Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

BACKGROUND: Antenatal corticosteroids (ACS) can significantly improve the outcomes of preterm infants. This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units (NICU) and to explore perinatal factors associated with ACS use, using the largest contemporary cohort of very preterm infants in China. METHODS: This cross-sectional study enrolled all infants born at 24 +0 to 31 +6 weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st, 2019 to December 30th, 2019. The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery. Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage. RESULTS: A total of 7828 infants were enrolled, among which 6103 (78.0%) infants received ACS. ACS use rates increased with increasing gestational age (GA), from 177/259 (68.3%) at 24 to 25 weeks' gestation to 3120/3960 (78.8%) at 30 to 31 weeks' gestation. Among infants exposed to ACS, 2999 of 6103 (49.1%) infants received a single complete course, and 33.4% (2039/6103) infants received a partial course. ACS use rates varied from 30.2% to 100% among different hospitals. Multivariate regression showed that increasing GA, born in hospital (inborn), increasing maternal age, maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS. CONCLUSIONS The use rate of ACS remained low for infants at 24 to 31 weeks' gestation admitted to Chinese NICUs, with fewer infants receiving a complete course. The use rates varied significantly among different hospitals. Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.
Humans ; Infant, Newborn ; Infant ; Pregnancy ; Female ; Gestational Age ; Infant, Premature ; Intensive Care Units, Neonatal ; Cross-Sectional Studies ; Adrenal Cortex Hormones/therapeutic use*

Objective    To summarize the early outcomes of totally thoracoscopic minimally invasive aortic valve replacement (AVR) and double valve replacement (DVR). Methods    The clinical data of patients who underwent totally thoracoscopic minimally invasive AVR or DVR in Guangdong Provincial People’s Hospital from April 2020 to January 2021 were retrospectively analyzed. The patients were divided into an AVR group and a DVR group according to the surgical method, and the clinical data of the two groups were compared. Results    Finally 22 patients were enrolled, including 14 males and 8 females with an average age of 50.0±11.2 years at operation. Eight patients were degenerative disease, 8 were rheumatic heart disease combined with valvular disease, and 6 were bicuspid aortic valve. Out of the 22 patients, 16 underwent AVR alone, and 6 underwent DVR. All patients completed the operation successfully, and there was no death. Perivalvular leakage during surgery occurred in 2 patients. The average cardiopulmonary bypass time was 187.0±39.9 minutes, and aortic cross-clamping time was 117.0 (99.0, 158.0) minutes. Duration of mechanical ventilation and intensive care unit stay was 9.5 (4.8, 18.3) hours and 41.0 (34.0, 64.0) hours, respectively. The volume of chest drainage at the first 24 hours after surgery was 214.0±124.6 mL, and the postoperative hospital stay was 5.5 (4.0, 8.3) days. The cardiopulmonary bypass time and aortic cross-clamping time in the DVR group were longer than those in the AVR group, and the volume of chest drainage at 24 hours after surgery was more than that in the AVR group, with a statistical difference (P<0.05). Echocardiography before hospital discharge showed paravalvular leakage in 1 patient. There was no death during follow-up of 5.9±3.0 months. Conclusion    The early outcome of totally thoracoscopic minimally invasive AVR and DVR is satisfactory, and the approach of surgery is worth exploring.

Objective    To investigate the predictive value of right atrial myocardial fibrosis in the prognosis of isolated tricuspid regurgitation surgery after left heart valve surgery. Methods    The patients who underwent tricuspid valvuloplasty by the same operator in Guangdong Provincial People's Hospital from April 2016 to August 2021 due to long-term isolated severe tricuspid regurgitation after left heart valve surgery were included in the study. According to the degree of right atrial myocardial fibrosis, the patients were divided into three groups: a mild group, a moderate group, and a severe group. The clinical data of these patients were compared and analyzed. Results    A total of 75 patients were enrolled, including 16 males and 59 females with an average age of 57.0±8.4 years. There were 30 patients in the mild group, 29 patients in the moderate group and 16 patients in the severe group. In terms of the preoperative data, there were statistical differences in cardiac function grade, right atrial diameter, tricuspid incompetence area among the three groups (P<0.05). In terms of the postoperative data, there were statistical differences among the three groups in the cardiopulmonary bypass time, mechanical ventilation time, ICU monitoring time, complication rate and mortality (P<0.05). Further pairwise comparison showed that, compared with the mild group, the severe group had longer mechanical ventilation time (P=0.024), longer ICU monitoring time (P=0.003) and higher incidence of postoperative complications (P=0.024), while the moderate group had no statistical difference in all aspects (P>0.05); compared with the moderate group, the severe group had longer ICU monitoring time (P=0.021) and higher incidence of complications (P=0.006). Conclusion    The early outcome of tricuspid valvuloplasty in patients with isolated tricuspid regurgitation after left heart valve surgery with severe right atrial myocardial fibrosis is worse than that in the patients with mild and moderate fibrosis, suggesting that the degree of myocardial fibrosis in the right atrium can be a predictor of the effect of tricuspid regurgitation surgery and a judgement indicator of the surgery timing.

Objective:To evaluate the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province.Methods:Information on the reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was collected through the National Population Health Science Data Center and the China Disease Prevention and Control Information System. In addition, the trend of Japanese encephalitis reported incidence rate in Gansu province before and after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program was analyzed using an interrupted time-series design.Results:The annual reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was 0.448/per 100 000. However, after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program in Gansu province in 2008, the amount of change in the level of Japanese encephalitis reported incidence rate was -2.223/per 100 000 ( t=-2.90, P=0.007), the amount of change in the slope of Japanese encephalitis reported incidence rate was 0.082 ( t=2.87, P=0.008) with the slope of Japanese encephalitis reported incidence rate as 0.071 ( β1+ β3=0.071). Conclusions:The Japanese encephalitis vaccine has achieved good prevention and control effects in Gansu province in the short term after its inclusion in the expanded immunization program, but outbreaks of Japanese encephalitis have still occurred. Therefore, in the future, Gansu province should promptly adjust the immunization strategy of the Japanese encephalitis vaccine, and strengthen the vaccination of the adult population, especially the rural adult population in the southeastern region of Gansu province, based on the continued focus on the works on Japanese encephalitis vaccination for children and adolescents.

OBJECTIVE:To optimize the formulation of Phencynonate hydrochloride transdermal patch. METHODS:Phencynonate hydrochloride transdermal patch was prepared by solvent evaporation method. Using 48 h accumulative transdermal volume as index,single factor test and Box-Behnken design-response surface methodology were used to optimize drug dosage,the amount of transdermal enhancers azone and pressure-sensitive adhesive,and evaluate the appearance,adhesion of the formulation prepared by the best prescription. RESULTS:The optimized formulation was as follows as 263 mg drug dosage,165 mg azone, 1.94 g pressure-sensitive adhesive and 1.6 g methanol. 48 h accumulative transdermal volume of prepared patch was(119.48 ± 2.95)μ g/cm2(n=5),related error of which to predicted value was 2.48%. The prepared patch showed smooth surface and incision,good adhesiveness. CONCLUSIONS:Phencynonate hydrochloride transdermal patch is prepared successfully,its accumulative transdermal volume is in agreement with predicted standard.

BACKGROUND:Cervical Open-door laminoplasty with unilateral mass screw fixation and laminectomy with bilateral mass screw fixation are both procedures that treat cervical spondylotic myelopathy by expanding the space available for the spinal cord. Effectiveness and safety of two operative methods remain unclear. OBJECTIVE:To investigate the biocompatibility of implant and host between open-door laminoplasty with unilateral mass screw fixation and laminectomy with bilateral mass screw fixation to treat multi-segment cervical spondylotic myelopathy. METHODS: Data of 117 patients with multi-segment cervical spondylotic myelopathy (≥ 3 segments) were retrospectively analyzed. Sixty-five cases underwent open-door laminoplasty with unilateral mass screw fixation (laminoplasty group). Fifty-two cases underwent laminectomy with bilateral mass screw fixation (laminectomy group). Clinical outcomes were evaluated by the Japanese Orthopaedic Association scoring system and by recovery rate. Cervical curvature index and cervical range of motion were assessed by X-ray films in both groups. RESULTS AND CONCLUSION:The average folow-up time was 28 months (range 12-59 months) in both groups. No C5 nerve root palsy occurred in the two groups. Japanese Orthopaedic Association scores were greater during final folow-up than pre-fixation in both groups (P < 0.01). No significant difference in Japanese Orthopaedic Association score, recovery rate, and final folow-up cervical curvature index was detected in both groups (P > 0.05). Cervical range of motion was lower during final folow-up than pre-fixation in both groups (P < 0.01). Results confirmed that open-door laminoplasty with unilateral mass screw fixation and laminectomy with bilateral mass screw fixation have similar effectiveness in the improvement of neurological function, relieving pain and reducing complications, but wil greatly reduce the cervical range of motion.

ObjectivesTo investigate the expression of glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine asparate protease-12 (caspase-12) and neuronal apoptosis in the brain of zebraifsh larvae after hypoxia reperfusion, and the neuroprotective effect of taurine.Methods Five day old post-fertilization zebraifsh larvae were randomly assigned into 3 groups, control group, hypoxia reperfusion group (model group) and taurine group, and the taurine group was further divided into 3 subgroups according to different concentrations (1 mmol/L, 5 mmol/L, 10 mmol/L) with 100 zebraifsh larvae each. The behavior, recovery time and median survival time of those zebraifsh larvae after hypoxia with 1h reperfusion were observed and recorded. The pathological changes and apoptosis of neurons were detected by Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling. The expression of GRP78, CHOP and caspase-12 in the brain of zebrafish larvae were detected by Western blot.Results Compared with the model group, the recovery time was shortened, the median survival time was extended, the Nissl stained neurons was increased and the apoptotic neurons were decreased in the taurine groups. GRP78, CHOP and caspase-12 were expressed in model group and taurine group. The expression of GRP78, CHOP and caspase-12 was much lower in taurine group than in model group.Conclusions Hypoxia reperfusion may induce endoplasmic reticulum stress and taurine may be neuroprotective against hypoxia reperfusion by down-regulating GRP78, CHOP and caspase-12.

Many factors,especially perinatal asphyxia,can lead to varying degrees of hypoxia brain injury in fetus or newborns within perinatal period.So far,the mechanisms of neonatal cerebral damage caused by hypoxia during the perinatal period have not been clearly demonstrated,and there have no effective drugs or therapeutic methods to improve hypoxia-induced cerebral damage.This review focuses on the recent progress of zebrafish as a model organism of using in research of hypoxia brain injury,including the anatomic and behavior basis,model making,research strategies and the advantages of neurotrophic drug screening.The application of zebrish in the research of neonatal hypoxic brain injury is promising,and may provide a new tool as research in finding out the therapy strategies of hypoxic-ischemic encephalopathy.