OBJECTIVE: This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD).
METHODS: PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed.
RESULTS: Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings.
CONCLUSIONS: The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.

UNASSIGNED: Our study aimed to assess the association between UCP2 gene 3\' untranslated region insertion/deletion (3\'UTR I/D) and A55V (alanine/valine) polymorphisms and neural tube defects (NTDs) susceptibility.
UNASSIGNED: According to pre-determined inclusion and exclusion criteria, the article search was conducted to search articles published before October 2023. Two authors independently screened the included articles and extracted their basic characteristics. After quality evaluation, the meta-analysis and trial sequential analysis (TSA) were conducted using RevMan 5.4, Stata/MP 17, and TSA 0.9.5.10 Beta. Subgroup analysis was conducted based on country and case group composition. Sensitivity analysis was conducted using a one-by-one exclusion method. Begg\'s and Egger\'s tests were used to evaluate publication bias.
UNASSIGNED: A total of seven articles were included. Overall meta-analysis revealed significant heterogeneity among the included studies for 3\'UTR I/D polymorphism of the UCP2 gene. Significant statistical data indicated that those with the DD genotype and D allele had higher chances of NTD compared to those with the II genotype and the I allele, respectively. The combined result of II vs. ID was not statistically significant. A55V variation showed no statistical significance in the risk of NTD, despite the absence of significant heterogeneity across the included studies. Most of the heterogeneity was resolved after subgrouping, and a higher risk of the ID genotype was found than the II genotype for Chinese people. Genotyping NTD patients or their mothers was not a factor affecting the heterogeneity. Sensitivity analysis and publication bias analysis suggested that positive findings supported our results.
UNASSIGNED: The UCP2 gene 3\'UTR I/D polymorphism increased the likelihood of developing NTDs in the Chinese population, with the D allele being the risk factor, which contributed to the understanding of the genetic basis of NTDs. TSA indicated that more high-quality original studies were needed in the future for further validation.

BACKGROUND: The benefits and risks of Xileisan (XLS) in the treatment of ulcerative colitis (UC) remain unclear.
OBJECTIVE: The present study aimed to evaluate the efficacy and safety of the combination of XLS and mesalazine when treating UC.
METHODS: We searched eight databases for clinical trials evaluating the combination of XLS and mesalazine in the treatment of UC, up to January 2024. Meta-analysis and trial sequential analysis (TSA) were performed using Revman 5.3 and TSA 0.9.5.10 beta, respectively.
RESULTS: The present study included 13 clinical studies involving 990 patients, of which 501 patients received XLS combined with mesalazine while 489 patients received mesalazine alone. The meta-analysis showed that, in terms of efficacy, the combination of XLS and mesalazine significantly improved the clinical efficacy rate by 22% [risk ratio (RR) = 1.22; 95%CI: 1.15-1.28; P < 0.00001] and mucosal improvement rate by 25% (RR = 1.25; 95%CI: 1.12-1.39; P = 0.0001), while significantly reducing the duration of abdominal pain by 2.25 days [mean difference (MD) = -2.25; 95%CI: -3.35 to -1.14; P < 0.0001], diarrhea by 2.06 days (MD = -2.06; 95%CI: -3.92 to -0.20; P = 0.03), hematochezia by 2.32 days (MD = -2.32; 95%CI: -4.02 to -0.62; P = 0.008), tumor necrosis factor alpha by 16.25 ng/mL (MD = -16.25; 95%CI: -20.48 to -12.01; P < 0.00001), and interleukin-6 by 14.14 ng/mL (MD = -14.14; 95%CI: -24.89 to -3.39; P = 0.01). The TSA indicated conclusiveness in the meta-analysis of the efficacy endpoints. In terms of safety, the meta-analysis revealed that the combination of XLS and mesalazine did not increase the occurrence of total and gastrointestinal adverse events, abdominal distension, and erythema (P > 0.05). The TSA showed non conclusive findings in the meta-analysis of the safety endpoints. Harbord\'s test showed no publication bias (P = 0.734).
CONCLUSIONS: Treatment with XLS alleviated the clinical symptoms, intestinal mucosal injury, and inflammatory response in patients with UC, while demonstrating good safety.

BACKGROUND: The efficacy, effectiveness, and safety of the approved nirmatrelvir/ritonavir regimen for treatment of laboratory-confirmed mild/moderately severe COVID-19 remains unclear.
METHODS: We systematically identified randomized controlled trials (RCTs) and real-world studies (RWS; observational studies) of the efficacy/effectiveness and/or safety of the approved nirmatrelvir/ritonavir regimen for COVID-19. We pooled appropriate data (adjusted estimates for RWS) using an inverse variance, random-effects model. We calculated statistical heterogeneity using the I 2 statistic. Results are presented as relative risk (RR) with associated 95% CI. We further assessed risk of bias/study quality and conducted trial sequential analysis of the evidence from RCTs.
RESULTS: We included 4 RCTs (4,070 persons) and 16 RWS (1,925,047 persons) of adults (aged ≥18 years). One and 3 RCTs were of low and unclear risk of bias, respectively. The RWS were of good quality. Nirmatrelvir/ritonavir significantly decreased COVID-19 hospitalization compared with placebo/no treatment (RR = 0.17; 95% CI, 0.10-0.31; I 2 = 77.2%; 2 RCTs, 3,542 persons), but there was no significant difference for decrease of worsening severity (RR = 0.82; 95% CI, 0.66-1.01; I 2 = 47.5%; 3 RCTs, 1,824 persons), viral clearance (RR = 1.19; 95% CI, 0.93-1.51; I 2 = 82%; 2 RCTs, 528 persons), adverse events (RR = 1.41; 95% CI, 0.92-2.14; I 2 = 70.6%; 4 RCTs, 4,070 persons), serious adverse events (RR = 0.82; 95% CI, 0.41-1.62; I 2 = 0%; 3 RCTs, 3,806 persons), and all-cause mortality (RR = 0.27; 95% CI, 0.04-1.70; I 2 = 49.9%; 3 RCTs, 3,806 persons), although trial sequential analysis suggested that the current total sample sizes for these outcomes were not large enough for conclusions to be drawn. Real-world studies also showed significantly decreased COVID-19 hospitalization (RR = 0.48; 95% CI, 0.37-0.60; I 2 = 95.0%; 11 RWS, 1,421,398 persons) and all-cause mortality (RR = 0.24; 95% CI, 0.14-0.34; I 2 = 65%; 7 RWS, 286,131 persons) for nirmatrelvir/ritonavir compared with no treatment.
CONCLUSIONS: Nirmatrelvir/ritonavir appears to be promising for preventing hospitalization and potentially decreasing all-cause mortality for persons with mild/moderately severe COVID-19, but the evidence is weak. More studies are needed.

BACKGROUND: Acupuncture has been shown for the treatment of allergic rhinitis in previous studies. Nevertheless, relevant evidence was lacked for paediatric patients with allergic rhinitis. We aim to validate the efficacy of acupuncture for allergic rhinitis in children by meta-analysis and trial sequence analysis.
METHODS: Comprehensive search of eight databases were conducted until August 27, 2023. Randomized controlled trials comparing acupuncture alone or in combination with drugs versus medication in children with AR were included. The primary outcome was total nasal symptom score (TNSS). The secondary outcomes were serum immunoglobulin E levels, and relapse rates.
RESULTS: Thirteen studies involving 1186 participants were included. In results, acupuncture group (AC group) versus medication group (Med group) shows no significant difference in the treatment of AR in children (risk ratio [RR] = 1.10, 95% CI = 0.97 to 1.24, p = 0.13), while TSA suggested the included sample size did not exceed required information size (RIS). Significant differences were found between the AC + Med group versus the Med group (RR = 1.29, 95% CI = 1.17 to 1.42, p < 0.00001), with sufficient sample size. Results in serum IgE after treatment which favored the Med group (MD = 51.94, 95% CI [22.24, 81.65], p = 0.0006). In terms of relapse rate, The AC group had a lower relapse rate than the Med group (RR = 0.40, 95% CI = 0.26-0.63, p < 0.0001).
CONCLUSIONS: Acupuncture is an efficacious treatment for allergic rhinitis in children, but this conclusion might be limited by the generally low quality of evidence. TSA suggested additional high-quality trials with larger sample sizes and longer treatment durations were needed.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions.
OBJECTIVE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs).
METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses.
RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias.
CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs.
BACKGROUND: PROSPERO registration number: CRD42023427508.

UNASSIGNED: Postoperative neurocognitive dysfunction (PNCD) commonly occurs after surgery and prolongs hospital stays. Both direct noxious stimuli to the central nervous system and systemic inflammation have been implicated. Due to their potent anti-inflammatory effects, corticosteroids have been utilised to attenuate the incidence and severity of PNCD. This systematic review and meta-analysis strived to evaluate the prophylactic role of perioperative corticosteroids for PNCD.
UNASSIGNED: A search was run in pre-defined databases for randomised controlled trials (RCTs) assessing the role of corticosteroids in preventing PNCD. The incidence of PNCD within 1 month was the primary outcome. Secondary outcomes included the use of antipsychotic medications for the treatment, postoperative infection, and hospital length of stay. The results are exhibited as odds ratio (OR) and the mean difference (MD) with 95% confidence interval (CI).
UNASSIGNED: Fifteen RCTs comprising 15,398 patients were included. The incidence of PNCD was significantly lower in the corticosteroid group than in the control group, with a pooled OR of 0.75 (95% CI 0.58, 0.96; P = 0.02; I2 = 66%). Trial sequential analysis showed the clinical benefit of corticosteroids in preventing PNCD; however, the requisite information size is still inadequate. The sub-group analysis supported the prophylactic effect of corticosteroids on delirium prevention but not on delayed neurocognitive recovery.
UNASSIGNED: Our meta-analysis revealed statistically significant protective effects of corticosteroids on the incidence of PNCD. However, further studies are still needed to confirm the protective role of this commonly used and relatively safe strategy for preventing PNCD.

Background: In recent years, videolaryngoscopy has increasingly been utilized as an alternative to fiberoptic bronchoscopy in awake intubation. Nonetheless, it remains uncertain whether videolaryngoscopy represents a viable substitute for fiberoptic bronchoscopy. We conducted this systematic review with a meta-analysis to compare videolaryngoscopy and fiberoptic bronchoscopy for awake intubation. Methods: We systematically searched for all randomized controlled trials (RCTs) comparing videolaryngoscopy and fiberoptic bronchoscopy for awake intubation. The Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE were systematically queried through August 2023. Our primary outcome measure was the duration of intubation. Secondary outcomes encompassed the rate of successful intubation on the initial attempt, failed intubation, patient-reported satisfaction, and any complications or adverse events potentially stemming from the intubation procedure. The Cochrane Risk of Bias Tool for RCTs was employed to evaluate all studies for evidence of bias. The GRADE approach was utilized to gauge the certainty of the evidence. Results: Eleven trials involving 873 patients were ultimately included in our review for data extraction. Meta-analysis demonstrated that videolaryngoscopy decreased the duration of intubation compared to fiberoptic bronchoscopy (SMD -1.9671 [95% CI: -2.7794 to -1.1548] p < 0.0001), a finding corroborated in subgroup analysis by the type of videolaryngoscope (SMD -2.5027 [95% CI: -4.8733 to -0.1322] p = 0.0385). Additionally, videolaryngoscopy marginally lowered the risk of experiencing a saturation below 90% during the procedure (RR -0.7040 [95% CI: -1.4038 to -0.0043] p = 0.0486). No statistically significant disparities were observed between the two techniques in terms of failed intubation, initial successful intubation attempt, or sore throat/hoarseness. With regard to patient-reported satisfaction, a pooled analysis was precluded due to the variability in evaluation methods employed across the trials to assess this outcome. Lastly, trial sequential analysis (TSA) conducted for intubation time (primary outcome) affirmed the conclusiveness of this evidence; TSA performed for secondary outcomes failed to yield conclusive evidence, indicating the necessity for further trials. Conclusions: Videolaryngoscopy for awake tracheal intubation diminishes intubation time and the risk of experiencing a saturation below 90% compared to fiberoptic bronchoscopy.

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