Comparison of the effectiveness of probiotic supplementation in glucose metabolism, lipid profile, inflammation and oxidative stress in pregnant women.

Objective: The optimal probiotic supplementation in pregnant women has not been thoroughly evaluated. By employing a network meta-analysis (NMA) approach, we compared the effectiveness of different probiotic supplementation strategies for pregnant women. Methods: A comprehensive search across multiple databases was performed to identify studies comparing the efficacy of probiotic supplements with each other or the control (placebo) among pregnant women. Results: This NMA, including 32 studies, systematically evaluated 6 probiotic supplement strategies: Lactobacillus, Lacticaseibacillus rhamnosus and Bifidobacterium (LRB), Lactobacillus acidophilus and Bifidobacterium (LABB), Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum (LLB), multi-combination of four probiotics (MP1), and multi-combination of six or more probiotics (MP2). Among these strategies, LLB, MP1, and MP2 all contain LABB. The NMA findings showed that MP1 was the most effective in reducing fasting blood sugar (FBS) (surface under the cumulative ranking curve [SUCRA]: 80.5%). In addition, MP2 was the most efficacious in lowering the homeostasis model assessment of insulin resistance (HOMA-IR) (SUCRA: 89.1%). LABB was ranked as the most effective in decreasing low-density lipoprotein cholesterol (LDLC) (SUCRA: 95.5%), total cholesterol (TC) (SUCRA: 95.5%), and high-sensitivity C-reactive protein (hs-CRP) (SUCRA: 94.8%). Moreover, LLB was ranked as the most effective in raising total antioxidant capacity (TAC) (SUCRA: 98.5%). Conclusion: Multi-combination of probiotic strains, especially those strategies containing LABB, may be more effective than a single probiotic strain in glycolipid metabolism, inflammation, and oxidative stress of pregnant women.

Blood Group Antigen A Carriers Exhibit an Extended Progression-Free Survival with no more Immune-Related Adverse Events.

Extensive investigations have been conducted regarding the potential correlation between blood type and the immune system, as well as cancer risk in the Southern Chinese population. However, the prognostic value of the blood group and its genetic determinants in the context of immune checkpoint inhibitor (ICI) treatment remains unclear. Therefore, the associations between the ABO blood group and its single nucleotide polymorphisms (SNPs) were examined in relation to ICI treatment outcomes in 370 eligible patients with cancer. This approach allowed us to derive the blood group from the SNPs responsible for blood group determination. In the discovery cohort (N = 168), antigen A carriers (blood types A and AB) exhibited an extended progression-free survival (PFS; hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34-0.98). The association results from the SNP-derived blood were consistent with those from the measured blood group. In the validation cohort (N = 202), Cox regression analysis revealed that the antigen A carriers (rs507666 AA+GA genotype carriers) experienced significantly extended PFS compared with the non-antigen A carriers (HR = 0.61, 95% CI = 0.40-0.93). Therefore, a longer PFS was observed in antigen A carriers (P value = 0.003, HR = 0.60, 95% CI = 0.44-0.84). Furthermore, haplotype 2 carriers (rs507666 GA and rs659104 GG) demonstrated both extended PFS and improved overall survival. Notably, the presence of antigen A was not associated with the occurrence of overall immune-related adverse events (irAEs) or organ-specific toxicity. In summary, our findings revealed that antigen A carriers did not experience a higher incidence of irAEs while exhibiting better immunotherapy efficacy.

Multidimensional evaluation of teaching strategies for pharmacology based on a comprehensive analysis involving 21,269 students.

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education. Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined. Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students' theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%). Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students.

Expression of IGLL1 Gene and Its Clinical Significance in Pediatric T-ALL / 中国实验血液学杂志

OBJECTIVE@#To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients.@*METHODS@#A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed.@*RESULTS@#The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients.@*CONCLUSION@#In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.

The Effect of Voriconazole on Tacrolimus in Kidney Transplantation Recipients: A Real-World Study.

Tacrolimus is an immunosuppressant with a narrow therapeutic window. Tacrolimus exposure increased significantly during voriconazole co-therapy. The magnitude of this interaction is highly variable, but it is hard to predict quantitatively. We conducted a study on 91 kidney transplantation recipients with voriconazole co-therapy. Furthermore, 1701 tacrolimus concentration data were collected. Standard concentration adjusted by tacrolimus daily dose (C/D) and weight-adjusted standard concentration (CDW) increased to 6 times higher during voriconazole co-therapy. C/D and CDW increased with voriconazole concentration. Patients with the genotype of CYP3A5 *3/*3 and CYP2C19 *2/*2 or *2/*3 were more variable at the same voriconazole concentration level. The final prediction model could explain 54.27% of the variation in C/D and 51.11% of the variation in CDW. In conclusion, voriconazole was the main factor causing C/D and CDW variation, and the effect intensity should be quantitative by its concentration. Kidney transplant recipients with CYP3A5 genotype of *3/*3 and CYP2C19 genotype of *2/*2 and *2/*3 should be given more attention during voriconazole co-therapy. The prediction model established in this study may help to reduce the occurrence of rejection.

Magnesium Isoglycyrrhizinate Attenuates Anti-Tuberculosis Drug-Induced Liver Injury by Enhancing Intestinal Barrier Function and Inhibiting the LPS/TLRs/NF-κB Signaling Pathway in Mice.

Liver injury caused by first-line anti-tuberculosis (anti-TB) drugs accounts for a high proportion of drug-induced liver injury (DILI), and gut microbiota and intestinal barrier integrity have been shown to be involved in the development of DILI. Magnesium isoglycyrrhizinate (MgIG) is the fourth-generation glycyrrhizic acid preparation, which is well documented to be effective against anti-TB DILI, but the underlying mechanism is largely unclear. In the present study, we established a BALB/c mice animal model of the HRZE regimen (39 mg/kg isoniazid (H), 77 mg/kg rifampicin (R), 195 mg/kg pyrazinamide (Z), and 156 mg/kg ethambutol (E))-induced liver injury to investigate the protective effect of MgIG against anti-TB DILI and underlying mechanisms. The results demonstrated that intraperitoneal injection of MgIG (40 mg/kg) significantly ameliorated HRZE-induced liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and malondialdehyde (MDA) levels and improved liver pathological changes. Species composition analysis of gut microbiota showed that Lactobacillus was the only probiotic that was down-regulated by HRZE and recovered by MgIG. In addition, MgIG attenuated HRZE-induced intestinal pathology, significantly decreased HRZE-induced intestinal permeability by increasing the protein expression of tight junction protein 1 (ZO-1) and occludin, decreased HRZE-induced high lipopolysaccharide (LPS) levels, and further markedly attenuated mRNA expression levels of TNF-α, IL-6, TLR2, TLR4, and NF-κB. Supplementation with Lactobacillus rhamnosus JYLR-005 (>109 CFU/day/mouse) alleviated HRZE-induced liver injury and inflammation in mice. In summary, MgIG effectively ameliorated HRZE-induced liver injury by restoring the abundance of Lactobacillus, enhancing intestinal barrier function, and further inhibiting the activation of the LPS/TLRs/NF-κB signaling pathway. Regulating gut microbiota and promoting the integrity of intestinal barrier function may become a new direction for the prevention and treatment of anti-TB DILI.

Factors Affecting Voriconazole Trough Concentration and Optimal Maintenance Voriconazole Dose in Chinese Children.

Voriconazole is a triazole antifungal agent commonly used for the treatment and prevention of invasive aspergillosis (IA). However, the study of voriconazole's use in children is limited. The present study was performed to explore maintenance dose to optimize voriconazole dosage in children and the factors affecting voriconazole trough concentration. This is a non-interventional retrospective clinical study conducted from 1 January 2016 to 31 December 2020. The study finally included 94 children with 145 voriconazole trough concentrations. The probability of achieving a targeted concentration of 1.0-5.5 µg/mL with empiric dosing increased from 43 (45.3%) to 78 (53.8%) after the TDM-guided adjustment. To achieve targeted concentration, the overall target maintenance dose for the age group of less than 2, 2 to 6, 6 to 12, and 12 to 18 years old was approximately 5.71, 6.67, 5.08 and 3.31 mg·kg-1/12 h, respectively (p < 0.001). Final multivariate analysis found that weight (p = 0.019), dose before sampling (p < 0.001), direct bilirubin (p < 0.001), urea nitrogen (p = 0.038) and phenotypes of CYP2C19 were influencing factors of voriconazole trough concentration. These factors can explain 36.2% of the variability in voriconazole trough concentration. Conclusion: In pediatric patients, voriconazole maintenance doses under the target concentration tend to be lower than the drug label recommended, but this still needs to be further studied. Age, body weight, dose, direct bilirubin, urea nitrogen and phenotypes of CYP2C19 were found to be influencing factors of voriconazole concentration in Chinese children. The influence of these factors should be taken into consideration during voriconazole use.