OBJECTIVE To investigate and analyze the current management of drug clinical trial institutions in Jiangxi Province and the situation of undertaking drug clinical trials after the implementation of the filing system. METHODS A survey was conducted on 38 new institutions （obtained qualifications during the implementation of the filing system） and old institutions （obtained qualifications during the implementation of the recognition system） that had completed drug clinical trial institution qualification filing for more than one year in Jiangxi Province. The survey focused on the basic information of the institutions， the number of registered principal investigator （PI）， institutional hardware and information construction， personnel allocation and training， and drug registration clinical trials undertaken by the institutions. RESULTS Of 38 institutions surveyed， there were 22 general hospitals and 16 specialized hospitals； there were 24 old institutions and 14 new institutions. Whether in general hospitals or specialized hospitals， the old institutions were better than the new institutions in the number of approved beds， the number of outpatients， the number of inpatients， the number of specialties， and the number of PI； both old and new institutions had separate offices； all new institutions were set up with GCP pharmacy. The adoption of clinical trial management system in new institutions is significantly less than in old institutions. In the general hospital， both the number of full-time managers and the number of quality controllers in old institutions were significantly more than in the new institutions， while the opposite was true at the level of specialized hospitals. In terms of centralized training on GCP， new institutions were all better than the old ones. Whether in general hospitals or specialized hospitals， the number of drug registration clinical trial projects undertaken by new institutions was significantly less than that of old ones. CONCLUSIONS The new institutions are worse than the old institutions in comprehensive strength and information construction of hospitals， and the number of clinical trials undertaken by new institutions is also less than old institutions.

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective: To comprehensively evaluate the clinical efficacy of a single dose of tranexamic acid (TXA) in reducing perioperative blood loss in patients undergoing craniomaxillofacial plastic and cosmetic surgery through meta-regression analysis. Methods: Embase, PubMed, Wanfang Data, VIP database, China National Knowledge Infrastructure (CNKI), the Chinese Clinical Trial Registry (ChiCTR) and Cochrane Central Register of Controlled Trials (CENTRAL) were electronically retrieved to collect clinical studies evaluating efficacy of perioperative TXA administration in patients undergoing craniomaxillofacial plastic and cosmetic surgery, from inception to August 2024. Quality assessment of randomized controlled trials (RCTs) was performed using Cochrane Collaboration's Risk of Bias Tool. Based on the results of methodological heterogeneity, corresponding meta-analyses were conducted using either random-effects or fixed-effects models in R programming software. Results: Thirty-one articles were included, involving 2 072 patients who underwent craniomaxillofacial plastic and cosmetic surgeries. Among these patients, 1 051 were in the TXA treatment group, and 1 021 were in the control group. The paired meta-analysis showed that compared with the control group, the use of TXA significantly reduced bleeding volume in perioperative patients [standardized mean difference (SMD)=-1.13; 95%CI (-1.47, -0.80), P<0.001]. Subgroup analysis revealed that TXA significantly reduced intraoperative bleeding volume in patients across different surgeries, with the order of efficacy as follows: orthognathic surgery [SMD=-1.44; 95%CI (-2.07, -0.80), P<0.001], cleft palate repair [SMD=-1.32; 95%CI (-2.14, -0.50), P<0.001], rhinoplasty [SMD=-0.97; 95%CI (-1.63, -0.30), P<0.001], and craniosynostosis [SMD=-0.96; 95%CI (-1.40, -0.53), P=0.040]. The result of the meta regression showed there was no significant difference in the hemostatic effect of TXA on patients with increasing doses (5, 10, 15, 20, 25 mg/kg) (P=0.650). Sensitivity analysis verified that the pooled values were stable and reliable. The Egger's test indicated a certain degree of publication bias (Z=-3.40, P<0.001). Conclusion: Existing evidence suggests that TXA effectively reduces perioperative blood loss in patients undergoing craniofacial plastic surgery, regardless of its dosage administered.

Objective·To study the alterations in vestibular hair cell morphology and function of ATPase plasma membrane Ca2+transporting 2 oblivion(Atp2b2 Oblivion)heterozygous mice at different ages.Methods·Atp2b2 Oblivion heterozygous male mice aged 2 months and 8 months were selected with ten in each kind and C57BL/6J wild-type mice with the same gender,age and number were selected as the control group.Expression patterns of ATP2B2 in vestibular hair cells and numbers of hair cells in the striola zone and the extra striola zone in the two groups of mice at different ages were observed and calculated respectively through immunofluorescence assay.Hair bundle structures were detected by scanning electron microscopy(SEM),and mitochondria and ribbon synapse structures were observed by transmission electron microscopy(TEM).Vestibular evoked potential(VsEP),vestibular evoked myogenic potential(VEMP),rotarod rod test,and balance beam test were adopted for the evaluation of vestibular functions.Results·ATP2B2 was mainly expressed in the hair bundle of vestibular hair cells in the two groups of mice.Hair cell numbers in the striola zone and the extra-striola zone did not exhibit any differences between Atp2b2 Oblivion heterozygous mutant mice and wild-type mice of 2-month-old and 8-month-old.No visible structural abnormality in the hair bundle could be seen through SEM.TEM results implied no morphological abnormality in mitochondria or ribbon synapses in the 2-month-old heterozygous mutant mice,while vacuolar degeneration was discovered in the mitochondria under the cuticular plate in the 8-month-old heterozygous mutant mice with the normal ribbon synapses and the normal mitochondria near the innervation site.VsEP and VEMP thresholds of 2-month-old and 8-month-old Atp2b2 Oblivion heterozygous mutant mice were significantly elevated compared with the wild-type mice.Analysis of VsEP waveform manifested prolonged P1 latency and declined P1N1 amplitude in heterozygous mutant mice(P＜0.05).Results of rotarod rod test and balance beam test acquired from 2-month-old Atp2b2 Oblivion heterozygous mutant mice were not significantly different from the wild-type mice,while the ability of the mutant mice to accomplish the tests descended significantly at 8 months of age compared with the wild-type mice(P＜0.05).Conclusion·Atp2b2 Oblivion heterozygous mutant mice showed defective vestibular electrophysiological function at 2 months old,and abnormalities in vestibule-related behaviors can be detected at 8 months old.The vestibular function ofAtp2b2 Oblivion heterozygous mutant mice deteriorate progressively.

Objective Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.

Objective Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.

Objective To investigate the clinical characteristics,diagnosis,treatment,and prognosis of descending necrotizing mediastinitis(DNM)to provide a reference for the early diagnosis and timely treatment of DNM.Methods Data on DNM in China was electronically retrieved from the core databases and comprehensively reviewed from June 2012 to June 2023.The infection,pathogenic microorganisms,main symptoms,comorbidities and treatment methods of DNM were analyzed.Results The data of a total of 781 DNM patients,with an average age of(52.97±5.64)years,were retrieved,including 554 males and 227 females.Odontogenic source,tonsillitis,pharyngeal abscess,sialoadenitis,upper respiratory tract infection,foreign body injury,or iatrogenic traumatic procedures are common causes.Among these,odontogenic infection is the most common source.Streptococcus sp.(n=217)and Staphylococcus sp.(n=82)were most isolated,followed by Klebsiella pneumoniae and Pseudomonas aeruginosa(equally n=59).A total of 69.4％(542/781)of DNM patients recruited in this study were discovered to have various comorbidities,and more than one-third of these patients(n=185)had diabetes.Of the broad antibiotics,carbapenem was most frequently used as treatment,and vancomycin was the most frequently coadministered.The mediastinal drainage approach varies widely,and the optimal regimen is still unknown.Seventy-two patients were treated with video-assisted thoracoscopic/mediastinoscopic surgical drainage,22 patients were treated with percutaneous catheter drainage,30 underwent the transcervical approach,and 40 underwent thoracotomy.A total of 617 patients who were selected underwent the appropriate combined operation for surgical drainage according to the specific location of the infected focus.The overall mortality rate of all 781 DNM pa-tients included was 11.2％.Conclusion The most effective diagnosis and treatment of DNM is a high degree of clini-cal vigilance followed by prompt and adequate drainage with intensive care,including hemodynamic monitoring,nutri-tional support,computer tomographic scanning repeated as necessary,and combined use of systemic antibiotics.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.