Previous studies demonstrated significant roles of autophagy in the pathogenesis of sepsis, but few studies focused on the effect of autophagy-related SNPs on sepsis susceptibility. In this present study, five polymorphisms of ATG5/ATG16L1 were investigated for the possible risk on sepsis in a Chinese Han population. Our results showed that ATG5 expression levels decreased with the severity of sepsis, and rs506027 T > C and rs510432 G > A were associated with sepsis progression and mortality. Moreover, the rs506027 TT and rs510432 GG carriers also exhibited increased expression levels of ATG5. Functional assays showed that ATG5 knockdown elevated the secretion of pro-inflammatory cytokines in THP-1 cells, and the extracted mononuclear cell of the risk C-A carriers exhibited decreased ATG5 expression levels, leading to enhanced releases of TNF-α and IL-1β under LPS stimulation in vitro. Furthermore, ATG5 T-G haplotype mutation showed higher promoter activities compared to C-A haplotype mutation, suggesting the effect of these SNPs on ATG5 gene transcription. Taken together, these results above indicated that these two ATG5 promoter polymorphisms may be functional and clinically significant for sepsis progression, underscoring its potentially therapeutic implications for sepsis and other inflammatory diseases.

Background. Postcholecystectomy syndrome (PCS) has become a common postoperative syndrome that requires systematic and comprehensive therapy to achieve adequate clinical control. Acupuncture and related therapies have shown clinical effects for PCS in many studies. However, systematic reviews/meta-analyses (SRs/MAs) for them are lacking. Objective. To evaluate the efficacy and safety of acupuncture in the treatment of PCS using randomized controlled trials (RCTs). Methods. Potentially eligible studies were searched in the following electronic databases up to 1 February 2020: PubMed, Embase, Cochrane Library, Web of Science (WoS), Chinese databases (Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), and China Science and Technology Journal Database (VIP)), and other sources (WHO ICTRP, ChiCTR, Clinical Trials, and Grey Literature Database). The RevMan 5.3 was employed for analyses. The Cochrane Collaboration’ risk of bias tool was used to assess the risk of bias (ROB). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of the evidence. Results. A total of 14 RCTs with 1593 participants were included in this SR. MA showed that acupuncture in combination with conventional medicine (CM) did not show statistical differences in reduction in pain. However, acupuncture in combination with CM significantly reduced the incidence of postoperative nausea and vomiting (PONV) (RR, 0.71; 95% CI, 0.55–0.92) and improved gastrointestinal function recovery compared to the CM group. Acupuncture combined with traditional Chinese medicine and CM, and acupuncture as monotherapy may improve gastrointestinal function recovery with acceptable adverse events. Conclusion. Acupuncture may be an effective and safe treatment for PCS. However, this study lacks conclusive evidence due to poor quality evidence, limited data, and clinical heterogeneity of acupuncture methods in the included studies.

Background: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. Results: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1β and IL-6). Conclusion: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.

Previous studies have indicated that the monocyte chemo-attractant protein 1 (MCP-1), also referred to as C-C motif chemokine ligand 2 (CCL2), plays a significant role in the pathogenesis of sepsis, and this study investigated the clinical relevance of two MCP-1 gene polymorphisms on sepsis onset and progression. The Multiplex SNaPshot genotyping method was used to detect MCP-1 gene polymorphisms in the Chinese Han population (403 sepsis patients and 400 controls). MCP-1 mRNA expression levels were measured using real-time quantitative PCR, and enzyme-linked immunosorbent assays were used to analyze MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1β) plasma concentrations. The rs1024611 polymorphism analysis showed lower frequencies of minor homozygous genotype (AA) and allele (A) in sepsis patients compared to the healthy controls (19.4% vs. 31.5%, P = 0.0001 and 45.9% vs. 54.8%, P = 0.0004, respectively). And the frequencies of GG genotype and G allele were lower in sepsis patients compared to the controls (19.6% vs. 31.3%, P = 0.0002 and 46.0% vs. 54.5%, P = 0.0007, respectively). The rs1024611 AG/GG and rs2857656 GC/CC genotypes were both overrepresented in patients with severe sepsis (both P = 0.0005) and septic shock (P = 0.010 and P = 0.015, respectively) compared to the patients with mild sepsis. Moreover, among sepsis patients, the rs1024611 AG/GG and rs2857656 GC/CC carriers exhibited significant increases in expression levels of MCP-1 (P = 0.025), TNF-α (P = 0.034) and IL-6 (P = 0.043) compared with the rs1024611 AA or rs2857656 GG carriers. This study provides valuable clinical evidence that the MCP-1/CCL2 polymorphisms rs1024611 and rs2857656 are associated with sepsis susceptibility and development. We conclude that MCP-1/CCL2 plays a significant role in the pathogenesis of sepsis, which has potentially important therapeutic implications.

Background Allergic rhinitis (AR) is a common symptomatic, inflammatory, and immunological disorder of nasal mucosa. Multiple clinical trials and systematic reviews have implicated acupuncture methods as potentially effective treatment strategies for AR, however, considering the great burden of AR, it is crucial to explore the most recent clinical evidence supporting acupuncture in AR. Besides, the methodologies reported in previous studies as well as those commonly applied during clinical practices greatly vary. Herein, we conducted network meta-analysis to compare the effectiveness of diverse acupuncture methods for AR treatment. Methods We conducted a literature search for relevant reports published from inception to 1 July 2020 in several scientific databases, including PubMed, Embase, Cochrane library, Web of Science, CNKI, WF, VIP, CBM, AMED as well as related registration platforms. Primary outcomes as reported in the identified studies were assessed using nasal symptoms. All Meta-analyses were performed with RevMan, ADDIS, and STATA software. To ensure consistency among our reviewers, the intra-class correlation coefficient was used. Results Exactly 39 studies with 3433 participants were covered in this meta-analysis. The meta-analysis demonstrated that all acupuncture types were superior to sham acupuncture in terms of total nasal symptom score and rhinoconjunctivitis quality of life questionnaire. Moxibustion was recommended as the most effective intervention as it reduced nasal symptoms in 6 treatments. On the other hand, manual acupuncture plus conventional medicine was recommended as the most effective intervention in improving the quality of life in 9 treatments. Notably, moxibustion was recommended as the most effective intervention that changed the content of IgE in 9 treatments. Moreover, adverse events of these interventions were acceptable. Conclusion Our findings revealed that all acupuncture methods are effective and safe for AR. Moreover, either moxibustion or manual acupuncture plus conventional medicine are potentially the most effective treatment strategies for AR. Based on these findings, it is evident that acupuncture therapy is not inferior to pharmacologic therapy. Therefore, for AR patients who are either unresponsive to conventional medicine or are intolerant to adverse events, acupuncture therapy should be administered. However, the quality of these included trials was mainly ranked as moderate quality, we recommend additional well-designed RCTs with larger sample sizes to validate these findings.