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1.
EFORT Open Rev ; 9(6): 458-466, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38828978

Purpose: For many decades, patients recovering from wound closure have been instructed not to bathe. Although studies have shown that earlier postoperative bathing does not increase the risk of wound infection, it remains rare in practice for patients to be allowed earlier postoperative bathing. We performed this meta-analysis to determine how earlier bathing affected rates of wound infection, other complications, and patient satisfaction. Methods: This systematic review conforms to PRISMA guidelines. The PubMed, EMBASE, Medline, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception dates to December 31, 2022. We estimated pooled values for the efficacy of trial of earlier bathing versus delayed bathing using the odds ratio and their associated 95% CI, and we used the I 2 statistic to assess heterogeneity between studies contributing to these estimates. Results: Of the 1813 articles identified by our search, 11 randomized controlled trials including 2964 patients were eligible for inclusion. The incidence of wound infection did not differ significantly between the earlier bathing and delayed bathing groups, nor did rates of other wound complications such as redness and swelling, or wound dehiscence. However, the incidence of hematoma in the delayed bathing group was higher than in the earlier bathing group. Reported patient satisfaction was significantly higher in the earlier bathing group. Conclusion: The medical community, health authorities, and government should create and disseminate clinical practice guidelines to guide patients to evidence-based beneficial treatment.

2.
EFORT Open Rev ; 9(6): 479-487, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38828985

Purpose: Knee arthroplasty is an effective treatment for severe knee degeneration; however, periprosthetic joint infection (PJI) is one of its serious complications. Single- and two-stage revision are common treatments, but few studies have compared single- and two-stage revision for PJI after knee arthroplasty. This study aimed to compare the reinfection and reoperation rates of single- and two-stage revision through meta-analysis. Methods: The review process was conducted according to the PRISMA guidelines. We searched the PubMed, Medline, Embase and Cochrane Central Register of Controlled Trials databases for trials comparing single- and two-stage revision for PJI after knee arthroplasty from the respective inception dates to April 2023. Two researchers individually screened the studies, performed the literature quality evaluation and data extraction and used Stata 17 software for data analysis. Results: The meta-analysis showed that the reinfection rate was significantly lower in the single-stage revision group than in the two-stage revision group. While the reoperation rates demonstrated no statistically significant difference between the two groups. We presented descriptive results because the discrepancies in the knee function scores and data reported in the studies meant that these data could not be combined in the meta-analysis. Conclusion: Based on the available research, single-stage revision is a reliable option for PJI after knee arthroplasty. However, when developing the best treatment strategy, it is still necessary to consider the individual circumstances and needs of the patient, as well as the risks of postoperative rehabilitation and complications.

3.
J Sports Sci Med ; 23(2): 289-304, 2024 Jun.
Article En | MEDLINE | ID: mdl-38841637

Perception is an essential component of children's psychological development, which is foundational to children's ability to understand and adapt to their external environment. Perception is also a crucial tool for understand and navigating one's surroundings, enabling children to identify objects and react appropriately to settings or situations. Substantial evidence indicates that engaging in physical activity is beneficial for the development of children's perceptual abilities, as the two are closely intertwined. Still, more research is necessary to gain a full understanding of the impact of physical activity on children's perception. To further identify and quantify the effects of physical activity on a number of specific perceptions in children. Systematic review and meta-analysis. Searches were performed using five online databases (i.e., PubMed, SPORTDiscus, PsycINFO, Web of Science, and Cochrane Library) for articles published up to and including June 2023 to identify eligible citations. A total of 12 randomized controlled trials, encompassing 1,761 children under the age of 12, were analyzed. Overall, physical activity as an intervention showed a notable effect on the development of children's perceptions. The meta-analysis indicated that participating in physical activity for 30 minutes around, daily, had a greater impact on children's visual perception and executive functioning than on their motor perception, body perception, and global self-worth (SMD = 1.33, 95% CI: 0.75, 1.91, p < 0.001). The effects of physical activity on children's perception performance varied by participant characteristics, with physical activity having better effects on body perception and overall self-worth in children who were obese or overweight. Furthermore, physical activity can also enhance executive function and attention in children with developmental coordination disorders. The effects of physical activity on children's perception performance varied according to the intervention time, with different activity durations resulting in different perception performances. Therefore, parents and educators must prioritize an appropriate length of physical activity time for children to ensure their optimal growth and development. Registration and protocol CRD42023441119.


Executive Function , Exercise , Perception , Humans , Child , Exercise/psychology , Perception/physiology , Executive Function/physiology , Child Development , Visual Perception , Randomized Controlled Trials as Topic , Body Image
4.
Front Neurol ; 15: 1405183, 2024.
Article En | MEDLINE | ID: mdl-38827573

Aim: To identify the associations of 19 single nucleotide polymorphisms (SNPs) in genes involved in inflammation and endothelial function and carotid atherosclerosis with subsequent ischemic stroke and other vascular events in the high-risk stroke population. Methods: This was a multicenter community-based sectional survey and prospective cohort study in Sichuan, southwestern China. Eight communities were randomly selected, and the residents in each community were surveyed using a structured face-to-face questionnaire. Carotid ultrasonography and DNA information were obtained from 2,377 out of 2,893 individuals belonging to a high-risk stroke population. Genotypes of the 19 SNPs in genes involved in inflammation and endothelial function were measured. All the 2,377 subjects were followed up for 4.7 years after the face-to-face survey. The primary outcome was ischemic stroke, and the secondary outcome was a composite of vascular events. Results: Among the 2,377 subjects, 2,205 (92.8%) completed a 4.7-year follow-up, 947 (42.9%) had carotid atherosclerosis [372 (16.9%) carotid vulnerable plaque, 405 (18.4%) mean IMT > 0.9 mm, 285 (12.0%) carotid stenosis ≥15%]. Outcomes occurred in 158 (7.2%) subjects [92 (4.2%) ischemic stroke, 17 (0.8%) hemorrhagic stroke, 48 (2.2%) myocardial infarction, and 26 (1.2%) death] during follow-up. There was a significant gene-gene interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 in the 19 SNPs. The multivariate logistic regression model revealed that carotid atherosclerosis and the high-risk interactive genotypes among the three SNPs were independent with a higher risk for ischemic stroke (OR = 2.67, 95% CI: 1.52-6.78, p = 0.004; and OR = 3.11, 95% CI: 2.12-9.27, p < 0.001, respectively) and composite vascular events (OR = 3.04, 95% CI: 1.46-6.35, p < 0.001; and OR = 3.23, 95% CI: 1.97-8.52, p < 0.001, respectively). Conclusion: The prevalence of carotid atherosclerosis was shown to be very high in the high-risk stroke population. Specific SNPs, interactions among them, and carotid atherosclerosis were independently associated with a higher risk of ischemic stroke and other vascular events.

5.
Front Neurol ; 15: 1405773, 2024.
Article En | MEDLINE | ID: mdl-38770522

Background: Tranexamic acid (TXA) is an antifibrinolytic drug associated with reduced blood loss in a range of surgical specialties. This meta-analysis aimed to compare the efficacy and safety of TXA in cervical surgery, focusing on its effects on intraoperative blood loss and related outcomes. Methods: We searched the PubMed, EMBASE, Medline, and Cochrane Library databases to identify all literature related to TXA used in cervical spinal surgery. Intraoperative blood loss, postoperative drainage volume, total blood loss, postoperative hematological variables, and complications were analyzed. Results: Eight trials met the inclusion criteria. The pooled results showed that intraoperative blood loss, total blood loss, and postoperative drainage volume were significantly lower in the TXA group than in the control group. The hemoglobin and hematocrit on postoperative day 1 was significantly higher in the TXA group than in the control group. There was no significant difference in complications between the two groups. Conclusion: The available evidence indicates that TXA effectively reduces blood loss in cervical spinal surgery while maintaining a favorable safety profile, without increasing associated risks. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023459652.

6.
Virulence ; 15(1): 2352476, 2024 12.
Article En | MEDLINE | ID: mdl-38741276

Staphylococcus aureus (S. aureus) is well known for its biofilm formation ability and is responsible for serious, chronic refractory infections worldwide. We previously demonstrated that advanced glycation end products (AGEs), a hallmark of chronic hyperglycaemia in diabetic tissues, enhanced biofilm formation by promoting eDNA release via sigB upregulation in S. aureus, contributing to the high morbidity and mortality of patients presenting a diabetic foot ulcer infection. However, the exact regulatory network has not been completely described. Here, we used pull-down assay and LC-MS/MS to identify the GlmS as a candidate regulator of sigB in S. aureus stimulated by AGEs. Dual-luciferase assays and electrophoretic mobility shift assays (EMSAs) revealed that GlmS directly upregulated the transcriptional activity of sigB. We constructed NCTC 8325 ∆glmS for further validation. qRT-PCR analysis revealed that AGEs promoted both glmS and sigB expression in the NCTC 8325 strain but had no effect on NCTC 8325 ∆glmS. NCTC 8325 ∆glmS showed a significant attenuation in biofilm formation and virulence factor expression, accompanied by a decrease in sigB expression, even under AGE stimulation. All of the changes, including pigment deficiency, decreased haemolysis ability, downregulation of hla and hld expression, and less and sparser biofilms, indicated that sigB and biofilm formation ability no longer responded to AGEs in NCTC 8325 ∆glmS. Our data extend the understanding of GlmS in the global regulatory network of S. aureus and demonstrate a new mechanism by which AGEs can upregulate GlmS, which directly regulates sigB and plays a significant role in mediating biofilm formation and virulence factor expression.


Bacterial Proteins , Biofilms , Gene Expression Regulation, Bacterial , Glycation End Products, Advanced , Staphylococcal Infections , Staphylococcus aureus , Virulence Factors , Biofilms/growth & development , Staphylococcus aureus/genetics , Staphylococcus aureus/pathogenicity , Virulence Factors/genetics , Glycation End Products, Advanced/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Staphylococcal Infections/microbiology , Sigma Factor/genetics , Sigma Factor/metabolism , Humans
7.
bioRxiv ; 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38746105

Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein Brain tumor (Brat) promotes degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and in uncommitted intermediate neural progenitors (immature INPs). We identified Ubiquitin-specific protease 5 (Usp5) as a Brat interactor essential for the degradation of Brat target mRNAs in both cell types. Usp5 promotes Brat-dedadenylase pre-complex assembly in mitotic neural stem cells (neuroblasts) by bridging Brat and the scaffolding components of deadenylase complexes lacking their catalytic subunits. The adaptor protein Miranda binds the RNA-binding domain of Brat, limiting its ability to bind target mRNAs in mitotic neuroblasts. Cortical displacement of Miranda activates Brat-mediated mRNA decay in immature INPs. We propose that the assembly of an enzymatically inactive and RNA-binding-deficient pre-complex poises mRNA degradation machineries for rapid activation driving timely developmental transitions.

8.
Discov Oncol ; 15(1): 169, 2024 May 16.
Article En | MEDLINE | ID: mdl-38753185

OBJECTIVES: The objective of this study was to evaluate the influence of marital status on overall survival (OS) and develop a nomogram for predicting 5-year OS in chondrosarcoma (CHS) patients. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify CHS patients diagnosed between 2010 and 2018. Survival rates were calculated using Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analyses. An independent cohort was used for external validation of the nomogram. Performance evaluation of the nomogram was conducted using Harrell's concordance index (C-index), calibration plot, and decision curve analysis (DCA). RESULTS: In the SEER cohort, Kaplan-Meier analysis showed significant differences in OS among CHS patients with different marital statuses (P < 0.001), with widowed patients having the lowest OS. In terms of gender, there were significant survival differences based on marital status in females (P < 0.001), but not in males (P = 0.067). The OS of married and single females is significantly higher than that of married (P < 0.001) and single male (P = 0.006), respectively. Kaplan-Meier curves showed no significant difference in OS between groups stratified by either gender or marital status in the external cohort. Univariate and multivariate analyses confirmed that age at diagnosis, gender, marital status, tumor size, histological type, tumor grade, SEER stage, and surgery were independent prognostic factors for OS. The nomogram demonstrated high internal and external validation C-indexes of 0.818 and 0.88, respectively. Calibration plots, DCA curve, and Kaplan-Meier curve (P < 0.001) confirmed the excellent performance and clinical utility of the nomogram. CONCLUSIONS: Marital status was an independent factor influencing OS in CHS patients, with widowed patients having the worst prognosis. The OS of both married and single females is significantly higher than that of their male counterparts. However, these findings require further validation in a large independent cohort. While the contribution of marital status on predicting OS appears modest, our nomogram accurately predicted 5-year OS and identified high-risk groups, providing a valuable tool for clinical decision-making.

10.
Pharmacol Res ; 204: 107200, 2024 Jun.
Article En | MEDLINE | ID: mdl-38710241

Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.


Antineoplastic Agents , Low Density Lipoprotein Receptor-Related Protein-6 , Molecular Targeted Therapy , Neoplasms , Humans , Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Low Density Lipoprotein Receptor-Related Protein-6/genetics , Neoplasms/drug therapy , Neoplasms/metabolism , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Wnt Signaling Pathway/drug effects
11.
Theranostics ; 14(7): 2915-2933, 2024.
Article En | MEDLINE | ID: mdl-38773976

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.


Immunotherapy , Neoadjuvant Therapy , Pyroptosis , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/immunology , Stomach Neoplasms/therapy , Stomach Neoplasms/pathology , Neoadjuvant Therapy/methods , Tumor Microenvironment/immunology , Immunotherapy/methods , Male , Prognosis , Female , Biomarkers, Tumor/metabolism , Middle Aged , Gene Expression Regulation, Neoplastic , Multiomics
12.
J Pharmacol Exp Ther ; 2024 May 30.
Article En | MEDLINE | ID: mdl-38816229

Background: Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and even cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Methods: Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS). The therapeutic effect of TUDCA was evaluated by body weight loss, disease activity index (DAI), colon length, and spleen weight ratio. Tissue pathology was assessed using H&E staining, while the levels of pro-inflammatory and anti-inflammatory cytokines in colonic tissue were quantified via enzyme-linked immunosorbent assay (ELISA). Tight junction proteins were detected by immunoblotting and intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran. Moreover, the gut microbiota was profiled using high-throughput sequencing of the 16S rDNA gene. Results: TUDCA alleviated the colitis in mice, involving reduced DAI, attenuated colon and spleen enlargement, ameliorated histopathological lesions, and normalized the levels of pro-inflammatory and anti-inflammatory cytokines. Furthermore, TUDCA treatment inhibited the downregulation of intestinal barrier proteins including ZO-1 and occludin, thus reducing intestinal permeability. The analysis of gut microbiota suggested that TUDCA modulated the dysbiosis in mice with colitis, especially for the remarkable rise in Akkermansia Conclusion: TUDCA exerted a therapeutic efficacy in DSS-induced colitis by reducing intestinal inflammation, protecting intestinal barrier integrity, and restoring gut microbiota balance. Significance Statement This study demonstrates the potential therapeutic benefits of Tauroursodeoxycholic acid (TUDCA) in ulcerative colitis (UC). TUDCA effectively alleviated colitis symptoms in mice, including reducing inflammation, restoring intestinal barrier integrity and the dysbiosis of gut microbiota. This work highlights the promising role of TUDCA as a potentially alternative treatment, offering new insights into managing this debilitating condition.

13.
Front Oncol ; 14: 1334592, 2024.
Article En | MEDLINE | ID: mdl-38665948

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

14.
Front Immunol ; 15: 1373371, 2024.
Article En | MEDLINE | ID: mdl-38686375

Background: Serum creatinine (Cr) and albumin (Alb) are important predictors of mortality in individuals with various diseases, including acute pancreatitis (AP). However, most previous studies have only examined the relationship between single Cr or Alb levels and the prognosis of patients with AP. To our knowledge, the association between short- and long-term all-cause mortality in patients with AP and the blood creatinine to albumin ratio (CAR) has not been investigated. Therefore, this study aimed to evaluate the short- and long-term relationships between CAR and all-cause mortality in patients with AP. Methods: We conducted a retrospective study utilizing data from the Medical Information Market for Intensive Care (MIMIC-IV) database. The study involved analyzing various mortality variables and obtaining CAR values at the time of admission. The X-tile software was used to determine the optimal threshold for the CAR. Kaplan-Meier (K-M) survival curves and multivariate Cox proportional hazards regression models were used to assess the relationship between CAR and both short- and long-term all-cause mortality. The predictive power, sensitivity, specificity, and area under the curve (AUC) of CAR for short- and long-term mortality in patients with AP after hospital admission were investigated using Receiver Operating Characteristic analysis. Additionally, subgroup analyses were conducted. Results: A total of 520 participants were included in this study. The CAR ideal threshold, determined by X-tile software, was 0.446. The Cox proportional hazards model revealed an independent association between CAR≥0.446 and all-cause mortality at 7-day (d), 14-d, 21-d, 28-d, 90-d, and 1-year (y) before and after adjustment for confounders. K-M survival curves showed that patients with CAR≥0.446 had lower survival rates at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y. Additionally, CAR demonstrated superior performance, with higher AUC values than Cr, Alb, serum total calcium, Glasgow Coma Scale, Systemic Inflammatory Response Syndrome score, and Sepsis-related Organ Failure Assessment score at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y intervals. Subgroup analyses showed that CAR did not interact with a majority of subgroups. Conclusion: The CAR can serve as an independent predictor for short- and long-term all-cause mortality in patients with AP. This study enhances our understanding of the association between serum-based biomarkers and the prognosis of patients with AP.


Creatinine , Intensive Care Units , Pancreatitis , Serum Albumin , Humans , Male , Pancreatitis/mortality , Pancreatitis/blood , Pancreatitis/diagnosis , Female , Retrospective Studies , Middle Aged , Creatinine/blood , Aged , Prognosis , Serum Albumin/analysis , Biomarkers/blood , Databases, Factual , Adult
15.
RNA ; 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38627019

The sequence-specific RNA-binding protein Pumilio controls Drosophila development; however, the network of mRNAs that it regulates remains incompletely characterized. In this study, we utilize knockdown and knockout approaches coupled with RNA-Seq to measure the impact of Pumilio on the transcriptome of Drosophila cells in culture. We also use an improved RNA co-immunoprecipitation method to identify Pumilio-bound mRNAs in Drosophila embryos. Integration of these datasets with the locations of Pumilio binding motifs across the transcriptome reveal novel direct Pumilio target genes involved in neural, muscle, wing, and germ cell development, and cellular proliferation. These genes include components of Wnt, TGF-beta, MAPK/ERK, and Notch signaling pathways, DNA replication, and lipid metabolism. We identify the mRNAs regulated by the CCR4-NOT deadenylase complex, a key factor in Pumilio-mediated repression, and observe concordant regulation of Pumilio:CCR4-NOT target mRNAs. Computational modeling reveals that Pumilio binding, binding site number, clustering, and sequence context are important determinants of regulation. In contrast, we show that the responses of direct mRNA targets to Pumilio-mediated repression are not influenced by their content of optimal synonymous codons. Moreover, contrary to a prevailing model, we do not detect a role for CCR4-NOT in the degradation of mRNAs with low codon optimality. Together, the results of this work provide new insights into the Pumilio regulatory network and mechanisms, and the parameters that influence the efficacy of Pumilio-mediated regulation.

16.
J Pharm Policy Pract ; 17(1): 2325516, 2024.
Article En | MEDLINE | ID: mdl-38628567

Background: Proprietary Chinese medicine (PCM) is widely used in the Guangdong-Hong Kong-Macau Greater Bay Area (GBA) of China. However, the regulatory frameworks and procedures for PCM registration in the region are not well-established, and there are differences among the three jurisdictions. The study is aimed to compare the legal basis, regulatory guidelines, application requirements, and evaluation criteria in each jurisdiction. Methods: We conducted a comprehensive review of the registration application processes for PCMs in the Chinese mainland, Hong Kong, and Macau based on publicly available information from respective regulators. Results: The study found that the registration application process in the GBA was complex and time-consuming, with differences in requirements and procedures among the three jurisdictions. The study also identified several challenges faced by PCM manufacturers, such as the lack of harmonisation of regulatory requirements and procedures and the requirement of package inserts and labelling for PCM products. The study proposed recommendations for improving the registration process and promoting the development of the PCM industry in the GBA. Conclusion: This study provides a comprehensive understanding of the PCM product license application procedures and requirements in the GBA, coupled with discernment of their similarities and disparities, equips applicants with the knowledge to formulate an appropriate strategy for obtaining product approval. Exploring potential methods for harmonising the regulatory process stands to benefit manufacturers, regulators, and patients by improving efficiency and curtailing costs.

17.
Sci Adv ; 10(15): eadg7894, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38608012

During Drosophila oogenesis, the Oskar (OSK) RNA binding protein (RBP) determines the amount of germ plasm that assembles at the posterior pole of the oocyte. Here, we identify mechanisms that subsequently regulate germ plasm assembly in the early embryo. We show that the Smaug (SMG) RBP is transported into the germ plasm of the early embryo where it accumulates in the germ granules. SMG binds to and represses translation of the osk messenger RNA (mRNA) as well as the bruno 1 (bru1) mRNA, which encodes an RBP that we show promotes germ plasm production. Loss of SMG or mutation of SMG's binding sites in the osk or bru1 mRNA results in excess translation of these transcripts in the germ plasm, accumulation of excess germ plasm, and budding of excess primordial germ cells (PGCs). Therefore, SMG triggers a posttranscriptional regulatory pathway that attenuates the amount of germ plasm in embryos to modulate the number of PGCs.


Drosophila , Lizards , Animals , Cytoplasm , Germ Cells , RNA, Messenger/genetics , Cell Count
18.
Int Wound J ; 21(4): e14718, 2024 Apr.
Article En | MEDLINE | ID: mdl-38571455

This study comprehensively compared the effects of laparoscopic and open radical cystectomies on postoperative wound infections and complications in patients with bladder cancer. We conducted a systematic search for relevant studies in PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases, from database inception to October 2023. Two researchers independently screened the literature, extracted data, and assessed the quality based on the inclusion and exclusion criteria. Data analysis was performed using Stata 17.0 software. Overall, 16 studies involving 1427 patients with bladder cancer were included. The analysis revealed that, compared with open radical cystectomy, laparoscopic radical cystectomy significantly reduced the incidence of wound infections (odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.23-0.64, p < 0.001) and complications (OR = 0.35, 95%CI: 0.26-0.47, p < 0.001) and significantly shortened the hospital stay duration (standardised mean difference [SMD] = -1.85, 95%CI: -2.34 to -1.36, p < 0.001). Thus, this study determined that laparoscopic radical cystectomy for the treatment of bladder cancer effectively reduced the occurrence of wound infections and complications, and significantly shortened the patient's hospital stay, demonstrating notable therapeutic effectiveness worthy of clinical application.


Laparoscopy , Urinary Bladder Neoplasms , Humans , Cystectomy/adverse effects , Surgical Wound Infection/etiology , Surgical Wound Infection/surgery , Treatment Outcome , Urinary Bladder Neoplasms/surgery , Laparoscopy/adverse effects
19.
Front Med (Lausanne) ; 11: 1342706, 2024.
Article En | MEDLINE | ID: mdl-38596787

Chromobacterium violaceum (C. violaceum) is a gram-negative bacillus that is widespread in tropical and subtropical areas. Although C. violaceum rarely infects humans, it can cause critical illness with a mortality rate above 50%. Here, we report the successful treatment of a 15-year-old male who presented with bloodstream infection of C. violaceum along with sepsis, specific skin lesions, and liver abscesses. Cardiogenic shock induced by sepsis was reversed by venoarterial extracorporeal membrane oxygenation (VA ECMO). Moreover, C. violaceum-related purpura fulminans, which is reported herein for the first time, was ameliorated after treatment. This case report demonstrates the virulence of C. violaceum with the aim of raising clinical awareness of this disease.

20.
Int Wound J ; 21(3): e14726, 2024 Mar.
Article En | MEDLINE | ID: mdl-38453151

This umbrella review aim to explore the effect of topical antibiotics in infection prevention after primary joint arthroplasty, and provide a specific theoretical basis for clinical treatment. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, EMBASE, Medline, and the Cochrane Library on infection prevention by topical antibiotics from inception to 10 April 2023. The two researchers individually and strictly screened the literature according to the inclusion and exclusion criteria, performed the literature quality evaluation and data extraction, and used Stata 17 for data analysis. This study included six studies with one systematic review and five meta-analyses. The pooled analysis showed that topical antibiotic administration effectively reduced the incidence of overall infection and periprosthetic joint infection. However, it does not reduce the risk of superficial infection. Besides, the topic of antibiotics significantly increases the incidence of other sterile complications of the incision. According to the current evidence, topical application of antibiotics can reduce the incidence of overall infection and periprosthetic joint infection after primary joint arthroplasty. Although it increases the incidence of complications such as delayed healing of incisions, the pros and cons should be weighed in clinical decision making. However, they should not be discarded due to side effects.


Prosthesis-Related Infections , Surgical Wound , Humans , Anti-Bacterial Agents/therapeutic use , Arthroplasty/adverse effects , Prosthesis-Related Infections/prevention & control , Systematic Reviews as Topic , Meta-Analysis as Topic
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