Calcific aortic valve disease(CAVD)is the most common disease affecting the heart valves,character-ized by thickening,fibrosis,and mineralization of the aortic valve leaflets.Currently,there is no effective pharmacologi-cal treatment.Aortic valve calcification is a complex and multifactorial process involving valve inflammation,fibrosis,calcification,valve thickening and outflow tract obstruction.The exact pathophysiological mechanisms of CAVD are not fully understood,but many studies have suggested that innate immune cells play a key role in the development of aortic valve calcification.This review focuses on the current role of innate immune cells in the development of CAVD.

Objective:To investigate the clinical characteristics and surgical effects of acute calculous cholecystitis (ACC) in high altitude area of Tibet.Methods:The retrospective cohort study was conducted. The clinicopathological data of 182 ACC patients who underwent surgery in the 954th Hospital of Army from January 2016 to December 2020 were collected. There were 56 males and 126 females, aged (41±13)years. Of the 182 patients, 61 cases undergoing open cholecystec-tomy were divided into the open group, and 121 cases undergoing laparoscopic cholecystectomy (LC) were divided into the laparoscopic group. Observation indicators: (1) clinical characteristics of ACC in high altitude area; (2) surgical situations; (3) postoperative complications; (4) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect postopera-tive complications of patients up to October 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Clinical characteristics of ACC in high altitude area. Of the 182 patients, cases with symptom duration as <3 days, 3 days to 1 month, >1 month and ≤12 months, >12 months were 37, 43, 57, 45, respectively. Seventy-seven of the 182 patients were combined with other diseases before surgery. (2) Surgical situations. Two cases in the open group were found common bile duct stones during the operation, and underwent choledochotomy and T-tube drainage. Nine cases in the laparoscopic group were converted to laparotomy, including 3 cases with severe abdominal adhesion and ineffective hemostasis, 6 cases with anatomical variation of Calot triangle. The conversion to laparotomy rate was 7.438%(9/121). The other patients in the open group and the laparoscopic group completed surgery successfully. The operation time, volume of intraoperative blood loss, time to postoperative first out-of-bed activities, time to postoperative first flatus, cases with indwelling drainage tube, cases with acute simple cholecystitis, acute suppurative cholecystitis, acute gangrene cholecystitis, gallbladder perforation of disease pathological type, postoperative white cell count, postoperative neutrophil percentage, duration of postoperative hospital stay were (109±42)minutes, 50(45,100)mL, (16.1±1.5)hours, (31.4±11.9)hours, 33, 25, 27, 6, 3, (6.8±1.9)×10 9/L, 72.7%±7.4%, (7.3±1.7)days for the open group. The above indicators were (98±43)minutes, 20(20,50)mL, (12.9±1.4)hours, (26.7±12.1)hours, 51, 56, 51, 9, 5, (7.1±2.4)×10 9/L, 70.5%±8.7%, (6.4±1.7)days for the laparoscopic group. There were significant differences in the volume of intraopera-tive blood loss, time to postoperative first out-of-bed activities, time to postoperative first flatus, duration of postoperative hospital stay between the two groups ( Z=?6.75, t=14.41, 2.46, 3.45, P<0.05). There was no significant difference in the operation time, cases with indwelling drainage tube, diseases pathological type, postoperative white cell count, postoperative neutrophil percentage between the two groups ( t=1.66, χ2=2.33, 0.84, t=?0.71, 1.66, P>0.05). (3) Postoperative complica-tions. Postoperative complications occurred in 7 of the 61 patients in the open group and 5 of the 121 patients in the laparoscopic group. There was no significant difference in the postoperative complications between the two groups ( χ2=2.46, P>0.05). (4) Follow-up. Of the 182 patients, 115 cases including 35 cases in the open group and 80 cases in the laparoscopic group were followed up for 12(range, 3?24)months. During the follow-up, 1 case of the 35 patients in the open group had abdominal pain and jaundice, which was diagnosed as choledocholithiasis. The patient was improved after stone removal with endoscopic retrograde cholangiopancreatography. Two cases of the 35 patients in the open group had upper abdominal pain with fever and were improved after anti-infection treatment. Of the 80 patients in the laparoscopic group, 1 case had upper abdominal pain and 1 case had dyspepsia and anorexia, respectively. The two cases were improved after symptomatic treatment. Conclusions:Patients with ACC in the high altitude area of Tibet have high ratio of preoperative complications, long diseases history and high incidence rates of pyogenic perforation of the gallbladder. Patients with ACC in the high altitude area undergoing LC is safe and effective. Compared with open cholecystectomy, LC have less volume of intraoperative blood loss, faster postoperative recovery and shorter duration of postoperative hospital stay.

Objective:To evaluate the efficacy of acrivastine alone or in combination with loratadine in the treatment of chronic refractory urticaria.Methods:From March 2017 to December 2018, a multicenter, randomized, controlled clinical study was conducted in 4 centers. Patients with chronic refractory urticaria were randomly divided into two groups, i.e., combined treatment group receiving oral acrivastine capsules 8 mg thrice a day plus oral loratadine tablets 10 mg once a day, and acrivastine alone group receiving oral acrivastine capsules 8 mg thrice a day plus a placebo 10 mg once a day. The course of treatment was 4 weeks. Visits were scheduled at baseline and after 1, 2 and 4 weeks of treatment. At the same time, clinical data were collected, and adverse events were recorded. Symptom scores were evaluated based on degree of itching, number and size of wheals, duration of each attack and number of attacks per week, and symptom score reduce index (SSRI) was used to evaluate the efficacy. Repeated measures analysis of variance and chi-square test were used to evaluate the efficacy and safety.Results:Fifty-three patients in the combined treatment group and 59 in the acrivastine alone group were included in the efficacy analysis. Before treatment, there was no significant difference in symptom score or visual analogue score between the two groups. After 2 weeks of treatment, 19 patients were cured and 10 achieved marked improvement in the combined treatment group, with a response rate of 54.72%; 15 were cured and 6 achieved marked improvement in the acrivastine alone group, with a response rate of 35.59%. After 4 weeks of treatment, 23 patients were cured and 9 achieved marked improvement in the combined treatment group, with a response rate of 60.38%; 20 were cured and 2 achieved marked improvement in the acrivastine alone group, with a response rate of 37.29%. After 2 and 4 weeks of treatment, the response rates were significantly higher in the combined treatment group than in the acrivastine alone group ( χ2 = 4.13, 5.96 respectively, both P < 0.05) . The SSRI significantly differed among different follow-up time points, as well as between the 2 groups ( F = 8.62, 4.38 respectively, both P < 0.05) . Multivariate analysis of variance showed that SSRI was significantly higher in the combined treatment group (0.63 ± 0.05, 0.68 ± 0.05, respectively) than in the acrivastine alone group (0.47 ± 0.05, 0.51 ± 0.05, respectively) after 2 and 4 weeks of treatment (both P < 0.05) . Drug-related adverse reactions, including drowsiness, stomach upsets, headache and liver function abnormality, occurred in 7 patients in the combined treatment group, as well as in 3 in the acrivastine alone group. Conclusion:Acrivastine is safe and effective for the treatment of chronic refractory urticaria, and acrivastine combined with loratadine can markedly improve the efficacy.

OBJECTIVE： To systematically evaluate effectiveness and safety of single antiplatelet therapy （SAPT） versus dual antiplatelet therapy （DAPT） on short-term complications after transcatheter aortic valve implantation （TAVI）， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Cochrane clinical controlled trials registry， Web of Science， CNKI， Wanfang database， CBM and Chinese Clinical Trial Registry， RCTs and observational studies about effectiveness （all-cause mortality， incidence of stroke and incidence of myocardial infarction 30 days after operation） and safety （the incidence of bleeding events at 30 days after operation） of SAPT versus DAPT on short-term complications of TAVI were collected during the date of database establishment to Jan. 2019. After data extraction of included studies and quality evaluation with Cochrane system evaluator manual 5.1.0 （for RCT） and the Newcastle-Ottawa Scale （NOS） （for observational studies）， Meta-analysis was conducted by using Rev Man 5.3 statistical software. RESULTS： Totally 3 RCTs and 7 cohort studies were included， involving 3 188 patients. Results of Meta-analysis showed that the incidence of all-cause mortality 30 days after operation [OR＝0.48， 95％ CI （0.32， 0.73）， P＜0.001] and the incidence of bleeding events 30 days after operation [OR＝0.43， 95％CI （0.30， 0.59）， P＜0.001] in SAPT group were significantly lower than DAPT group， with statistical significance. There was no statistical significance in the incidence of stroke 30 days after operation [OR＝0.63， 95％CI （0.38， 1.06） ， P＝0.08] or the incidence of myocardial infarction 30 days after operation [OR＝1.09， 95％CI （0.46， 2.59）， P＝0.85] between 2 groups. CONCLUSIONS： Compared with DAPT， SAPT can decrease the incidence of all-cause mortality 30 days after TAVI and the incidence of bleeding events 30 days after TAVI.

OBJECTIVE： To systematically evaluate the effects of dual-antiplatelet medication time on efficacy and safety of postoperative complications after transcatheter aortic valve implantation （TAVI）， and to provide evidence-based reference for the formulation of antiplatelet therapy after TAVI. METHODS： Retrieved from Cochrane clinical controlled trial registration center， PubMed， Embase， Web of Science， Wanfang database and CJFD， during database establishment to Feb. 2019， RCTs and observational study about efficacy （all-cause mortality and incidence of stroke） and  safety （the incidence of major bleeding events） the effects of dual-antiplatelet therapy for postoperative complications after TAVI at different time points were collected. After data extraction of clinical studies met inclusion criteria， quality evaluation with Cochrane bias risk evaluation tool 5.1.0 （for RCT） or Newcastle- Ottawa Scale （for observational study）， Meta-analysis was conducted by using Rev Man 5.3 and Stata 14.0 statistical software. Meta-regression analysis was also conducted for outcome and different treatment duration. RESULTS： A total of 3 RCTs and 10 observational studies were included， involving 2 868 patients. The results of Meta-analysis showed that the incidence of all-cause mortality one month and 6 months after medication were 0.05 [95％CI （0.03， 0.07）， P＜0.001] and 0.07 [95％CI （0.05， 0.08）， P＜0.001]. The incidence of major bleeding events 1， 3 and 6 months after medication were 0.14 [95％CI （0.08，0.19）， P＜0.001]， 0.11 [95％CI （0.03， 0.19）， P＝0.007] and 0.13 [95％CI （0.05， 0.22）， P＝0.002]. The incidence of stroke after one month after medication was 0.04 [95％CI （0.03， 0.05）， P＜0.001]. Results of Meta-regression analysis showed that the all-caused mortality [regression coefficient＝0.005 7， 95％CI （－0.001 6， 0.013 0）， P＝0.116]， major bleeding [regression coefficient＝－0.000 5，95％CI（－0.022 4，0.021 4）， P＝0.959] or the incidence of stroke [regression coefficient＝0.001 4， 95％CI （－0.003 8， 0.006 5）， P＝0.570] were not related to medication duration of dual-antiplatelet therapy.  CONCLUSIONS： The prolongation of the medication time of the dual-antiplatelet therapy has no significant effect on the efficacy and safety of TAVI.

Nerve growth factor (NGF) can promote the development, differentiation and regeneration of neurons. Recently, in order to efficiently produce human NGF (hNGF) drugs with better efficacy, we created transgenic mice expressing hNGF specifically in their salivary glands, and purified highly active hNGF protein from their saliva. Some studies reported that the NGF secretion in mouse saliva is affected by gender and age. Here, in order to select hNGF transgenic mice with high NGF secretion for saliva collection and hNGF purification, we divided transgenic mice into 4 groups, including 28-day-old young males and females, 63-day-old adult males and females. We compared their saliva volume, total salivary protein amount, salivary mNGF protein amount and salivary hNGF protein amount. The results showed that the saliva volume as well as amounts of total salivary protein, salivary mNGF protein and salivary hNGF protein secreted by 63-day-old transgenic mice were significantly higher than those secreted by sex-match 28-day-old transgenic mice, and the salivary hNGF protein amount secreted by male transgenic mice at the age of 63 days was significantly higher than that of female transgenic mice at the same age; Among 4 groups of mice, 63-day-old male transgenic mice secreted the highest salivary hNGF content, which was about 46 times higher than that secreted by the 28-day-old female transgenic mice. Therefore, 63-day-old male transgenic mice should be selected for saliva collection and hNGF purification.
Animals ; Cell Differentiation ; Female ; Humans ; Male ; Mice ; Mice, Transgenic ; Nerve Growth Factor ; Saliva

PURPOSE: Evidence on the contribution of genes to the hereditary predisposition to pulmonary arterial hypertension (PAH) is limited. MATERIALS AND METHODS: In this study, we hypothesized that single nucleotide variants in vascular endothelial growth factor (VEGF) gene may alter gene function and expression and may be associated with PAH risk. Five putatively functional loci (rs699947C>A and rs833061T>C in the promoter, rs3025040C>T, rs10434G>A and rs3025053G>A in the 3'-UTR) in the VEGF gene were genotyped and analyzed in a retrospective study of 587 patients with PAH and 736 healthy subjects from southern China. RESULTS: We found that the rs833061T>C polymorphism was significantly associated with PAH risk, while the other single nucleotide polymorphisms were not. Compared to carriers with TT genotype, those with rs833061C variant genotype (CT/CC) had an increased risk of PAH (odds ratio=1.47, 95% confidence interval=1.18–1.83, p=0.001). Functional assays indicated that CT/CC variant genotype had significantly higher mRNA levels of VEGF in peripheral blood mononuclear cells than TT genotype (p=0.021). Luciferase reporter assay indicated that having a C allele conferred a significantly higher transcription activity than that with a T allele. CONCLUSION: Our findings suggest that the functional polymorphism rs833061T>C in VEGF gene promoter modulates VEGF expression and may be a valuable biomarker for predicting PAH susceptibility.
Alleles ; Asian Continental Ancestry Group* ; China ; Genotype ; Healthy Volunteers ; Humans ; Hypertension* ; Luciferases ; Polymorphism, Single Nucleotide ; Retrospective Studies ; RNA, Messenger ; Vascular Endothelial Growth Factor A*

Objective To compare the clinical characteristics,and outcomes of patients with heart failure with different left ventricular ejection fractions (LVEF).Methods A total of 1 182 hospitalized patients with heart failure (HF) were enrolled and retrospectively studied in the present study.The patients were stratified by LVEF as reduced (HFrEF,LVEF ＜ 40％,n =313),mid-range (HFmrEF,40％ ≤ LVEF ＜50％,n =287) and preserved (HFpEF,LVEF≥50％,n =582) ejection fraction groups.Among the 1 182 cases,941 of them (81.3％,84.9％,and 84.0％ inHFrEF,HFmrEF and HFpEF groups,respectively) were followed up for an median duration of 27.3 months.Results (1) Among the study patients,26.5％ were in HFrEF,24.3％ in HFmrEF,and 49.2％ in HFpEF groups.(2) Ischemic heart disease with HFmrEF was more frequent than that in patients with HFrEF.The average age,percentage of female subjects,systolic blood pressure,uric acid,N terminal B-type natriuretic peptide precursor (NT-proBNP),hemoglobin,and the incidence of hypertensive heart disease,anemia,atrial fibrillation in patients with HFmrEF were higher than those in patients with HFrEF,but lower than those in patients with HFpEF (all P ＜0.01).(3) The all-cause cumulative mortality was 10.8％ at 1 year,20.6％ at 2 years and 35.9％ at 5 years.No difference was observed in the all-cause cumulative mortality at 1 year,2 years,5 years among the three groups (all P ＞ 0.05).Conclusions The HFmrEF patients,as a new and distinct group,were with many intermediate characteristics compared with HFrEF and HFpEF subjects.However,the all-cause mortality was not significantly differeut among HF patients with different LVEF.

Objective To summarize the clinical experience of patient diagnosed with Niemaoh-Pick disease being pregnant after liver transplantation. Methods Clinical data of one case of type B Niemaoh-Pick disease being pregnant after liver transplantation were retrospectively analyzed. Results The patient successfully underwent liver transplantation combined with splenic artery ligation on July 8, 2011. She was well recovered postoperatively. After surgery, she received conventional anti-rejection treatment, and gradually switched to use of tacrolimus at a dosage of 2.5 mg/d. The serum drug concentration was maintained at 2 ng/mL. In September 2015, she was successfully pregnant. On June 2, 2016, she delivered a male infant through cesarean section. She could breastfeed the infant in a low quantity early after delivery. Both the mother and infant were followed up until submission date. The mother was physically stable and the infant grew normally. Conclusions Patients diagnosed with Niemaoh-Pick disease can obtain favorable clinical outcomes of pregnancy and delivery after liver transplantation.

Objective To evaluate the clinical performance of chemiluminescent immunoassay (CLIA) on anti-nuclear antibody(ANA) specific autoantibodies testing.Methods A multi-center clinical study A total of 811 Sera samples were collected from 6 collaborating hospitals during the period of April to July 2016, and tested with CLIA and line immunoassay (LIA) in parallel for autoantibodies to ribonucleoprotein(RNP), smith antigen(Sm), SSA/Ro60,SSB/La, centromere protein B(CENPB), double-stranded DNA(dsDNA), nucleosome(Nuc), and ribosome P protein(Rib-P).The positive rate,specificity and qualitative coincidence rate for each antibody between CLIA and LIA methods were analyzed.All discrepant samples for systemic lupus erythematosus (SLE) highly specific autoantibodies (including anti-Sm, dsDNA, Nuc and Rib-P) were retested by enzyme linked immunosorbent assay (ELISA) and further analyzed with SLE disease cohort using McNemar test.Results The positive rate and specificity of CLIA and LIA for antibodies to ANA specific antigens were comparable.Excellent qualitative coincidence were found between CLIA and LIA for the detection of anti-RNP, SSA/Ro60, SSB/La and CENPB (Kappa>0.75), while the coincidence rate foranti-Sm, dsDNA, Nuc and Rib-P detection were moderate (0.4