Efficacy, immunogenicity and safety of respiratory syncytial virus prefusion F vaccine: systematic review and meta-analysis.

OBJECTIVE: A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV) prefusion F vaccine. METHODS: We conducted a comprehensive search across PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to retrieve articles related to the efficacy, immunogenicity, and safety of RSV prefusion F vaccines, published through September 8, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 22 randomized controlled trials involving 78,990 participants were included in this systematic review and meta-analysis. The RSV prefusion F vaccine exhibited a vaccine effectiveness of 68% (95% CI: 59-75%) against RSV-associated acute respiratory illness, 70% (95% CI: 60-77%) against medically attended RSV-associated lower respiratory tract illness, and 87% (95% CI: 71-94%) against medically attended severe RSV-associated lower respiratory tract illness. Common reported local adverse reactions following RSV prefusion F vaccination include pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, arthralgia, nausea, and chills. CONCLUSIONS: Our meta-analysis suggests that vaccines using the RSV prefusion F protein as antigen exhibit appears broadly acceptable efficacy, immunogenicity, and safety in the population. In particular, it provides high protective efficiency against severe RSV-associated lower respiratory tract disease.

Eukaryotic Extension Factor 2 Kinase may Affect the Occurrence and Development of Glioblastoma Through Immune Cell Infiltration.

Glioblastoma (GBM) is one of the most common malignancies among primary brain tumors in adults, featuring a poor prognosis and a high recurrence rate. Eukaryotic elongation factor 2 kinase (eEF2K) is a calcium/calmodulin-dependent protein kinase that is involved in promoting tumor cell proliferation, migration, invasion, and survival. However, its expression level in GBM, its prognostic impact and correlation with immune infiltration are not yet known. In this study, we used The Cancer Genome Atlas (TCGA) database to explore the potential molecular mechanisms of eEF2K in GBM development and clinical prognosis in terms of gene expression, survival status, immune infiltration, and associated cellular pathways. We found that eEF2K expression levels were elevated in GBM, but eEF2K was not associated with the prognosis of GBM patients; eEF2K expression in GBM was associated with multiple immune cell infiltrations. These results show a statistical correlation between eEF2K expression and the development of GBM and immune cell infiltration, which helps us to understand the roles of eEF2K in GBM from different perspectives.

Chemical Peeling with a Modified Phenol Formula for the Treatment of Facial Freckles on Asian Skin.

BACKGROUND: Chemical peeling is an efficient method for the treatment of pigment disorders. For freckles, medium-depth to deep peeling using a phenol solution is one of the most effective chemical peels, and modifications of facial skin can be observed up to 20 years after peeling. However, applying phenol to the skin may cause serious side effects. Phenol peeling has been rarely used in Asia due to its tendency to cause permanent pigmentary changes and hypertrophic scars. METHODS: In total, 896 Chinese inpatients with facial freckles were enrolled in this study. The phenol formula was modified with crystalline phenol, dyclonine, camphor, anhydrous alcohol and glycerin and adjusted to a concentration of 73.6-90.0%. The entire peeling treatment was divided into two procedures performed separately on 2 days. RESULTS: All patients exhibited 26% or greater improvement, and 99.66% of patients exhibited 51% or greater improvement (good and excellent). Scarring and systemic complications were not observed in any patient. CONCLUSIONS: The modified phenol formula is very effective and safe for the treatment of facial freckles in Asian patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comprehensive analysis of clinical prognosis and biological significance of CNIH4 in cervical cancer.

BACKGROUND: Cornichon homolog 4 (CNIH4) belongs to the CNIH family. It functions as an oncogene in many tumors. However, CNIH4's significance in the immune landscape and its predictive potential in cervical cancer (CESC) is unexplored. METHODS: CNIH4 levels and its effect on the survival of patients with CESC were evaluated using data retrieved from The Cancer Genome Atlas (TCGA). The oncogenic effect of CNIH4 in CESC was determined using small interfering RNA-mediated transfected cell lines and tumorigenesis experiments in animal models. RESULTS: Higher expression of CNIH4 was found in advanced tumor and pathological stages, as well as lymph node metastasis. CNIH4 expression correlated positively with the infiltration of macrophages M2 and resting dendritic cells into the affected tissue. Additionally, functional enrichment of RNA-sequencing of CNIH4-knocked down CESC cell lines showed the association of CNIH4 to the PI3K-Akt signaling pathway. Single-sample gene set enrichment analysis highlighted several immune pathways that were elevated in the CESC samples with enhanced levels of CNIH4, including Type-I and Type-II IFN-response pathways. The impact of CNIH4 on drug sensitivity was further assessed using the GDSC database. As CNIH4 is linked to the immune landscape in CESC, this study determined a four-gene risk prediction signature utilizing CNIH4-related immunomodulators. The risk score quantified from the prediction signature was an independent predictive indicator in CESC. Receiver operating characteristic curve analysis verified the good predictive ability of the four-gene signature in TCGA-CESC cohort. Thus, the CNIH4-related model showed potential as an auxiliary TNM staging system tool. CONCLUSION: CNIH4 may be an effective predictive biomarker for patients with cervical cancer, thus providing new ideas and research directions for CESC.

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms.

Background: Radiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer. Methods: The present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays. Results: This process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC. Conclusion: To summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC.

Hypoxic preconditioning up-regulates DJ-1 protein expression in rat heart-derived H9c2 cells through the activation of extracellular-regulated kinase 1/2 pathway.

Myocardial preconditioning is a powerful phenomenon that can attenuate ischemia/reperfusion-induced oxidant stress and elicit delayed cardioprotection. Its mechanisms involve activation of intracellular signaling pathways and up-regulation of the protective antioxidant proteins. DJ-1 protein, as a multifunctional intracellular protein, plays an important role in attenuating oxidant stress and promoting cell survival. In the present study, we investigated whether DJ-1 is up-regulated during the late phase of hypoxic preconditioning (HP) and the up-regulation of DJ-1 is mediated by extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway. Rat heart-derived H9c2 cells were exposed to HP. Twenty-four hours later cells were subjected to hypoxia/reoxygenation (H/R) and then cell viability, lactate dehydrogenase (LDH), intracellular reactive oxygen species (ROS), ERK1/2 phosphorylation, and DJ-1 protein were measured appropriately. The results showed that HP efficiently attenuated H/R-induced viability loss and LDH leakage. In addition, HP promoted ERK1/2 activation, up-regulated DJ-1 protein expression, inhibited H/R induced the elevation of ROS. However, when ERK1/2 phosphorylation was specifically inhibited by U0126, the increase in DJ-1 expression occurring during HP was almost completely abolished and, as a result, the delayed cardioprotection induced by HP was abolished, and the inhibitory effect of HP on H/R-induced oxidant stress was also reversed. Furthermore, knocking down DJ-1 by siRNA attenuated the delayed cardioprotection induced by HP. Our data indicate that HP can up-regulate DJ-1 protein expression through the ERK1/2-dependent signaling pathway. Importantly, DJ-1 might be involved in the delayed cardioprotective effect of HP against H/R injury.

Growth factors-based platelet lysate rejuvenates skin against ageing through NF-κB signalling pathway: In vitro and in vivo mechanistic and clinical studies.

INTRODUCTION: Platelets benefit tissue regeneration by secreting growth factors, and platelet products, for example, platelet lysate (PL), have been clinically applied for tissue rejuvenation. To determine the anti-ageing efficacy and mechanism of human PL (hPL) on skin, this study conducted clinical retrospective analysis, nude mice-based in vivo study and human dermal fibroblasts (HDFs)-based in vitro study. METHODS: Flow cytometry was employed for quality control of hPL, and ELISA was used for quantification of growth factors (EGF, IGF-1, PDGF and TGF-ß) in hPL. After d-galactose modelling, skin texture grading, histopathological observation, immunofluorescence analysis and oxidative stress assays were conducted on nude mice, while SA-ß-gal staining, CCK-8 and wound healing assays were conducted on HDFs. qPCR and western blot were conducted to clarify hPL's mechanism. RESULTS: The clinical retrospective data showed that hPL obviously rejuvenated human skin appearances without adverse events. The animal data showed that hPL exerted rejuvenative effects on skin, and the cellular data showed that hPL significantly promoted the proliferation and migration of HDFs and suppressed senescence-associated secretory protein secretion and senescence state of senescent HDFs by suppressing NF-κB pathway. The NF-κB-dependent mechanism was verified positively by using P65 siRNA and negatively by using prostratin. Furthermore, EGF, IGF-1, PDGF and TGF-ß were found as the main ingredients in hPL, which contributed to the efficacy and mechanism of hPL. CONCLUSION: This study provided novel knowledge of hPL, making it ideal for skin rejuvenation.

Dendrobium officinale polysaccharide ameliorates polycystic ovary syndrome via regulating butyrate dependent gut-brain-ovary axis mechanism.

Research has shown that dendrobium officinale polysaccharide (DOP) can promote follicular development and inhibit the apoptosis of ovarian granular cells in PCOS rats. However, DOP cannot be absorbed directly by the stomach and small intestine but is degraded into short-chain fatty acids by gut microbiota in the large intestine and regulates the composition of gut microbiota. How DOP improved ovarian function in PCOS rats through the blood-brain barrier is unclear. In this study, we generated letrozole-induced PCOS rat models and studied the therapeutic effect and mechanism of DOP. 16S rRNA amplicon sequencing analysis, GC-MS short-chain fatty acid detection, and Gene Expression Omnibus database searching were conducted to screen the significantly changed pathways, and a series of experiments, such as enzyme-linked immunosorbent assay, RT-qPCR, Western blot, and immunohistochemistry, were performed. We found that DOP treatment could improve ovarian morphology and endocrine disorders, restore the normal estrus cycle, increase gut microbiota α diversity, and alter ß diversity and enrichment of butyrate-producing bacterium in PCOS rats. In addition, compared with PCOS rats, those treated with DOP exhibited higher butyrate and polypeptide YY levels, possibly due to the regulation of G protein-coupled receptor 41 expression. These results indicated that DOP relieved the symptoms of PCOS rats which may be related to the mechanism of butyrate dependent gut-brain-ovary axis protection.

Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorate Skin Aging of Nude Mice Through Autophagy-Mediated Anti-Senescent Mechanism.

Skin aging is a currently irreversible process, affected by increased oxidative stress, activated cellular senescence, and lacked regeneration of the dermal layer. Mesenchymal stem cells (MSCs), such as human umbilical cord-derived MSCs (hucMSCs), have pro-regeneration and anti-aging potencies. To explore whether hucMSCs can be used to treat skin aging, this study employed skin-aging model of nude mice to conduct in vivo assays, including biochemical analysis of superoxide dismutase (SOD) and malondialdehyde (MDA), gross observation, histopathological observation, and immunohistochemical analysis. To clarify how hucMSCs work on skin aging, this study employed skin-aging model of human dermal fibroblasts (HDFs) to conduct in vitro assays by applying conditional medium of hucMSCs (CMM), including wound healing assay, senescence staining, flow cytometric oxidative detection, real time PCR, and western blot analysis. The in vivo data demonstrated that hucMSCs dose-dependently removed wrinkles, smoothed skin texture, and increased dermal thickness and collagen production of aged skin by reversing SOD and MDA levels and up-regulating Col-1 and VEGF expressions, indicating anti-oxidative and pro-regenerative effects against skin aging. The in vitro data revealed that hucMSCs significantly reversed the senescence of HDFs by promoting cell migration, inhibiting ROS production, and restoring the overexpressions of oxidative and senescent markers through paracrine mode of action, and the paracrine mechanism was mediated by the inhibition of autophagy. This study provided novel knowledge regarding the anti-aging efficacy and paracrine mechanism of hucMSCs on skin, making hucMSCs-based therapy a promising regime for skin aging treatment.

Comparative effectiveness of different therapies for treating striae distensae: A systematic review and network meta-analysis.

BACKGROUND: Striae distensae (SD) are common and aesthetically undesirable dermal lesions. The aim of this study is to comprehensively evaluate the effectiveness of different therapies in treating striae distensae using network meta-analysis. METHODS: A systematic search of electronic databases up to December 1, 2019 was conducted. Randomized controlled trails (RCTs) examining the effectiveness of different methods in treating striae distensae were included. The primary outcomes are clinical effective rate and patient's satisfaction degree. Risk of bias was assessed by the Cochrane risk of bias tool. Network meta-analysis was based on Bayesian framework. RESULTS: Fourteen trails that met the criteria with 651 subjects were included. The results of the network meta-analysis show that topical tretinoin combined bipolar radiofrequency showed the highest probability of being the best method to improve the clinical effectiveness and patient satisfaction rate of treating SD (84.5% and 95.7% respectively), closely followed by bipolar radiofrequency (75.3% and 84.3% respectively). Among laser treatment, CO2 fractional laser is superior to other lasers in the clinical effectiveness and patient satisfaction (72.0% and 58.1% respectively). Statistics showed the topical tretinoin was the worst-performing option in improving the clinical effectiveness and patient satisfaction rate of SD treatment (5.4% and 5.1% respectively). CONCLUSION: Based on the results of network meta-analysis, we recommend treating striae distensae with bipolar radio frequency combined topical tretinoin. The commonly used CO2 fractional laser can be considered as alternative treatment candidate. Additional large-scale RCTs are necessary to obtain more precise estimates of their relative efficacy.

Role of tranexamic acid in nasal surgery: A systemic review and meta-analysis of randomized control trial.

OBJECTIVE: Nasal surgeries (such as Functional Endoscopic Sinus Surgery, Rhinoplasty, and Septorhinoplasty) are popular procedures. But perioperative bleeding, eyelid edema, and periorbital ecchymosis remain problems. Tranexamic acid (TXA) is an antifibrinolytic, and it was used to reduce the perioperative bleeding. However, there is no enough evidence judging its safety and efficiency. Therefore, a meta-analysis is conducted by us to evaluate the role of TXA in patients undergoing nasal surgeries. METHOD: A search of the literature was performed until June 2018; the PubMed, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases were searched for related articles using search strategy. Two authors independently assessed the methodological quality of the included studies and extracted data. Surgical information and postoperative outcomes were analyzed. Only randomized controlled trial (RCT) articles were included, and subgroup analysis was established to deal with heterogeneity. RevMan 5.3 software was selected to conduct the meta-analysis. RESULT: Eleven RCTs were included in our meta-analysis. There were significant differences in blood loss (P < .001), surgical field quality (P < .001), edema rating of upper (P < .001) and lower (P < .001) eyelid, ecchymosis rating of upper (P < .001) and lower eyelid (P < .001) when comparing the TXA group to the placebo group. However, the difference in operation time (P = .57) was not significant between the two groups. CONCLUSION: Perioperative TXA could reduce the blood loss and improve the quality of surgery field during nasal surgery, and it was helpful for reducing the edema and ecchymosis after nasal surgeries, but it has little influence in reducing the operation time.