Objective:To investigate the association between air pollutant exposure levels and the risk of atrial fibrillation and to evaluate the mediating role of serum uric acid levels in the association between air pollutant levels and atrial fibrillation risks.Methods:This study was a case-control study, and the data of the atrial fibrillation group was derived from atrial fibrillation patients diagnosed at the Zhongda Hospital, Affiliated to Southeast University, from January 2014 to April 2021, and data of control group was derived from those without atrial fibrillation at the screening in Qixia District, Nanjing City, in March to April 2019. A 1∶1 propensity score matching was performed with the matched variables of age and sex. Air pollutant exposure data were collected from 9 air quality monitoring stations in Nanjing from January 2014 to April 2021, including NO 2, CO, PM 2.5 and PM 10. Exposure to air pollutants was converted to respiratory exposure levels according to an approximate formula. Multivariate logistic regression models were used to analyze the association between air pollutants and the risk of atrial fibrillation. Mediation analysis was used to investigate the mediating role and magnitude of serum uric acid in the association pathway between the four air pollutants (PM 2.5, PM 10, NO 2, and CO) and atrial fibrillation. Results:The atrial fibrillation group was aged (68.7±11.3) years, with 544 (51.8%) males; the control group was aged (68.5±8.9) years, with 543 (51.7%) males. Multivariate logistic regression models suggested that individual exposure levels of all four air pollutants were associated with the increased risks of atrial fibrillation. Every 1 μg·kg -1·d -1 increased in NO 2 was associated 12.1% increased risk of atrial fibrillation among the individuals ( OR=1.121, 95% CI:1.098-1.144); For every 1 μg·kg -1·d -1 increased in CO, the individual risk of atrial fibrillation increased by 0.7% ( OR=1.007, 95% CI: 1.006-1.008). For each 1 μg·kg -1·d -1 increase in PM 2.5 exposure level, the individual risk of atrial fibrillation increased by 14.2% ( OR=1.142, 95% CI: 1.120-1.164). For each 1 μg·kg -1·d -1 increase in PM 10 exposure level, the individual risk of atrial fibrillation increased by 3.7% ( OR=1.037, 95% CI: 1.028-1.046). The results of the mediation analysis suggested that serum uric acid levels mediated 5.6% ( P=0.032) causal effects of PM 2.5 on atrial fibrillation risks and 7.5% ( P=0.010) mediated by CO. Conclusion:Air pollutant exposure was a risk factor for the development of atrial fibrillation and uric acid mediated the increased risk of atrial fibrillation by PM 2.5 and CO.

Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Hypoglycemic Agents/therapeutic use* ; Liver Cirrhosis/pathology* ; Biopsy ; Patients ; Liver/pathology* ; Fibrosis

[摘 要] 目的：探讨肝转移对晚期胃癌患者免疫治疗效果的影响。方法：收集2019年2月至2022年1月在南京医科大学附属常州第二人民医院肿瘤中心接受过免疫治疗的晚期胃癌患者的临床资料，进行回顾性分析，利用卡方检验或Fisher确切概率法进行基线特征比较，利用卡方检验和Kaplan-Meier生存分析方法进行有肝转移与无肝转移胃癌患者的疗效和生存期的比较。结果：共有48例晚期胃癌患者纳入分析，根据有无肝转移将患者分为肝转移队列（n=20）和无肝转移队列（n=28）。有肝转移较无肝转移胃癌患者体力状况更差。肝转移队列与无肝转移队列的ORR分别为15.0%和35.7%（P>0.05），DCR分别为65.0%和82.1%（P>0.05）；中位PFS在两组分别为5.0个月和11.2个月（HR=0.40，P<0.05），中位OS分别为12.0个月和19.0个月（P>0.05）。结论：胃癌肝转移患者免疫治疗的疗效差于无肝转移的患者。

Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.
Mice ; Animals ; Humans ; Male ; Kartagener Syndrome/metabolism* ; Cilia/metabolism* ; Semen ; Genetic Testing ; RNA, Messenger ; Mutation

Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.

Drug-induced liver injury (DILI) is one of the common adverse drug reactions and is the main cause of withdrawal of drugs after marketing, which has attracted more and more attention of the public, and herb-induced liver injury (HILI) is a special type of DILI. In recent years, the frequent occurrence of HILI not only seriously endangers the health of patients, but also causes the controversy over the safety of traditional Chinese medicine. Therefore, this article reviews the potential risk factors for HILI from the three aspects of "patient", "drug", and "use", so as to provide a basis for the objective identification, prevention, and control of HILI and a reference for the construction of traditional Chinese medicine pharmacovigilance system represented by liver injury.

Extracellular vesicles (EVs), also known as membrane vesicles, are vesicular bodies secreted by eukaryotic cells and bacteria. EVs can carry proteins, DNA, RNA, and various metabolites for the exchange and transmission of substances between cells. They play contents-dependent physiological functions, such as delivering nutrients, participating in immune response, and treating cancers. Currently, most studies focus on the exploration of vesicles secreted by eukaryotic cells and gram-negative bacteria, while few studies focus on gram-positive bacteria. This review summarized the production, content composition, physiological function, and engineering of EVs secreted by gram-positive bacteria, and prospected future perspectives in this area.
Bacteria/metabolism* ; Extracellular Vesicles/metabolism* ; Gram-Negative Bacteria ; Gram-Positive Bacteria/metabolism* ; Proteins/metabolism*

Objective: To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied. Methods: Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded. Results: The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild. Conclusions The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.

Background and objective A great individual differences to chemotherapeutic effects existed in the patient with advanced lung cancer. How to choose the optimum regimens to achieve the individuation and maximum effect of chemotherapy for lung cancer is worth exploring. hTe study was designed to examine the effect of ex vitro chemo-sensitivity assay in xeno-free culture of autologous malignant effusion cells from patients with advanced lung adenocarcinoma.Methods hTe 50 treatment-naive patients with lung adenocarcinoma complicated with malignant pleural or pericardial effusions were enrolled. Effusions of all cases had been controlled by closed drainage and 300 mL-500 mL of which were retained under sterile condition from 25 cases (Chemo-sensitivity group). Primary malignant effusion cells were isolated from autologous effusions of the patients. hTen, xeno-free culture (average 11 days) were intervened with 8 chemotherapeutic drugs commonly used in clinical practice and were determined by CCK-8 assay. Optimum regimens were selected for chemotherapy based on the results of chemosensitivity test. As a contrast, chemotherapy regimens for the other 25 patients (Control group) were on the basis of physician’s clinical experience.Results Atfer four cycles of chemotherapy, in Chemo-sensitivity group, 17 (68.0%) cases were determined for partial response (PR), 5 (20.0%) cases for stable disease (SD), and the objective response rate (ORR) was 68.0%, the disease control rate (DCR) was 88.0%. Meanwhile, in Control group, 9 (36.0%) cases were determined for PR, 7 (28.0%) cases for SD, and, the ORR was 36.0%, the DCR was 64.0%. hTere were signiifcant differences between the two groups in ORR and DCR (P<0.05). To the end of follow-up, there were 21 cases of death in Chemo-sensitivity group as well as 22 cases in Control group. hTe mean progression-free survival (PFS) in Chemo-sensitivity group and Control group respec-tively were 10.0 months and 5.8 months, and the mean overall survival (OS) in the two groups were 30.2 months and 21.2 months respectively. hTere were also signiifcant differences between the two groups in PFS and OS (P<0.05). Furthermore, the adverse reactions in both groups were mild and controllable.Conclusion Xeno-free culture of autologous malignant effu-sion cells from patients with advanced lung adenocarcinoma andex vitro chemo-sensitivity assay are beneifcial to the rational choices of chemotherapeutic agents used in patients with lung adenocarcinoma complicated with malignant effusions, which is a worthy trial in personalized cell culture for individualized cancer therapy and further studies.

Objective To evaluate the performance of self‐established angiotensin converting enzyme (ACE) detection system . Methods The performance evaluation of ACE reagent kit produced by the Jiuqiang Company including precision ,linearity ,correla‐tion with the reference reagent and reportable range were conducted by using the automatic biochemical analyzer according to the re‐quirements of the EP5‐A2 and EP9‐A documentation in the Clinical and Laboratory Standards Institute (CLSI) .Results Intra‐as‐say CV of the system were 6 .87% ,2 .39% and inter‐assay CV were 6 .09% ,1 .81% ,respectively .During the day CV were 8 .00 %and 2 .8% respectively ,which were less than those provided by the manufacturer (<10% );the lenearity result was R2 =0 .99 .The correlation coefficient (r) of the system comparing with the reference reagent was 0 .990 56 ,moreover the average bias was 8 .55% , showing good correlation ;the repotable range was 9 .0U/L‐600U/L .Conclusion Self‐established ACE detection system can meet the requirements for clinical application .