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Abstract Background Currently, few studies focus on the association between gut microbiota and systemic lupus erythematosus (SLE), and much less studies consider the effect of drug usage. Proton pump inhibitors (PPIs) are commonly used to treat drug-related gastrointestinal damage in SLE patients. Therefore, the purpose of this study is to examine the gut microbiota of SLE patients using PPIs. Methods Fecal samples from 20 SLE patients with PPIs (P-SLE), 20 SLE patients without PPIs (NP-SLE) and 17 healthy controls (HCs) were obtained. The structure of the bacterial community in the fecal samples was analyzed by 16S rRNA gene sequencing. Redundancy analysis (RDA) was performed to observe the relationship between clinical variables and microbiome composition in P-SLE and NP-SLE patients. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, functional capabilities of microbiota were estimated. Network analysis was performed to analyze the association of metabolic pathway alterations with altered gut microbiota in P-SLE and NP-SLE patients. Results P-SLE patients exhibited increased alpha-diversity and an altered composition of the gut microbiota compared with NP-SLE patients. The alpha-diversity of NP-SLE patients was significantly lower than HCs but also of P-SLE patients, whose alpha-diversity had become similar to HCs. Compared with NP-SLE patients, the relative abundances of Lactobacillus, Roseburia, Oxalobacter, and Desulfovibrio were increased, while those of Veillonella, Escherichia, Morganella, Pseudomonas and Stenotrophomonas were decreased in P-SLE patients. RDA indicated that PPI use was the only significant exploratory variable for the microbiome composition when comparing SLE patients. KEGG analysis showed that 16 metabolic pathways were significantly different between NP-SLE and P-SLE patients. These metabolic pathways were mainly associated with changes in Escherichia, Roseburia, Stenotrophomonas, Morganella and Alipipes as determined by the network analysis. Conclusions PPI use is associated with an improved microbiome composition of SLE patients as it 1) increases alpha-diversity levels back to normal, 2) increases the abundance of various (beneficial) commensals, and 3) decreases the abundance of certain opportunistic pathogenic genera such as Escherichia. Validation studies with higher patient numbers are however recommended to explore these patterns in more detail.

ObjectiveGut fungi, as symbiosis with the human gastrointestinal tract, may regulate physiology via multiple interactions with host cells. The plausible role of fungi in systemic lupus erythematosus (SLE) is far from clear and need to be explored.MethodsA total of 64 subjects were recruited, including SLE, rheumatoid arthritis (RA), undifferentiated connective tissue diseases (UCTDs) patients and healthy controls (HCs). Fecal samples of subjects were collected. Gut fungi and bacteria were detected by ITS sequencing and 16S rRNA gene sequencing, respectively. Alpha and beta diversities of microbiota were analyzed. Linear discriminant analysis effect size analysis was performed to identify abundance of microbiota in different groups. The correlation network between bacterial and fungal microbiota was analyzed based on Spearman correlation.ResultsGut fungal diversity and community composition exhibited significant shifts in SLE compared with UCTDs, RA and HCs. Compared with HCs, the alpha and beta diversities of fungal microbiota decreased in SLE patients. According to principal coordinates analysis results, the constitution of fungal microbiota from SLE, RA, UCTDs patients and HCs exhibited distinct differences with a clear separation between fungal microbiota. There was dysbiosis in the compositions of fungal and bacterial microbiota in the SLE patients, compared to HCs. Pezizales, Cantharellales and Pseudaleuria were enriched in SLE compared with HCs, RA and UCTDs. There was a complex relationship network between bacterial and fungal microbiota, especially Candida which was related to a variety of bacteria.ConclusionThis study presents a pilot analysis of fungal microbiota with diversity and composition in SLE, and identifies several gut fungi with different abundance patterns taxa among SLE, RA, UCTDs and HCs. Furthermore, the gut bacterial-fungal association network in SLE patients was altered compared with HCs.

AbstractObjective To investigate the effect of antimalarials on cancer risk in patients with systemic lupus erythematosus (SLE).Methods PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from their inception to October 3, 2020. Relative risk (RR) with 95% confidence intervals (CI) was used to evaluate the results. Subgroup analyses were used to assess heterogeneity. A funnel plot was used to explore publication bias. STATA was applied for all analyses.Results A total of nine studies consisted of four nested case–control, two case–cohort and three cohort studies were included. The results showed that antimalarials might reduce the risk of cancer in SLE (RR = 0.68, 95%CI: 0.55–0.85). In the subgroup analysis of four nested case–control and two case–cohort studies, the pooled RR was estimated as 0.69 (95% CI: 0.60–0.80). In four studies about hydroxychloroquine, the pooled RR was estimated as 0.70 (95% CI: 0.53–0.93). Antimalarials might reduce the risk of cancer in SLE among the Asian population (RR = 0.66; 95% CI: 0.49–0.88) (I2 = 43.1%, p = .173). And the consistent result was also found in SLE from multiple centres (RR = 0.72; 95%CI: 0.60–0.87) (I2 = 0%, p = .671). On disease course- and comorbidities-matched studies, the pooled RRs were 0.69 (95% CI: 0.52–0.93) and 0.59 (95% CI: 0.46–0.75), respectively.Conclusion Results of this meta-analysis showed that antimalarial drugs might be protective factors for cancer in SLE. Hydroxychloroquine might be a protective factor for cancer in SLE patients.KEY MESSAGESAntimalarials might be protective factors for cancer in SLE.Hydroxychloroquine might be a protective factor for cancer in SLE patients.The first article to perform the meta-analysis of antimalarial drugs on the risk of cancer in SLE patients.

The aim of this study was to probe the potential anti-H. pylori activity of the synthetic antimicrobial peptide pexiganan, which is an analog of the peptide magainin, and its nanoparticles (PNPs) that were prepared in our laboratory. To compare their antibacterial effects in vitro and in vivo, studies of H. pylori growth inhibition, kinetics and resistance assays were undertaken. The gastric mucoadhesive efficiency and H. pylori clearance efficiency of pexiganan and PNPs were evaluated in rats and mice infected with H. pylori. The eradication of H. pylori was determined using urease tests and a microbial culture method. We observed that PNPs adhered to gastric mucosa more effectively owing to a prolonged stay in the stomach, which resulted in a more effective H. pylori clearance. In addition, PNPs had greater anti-H. pylori effect than pexiganan in infected mice. The amount of pexiganan required to eradicate H. pylori was significantly less using PNPs than the corresponding pexiganan suspension. The results confirmed that PNPs improved peptide stability in the stomach and more effectively eradicated H. pylori from mice stomachs than pexiganan.

Abstract Background Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR). Methods A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1–4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis. Results A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05–1.12, P

A 68-year-old man presented with chest distress recurring for the past 10 years. An echocardiogram demonstrated bicuspid aortic valve malformation with severe aortic stenosis and ventricular septal thickness of 22 mm. The patient underwent successful transcatheter aortic valve replacement (TAVR). Six months later, he complained of worsening dyspnea and chest distress (New York Heart Association Class III) on exertion. Besides a functional normal AV prosthesis, the echocardiography indicated the left ventricular outflow tract obstruction peak gradient of 122 mmHg at rest. Alcohol septal ablation was performed as the patient was unable to tolerate morrow procedure. His symptoms were relieved immediately after ablation, and no major cardiovascular events were observed during the 20-month follow-up. In conclusion, among patients with concomitant hypertrophic obstructive cardiomyopathy and severe aortic valvular stenosis, consideration for TAVR and alcohol septal ablation should only be made for patients who are at high surgical risk or cannot tolerate thoracotomy.

Objectives Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.Methods Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.Results Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p

Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.

Background: Fractional flow reserve (FFR) is currently considered as the gold standard for evaluating the functional significance of coronary stenosis. However, its potential benefits in real-world practice remain unknown in China. This study aimed to test the hypothesis that the use of FFR is associated with improved outcome and reduced cost in Chinese real-world clinical practice. Methods: A retrospective cohort study was carried out using the database of Second Affiliated Hospital of Zhejiang University, a tertiary and high-volume center in China. Clinical events were compared using the Cox proportional hazards model during a median follow-up of 13 months. Results: The study cohort consisted of 366 consecutive patients referred for coronary revascularization with adjunct FFR and 366 matched controls, from 2010 to 2014. Major adverse cardiac events (MACEs) (death, myocardial infarction, repeated revascularization, or hospitalization for angina) at 4 years were found in 12.0% of angiography-guided patients and 4.9% in the FFR-guided group (P < 0.001). The mean number of implanted stents was significantly lower in FFR treated subjects (0.52 ± 0.82 stents) compared with the angiography-guided group (0.93 ± 0.96 stents) (P < 0.001). No difference in overall costs at initial hospitalization was observed between angiography-guided percutaneous coronary intervention (PCI) compared with FFR-guided PCI (RMB 33,000 Yuan, range: RMB 7393-44,700 Yuan) versus RMB 21,200 Yuan (RMB 19,100-47,100 Yuan) (P = 0.54). However, costs for MACEs during follow-up were significantly reduced in the FFR-guided arm (P < 0.001). Conclusions: In the contemporary clinical practice, FFR-guided PCI is associated with decreased use of stents, improved clinical outcome, and reduced costs, compared with angiography-guided PCI.

Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion (IR) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired in hypercholesterolemia. Therefore, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats. In the present study, normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate, were continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined. We found that both sevoflurane and ischemic postconditioning significantly improved heart pump function, reduced infarct size and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β in the healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic postconditioning improved left ventricular hemodynamics, reduced infarct size and increased the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.