The benefit of omeprazole exposure on all-cause mortality and length of ICU/hospital stay might vary with age in critically ill pediatric patients: A cohort study.

PURPOSE: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients. MATERIALS AND METHODS: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization. RESULTS: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (ß -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (ß 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup. CONCLUSIONS: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs.

Distinctive cortical morphological patterns in primary trigeminal neuralgia: a cross-sectional clinical study.

PURPOSE: The characteristics of surface-based morphological patterns to primary trigeminal neuralgia (PTN) are still not well understood. This study aims to screen the useful cortical indices for the prediction of PTN and the quantification of pain severity. METHODS: Fifty PTN patients and 48 matched healthy subjects enrolled in the study from March 2016 to August 2021. High-resolution T1 data were performed at 3.0 Tesla scanner and were analyzed with FreeSurfer software to detect the abnormalities of cortical mean curve (CMC), cortical thickness (CT), surface area (SA), and cortical volume (CV) in PTN patients compared to healthy controls. Logistic regression analysis was conducted to determine whether certain morphological patterns could predict PTN disorder. Then, the relationships of cortical indices to the pain characteristics in patient group were examined using linear regression model. RESULTS: Distinctive cortical alterations were discovered through surface-based analysis, including increased temporal CMC, decreased insular CT and fusiform SA, along with decreased CV in several temporal and occipital areas. Moreover, the difference of temporal CMC was greater than other cortical parameters between the two groups, and the combination of certain morphological indices was of good value in the diagnosis for PTN. Besides, CT of left insula was negatively associated with the pain intensity in PTN patients. CONCLUSION: The patients with PTN demonstrate distinctive morphological patterns in several cortical regions, which may contribute to the imaging diagnosis of this refractory disorder and be useful for the quantification of the orofacial pain. CLINICAL TRIALS: The registry name of this study in https://clinicaltrials.gov/ : Magnetic Resonance Imaging Study on Patients with Trigeminal Neuralgia (MRI-TN) https://clinicaltrials.gov/ ID: NCT02713646 A link to the full application: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02713646&cntry=&state=&city=&dist= The first patient with primary trigeminal neuralgia was recruited on November 28, 2016.

A meta-analysis of associations of IL-10 gene polymorphisms with acute leukemia susceptibility.

BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.

[Preparation and Tumor Targeting Analysis of Cell Membrane Nanovesicles Derived from Breast Cancer Cells].

Objective: To prepare cell membrane nanovesicles (NVs) derived from breast cancer cells, to explore their basic characteristics, tumor cell endocytosis, and in vivo distribution in a tumor-bearing mouse model, and to investigate their tumor targeting properties. Methods: 4T1 breast cancer cells were cultured in vitro. The cell membrane of 4T1 cells was isolated through ultracentrifugation and NVs were formulated with a liposome extruder. The size distribution of NVs was determined by way of dynamic light scattering, and the morphology properties of the NVs were examined with transmission electron microscope. The stability of NVs was analyzed by measuring the diameter changes of NVs submerged in phosphate-buffered saline (PBS). The biocompatibility of NVs was investigated by measuring the viability of dendritic cells treated with NVs at different concentrations (5, 10, 20, 50, and 100 mg·L -1) by CCK-8 assay. Fluorescence microscopy was used to analyze the cellular uptake of NVs by breast cancer cells. A mice model of breast cancer model was established with mice bearing subcutaneous xenograft of 4T1 cells. The mice were treated with Cy5.5-labeled NVs injected via the tail vein and the in vivo distribution of NVs was analyzed with an imaging system for small live animals. Results: The results showed that NVs derived from 4T1 breast cancer cells were successfully prepared. The NVs had a mean diameter of 123.2 nm and exhibited a hollow spherical structure under transmission electron microscope. No obvious change in the size of the NVs was observed after 7 days of incubation in PBS solution. CCK-8 assay results showed that the viability of dendritic cells treated with NVs at different concentrations was always higher than 90%. Fluorescence microscopic imaging showed that NVs could be efficiently internalized into breast cancer cells. in vivo biodistribution analysis revealed that breast cancer cell-derived NVs showed higher distribution in tumor tissue than the NVs prepared with normal cells did. Conclusion: We successfully prepared cell membrane NVs derived from 4T1 breast cancer cells. These NVs had efficient cellular uptake by breast cancer cells and sound tumor targeting properties.

Generation and identification of endothelial-specific Hrh2 knockout mice.

Histamine H2 receptor (HRH2) is closely associated with the development of cardiovascular and cerebrovascular diseases. However, systematic Hrh2 knockout mice did not exactly reflect the HRH2 function in specific cell or tissue types. To better understand the physiological and pathophysiological functions of endothelial HRH2, this study constructed a targeting vector that contained loxp sites flanking the ATG start codon located in Hrh2 exon 2 upstream and a neomycin (Neo) resistance gene flanked by self-deletion anchor sites within the mouse Hrh2 allele. The targeting vector was then electroporated into C57BL/6J embryonic stem (ES) cells, and positively targeted ES cell clones were micoinjected into C57BL/6J blastocysts, which were implanted into pseudopregnant females to obtain chimeric mice. The F1 generation of Hrh2flox/+ mice was generated via crossing chimeric mice with wild-type mice to excise Neo. We also successfully generated endothelial cell-specific knockout (ECKO) mice by crossing Hrh2flox/+ mice with Cdh5-Cre mice that specifically express Cre in endothelial cells and identified that Hrh2 deletion was only observed in endothelial cells. Hrh2flox/+ and Hrh2ECKO mice were normal, healthy and fertile and did not display any obvious abnormalities. These novel animal models will create new prospects for exploring roles of HRH2 during the development and treatment of related diseases.

Effects of pamidronate disodium on the loss of osteoarthritic subchondral bone and the expression of cartilaginous and subchondral osteoprotegerin and RANKL in rabbits.

BACKGROUND: Osteoarthritis (OA) is a major health problem in the increasingly elderly population. Therefore, it is crucial to prevent and treat OA at an early stage. The present study investigated whether pamidronate disodium (PAM), a bone-loss inhibitor, can significantly prevent or reverse the progression of early anterior cruciate ligament transection (ACLT)-induced OA. Whether therapeutic intervention is associated with regulation of the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), metalloproteinase-9 (MMP-9) or Toll-like receptor-4 (TLR-4) in cartilage and/or subchondral bone was also investigated. METHODS: 60 New Zealand rabbits were randomized into four groups: Sham-operated (n = 20); ACLT (n = 20); short-term treatment with PAM (PAM-S, n = 10) and long-term treatment with PAM (PAM-L, n = 10). For cartilage and subchondral bone testing, rabbits from Sham and ACLT groups were harvested at 2, 4, 6, and 14 weeks. Rabbits were given PAM from the 4th week after ACLT operation in PAM-S and PAM-L group, and were harvested at 6 and 14 weeks, respectively. Trabecular characteristics and cartilage changes were detected using Micro-CT, safranin O and rapid green staining, respectively. Immunohistochemical staining for OPG and RANKL were also performed. OPG, RANKL, MMP-9 and TLR-4 expression was evaluated by western blot analysis. RESULTS: Micro-CT and histology analyses indicated that PAM treatment for 2 or 10 weeks could completely prevent or reverse osteoarthritic subchondral bone loss and cartilage surface erosion. Immunohistochemistry and western blot analysis indicated that expression of OPG and RANKL increased, although RANKL expression increased more significantly than that of OPG. Therefore the ratio of OPG to RANKL was lower in the ACLT group. However, the ratio of OPG to RANKL in the PAM group was significantly higher than that in the ACLT group. Additionally, expression of MMP-9 and TLR-4 were upregulated in the ACLT group and downregulated in the PAM treated groups. CONCLUSIONS: PAM can significantly inhibit and even reverse early osteoarthritic subchondral bone loss, thus alleviating the process of cartilaginous degeneration. The mechanisms involved may be associated with the upregulation of OPG expression, and downregulation of RANKL, MMP-9 and TLR-4 expression.

[Preoperative evaluation of vascular involvement and general resectability of pancreatic carcinoma by using 64-slice spiral computed tomographical angiography].

OBJECTIVE: To assess for preoperative evaluation of 64-slice spiral computed tomographical angiography (64-SCTA) to predict vascular involvement and general resectability of pancreatic malignant tumors. METHODS: The material of 64-SCTA in 34 cases were retrospectively analyzed. Preoperative imaging findings were correlated with intraoperative and histopathologic results. RESULTS: For the arterial tumor invasion based on 64-SCTA findings, 1 grade was in 8 cases; 2 grade, 6 cases; 3 grade, 8 cases; 4 grade, 10 cases;5 grade, 2 cases.Regarding respectability, the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) were 92.9%, 95.0%,94.1%, 92.9%, 95.0%. Kappa value was 0.879 (P < 0.01). Receiver operator characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.943 (P < 0.01). For the venous tumor infiltration, 1 grade was in 0 case; 2 grade, 6 cases; 3 grade, 6 cases; 4 grade, 13 cases; 5 grade, 9 cases. Regarding respectability, these values for those tumors with vein invasion were 78.6%, 95.0%, 88.2%, 91.7%, 86.4%. Kappa value was 0.752 (P < 0.01). ROC analysis showed an AUC of 0.927 (P < 0.01). CONCLUSION: 64-SCTA can provide reliable information for vascular involvement and general resectability of pancreatic malignant tumors. 64-SCTA has high value in clinical application.

Bioequivalence Study of Miglitol Orally Disintegrating Tablets in Healthy Chinese Volunteers Under Fasting Condition Based on Pharmacodynamic and Pharmacokinetic Parameters.

To investigate the bioequivalence of miglitol orally disintegrating tablets in healthy Chinese volunteers based on pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Additionally, the safety profile was estimated. Two randomized, open-label, single-dose, crossover trials were conducted under fasting conditions. In the PD trial (CTR20191811), 45 healthy volunteers were randomly divided into 3 groups in a 1:1:1 ratio and administered sucrose alone or coadministered with 50 mg of miglitol orally disintegrating tablet test or reference formulation/sucrose. In the PK trial (CTR20191696), 24 healthy volunteers were randomized (1:1) to receive the test or reference formulation (50 mg). Blood samples were collected at 15 and 17 sampling points per cycle in the PD and PK trials, respectively. Plasma miglitol and serum glucose concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry method. Serum insulin concentrations were measured using electrochemiluminescent immunoassay. Statistical analyses for the PD and PK parameters were subsequently performed. The volunteers' physical indicators were monitored and documented during the entire study to estimate drug safety. The PD and PK parameters of the two formulations were similar. The main PD and PK end points were both within the prespecified range of 80%-125%. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were similar between the test and reference formulation groups, and no serious TEAEs or deaths occurred during the 2 trials. These 2 formulations were demonstrated to be bioequivalent and well tolerated in healthy Chinese volunteers under fasting condition.

Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta-Analyses.

Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual meta-analyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.

Development and analysis of a comprehensive diagnostic model for aortic valve calcification using machine learning methods and artificial neural networks.

Background: Although advanced surgical and interventional treatments are available for advanced aortic valve calcification (AVC) with severe clinical symptoms, early diagnosis, and intervention is critical in order to reduce calcification progression and improve patient prognosis. The aim of this study was to develop therapeutic targets for improving outcomes for patients with AVC. Materials and methods: We used the public expression profiles of individuals with AVC (GSE12644 and GSE51472) to identify potential diagnostic markers. First, the R software was used to identify differentially expressed genes (DEGs) and perform functional enrichment analysis. Next, we combined bioinformatics techniques with machine learning methodologies such as random forest algorithms and support vector machines to screen for and identify diagnostic markers of AVC. Subsequently, artificial neural networks were employed to filter and model the diagnostic characteristics for AVC incidence. The diagnostic values were determined using the receiver operating characteristic (ROC) curves. Furthermore, CIBERSORT immune infiltration analysis was used to determine the expression of different immune cells in the AVC. Finally, the CMap database was used to predict candidate small compounds as prospective AVC therapeutics. Results: A total of 78 strong DEGs were identified. The leukocyte migration and pid integrin 1 pathways were highly enriched for AVC-specific DEGs. CXCL16, GPM6A, BEX2, S100A9, and SCARA5 genes were all regarded diagnostic markers for AVC. The model was effectively constructed using a molecular diagnostic score system with significant diagnostic value (AUC = 0.987) and verified using the independent dataset GSE83453 (AUC = 0.986). Immune cell infiltration research revealed that B cell naive, B cell memory, plasma cells, NK cell activated, monocytes, and macrophage M0 may be involved in the development of AVC. Additionally, all diagnostic characteristics may have varying degrees of correlation with immune cells. The most promising small molecule medicines for reversing AVC gene expression are Doxazosin and Terfenadine. Conclusion: It was identified that CXCL16, GPM6A, BEX2, S100A9, and SCARA5 are potentially beneficial for diagnosing and treating AVC. A diagnostic model was constructed based on a molecular prognostic score system using machine learning. The aforementioned immune cell infiltration may have a significant influence on the development and incidence of AVC.

Associations of FOXP3 gene polymorphisms with susceptibility and severity of preeclampsia: A meta-analysis.

OBJECTIVE: FOXP3 single nucleotide polymorphisms (SNPs) were recently elucidated to influence the development of preeclampsia (PE), but the results on this issue still remained controversial. Thus, a meta-analysis was implemented to systematically investigate the roles of FOXP3 SNPs in PE. METHODS: Eligible publications were identified by retrieving relevant electronic databases. Meanwhile, the association intensity was estimated by calculating odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models. RESULTS: Totally eight investigations involving 3446 subjects were enrolled in the final meta-analysis. The AC and AC + CC genotypes of FOXP3 rs3761548 were related to the susceptibility of PE in over-dominant (OR = 1.19, 95%CI = 1.02-1.38, P = 0.03) and recessive (OR = 0.59, 95% CI: 0.36-0.97, P = 0.04) models. Furthermore, correlation between rs2232365 and PE was observed in recessive model (GG vs. GA + AA) (OR = 0.79, 95%CI: 0.65-0.97, P = 0.03). Moreover, rs2232365 GA and GG + GA genotypes were associated with the severity of PE. However, rs4824747, rs3761547 and rs2280883 polymorphisms had no significant impact on PE susceptibility. CONCLUSIONS: FOXP3 rs3761548 and rs2232365 SNPs influenced the PE susceptibility and therefore may be potential biomarkers for prediction of PE risk.

Proton Pump Inhibitors and Cancer Risk: An Umbrella Review and Meta-analysis of Observational Studies.

OBJECTIVES: Increasing evidence suggested that proton pump inhibitors (PPIs) use might affect the development of cancers, but previous conclusions remain controversial. Therefore, an umbrella review was performed to clarify the associations between PPIs and various types of cancer by summarizing the existing meta-analyses and systematic reviews. METHODS: We searched PubMed, Cochrane Library, Embase, CNKI, Wanfang, and VIP database up to June 2022 for eligible meta-analyses or systematic reviews. The summary effect size, 95% CI, heterogeneity, small study effect, and 95% prediction interval were considered in the present study. A Measurement Tool to Assess Systematic Review 2 and grading of recommendation, assessment, development, and evaluation were used to assess methodological quality and evidence. RESULTS: The umbrella review included 21 meta-analyses containing 65 studies and 10 cancer types with 6.8 million subjects. The results showed that PPI use was significantly associated with increased risks of certain types of cancer, including gastric cancer (odds ratio [OR]: 2.07; 95% CI, 1.30 to 3.29), pancreatic cancer (OR: 1.73; 95% CI, 1.23 to 2.44), colorectal cancer (OR: 1.84; 95% CI, 1.26 to 2.67), and liver cancer (OR: 1.80; 95% CI, 1.27 to 2.54), but was not associated with esophageal cancer. In addition, PPI use was associated with decreased risk of breast cancer (OR: 0.69; 95% CI, 0.50 to 0.96). CONCLUSIONS: These findings suggested that clinicians should pay more attention to the occurrence of gastric cancer, pancreatic cancer, colorectal cancer, and liver cancer in patients who used PPIs, and PPI prescription should be written only when an accurate specific diagnosis has been made. Furthermore, additional PPIs to the treatment regimen may be benefit for women with a higher-than-average risk of breast cancer.

Cardiovascular effects associated with chimeric antigen receptor T cell therapy in cancer patients: A meta-analysis.

Background: Although numerous studies confirmed the marked efficacy of chimeric antigen receptor T cells (CAR-T cells) in many hematologic malignancies, severe cardiovascular toxicities remain to be a major obstacle when incorporating this technology. Furthermore, previous individual investigations regarding the cardiovascular toxicities of CAR-T cell therapy also reported controversial conclusions. Therefore, a meta-analysis was performed to further evaluate the impacts of CAR-T cell therapy on cardiovascular toxicities. Methods: The PubMed, Embase, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to April 2022. All analyses were carried out using the R 4.1.0 software. Results: Eventually, 25 related studies consisting of 2,059 patients were enrolled in the current meta-analysis. We discovered that the pooled incidence rate of the all-cause mortality rate was 14.1% and that the pooled incidence rates of overall cardiovascular (CV) events and CV events with cytokine release syndrome (CRS) grade ≥ 2 were 25.6% and 14.2%, respectively. The pooled incidence of hypotension was 28.6%. Further analysis showed that the incidence rates of arrhythmias, cardiovascular dysfunction, heart failure (HF), CV deaths, acute coronary syndrome (ACS), cardiomyopathy, cardiac arrest, and other CV events were 19.2%, 8.0%, 5.3%, 1.8%, 2.5%, 2.9%, 1.3%, and 1.9%, respectively. Conclusion: Cancer patients treated with CAR-T cell therapy were at risk for cardiovascular toxicities, of which the most common cardiovascular events were arrhythmias, cardiovascular dysfunction, and heart failure. These findings would contribute to achieving more rational and individualized use of CAR-T cells in clinical treatment.

[Diagnostic value of the signal intensity on T1-weighted images of MRI and 1H MRS for neonatal hypoxic-ischemic encephalopathy].

OBJECTIVE: To study the diagnostic value of the signal intensity on T1-weighted images of MRI and proton magnetic resonance spectroscopy (1H MRS) for neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: Thirty full-term neonates with HIE admitted into the Department of Neonatology of the First Affiliated Hospital of Medical College, Xi'an Jiaotong University between January, 2007 and December 2009 were enrolled. Ten normal neonates born at the same period served as control group. Cerebral MRI and 1H MRS examinations were performed within 15 days after birth. RESULTS: In the HIE group, the signal intensity of the posterolateral lentiform nucleus was higher than or equal to that of the posterior limb of internal capsule, but in the control group, the results were opposite, namely, the signal intensity of the postero-lateral lentiform nucleus was lower than that of the posterior limb of internal capsule. The ratios of lactic acid/creatinine and glutamate/creatinine in the basal ganglia and the frontal lobe shown by 1H MRS increased significantly in the HIE group compared with controls (P<0.05 or 0.01). The differences of the signal intensity between the posterolateral lentiform nucleus and the posterior limb of internal capsule were positively correlated with the ratios of lactic acid/creatinine and glutamate/creatinine shown by 1H MRS (P<0.05). CONCLUSIONS: The comparison of the signal intensity between the posterolateral lentiform nucleus and the posterior limb of internal capsule on T1-weighted images of the cerebral MRI is valuable for the diagnosis of neonatal HIE and the accuracy of diagnosis can be improved when combined with 1H MRS.

Association between TNF-α gene polymorphisms and susceptibility of myelodysplastic syndromes: a meta-analysis.

OBJECTIVE: Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases. Previous investigations reported that tumor necrosis factor-alpha (TNF-α) gene polymorphisms were associated with MDS susceptibility, but the results remained controversial. Thus, we conducted a meta-analysis to higher elucidate the correlation between TNF-α gene polymorphisms and MDS susceptibility. METHODS: The PubMed, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for eligible literatures published up to July 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association. RESULTS: Eight studies involving 1180 MDS patients and 1387 controls were included in this meta-analysis. For the TNF-α G308A polymorphism, we confirmed that the G allele (G versus A: P = 0.001), GG genotypes (GG versus GA: P = 0.005; GG versus GA + AA: P = 0.002), and GG + AA genotypes (GG + AA versus GA: P = 0.008) was significantly associated with decreased MDS susceptibility according to different genetic models. Furthermore, the G308A polymorphism was significantly correlated with decreased occurrence risk of MDS in the Caucasian population as compared with Asians in the above four genetic models (P < 0.05). However, no significant association was observed between the TNF-α G238A polymorphism and MDS risk. CONCLUSION: This research showed that TNF-α G308A polymorphism might be a potential biomarker in early clinical screening of MDS, which would contribute to improving the individualized prevention of MDS patients in clinic.

PARP1 as a prognostic biomarker for human cancers: a meta-analysis.

Aim: A comprehensive meta-analysis was carried out to evaluate the association between high PARP1 expression and clinical outcomes in diverse types of cancers. Materials & methods: The electronic databases for all articles about PARP1 expression and cancers were searched. Additionally, bioinformatics analysis was utilized to validate the results of the meta-analysis. Results: Fifty-two studies with a total of 7140 patients were included in the current meta-analysis. High PARP1 expression was found to be significantly associated with poor overall survival and recurrence in various cancers, which were further strengthened and complemented by the results of bioinformatic analysis. Furthermore, increased PAPR1 expression was also related to clinicopathological features. Conclusion: Our findings confirmed that PARP1 might be a promising biomarker for prognosis in human cancers.

Association of ABCB1 polymorphisms with carbamazepine metabolism and resistance in epilepsy: A meta-analysis.

OBJECTIVE: ABCB1 polymorphisms were previously demonstrated to be associated with the metabolism and resistance of carbamazepine (CBZ) in epilepsy, but the results still remained controversial. Therefore, we performed this meta-analysis to further evaluate the impacts of ABCB1 polymorphisms on CBZ metabolism and resistance. METHODS: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database and Wan Fang Database were searched for eligible publications up to 5 July 2021. The mean difference (MD), Odds ratio (OR) and 95 % confidence interval (CI) were calculated by Review Manager 5.3 software to assess the strength of the association. RESULTS: Twelve studies involving 2126 epilepsy patients were included in this meta-analysis. We found that the TC genotype (heterozygous model: TC vs. CC) of rs1045642 polymorphism was significantly connected with decreased CBZ concentration. Furthermore, this polymorphism was indicated to be associated with concentrations of carbamazepine-10, 11-epoxide (homozygote model: TT vs. CC; heterozygous model: TC vs CC; dominant model: TT + TC vs. CC; over-dominant model: TC vs. TT + CC) and carbamazepine-10, 11-trans dihydrodiol (heterozygous model: TC vs. CC; dominant model: TT + TC vs. CC). Moreover, the AG genotype of rs2032582 polymorphism was related to increased CBZ concentration in heterozygous (AG vs. GG), dominant (AA + AG vs. GG) and over-dominant (AG vs. AA + GG) models. Additionally, rs1128503 was associated with CBZ resistance in heterozygous model (TC vs. CC). CONCLUSIONS: ABCB1 rs1045642 and rs2032582 polymorphisms were associated with CBZ metabolism for epilepsy, and rs1128503 was related to CBZ resistance. These findings would contribute to improving individualized therapy of epileptic patients.

Copper-chelating therapeutic effect in Wilson disease with different clinical phenotypes and polymorphisms of ATP7B gene.

AIM:To investigate the copper-chelating therapeutic effect in Wilson disease (WD) with different clinical phenotypes and polymorphisms of ATP7B gene.METHODS:One hundred and twenty-two WD patients with different clinicalphenotypes were given DMPS intravenously and Gandou copper-chelating tablet orally for one month. The therapeutic effect was judged by modified Goldstein mothod. Exon 18 of ATP7B gene extracted from the DNA of patients and 20 healthy volunteers was amplified with PCR mutation and polymorphism were screened with SSCP technique.RESULTS:Four kinds of abnormal migration bands in PCR-SSCP were observed in 37 WD patients, mutation frequencies of three different disease phenotypes, and curative effect between mutation group and non-mutation group showed no statistically significant difference (P > 0.05), but the total effectiveness rates in patients with Wilson type or pseudosclerosis type were significantly higher than those of patients with hepatic type (X(2) = 6.17, P < 0.05).CONCLUSION:Most WD patients are compound heterozygotes, the patients with different clinical phenotypes have different response to copper-chelating therapy. Specific mutation, at least in part, plays a role in influencing the disease phenotypes and therapeutic effect.