The Impact of SARS-CoV-2 Infection on the Length of Stay in the Neuro-ICU:A Prospective Multicenter Cohort Study in Eight Neuro-ICU, China Between February and April 2023.

Purpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs. Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes. Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p>0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1-12) vs 4(1-8), p<0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p<0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death. Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients. Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.

Differential expression profiles of microRNAs in musk gland of unmated and mated forest musk deer (Moschus berezovskii).

BACKGROUND: The formation of musk is a complex biophysical and biochemical process that change with the rut of male forest musk deer. We have reported that the mating status of male forest musk deer might result to the variations of chemical composition and microbiota of musk and its yields. Critical roles for microRNAs (miRNAs) of multi-tissues were profiled in our previous study; however, the role for miRNAs of the musk gland remains unclear in this species. METHODS: In this study, we used Illumina deep sequencing technology to sequence the small RNA transcriptome of unmated male (UM) and mated male (UM) of Chinese forest musk deer. RESULTS: We identified 1,652 known miRNAs and 45 novel miRNAs, of which there were 174 differentially expressed miRNAs between UM and MM. chi-miR-21-5p, ipu-miR-99b and bta-miR-26a were up-regulated in UM among the 10 most differentially expressed miRNAs. Functional enrichment of the target genes showed that monosaccharide biosynthetic process, protein targeting, cellular protein catabolic process enriched higher in MM. Meanwhile, structural molecule activity, secretion by cell, regulated exocytosis and circulatory system process enriched more in UM, hinting that the formation of musk in UM was mediated by target genes related to exocytosis. The miRNA-mRNA pairs such as miR-21: CHD7, miR143: HSD17B7, miR-141/200a: Noc2 might involve in musk gland development and musk secretion, which need to be verified in future study.

miR-31-5p Regulates 14-3-3 ɛ to Inhibit Prostate Cancer 22RV1 Cell Survival and Proliferation via PI3K/AKT/Bcl-2 Signaling Pathway.

INTRODUCTION: Prostate cancer (PCa) is one of the most common malignancies, and almost all patients with advanced PCa will develop castration-resistant prostate cancer (CRPC) after receiving endocrine therapy. Effective treatment for patients with CRPC has not been established. Novel approaches are needed to identify therapeutic targets for CRPC. PURPOSE: Recent research studies have found that members of the 14-3-3 family play an important role in the development and progression of PCa. Previous results have shown that 14-3-3 ɛ is significantly upregulated in several cancers. This study aimed to identify novel miRNAs that regulate 14-3-3 ɛ expression and therapeutic targets for CRPC. METHODS: In this study, we used computation and experimental approaches for the prediction and verification of the miRNAs targeting 14-3-3 ɛ, and investigated the potential roles of 14-3-3 ɛ in the survival and proliferation of 22RV1 cells. RESULTS: We confirm that mir-31-5p is downregulated in 22RV1 cells and acts as a tumor suppressor by regulating 14-3-3 ɛ. Ectopic expression of miR-31-5p or 14-3-3 ɛ interference significantly inhibits cell proliferation, invasion, and migration in 22RV1 cells, as well as promotes cell apoptosis via the PI3K/AKT/Bcl-2 signaling pathway. Moreover, 14-3-3 ɛ is required for the miR-31-5p-mediated upregulation of the PI3K/AKT/Bcl-2 signaling pathway. CONCLUSION: Our findings provide information on the underlying mechanisms of miR-31-5p/14-3-3 ɛ in 22RV1 cell proliferation and apoptosis through the PI3K/AKT/Bcl-2 signaling pathway. These results suggest that miR-31-5p and 14-3-3 ɛ may potentially be utilized as novel prognostic markers and therapeutic targets for PCa treatment.

miR­27b­3p and miR­607 cooperatively regulate BLM gene expression by directly targeting the 3'­UTR in PC3 cells.

BLM RecQ like helicase (BLM) has a pivotal role in genetic recombination, transcription, DNA replication and DNA repair, which presents the possibility of using BLM as an anti­cancer target for treatment. However, the post­transcriptional control regulation of BLM gene expression is not fully understood and limits the application of drugs targeting BLM for carcinoma therapy in the future. MicroRNAs (miRNAs) inhibit gene expression through interaction with the 3' untranslated region (3'­UTR) of mRNA at the post­transcriptional stage. Therefore, the current study screened for miRNAs that regulate BLM gene expression, with software predicting that miRNA (miR)­27b­3p, miR­607, miR­361­3p, miR­628­5p and miR­338­3p. BLM gene expression levels in the PC3 prostate cancer cell line and RWPE­2 normal prostate epithelium cell line were detected by reverse transcription­quantitative PCR. Additionally, BLM mRNA levels were following miRNA overexpression for 24 and 48 h. For further miRNA filtration and validation, a dual­luciferase reporter system and western blot analysis were performed, which demonstrated that miR­27b­3p and miR­607 reduce BLM gene expression by directly targeting the BLM mRNA 3'­UTR. A Box­Behnken design experiment suggested that miR­27b­3p and miR­607 have synergetic mutual effects on BLM gene expression. Finally, the suppressive effect of miR­27b­3p and miR­607 on PC3 cell proliferation, colony formation, migration and invasion indicated the benefit of studying BLM as a drug target in cancer. In conclusion, the findings of the current provide evidence that miR­27b­3p and miR­607 have an oncosuppressive function in PC3 cells and cooperatively downregulate BLM expression at the post­transcriptional level.

Blood conservation strategies in cardiac valve replacement: A retrospective analysis of 1645 patients.

We aimed to evaluate whether blood conservation strategies including intraoperative autologous donation (IAD) could reduce perioperative blood transfusion for patients undergoing cardiac valve replacement including mitral valve replacement, aortic valve replacement (AVR), and double valve replacement (DVR).A total of 726 patients were studied over a 3-year period (2011-2013) after the implementation of IAD and were compared with 919 patients during the previous 36-month period (January 2008-December 2010). The method of small-volume retrograde autologous priming, strict blood transfusion standard together with IAD constituted a progressive blood-saving strategy.Baseline characteristics and preoperative information showed no statistically significant difference between IAD group and non-IAD group. Most of the postoperative morbidities are statistically the same in the 2 groups. Chest tube output (415.2 vs 1029.8 mL, P < 0.001) and postoperative respiratory failure (5.9% vs 8.6%, P = 0.039) favored the IAD group, whereas hematocrit levels were more favorable in the non-IAD group (30.3% vs 33.0% at the end of the operation, P < 0.001; 30.4% vs 31.5% at the time of discharge). The use of blood product transfusion was higher in the non-IAD group (22.6% vs 43.3%, P < 0.001). Binary multivariate logistic regression analysis showed that high age, non-IAD, DVR surgery, and absent smoking history are associated with a higher risk of intra-/postoperative blood transfusion.Blood conservation is effective and safe in cardiac valve replacement surgeries. The use of intraoperative autologous donation can lead to improved outcomes including a significantly lower rate of intra-/postoperative blood transfusion and postoperative complications.

[Intraoperative autologous based blood conservation strategies in mitral valve replacement].

OBJECTIVE: To evaluate whether intraoperative autologous donation (IAD) can reduce perioperative blood transfusion for patients underwent mitral valve replacement (MVR). METHODS: A total of 318 patients received implementation of IAD from January 2011 to December 2013 were analyzed retrospectively, and compared with 517 patients of the previous 36-month period (from January 2008 to December 2012). The method of small-volume retrograde autologous priming, strict blood transfusion standard along with IAD together constituted a progressive blood-saving strategy. Statistical methods including Students' t-test, Pearson's χ(2) test, Kruskal-Wallis analysis and multivariate Logistic regression model were used for comparisons of the data. RESULTS: There were no significant difference between IAD group and non-IAD group considering preoperative patient demographics, characteristics and preoperative comorbidities. However, IAD group significantly reduced number of patients transfused with intra/post-operative packed red-blood cell (PRBC) (55(17.0%) vs. 215 (42.1%), χ(2)=53.0, P=0.000), and had significantly reduced postoperative chest tube output (150(380) ml vs. 700(660) ml, H=195.648, P=0.000), length of stay ((16±6) d vs. (20±8)d, t=9.60, P=0.000). But hematocrit were lower in IAD group (30%±5% vs.33%±4% at end of operation, t=7.76, P=0.000; 30%±4% vs. 32%±5% at discharge, P=0.000, t=3.86). Multivariate logistic aggression analysis revealed that age, IAD and smoking history were factors influencing the probability of intra or postoperative blood transfusion. CONCLUSION: Implementation of blood conservation strategies based on intraoperative autologous donation in mitral valve replacement surgery can significantly reduce intra/postoperative blood transfusion as well as postoperative complications.