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Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus. This study aims to investigate the efficacy and safety of optional antimicrobial therapy for the treatment of complicated SSTIs (cSSTIs).We searched PubMed, Medline (Via Ovid SP), Embase (Via Ovid SP), and the Cochrane Central Register of Controlled Trials from their inception to March 22, 2021 for randomized controlled trials (RCTs) that studied the use of optional antimicrobial therapy for cSSTIs. Citations' screening, study selection, data extraction, and risk of bias assessment were independently performed by 2 authors. The primary outcomes were clinical and microbiological treatment success, and adverse events (AEs) were also assessed.A total of 48 trials covering 24,381 patients assessing 20 types of antimicrobial treatment modalities were included. Overall, omadacycline was associated with the highest beneficial effect on clinical and microbiological treatment success and with the largest rank probability based on surface under the cumulative ranking curve values, avarofloxacin was closely followed. Both had, however, omadacycline was related to moderately safety profiles. Lefamulin ranked as the best option was associated with the lowest risk of severe AEs. Subgroup analysis showed similar results. The quality of primary outcomes was moderate to low.The use of omadacycline was associated with higher rates of clinical and microbiological treatment success for the treatment of cSSTIs, with a relative low risk of AEs. Due to the limitations of the included RCTs, high-quality and well-designed RCTs are needed to further confirm the results.

Meta-analyses comparing different antithrombotic strategies were conducted to determine the optimal therapeutic regimen post transcatheter aortic valve implantation (TAVI). However, there were restricted high-quality direct comparisons across the different antithrombotic therapeutic regimens. We sought to explore the safety and efficacy of different antithrombotic therapy strategies after TAVI using network meta-analyses of randomized controlled trials (RCTs).We searched CENTRAL, PubMed, Embase and Medline through August 2021 for RCTs that directly compared different antithrombotic schemes in adults who had undergone TAVI. We conducted a pairwise and network meta-analysis measuring all-cause mortality, stroke, myocardial infarction, all bleeding and life-threatening or major bleeding events. The surface under the cumulative ranking (SUCRA) curve was estimated to rank the therapies. We evaluated the risk of bias and graded the quality of the evidence using established methods.Six RCTs of 2824 patients who underwent TAVI were analysed. The risk of all bleeding [relative risk (RR) 1.88 (1.34-2.64)] and life-threatening or major bleeding [RR 2.03 (1.27-3.24)] was significantly higher for dual antiplatelet therapy (DAPT) than single antiplatelet therapy (SAPT), whereas there was no significant difference in the risk of all-cause mortality [RR 1.01 (0.61-1.68)] between DAPT and SAPT. Oral anticoagulant (OAC) + SAPT (OACSAPT) had significantly higher rates of all bleeding and life-threatening or major bleeding events compared with SAPT ([RR 3.46 (2.23-5.36)], [RR 2.86 (1.50-5.45)]). The risk of all-cause mortality [RR 1.72 (1.14-2.59)] and all bleeding [RR 1.84 (1.38-2.44)] were significantly higher for OACSAPT than DAPT, whereas there was no significant difference in the risk of life-threatening or major bleeding events [RR 1.41 (0.89-2.23)] between DAPT and OACSAPT. There was no significant difference in stroke or myocardial infarction among the different antithrombotic strategies (SAPT, DAPT and OACSAPT). Additionally, patients receiving OACSAPT had the highest risks for all-cause mortality (SUCRA 3.5%) and life-threatening or major bleeding (SUCRA 2.3%). SAPT seemed to be superior to DAPT in terms of all-cause mortality (SUCRA SAPT: 76.7%, DAPT: 69.8%) and stroke (SUCRA 69.6%, 59.7%).Except for OACSAPT having a higher all-cause mortality than DAPT, patients who underwent TAVI had similar all-cause mortality, stroke and myocardial infarction rates among different antithrombotic regimens. Patients on SAPT had a significantly lower bleeding risk than those on DAPT and OACSAPT. Our study indicates that SAPT is the preferred therapeutic strategy when there is no indication for OAC or DAPT. Furthermore, the application of OACSAPT was ranked the worst among all antithrombotic regimens and should be averted due to an increased risk of all-cause mortality and all bleeding.

This study investigated the factors influencing intravenous methylprednisolone pulse (IVMP) therapy for recovering visual acuity in Chinese patients with aquaporin-4 (AQP4) antibody-seropositive neuromyelitis optica-related optic neuritis (NMO-ON). This retrospective case series included 243 affected eyes of 182 patients (36 male, 146 female) diagnosed with NMO-ON in the Neuro-Ophthalmology Clinic of Beijing Tongren Hospital from September 2012 to September 2020. All patients with AQP4-antibody seropositivity had clinical manifestations of acute ON, excluding other diagnoses and received IVMP treatment at 500 mg/day or 1000 mg/day for 3 days. Primary outcome was the extent of improvement in logMAR visual acuity after IVMP treatment. The therapeutic influences of sex, age, baseline visual acuity, therapeutic intervals, and IVMP dose on acute NMO-ON were analysed. Chi-square tests, Mann–Whitney U-tests, Kruskal–Wallis tests, Spearman’s correlation coefficients, and multiple linear regression were used for statistical analysis. Age ranged between 7 and 80 years (median age, 44; interquartile range [IQR], 29–52) years. Among the 243 eyes, the median improvement in logMAR visual acuity was 0.3 (IQR, 0–0.9). Therapeutic efficacy of IVMP was significantly higher in female than in male patients (Z = 2.117, P = 0.034). The treatment effect gradually decreased with increase in age at onset (Rs = 0.157, P = 0.015), and visual improvement was significantly lower in patients aged > 50 years than in those ≤ 50 years (Z = 2.571, P = 0.010). When patients had low visual acuity at onset, improvements were more obvious (rho = − 0.317, P (rho = 0.688, P rho = 0.228, P = 0.001). Dosage of methylprednisolone (1000 mg/day or 500 mg/day) did not significantly influence treatment efficacy (Z = 0.951 P = 0.342). Therefore, IVMP therapy can improve visual acuity in the affected eyes of patients with AQP4 antibody-seropositive NMO-ON with similar effect at 500 mg/day and 1000 mg/day doses. Sex, age at onset, and therapeutic intervals may influence the efficacy of IVMP in patients with NMO-ON.

Background Radiotherapy greatly benefits patients with tumors, but not all patients show favorable treatment response. This study investigated the impact of forkhead box protein C2 (FOXC2)-mediated a disintegrin and metalloprotease 12 (ADAM12) on the radiosensitivity of head and neck squamous cell carcinoma (HNSCC). Methods After transfection and ionizing radiation, the biological activities of HNSCC cells were assessed. The relationship between ADAM12 and FOXC2 was verified. A xenograft model was used to evaluate the effect of FOXC2 knockdown on HNSCC growth in the context of radiation therapy. Results FOXC2 and ADAM12 were upregulated in irradiated CAL-27 and HN4 cells. Knockdown of FOXC2 suppressed the malignant behaviors of CAL-27 and HN4 cells and inhibited the growth of transplanted tumors in nude mice. FOXC2 could bind ADAM12 promoter. Overexpression of ADAM12 reversed the promotion of FOXC2 silencing on the radiosensitivity of HNSCC cells. Conclusions FOXC2 regulates the radiosensitivity of HNSCC by targeting ADAM12.

Context Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. Objective To evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC. Materials and methods PubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225. Results In total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29–1.48), DCR (RR = 1.15, 95% CI 1.12–1.19), QOL (RR = 1.71, 95% CI 1.54–1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low. Conclusions Current moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results.

As age-related diseases, chronic kidney disease and hearing impairment (HI) cause a serious socioeconomic burden. Due to structural similarities, there is a certain connection between kidney function and hearing, but there has been no large-scale epidemiological study in China that further explored this connection. Thus, this study aimed to explore the association between indicator levels of kidney function and hearing impairment among middle-aged and elderly individuals in Tianjin, China.In 2020, 1539 participants aged 45 years or older from Tianjin, China, were recruited into this study. All participants completed questionnaire surveys and underwent physical examinations, laboratory examinations, and hearing tests. The estimated glomerular filtration rate (eGFR) was calculated from serum creatinine (Cre) levels. HI was measured using pure-tone audiometry, and audiologists determined the final diagnoses.The prevalence of HI was 49.97%. With each 1-mL/min/1.73 mThese findings suggest that eGFR and serum Cre are effective predictors of hearing loss. Thus, to decrease the burden of HI, hearing should be carefully monitored for people aged ≥45 years with elevated serum Cre and eGFR.

Background: Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal β-lactams for pediatric FN. Methods: PubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal β-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763. Results: Eighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal β-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate. Conclusions: Meropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.

Background Pre-treatment serum albumin (ALB) is a novel index that was identified in recent years and is considered to be closely related to the prognosis of nasopharyngeal carcinoma (NPC). However, the association between ALB and NPC remains controversial. Objective of review To assess the prognostic significance of pre-treatment serum ALB in patients with NPC. Type of review A systematic review and meta-analysis. Search strategy We searched PubMed, the Cochrane Library and the Web of Science for studies published up to August 2018. The keywords used were related to albumin, nasopharyngeal carcinoma and prognosis. Evaluation method We extracted the following data from all included studies: author, publication year, country, cancer centre, time points of randomisation, sample size, mean or median age, gender, TNM stage of NPC, cut-off value of pre-treatment serum albumin, number of high-grade cases and duration of follow-up. Then, we generated the pooled hazard ratios (HR) for overall survival (OS) and distant metastasis-free survival (DMFS) to perform this meta-analysis. Results Ten studies comprising 7339 cases were included. Lower pre-treatment serum ALB levels were significantly associated with worse OS (HR = 1.32, 95% CI 1.17-1.48) and DMFS (HR = 1.40, 95% CI 1.08-1.80). In general, our findings were further verified in the subgroup analyses based on three features, including cancer stage, cut-off value and analysis type. Conclusion A decreased level of pre-treatment serum albumin implies a poor prognosis and can be detected to define the risk stratification of NPC patients.

Objective: This study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC). Methods: The mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. Results: There were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC. Conclusion: This study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.