Azithromycin sequential therapy plus inhaled terbutaline for Mycoplasma Pneumoniae pneumonia in children: a systematic review and meta-analysis.

BACKGROUND: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy. METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations. RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low. CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.

Resting energy expenditure based on equation estimation can predict renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease.

AIMS: The aim of this study was to investigate the relationship between resting energy expenditure (REE) based on equation estimation and renal outcomes in patients with diabetes kidney disease (DKD). METHODS: A total of 124 patients were enrolled from a retrospective cohort of Type 2 Diabetes mellitus (T2DM) patients with biopsy-proven DKD. Renal outcome defined as End-Stage Renal Disease (ESRD). To compare the predictive ability of different REE estimation equations on ESRD. Patients' REE was assessed according to the estimating equation with the best predictive power, and then the relationship between REE and ESRD risk was fitted using a restricted cubic spline curve (RCS) plot and REE cutoff values were obtained. Grouping using cutoff values, and ultimately evaluate the relationship between REE and the risk of ESRD using a Multivariate Cox regression model. RESULTS: The strongest predictive validity for renal outcomes was the NDCKD-equation. The patients were divided into the higher-REE group (n = 78) and the lower-REE group (n = 46), based on the cutoff value. During the follow-up, 30 of 124 patients (24.2%) proceeded to ESRD. Multivariate Cox regression models showed that the risk of ESRD in patients with lower REE was 6.08 times increased compared with that in those with higher REE (HR = 6.08; 95% CI, 1.28-28.80, p = 0.023). CONCLUSION: These findings suggested that the lower REE was an independent risk factor for unfavorable renal outcomes in patients with DKD.

Circulating exosomal microRNAs as diagnostic and prognostic biomarkers in patients with diffuse large B-cell lymphoma.

Exosomal microRNAs (miRNAs) are potential biomarkers for a variety of tumors, but have not yet been studied in diffuse large B-cell lymphoma (DLBCL). Here, we investigated the use of exosomal miRNAs in DLBCL diagnosis and prognosis. A total of 256 individuals, including 133 DLBCL patients, 94 healthy controls (HCs), and 29 non-DLBCL concurrent controls (CCs), were enrolled. Exosomal miRNAs were profiled in the screening stage using microarray analysis, and miRNA candidates were confirmed in training, testing, and external testing stages using qRT-PCR. Follow-up information on the DLBCL patients was collected, and miRNAs were used to develop diagnostic and prognostic models for these patients. Five exosomal miRNAs (miR-379-5p, miR-135a-3p, miR-4476, miR-483-3p, and miR-451a) were differentially expressed between DLBCL patients and HCs with areas under the receiver operating characteristic curve (AUC) of 0.86, 0.90, and 0.86 for the training, testing, and external testing stages, respectively. Four exosomal miRNAs (miR-379-5p, miR-135a-3p, miR-4476, and miR-451a) were differentially expressed between patients with DLBCL and CCs, with an AUC of 0.78. One miRNA (miR-451a) was significantly associated with both progression-free survival (PFS) and overall survival (OS) of DLBCL patients, R analysis indicated the combination of miR-451a with international prognostic index was a better predictor of PFS and OS for these patients. Our study suggests that subsets of circulating exosomal miRNAs can be useful noninvasive biomarkers for the diagnosis of DLBCL and that the use of circulating exosomal miRNAs improves the identification of patients with newly diagnosed DLBCL with poor outcomes.

Testosterone and Cognitive Impairment or Dementia in Middle-Aged or Aging Males: Causation and Intervention, a Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: To investigate the association between testosterone levels and the risk of dementia and to assess the effectiveness of testosterone supplement treatment in patients with cognitive impairment or dementia. METHODS: We searched Pubmed, Cochrane Library, and EMBASE on September 30, 2019. RESULTS: The risk factor portion of the review included 27 studies with 18 599 participants. Studies revealed inconsistent findings on the association between testosterone levels and the risk of all-cause dementia or Alzheimer disease (AD). The result from our meta-analysis showed an increased risk of all-cause dementia with decreasing total testosterone (total-T, 4572 participants, hazard ratio: 1.14, 95% CI: 1.04-1.26). Some studies also found an increased risk of AD with a lower level of total-T, free testosterone, and bioavailable testosterone. Testosterone supplement treatment may improve general cognitive function and motor response in the short term as measured by the Developmental Test of Visual-Motor Integration (mean difference [MD]: 4.4, 95% CI: 1.20-7.59) and the Mini-Mental State Examination (MD: 3.4, 95% CI: 0.83-5.97) and verbal memory as measured by story recall delay at 3 months (MD: 8.4, 95% CI: 0.49-16.3). CONCLUSION: Lower levels of testosterone may be associated with an increased risk of all-cause dementia or AD. Testosterone supplement treatment may or may not improve general cognitive function in patients with cognitive impairment/AD.

Retrograde inferior vena caval perfusion for total aortic arch replacement surgery: a randomized pilot study.

OBJECTIVES: Antegrade cerebral perfusion (ACP) under moderate hypothermic circulatory arrest is used during total aortic arch replacement surgery (TARS) in patients with acute type A aortic dissection, but it is associated with high mortality and morbidity. We hypothesized that combining ACP with retrograde inferior vena caval perfusion (RIVP) improves outcomes. METHODS: This pilot study was prospective, randomized, controlled and assessor-blinded. Patients scheduled for TARS were randomly treated with either ACP or RIVP + ACP. The primary outcome was a composite of mortality and major complications including paraplegia, postoperative renal failure, severe liver dysfunction, and gastrointestinal complications. Secondary outcomes included neurological complications, length of intubation and requirement of blood products. RESULTS: A total of 76 patients were recruited (n = 38 per group). Primary outcome occurred in 23 patients (61%) in the ACP group and 16 (42%) in the RIVP + ACP group (OR: 0.60, 95% CI: 0.21-1.62; p = 0.31). There was a lower incidence of transient neurological deficits in the RIVP + ACP group (26% vs. 58%, OR: 0.26; 95% CI: 0.10-0.67,p = 0.006;). The RIVP + ACP group underwent shorter intubation (25 vs 47 h, p = 0.022) and required fewer blood products (red cells, 3.8 units vs 6.5 units, p = 0.047; platelet: 2.0 units vs 2.0 units, p = 0.023) compared with the ACP group. CONCLUSIONS: RIVP + ACP may be associated with lower incidence of transient neurological deficits, shorter intubation and less blood transfusion requirement than ACP alone during TARS. Multi-center, randomized trials with larger samples are required to determine whether RIVP + ACP is associated with lower rates of mortality and major complications. TRIAL REGISTRATION: Pilot study of a RCT registered in clinicaltrials.gov (NCT03607786), Registered 30 July, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03607786 .

The effects of testosterone on bone health in males with testosterone deficiency: a systematic review and meta-analysis.

BACKGROUND: Testosterone deficiency (TD) may induce a series of clinical symptoms. Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients' quality of life. Given the conflicting findings across studies, this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD. METHODS: Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane. Library were searched to December 2019. The risk of bias of individual included studies and the quality of the aggregate evidence were assessed using the GRADE approach. Our primary outcome was bone mineral density (BMD). Meta-analyses were performed. This systematic review was reported according to the PRISMA statement. RESULTS: A total of 52 randomized controlled trials (RCTs) were included. When compared with placebo, testosterone supplementation did not increase total BMD (short-term: 1081 participants, MD - 0.01 g/cm2, 95% CI - 0.02 g/cm2 to 0.01 g/cm2; long-term: 156 participants, MD 0.04 g/cm2, 95% CI - 0.07 g/cm2 to 0.14 g/cm2), lumbar spine, hip, or femur neck BMD. Furthermore, testosterone supplementation did not decrease the risk of falling or fracture. Lastly, it was found that testosterone supplementation did not increase the risk of cardiovascular events (1374 participants, RR 1.28, 95% CI 0.62 to 2.64), all-cause mortality (729 participants, RR 0.55, 95% CI 0.29 to 1.04), or prostatic events. However, testosterone supplementation may improve sexual function and quality of life (1328 participants, MD -1.32, 95% CI - 2.11 to - 0.52). CONCLUSIONS: The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive. However, supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events, all-cause mortality, or prostatic events. RCTs with a longer follow-up period are still required. TRIAL REGISTRATION: We registered our protocol in PROSPERO (CRD42018109738).

Direct head-to-head comparison of glycaemic durability of dipeptidyl peptidase-4 inhibitors and sulphonylureas in patients with type 2 diabetes mellitus: A meta-analysis of long-term randomized controlled trials.

We performed a meta-analysis of randomized controlled trials (RCTs) to compare the long-term glycaemic durability of dipeptidyl-peptidase 4 (DPP-4) inhibitors vs that of sulphonylureas (SUs) in patients with type 2 diabetes mellitus (T2DM), in terms of the changes in glycated haemoglobin (HbA1c) levels from an intermediate time point (26 or 52 weeks) to 104 weeks of treatment. The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant RCTs. Eight RCTs were included. Compared with SUs, DPP-4 inhibitors were associated with significantly smaller increases in the HbA1c level from 24 to 28 weeks to 104 weeks (mean difference [MD]: -0.16%, 95% confidence interval [CI]: -0.21 to -0.11; P < .001) and from 52 weeks to 104 weeks (MD -0.06%, 95% CI -0.10 to -0.02; P = .001). No significant heterogeneities were detected among the included comparisons (I2 = 0%). These results suggest that long-term treatment with DPP-4 inhibitors confers better durability of glycaemic response than treatment with SUs in patients with T2DM, which may indicate that DPP-4 inhibitors better preserve islet ß-cell function compared with SUs.

The association between the environmental endocrine disruptor bisphenol A and polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between bisphenol A (BPA) and polycystic ovary syndrome (PCOS). METHODS: A systematic review and meta-analysis using STATA software for observational studies. RESULTS: Nine studies involving 493 PCOS patients and 440 controls were included in this review. The meta-analysis demonstrated that PCOS patients had significantly higher BPA levels compared with control groups (standardized mean difference (SMD): 2.437, 95% confidence interval (CI): (1.265, 3.609), p < .001). For studies of serum samples detected by enzyme-linked immunosorbent assay (ELISA), subgroup analyses according to ethnicity, body mass index (BMI), sample size, detection method (high-performance liquid chromatography (HPLC) and ELISA), PCOS-to-control ratio and study quality displayed that high BPA levels were significantly associated with Caucasian PCOS patients (SMD: 0.615, 95% CI: (0.308, 0.922), p < .001), high BMI (SMD: 0.512, 95% CI: (0.180, 0.843), p = .002), high quality (SMD: 0.624, 95% CI: (0.391, 0.856), p < .001), and high HOMA-IR (SMD: 0.467, 95% CI: (0.121, 0.813), p = .008). CONCLUSIONS: Serum BPA may be positively associated with women with PCOS and BPA might be involved in the insulin-resistance and hyperandrogenism of PCOS. More evidence from high quality studies, advanced detection methods, and larger cohorts for observational trials are needed to further confirm the association between BPA and PCOS.

Combination of α-blocker and 5α-reductase inhibitor for treatment of benign prostatic hyperplasia.

PURPOSE: This study compared the efficacy of an α-blocker monotherapy alone with a combination of α-blocker plus 5α-reductase in treatment of benign prostatic hyperplasia (BPH). METHODS: Medline (PubMed), EMBASE, CENTRAL (Cochrane databases) and Google Scholar were searched until May 2015 using the following search terms: ([α-blocker] AND 5α-reductase inhibitor) AND benign prostatic hyperplasia; and benign prostatic hyperplasia AND (adrenergic alpha blockers OR 5 alpha reductase inhibitor). Randomized controlled trials (RCTs) that included men with a clinical diagnosis of BPH were included. Eligible studies had to have an intervention group that received combination therapy (5α reductase inhibitor plus α-blocker) and a control group that received only α-blocker. Quality assessment and sensitivity analysis were performed. RESULTS: Six studies were included. Combination therapy was found to significantly reduce urinary retention incidence rate (OR=0.286, 95%CI: 0.199 - 0.412, P.

Estradiol therapy and breast cancer risk in perimenopausal and postmenopausal women: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between estradiol therapy and incidence of breast cancer, taking into consideration of different types of combined progestogen, the duration of exposure and the type of regimen. METHOD: A systematic review and meta-analysis. RESULT: A total of 14 studies were included in our study. In estradiol-only therapy analysis, meta-analysis resulted a pooled OR =0.90, 95% CI (0.40, 2.02) from the RCTs and pooled OR = 1.11, 95% CI (0.98, 1.27) from observational studies. However, in the analysis of estradiol-progestogen therapy, the risk of breast cancer varies according to the type of progestogen and the duration with more than five years (OR = 2.43, 95% CI (1.79, 3.29)) presented a higher risk than using less than five years (OR = 1.49, 95% CI (1.03, 2.15)). CONCLUSIONS: Estradiol-only therapy carries no risk for breast cancer, while the breast cancer risk varies according to the type of progestogen. Estradiol therapy combined with medroxyprogesterone, norethisterone and levonorgestrel related to an increased risk of breast cancer, estradiol therapy combined with dydrogesterone and progesterone carries no risk. The breast cancer risk rise progressively by prolonged use, furthermore, comparing to sequential therapy, continuous therapy carries a higher risk.

Prevalence of sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome: a meta-analysis.

PURPOSE: This study aims to estimate the prevalence of sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) by conducting a meta-analysis. METHODS: Relevant publications were searched using PubMed, Embase, CBM, China National Knowledge Infrastructure, VIP and Wanfang databases up to August 2015. Studies that reported the prevalence of erectile dysfunction, premature ejaculation and total sexual dysfunction in men with CP/CPPS were included. RESULTS: A total of 24 studies involving 11,189 men were included. Overall prevalence of sexual dysfunction in men with CP/CPPS was 0.62 (95 % CI 0.48-0.75), while the prevalence of erectile dysfunction and premature ejaculation was 0.29 (95 % CI 0.24-0.33) and 0.40 (95 % CI 0.30-0.50), respectively. From 1999 to 2010, the prevalence of sexual dysfunction, erectile dysfunction and premature ejaculation was 0.65 (95 % CI 0.45-0.83), 0.27 (95 % CI 0.22-0.33) and 0.41 (95 % CI 0.27-0.55), respectively. From 2011 to 2014, the prevalence of sexual dysfunction, erectile dysfunction and premature ejaculation was 0.50 (95 % CI 0.22-0.75), 0.35 (95 % CI 0.29- 0.40) and 0.39 (95 % CI 0.37-0.41), respectively. CONCLUSION: The prevalence of sexual dysfunction in men with CP/CPPS was high, even though overall sexual dysfunction demonstrated a slightly decreasing trend. Furthermore, erectile dysfunction prevalence rate had an increasing trend in recent years. More prospective studies are needed to evaluate sexual dysfunction improvement with better management of CP/CPPS.

Effectiveness and safety of ShenXiong glucose injection for acute ischemic stroke: a systematic review and GRADE approach.

BACKGROUND: To appraise critically whether published trials of ShenXiong glucose injection for patients with acute ischemic stroke (AIS) are of sufficient quality, and in addition to rate the quality of evidence by using the GRADE approach (grading of recommendations, assessment, development, and evaluation, GRADE). METHODS: A literature search was performed in the Cochrane Library, MEDLINE, EMBASE, CBM, Chinese TCM (traditional Chinese medicine) Database, CNKI, VIP, WanFang Databases until January 2015. The limits were patients with AIS and randomized controlled trials (RCTs) or quasi-RCTs. Studies by which patients suffering intracerebral haemorrhage were excluded. RESULTS: Twelve studies fulfilled the inclusion criteria. We found significant benefits of ShenXiong glucose injection compared with conventional treatment in improving activities of daily living function at 4 weeks (MD = 34.12, 95 % CI: 29.07, 39.17), neurological function deficit at 2 weeks (MD = -5.39, 95% CI: -6.90, -3.87), 4 weeks (MD = -5.16, 95 % CI: -6.49, -3.83), and clinical effects at 4 weeks (RR = 1.17, 95% CI: 1.10, 1.24). No trials reported the effects of ShenXiong glucose injection on the risk of early, deterioration, or quality of life. No adverse events were reported within the whole follow-up period. CONCLUSIONS: The use of ShenXiong glucose injection may improve rehabilitation for patients with acute ischemic stroke, however, as the GRADE approach indicated low to moderate quality of available evidence as well as insufficient information about harm and patients preference, the recommendations were not provided for ShenXiong glucose injection taking as a therapeutic intervention to patients with acute ischemic stroke.

Validity and reproducibility of a revised semi-quantitative food frequency questionnaire (SQFFQ) for women of age-group 12-44 years in Chengdu.

To find a credible nutritional screening tool for evaluating relationship between nutritional status and diseases in Chengdu female residents, the reliability and validity of a revised semi-quantitative food frequency questionnaire (SQFFQ) were tested. The validity was assessed by comparing the SQFFQ with the 'standard' method of 3 days' dietary recall, and the reliability was assessed by comparing the first SQFFQ with the second SQFFQ at 4 weeks interval. Correlation analysis showed that, for reliability, the average correlation coefficient (CC) of 22 kinds of nutrients was 0.66 and reduced to 0.60 after adjusting for energy; the average of intra-class correlation coefficients (ICC) was 0.65. For validity, the average CC was 0.35 and remained stable after adjusting for CC of energy or nutrients. Validity of 17 nutrients in SQFFQ survey had correlation with result of 3 days' dietary recall. The results showed that the revised SQFFQ can be used for investigating the role of nutrients in development of disease in Chengdu female residents.

Prevalence of the polycystic ovary syndrome in female residents of Chengdu, China.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. The data on this syndrome in a Chinese community are limited. METHODS: A community-based cross-sectional survey was undertaken. Cluster-randomized sampling was used. Female residents of Chengdu aged between 12 and 44 were included according to the constituent ratio of the female population of Sichuan province. We used three diagnostic criteria to determine the prevalence: the National Institutes of Health diagnostic criteria of PCOS (NIH-1990), the revised Rotterdam diagnostic criteria of PCOS (Rott-2003), and the recommended diagnostic criteria of PCOS by the Androgen Excess Society (AES-2006). RESULTS: 1,645 participants were included. The prevalence of PCOS in women aged between 12 and 44 was 7.1, 11.2 and 7.4%, respectively, according to the three different criteria. After the onset of puberty, the prevalence of PCOS increased rapidly from 12 to 14 years of age, peaked between 15 and 24 and decreased gradually thereafter and reached its lowest point before menopause. CONCLUSIONS: The prevalence of PCOS in this study was in the PCOS prevalence range from existing studies. According to the trend of prevalence, PCOS might be a temporary condition.

Shuganjieyu capsule for major depressive disorder (MDD) in adults: a systematic review.

OBJECTIVES: Shuganjieyu capsule is a pure herbal pharmaceutical product for depression. Our objective was to explore the effectiveness and safety of Shuganjieyu capsule for the treatment of major depressive disorder in adults. METHOD: Eight computerized databases were searched. In addition, randomized controlled trials (RCTs) on Shuganjieyu capsule were hand-searched on seven key Chinese journals. Data were extracted and evaluated by two reviewers independently. Analysis was performed by intention-to-treat where possible. Prespecified subgroup analyses were different-dose regimens, patient spectrum, publication status, and treatment duration. RESULTS: Seven RCTs with 595 participants were included. Shuganjieyu capsule was superior than placebo in terms of response rate (RR = 2.42, 95% CI: 1.55-3.79; P = 0.0001), remission rate (RR = 4.29, 95% CI: 1.61-11.45; P = 0.004), the scores of the mean change from baseline of the HAM-D17 (MD = -4.17, 95% CI: -5.61 to -2.73; P < 0.00001) and from baseline of traditional Chinese medicine (TCM) syndrome score scale scores (MD = -6.00, 95% CI: -8.25 to -3.75; P < 0.00001). In addition, Shuganjieyu plus venlafaxine had a significantly higher response rate (RR = 1.56, 95% CI: 1.29-1.88; P < 0.00001) and was superior in terms of the scores of the mean change from baseline of the treatment emergent symptoms scale scores (MD = -0.74, 95% CI:-1.12 to -0.35; P = 0.0002) than venlafaxine alone. CONCLUSION: Shuganjieyu capsule is superior to placebo in terms of overall treatment effectiveness and safety. Both response rate and remission rate among patients treated with the combination of Shuganjieyu plus venlafaxine were significantly higher than those treated with venlafaxine alone. Due to the considerable risk of bias in majority of trials, recommendations for practice should be cautious, and additional, well-designed RCTs are needed in next step.

Analysis of research topics and trends in investigator-initiated research/trials (IIRs/IITs): A topic modeling study.

BACKGROUND: With the exponential growth of publications in the field of investigator-initiated research/trials (IIRs/IITs), it has become necessary to employ text mining and bibliometric analysis as tools for gaining deeper insights into this area of study. By using these methods, researchers can effectively identify and analyze research topics within the field. METHODS: This study retrieved relevant publications from the Web of Science Core Collection and conducted bioinformatics analysis. The latent Dirichlet allocation model, which is based on machine learning, was utilized to identify subfield research topics. RESULTS: A total of 4315 articles related to IIRs/IITs were obtained from the Web of Science Core Collection. After excluding duplicates and articles with missing abstracts, a final dataset of 3333 articles was included for bibliometric analysis. The number of publications showed a steady increase over time, particularly since 2000. The United States, Germany, the United Kingdom, the Netherlands, Canada, Denmark, Japan, Switzerland, and France emerged as the most productive countries in terms of IIRs/IITs. The citation analysis revealed intriguing trends, with certain highly cited articles showing a significant increase in citation frequency in recent years. A model with 45 topics was deemed the best fit for characterizing the extensively researched fields within IIRs/IITs. Our analysis revealed 10 top topics that have garnered significant attention, spanning domains such as community health, cancer treatment, brain development and disease mechanisms, nursing research, and stem cell therapy. These top topics offer researchers valuable directions for further investigation and innovation. Additionally, we identified 12 hot topics, which represent the most cutting-edge and highly regarded research areas within the field. CONCLUSION: This study contributes to a comprehensive understanding of the current research landscape and provides valuable insights for researchers working in this domain.

Correlation between surrogate endpoints and overall survival in unresectable hepatocellular carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

This study aimed to assess the therapeutic effect of immune checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma (uHCC) and investigate the correlation between surrogate endpoints and overall survival (OS). A systematic literature search included phase I, II, and III clinical trials comparing ICIs to placebo or other therapies for uHCC treatment. Correlations between OS and surrogate endpoints were evaluated using meta-regression analyses and calculating the surrogate threshold effect (STE). The correlation analysis showed a weak association between OS and progression-free survival (PFS), with an R2 value of 0.352 (95% CI: 0.000-0.967). However, complete response (CR) exhibited a strong correlation with OS (R2 = 0.905, 95% CI: 0.728-1.000). Subgroup analyses revealed high correlations between OS and PFS, CR, stable disease (SD), and DC in phase III trials (R2: 0.827-0.922). For the ICI + IA group, significant correlations were observed between OS and SD, progressive disease (PD), and grade 3-5 immune-related adverse events (irAEs) (R2: 0.713-0.969). Analyses of the correlation between survival benefit and risk of mortality across various time points showed a strong association within the first year (R2: 0.724-0.868) but a weak association beyond one year (R2: 0.406-0.499). In ICI trials for uHCC, PFS has limited utility as a surrogate endpoint for OS, while CR exhibits a strong correlation with OS. Subgroup analyses highlight high correlations between OS and PFS, SD, and DC in phase III trials. Notably, the ICI + IA group shows significant associations between OS and SD, PD, and grade 3-5 irAEs. These findings offer valuable insights for interpreting trial outcomes and selecting appropriate endpoints in future clinical studies involving ICIs for uHCC patients.

Serplulimab combined with gemcitabine, nab-paclitaxel and stereotactic body radiotherapy as the first-line treatment for patients with metastatic pancreatic adenocarcinoma in China: a multicentre, single-arm, phase II trial (ICSBR) protocol.

INTRODUCTION: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC. METHODS AND ANALYSIS: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300073237.

Frailty and in-hospital mortality in older patients with acute exacerbation of COPD: A real-world prospective cohort study.

BACKGROUND: Few evidence exists for the effect of frailty on the patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). OBJECTIVE: We explored the link between frailty and in-hospital death in AECOPD, and whether laboratory indicators mediate this association. METHODS: This was a real-world prospective cohort study including older patients with AECOPD, consisting of two cohorts: a training set (n = 1356) and a validation set (n = 478). The independent prognostic factors, including frail status, were determined by multivariate logistic regression analysis. The relationship between frailty and in-hospital mortality was estimated by multivariable Cox regression. A nomogram was developed to provide clinicians with a quantitative tool to predict the risk of in-hospital death. Mediation analyses for frailty and in-hospital death were conducted. RESULTS: The training set included 1356 patients (aged 86.7 ± 6.6 years), and 25.0 % of them were frail. A nomogram model was created, including ten independent variables: age, sex, frailty, COPD grades, severity of exacerbation, mean arterial pressure (MAP), Charlson Comorbidity Index (CCI), Interleukin-6 (IL-6), albumin, and troponin T (TPN-T). The area under the receiver operating characteristic curve (ROCs) was 0.862 and 0.845 for the training set and validation set, respectively. Patients with frailty had a higher risk of in-hospital death than those without frailty (HR,1.83, 95%CI: 1.14, 2.94; p = 0.013). Furthermore, CRP and albumin mediated the associations between frailty and in-hospital death. CONCLUSIONS: Frailty may be an adverse prognostic factor for older patients admitted with AECOPD. CRP and albumin may be part of the immunoinflammatory mechanism between frailty and in-hospital death.

Antidepressants for polycystic ovary syndrome.

BACKGROUND: The prevalence of depression in women with polycystic ovary syndrome (PCOS) is high; one study has shown it to be four times that of women without PCOS. Therefore, systematic evaluation of the effectiveness and safety of antidepressants for women with PCOS is important. OBJECTIVES: To evaluate the effectiveness and safety of antidepressants in treating depression and other symptoms in women with PCOS. SEARCH METHODS: We searched the following databases from inception to June 2012: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO and Chinese National Knowledge Infrastructure, the metaRegister of Controlled Trials (controlled-trials.com), the National Institute of Health Clinical Trials register (clinicaltrials.gov) and the World Health Organization International Trials Registry Platform search portal (www.who.int/trialsearch/Default.aspx). SELECTION CRITERIA: Only randomised controlled trials (RCTs) studying the effectiveness and safety of antidepressants for women with PCOS were included in this review. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed independently by two review authors, in parallel with data extraction. The risk of bias in the included study was assessed in six domains: 1. sequence generation; 2. allocation concealment; 3. blinding of participants, personnel and outcome assessors; 4. completeness of outcome data; 5. selective outcome reporting; 6. other potential sources of bias. MAIN RESULTS: We found no studies reporting any of our primary review outcomes (depression and allied mood disorder scores, quality of life and adverse events). Only one study with 16 women was eligible for inclusion. This study compared sibutramine versus fluoxetine in women with PCOS, and reported only endocrine and metabolic outcomes. It was unclear whether the participants had psychological problems at baseline. No significant difference was found between the groups for any of the measured outcomes. AUTHORS' CONCLUSIONS: There is no evidence on the effectiveness and safety of antidepressants in treating depression and other symptoms in women with PCOS.