Effects of epidural analgesia on intrapartum maternal fever and maternal outcomes: an updated systematic review and meta-analysis.

OBJECTIVE: Epidural-related maternal fever in women is a common clinical phenomenon that leads to adverse consequences for mothers and neonates. The meta-analysis aimed to quantify the risk for intrapartum maternal fever after epidural analgesia (EA) stratified according to parity. The secondary objective was to investigate the association between EA and maternal outcomes. METHODS: An electronic literature search of the Medline/PubMed, Embase, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure databases was performed to identify studies reporting the occurrence of intrapartum fever in parturients. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and meta-analysis was performed using Review Manager version 5.3. RESULTS: Seventeen randomized controlled trials (RCTs) (5959 parturients) were included. Odds ratios for maternal fever in the analysis were 4.17 (95% confidence interval (CI) 2.93-5.94) and 5.83 (95% CI 4.96-6.87), respectively. Results of subgroup analysis according to parity were consistent. EA significantly prolonged the length of the first stage of labor (MD 34.52 [95% CI 12.13-56.91]) and the second stage of labor (MD 9.10 [95% CI 4.51-13.68]). Parturients who received EA were more likely to undergo instrumental delivery (OR 2.03 [95% CI 1.44-2.86]) and oxytocin augmentation (OR 1.45 [95% CI 1.12-1.88]). There were no differences in cesarean delivery rates between the EA and non-EA groups. CONCLUSIONS: Parturients who received EA exhibited a higher incidence of intrapartum fever. Credibility of the subgroup analyses was low because the mixed group did not effectively represent multiparas.

Effects of Baduanjin exercise on quality-of-life and exercise capacity in patients with heart failure: A systematic review and meta-analysis.

PURPOSE: Exercise training is an efficient non-pharmacological intervention for patients with heart failure (HF). This study aimed to objectively evaluate the effects of Baduanjin exercise on the quality of life (QOL) and exercise capacity in patients with HF. METHODS: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data were searched from the date of their inception until 30 September 2022. All randomised controlled trials (RCTs) evaluating the effects of Baduanjin exercise on QOL and exercise capacity in patients with HF were selected. The primary outcomes were QOL, assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and exercise capacity, evaluated using the 6-min walking test (6-MWT). A meta-analysis was performed by comparing the MLHFQ domain scores. Review Manager 5.3 and Stata 14.0, were used for the data analysis. RESULTS: Baduanjin exercise showed a favourable improvement of the overall QOL (mean difference = -8.25; 95% confidence interval: -13.62 to -2.89; P = 0.003) and exercise capacity (mean difference = 118.49; 95% confidence interval: 52.57 to 184.41; P = 0.0004). Meta-analyses of the MLHFQ domain score indicated that Baduanjin exercise significantly improved the patients' physical (mean difference = -2.83; 95% confidence interval: -3.76, -1.90; P < 0.00001), emotional (mean difference = -2.52; 95% confidence interval: -3.67 to -1.37; P < 0.0001), and general QOL (mean difference = -2.61; 95% confidence interval: -5.17 to -0.06; P = 0.05), based on the decrease in the MLHFQ domain score. Marked statistical heterogeneity (I2> 70%) was observed for all the QOL and exercise capacity outcomes. CONCLUSIONS: Baduanjin exercise is a safe, feasible, and acceptable intervention that can improve the QOL and exercise capacity in patients with HF. However, more RCTs with rigorous research designs are needed to assist in the rehabilitation of such patients.

Delivery of Cas9-guided ABE8e into stem cells using poly(l-lysine) polypeptides for correction of the hemophilia-associated FIX missense mutation.

The coagulation factor 9 gene (FIX) point mutation contributes to most hemophilia B cases, providing ideal gene correction models. Here we identified the frequent mutation G20519A (R226Q) in FIX, which resulted in many severe and moderate hemophilia B patients. This study aimed to investigate the effect of HDR and base editing in correcting FIX mutant. We first constructed HEK293 and liver-derived cell lines Huh7 cells stabling carrying mutated FIX containing G20519A (HEK293-FIXmut and Huh7-FIXmut). Then, CRISPR/Cas9-based homology-directed repair (HDR) and base editing were used for the correction of this mutated point. We used Cas9 nickase (nCas9) mediated HDR and the advanced base editor ABE8e to correct G20519A and then measured the concentration and activity of FIX. Furthermore, we used the star-shaped poly(lysine) gene nanocarriers to deliver the ABE8e correction systems into HEK293-FIXmut and Huh7-FIXmut stem cells to correct mutated FIX. As a result, we found that gRNAs directed inefficient HDR in correcting G20519A. The ABE8e corrected the mutation efficiently in both HEK293-FIXmut and Huh7-FIXmut stem cells. In addition, the star-shaped poly(lysine) carriers delivered non-viral vectors into stem cells efficiently. The nanocarriers-delivered ABE8e system corrected mutated FIX in stem cells, and the stem cells secreted active FIX in high concentration. In conclusion, our study provides a potential alternative for correcting mutated FIX in hemophilia B patients.

Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis.

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.

High incidence and endemic spread of NDM-1-positive Enterobacteriaceae in Henan Province, China.

The emergence and spread of New Delhi metallo-ß-lactamase 1 (NDM-1)-producing carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to human health. In China, the bla(NDM-1 gene has been reported mostly in Acinetobacter spp. but is rarely found in Enterobacteriaceae. Here, we report a high incidence and endemic spread of NDM-1-producing CRE in Henan Province in China. Sixteen (33.3%) of the 48 CRE isolates obtained from patients during June 2011 to July 2012 were positive for bla(NDM-1), and the gene was found to be carried on plasmids of various sizes (∼ 55 to ∼ 360 kb). These plasmids were readily transferrable to recipient Escherichia coli by conjugation, conferred resistance to multiple antibiotics, and belonged to multiple replicon types. The bla(NDM-1)-positive CRE isolates were genetically diverse, and six new multilocus sequence typing (MLST) sequence types were linked to the carriage of NDM-1. Five of the isolates were classified as extensively drug-resistant (XDR) isolates, four of which also carried the fosA3 gene conferring resistance to fosfomycin, an alternative drug for treating infections by CRE. In each bla(NDM-1)-positive CRE isolate, the bla(NDM-1) gene was downstream of an intact ISAba125 element and upstream of the bleMBL gene. Furthermore, gene environment analysis suggested the possible transmission of bla(NDM-1)-containing sequences from Acinetobacter spp. to Klebsiella pneumoniae and Klebsiella oxytoca. These findings reveal the emergence and active transmission of NDM-1-positive CRE in China and underscore the need for heightened measures to control their further spread.

Mesenchymal stem cells induce granulocytic differentiation of acute promyelocytic leukemic cells via IL-6 and MEK/ERK pathways.

All-trans retinoic acid (ATRA) induces clinical remission in most acute promyelocytic leukemia (APL) patients by inducing terminal differentiation of APL cells toward mature granulocytes. Here we report that human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are capable of inducing granulocytic differentiation of the APL-derived NB4 cell line as well as primary APL cells and also cooperate with ATRA in an additive manner. Transwell coculture experiments revealed that UC-MSCs' differentiation-inducing effect was mediated through some soluble factors. Differentiation attenuation by IL-6Ra neutralization and induction by addition of exogenous IL-6 confirmed that IL-6 secreted by UC-MSCs was at least partially responsible for this differentiation induction process. Moreover, we found that UC-MSCs activated the MEK/ERK signaling pathway in promyelocytic cells and pharmacological inhibition of the MEK/ERK pathway reversed UC-MSC-induced differentiation, indicating that UC-MSCs exerted effect through activation of the MEK/ERK signaling pathway. These results demonstrate for the first time a stimulatory effect of MSCs on the differentiation of APL cells and bring a new insight into the interaction between MSCs and leukemic cells. Our data suggest that UC-MSCs/ATRA combination could be used as a novel therapeutic strategy for APL patients.

Expression and role of Toll-like receptors on human umbilical cord mesenchymal stromal cells.

BACKGROUND AIMS: Toll-like receptors (TLRs) play an important role in innate and adaptive immunity by recognizing pathogen-associated molecular patterns (PAMPs). METHODS: In the present study, we investigated the expression and role of TLRs on human umbilical cord mesenchymal stromal cells (UC-MSCs). The proliferation, differentiation and immunoregulatory activity of UC-MSCs primed with or without TLR ligands were determined. RESULTS: At the RNA level, the expression of TLR2, 4, 6 and 9 was relatively higher than that of other TLRs. However, TLR3 and TLR4 expression were relatively higher at the protein level. UC-MSCs expressed functional TLRs by nuclear factor-κB activation and cytokine expression assay. Poly-inosinic acid:cytidylic acid [Poly(I:C)] stimulation inhibited the proliferation of UC-MSCs, but the ligand of other TLRs had no significant effect. Poly(I:C) stimulation enhanced the adipogenic differentiation capability of UC-MSCs, but lipopolysaccharide inhibited the adipogenic differentiation. Poly(I:C) and CpG-oligonucleotide promoted the immunosuppressive potentiality of UC-MSCs, accompanied with the phosphorylation of interferon regulatory factor 3 (IRF3) and increased expression of indoleamine 2,3-dioxygenase and interferon ß, whereas activation of other TLR ligands (synthetic analog fibroblast-stimulating lipopeptide-1 and lipopolysaccharide) failed to affect the immunoregulatory activity of UC-MSCs. CONCLUSIONS: Taken together, our data demonstrated that TLR activation influenced the function of UC-MSCs, which might have important implications in future efforts to explore the clinical potentials of UC-MSCs.

[Effects of interferon-γ on biological characteristics and immunomodulatory property of human umbilical cord-derived mesenchymal stem cells].

The aim of this study was to investigate the effects of interferon (IFN)-γ on biological characteristics and immunomodulatory property of human umbilical cord-derived mesenchymal stem cells (hUC-MSC). hUC-MSC were treated with IFN-γ 10 ng/ml (IFN-γ group) or without IFN-γ (control group). The phenotype of hUC-MSC was detected by flow cytometry. The proliferation status was detected by CCK-8 method, and its differentiation ability was assessed by oil red O and von Kossa staining. The production of PGE-2 was measured by ELISA, and the mRNA expression levels of COX-2, IDO-1 and IDO-2 in hUC-MSC were detected by real-time quantitative PCR. Furthermore, the proliferation of human peripheral blood mononuclear cells (hPBMNC) was evaluated after co-culture with hUC-MSC, IFN-γ pretreatment or not. The results showed that after IFN-γ stimulation, the expression of SSEA-4 on hUC-MSC decreased significantly [(8.15 ± 2.94) vs (16.42 ± 8.5), P < 0.05], and the expression of CD54 increased [(96.64 ± 3.29) vs (84.12 ± 10.73), P = 0.051]. The immunomodulatory property of hUC-MSC on the proliferation of hPBMNC was enhanced (P < 0.05). All the above mentioned effects were IFN-γ concentration-dependent. When hUC-MSC were stimulated by IFN-γ for 24 h, the production of PGE-2 secreted by hUC-MSC decreased significantly (P < 0.01). The mRNA expression level of COX-2 also decreased though the difference did not reach to statistically significant level. Compared with control group, IDO-1 expression level in IFN-γ group increased significantly (P < 0.01), and the mRNA expression level of IDO-2 remained unchanged. It is concluded that IFN-γ can influence the phenotype of hUC-MSC and enhance the immunomodulatory property of hUC-MSC.