclincal Cushing's syndrome. The incidences of diabetic nephropathy ( DN ) , diabetic retinopathy ( DR ) , and diabetic peripheral neuropathy ( DPN ) were examined in all the patients. Results (1)The incidence of DN was gradually increased from 13.3％to 27.7％and 44.2％in patients with low, medium, and high cortisol level groups, showing a statistical difference among 3 groups ( P<0.05) . The incidences of DR in medium and high cortisol level groups were higher than that in low cortisol level group (40.6％and 47.7％vs 22.7％, both P<0.01). The incidence of DPN in high cortisol level group was higher as compared with low cortisol level group (60.5％ vs 38.7％, P<0.01). (2) Nocturnal serum cortisol level in patients with diabetic microvascular complications was higher than that in patients without complications [ (136.87 ± 105.78 vs 97.55 ± 93.48) nmol/L, P<0.01]. Nocturnal serum cortisol level in patients with multiple diabetic microvascular complications was higher than that in patients with single diabetic microvascular complication [ (151.66±114.54vs117.69±90.26)nmol/L,P<0.05].(3)Singlefactorlogisticregressionanalysisshowedthat higher nocturnal serum cortisol level was a risk factor for diabetic microvascular complications in addition to female, age, longer diabetic duration, higher fasting plasma glucose ( FPG ) . Multivariate logistic regression analysis showed that higher nocturnal serum cortisol level was still a risk factor for diabetic microvascular complications after adjusted by diabetic duration, FPG, HbA1C, and the use of insulin (P=0.013). Conclusion Nocturnal serum cortisol level seems to be a risk factor for diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

OBJECTIVETo investigate the effects of culture supernatant of human amnion mesenchymal stem cells (hAMSCs-CS) on biological characteristics of human fibroblasts.

METHODS(1) hAMSCs were isolated from deprecated human fresh amnion tissue of placenta and then sub-cultured. The morphology of hAMSCs on culture day 3 and hAMSCs of the third passage were observed with inverted phase contrast microscope. (2) Two batches of hAMSCs of the third passage were obtained, then the expression of vimentin of cells was observed with immunofluorescence method, and the expression of cell surface marker CD90, CD73, CD105, and CD45 was detected by flow cytometer. (3) hAMSCs-CS of the third passage at culture hour 72 were collected, and the content of insulin-like growth factor Ⅰ (IGF-Ⅰ), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF) were detected by enzyme-linked immunosorbent assay. (4) Human fibroblasts were isolated from deprecated human fresh prepuce tissue of circumcision and then sub-cultured. Human fibroblasts of the third passage were used in the following experiments. Cells were divided into blank control group and 10%, 30%, 50%, and 70% hAMSCs-CS groups according to the random number table (the same grouping method below), with 48 wells in each group. Cells in blank control group were cultured with DMEM/F12 medium containing 2% fetal bovine serum (FBS), while cells in the latter 4 groups were cultured with DMEM/F12 medium containing corresponding volume fraction of hAMSCs-CS and 2% FBS. The proliferation activity of cells was detected by cell counting kit 8 and microplate reader at culture hour 12, 24, 48, and 72, respectively, and corresponding volume fraction of hAMSCs-CS which causing the best proliferation activity of human fibroblasts was used in the following experiments. (5) Human fibroblasts were divided into blank control group and 50% hAMSCs-CS group and treated as in (4), with 4 wells in each group, at post scratch hour (PSH) 0 (immediately after scratch), 12, 24, 48, and 72, the migration distance of cells was observed and measured with inverted phase contrast microscope. (6) Human fibroblasts were grouped and treated as in (5), with 3 battles in each group, and apoptosis rate of cells was detected by flow cytometer. Data were processed with analysis of variance of factorial design, analysis of variance for repeated measurement, one-way analysis of variance, LSD test, and t test.

RESULTS(1) On culture day 3, most hAMSCs were in large form, and spindle-shaped with much prominences like fibroblasts or in flat polygonal shape. hAMSCs of the third passage were spindle-shaped. The expression of vimentin of hAMSCs of the third passage was strongly positive, and the expressions of surface markers CD90, CD73, and CD105 of the cells were positive, while the expression of CD45 of the cells was negative. (2) The content of IGF-Ⅰ, VEGF, EGF, and bFGF in hAMSCs-CS were respectively (11.7±1.0), (316±68), (6.1±0.4), and (1.49±0.05) pg/mL. (3) At culture hour 12-72, the proliferation activity of human fibroblasts in each hAMSCs-CS group was significantly higher than that in blank control group (with P values below 0.01), and the proliferation activity of human fibroblasts in 50% hAMSCs-CS group was the highest. (4) The width of scratch in two groups was nearly the same at PSH 0. The migration distance of cells in 50% hAMSCs-CS group was significantly longer than that in blank control group at PSH 12-72 (with P values below 0.01). (5) The apoptosis rate of human fibroblasts in blank control group was (16.2±2.4)%, which was significantly higher than that in 50% hAMSCs-CS group [(7.4±3.6)%, t=6.710, P<0.01].

CONCLUSIONShAMSCs-CS can promote proliferation and migration of human fibroblasts and inhibit the apoptosis of human fibroblasts.

Amnion ; cytology ; Apoptosis ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Culture Media, Conditioned ; chemistry ; Enzyme-Linked Immunosorbent Assay ; Epidermal Growth Factor ; metabolism ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Fibroblasts ; cytology ; drug effects ; Flow Cytometry ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Male ; Mesenchymal Stromal Cells ; chemistry ; Pregnancy ; Vascular Endothelial Growth Factor A ; metabolism