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Abstract Background Data on the effectiveness of erector spinae plane block (ESPB) for patients undergoing liver surgeries is limited and inconclusive. We hereby aimed to systematically review if ESPB can provide adequate analgesia after liver surgery. Methods PubMed, CENTRAL, Scopus, Embase, and gray literature were examined up to 25th April 2023 for randomized controlled trials (RCTs) comparing ESPB with control or spinal analgesia. Results Nine RCTs were included of which three compared ESPB with spinal analgesia. 24-hour opioid consumption did not differ significantly between ESPB vs. control (MD: -35.25 95% CI: -77.01, 6.52 I2 = 99%) or ESPB vs. spinal analgesia (MD: 2.32 95% CI: -6.12, 10.77 I2 = 91%). Comparing pain scores between ESPB and control, a small but significant effect favoring ESPB was noted at 12 h and 48 h, but not at 6–8 h and 24 h. Pain scores did not differ between ESPB and spinal analgesia. The risk of postoperative nausea and vomiting was also not significantly different between ESPB vs. control or spinal analgesia. GRADE assessment shows moderate certainty of evidence. Conclusion ESPB may not provide any significant postoperative analgesia in liver surgery patients. There was a tendency of reduced opioid consumption with ESPB. Limited data also showed that ESPB and spinal analgesia had no difference in pain scores and 24-hour analgesic consumption.

Abstract Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

Abstract The development of atherosclerosis (AS) is closely linked to changes in the plaque microenvironment, which consists primarily of the cells that form plaque and the associated factors they secrete. The onset of inflammation, lipid deposition, and various pathological changes in cellular metabolism that accompany the plaque microenvironment will promote the development of AS. Numerous studies have shown that oxidative stress is an important condition that promotes AS. The accumulation of reactive oxygen species (ROS) is oxidative stress’s most important pathological change. In turn, the effects of ROS on the plaque microenvironment are complex and varied, and these effects are ultimately reflected in the promotion or inhibition of AS. This article reviews the effects of ROS on the microenvironment of atherosclerotic plaques and their impact on disease progression over the past five years and focuses on the progress of treatment strategies based on scavenging ROS of nanoparticles for AS. Finally, we also discuss the prospects and challenges of AS treatment.

Abstract Background To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). Methods Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan–Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. Results We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150–2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255–2.182, P

Abstract Background According to epidemiological studies, gingivitis is a common disease. However, its morbidity, considerably varies among individual. This study aimed to investigate the epidemiological characteristics of gingivitis, including prevalence, severity, intraoral distribution, and associated risk factors, in children aged 6–12 years in Jinzhou, China. Methods A multistage, whole-group, randomized sample of 2880 children aged 6–12 years in Jinzhou City, China, was selected and clinically examined. Each selected child completed a questionnaire on sociodemographic factors and oral health behaviors in cooperation with the investigator and teacher. Gingival bleeding refers to the bleeding of 10% or more teeth under the condition of ingivitis. Gingivitis was further categorized into localized gingivitis (30% ≥ number of teeth positive for gingival bleeding ≥ 10%) and generalized gingivitis (number of positive for gingival bleeding > 30%). The score of gingival bleeding was recorded using the Gingival Index. Results The prevalence of gingivitis in children aged 6–12 years in Jinzhou was 28.58%, including 701 cases of localized gingivitis (24.3%) and 122 cases of generalized gingivitis (4.2%). There were 429 cases (28.3%) of gingivitis in males and 394 cases (28.9%) in females, with no statistically significant difference in prevalence between males and females (P > 0.05). Chi-square tests and binary logistic regression analysis showed that aging, dental calculus, plaque, and dental crowding were significantly associated with a high prevalence of gingivitis. Conclusions Our study showed that dental calculus, large amount dental plaque, poor oral health behavior, and oral health awareness are associated with the prevalence of gingivitis and maintaining children's oral health requires professional guidance and regular preventive care.

Abstract Background Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) and lethal-7a (let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer. Results HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3TR cells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3TR cells and an SKOV3TR xenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis. Conclusions To sum up, these data provide a model for overcoming PTX resistance in ovarian cancer. Graphical Abstract

Abstract Background Currently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF. Methods Female mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy. Results Ovary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Müllerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin α, and inhibin β was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group. Conclusion These results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF.

Abstract Background The number of cumulative confirmed cases of COVID-19 in the United States has risen sharply since March 2020. A county health ranking and roadmaps program has been established to identify factors associated with disparity in mobility and mortality of COVID-19 in all counties in the United States. The risk factors associated with county-level mortality of COVID-19 with various levels of prevalence are not well understood. Methods Using the data obtained from the County Health Rankings and Roadmaps program, this study applied a negative binomial design to the county-level mortality counts of COVID-19 as of August 27, 2020 in the United States. In this design, the infected counties were categorized into three levels of infections using clustering analysis based on time-varying cumulative confirmed cases from March 1 to August 27, 2020. COVID-19 patients were not analyzed individually but were aggregated at the county-level, where the county-level deaths of COVID-19 confirmed by the local health agencies. Clustering analysis and Kruskal–Wallis tests were used in our statistical analysis. Results A total of 3125 infected counties were assigned into three classes corresponding to low, median, and high prevalence levels of infection. Several risk factors were significantly associated with the mortality counts of COVID-19, where higher level of air pollution (0.153, P

Abstract Background The lack of effective treatment options for Alzheimer’s disease (AD) is of momentous societal concern. Synaptic loss is the hallmark of AD that correlates best with impaired memory and occurs early in the disease process, before the onset of clinical symptoms. We have developed a small-molecule, pyridazine-based series that enhances the structure and function of both the glial processes and the synaptic boutons that form the tripartite synapse. Previously, we have shown that these pyridazine derivatives exhibit profound efficacy in an amyloid precursor protein AD model. Here, we evaluated the efficacy of an advanced compound, LDN/OSU-0215111, in rTg4510 mice—an aggressive tauopathy model. Methods rTg4510 mice were treated orally with vehicle or LDN/OSU-0215111 (10 mg/kg) daily from the early symptomatic stage (2 months old) to moderate (4 months old) and severe (8 months old) disease stages. At each time point, mice were subjected to a battery of behavioral tests to assess the activity levels and cognition. Also, tissue collections were performed on a subset of mice to analyze the tripartite synaptic changes, neurodegeneration, gliosis, and tau phosphorylation as assessed by immunohistochemistry and Western blotting. At 8 months of age, a subset of rTg4510 mice treated with compound was switched to vehicle treatment and analyzed behaviorally and biochemically 30 days after treatment cessation. Results At both the moderate and severe disease stages, compound treatment normalized cognition and behavior as well as reduced synaptic loss, neurodegeneration, tau hyperphosporylation, and neuroinflammation. Importantly, after 30 days of treatment cessation, the benefits of compound treatment were sustained, indicating disease modification. We also found that compound treatment rapidly and robustly reduced tau hyperphosphorylation/deposition possibly via the inhibition of GSK3β. Conclusions The results show that LDN/OSU-0215111 provides benefits for multiple aspects of tauopathy-dependent pathology found in Alzheimer’s disease including tripartite synapse normalization and reduction of toxic tau burden, which, in turn, likely accounted for normalized cognition and activity levels in compound-treated rTg4510 mice. This study, in combination with our previous work regarding the benefit of pyridazine derivatives against amyloid-dependent pathology, strongly supports pyridazine derivatives as a viable, clinically relevant, and disease-modifying treatment for many of the facets of Alzheimer’s disease.

Abstract Background Fibroblast growth factor 23 (FGF23) and insulin-like growth factor binding protein 7 (IGFBP-7) are suggested to be biomarkers for predicting acute kidney injury (AKI). We compared them with proposed AKI biomarker of cystatin C (CysC), and aimed (1) to examine whether concentrations of these biomarkers vary with age, body weight, illness severity assessed by pediatric risk of mortality III score, and kidney function assessed by estimated glomerular filtration rate (eGFR), (2) to determine the association between these biomarkers and AKI, and (3) to evaluate whether these biomarkers could serve as early independent predictors of AKI in critically ill children. Methods This prospective single center study included 144 critically ill patients admitted to the pediatric intensive care unit (PICU) regardless of diagnosis. Serum and spot urine samples were collected during the first 24 h after PICU admission. AKI was diagnosed based on the AKI network (AKIN) criteria. Results Twenty-one patients developed AKI within 120 h of sample collection, including 11 with severe AKI defined as AKIN stages 2 and 3. Serum FGF23 levels were independently associated with eGFR after adjustment in a multivariate linear analysis (P