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Background: The determining effect of facial hard tissues on soft tissue morphology in orthodontic patients has yet to be explained. The aim of this study was to clarify the hard-soft tissue relationships of the lower 1/3 of the face in skeletal Class II-hyperdivergent patients compared with those in Class I-normodivergent patients using network analysis., Methods: Fifty-two adult patients (42 females, 10 males; age, 26.58 ± 5.80 years) were divided into two groups: Group 1, 25 subjects, skeletal Class I normodivergent pattern with straight profile; Group 2, 27 subjects, skeletal Class II hyperdivergent pattern with convex profile. Pretreatment cone-beam computed tomography and three-dimensional facial scans were taken and superimposed, on which landmarks were identified manually, and their coordinate values were used for network analysis., Results: (1) In sagittal direction, Group 2 correlations were generally weaker than Group 1. In both the vertical and sagittal directions of Group 1, the most influential hard tissue landmarks to soft tissues were located between the level of cemento-enamel junction of upper teeth and root apex of lower teeth. In Group 2, the hard tissue landmarks with the greatest influence in vertical direction were distributed more forward and downward than in Group 1. (2) In Group 1, all the correlations for vertical-hard tissue to sagittal-soft tissue position and sagittal-hard tissue to vertical-soft tissue position were positive. However, Group 2 correlations between vertical-hard tissue and sagittal-soft tissue positions were mostly negative. Between sagittal-hard tissue and vertical-soft tissue positions, Group 2 correlations were negative for mandible, and were positive for maxilla and teeth., Conclusion: Compared with Class I normodivergent patients with straight profile, Class II hyperdivergent patients with convex profile had more variations in soft tissue morphology in sagittal direction. In vertical direction, the most relevant hard tissue landmarks on which soft tissue predictions should be based were distributed more forward and downward in Class II hyperdivergent patients with convex profile. Class II hyperdivergent pattern with convex profile was an imbalanced phenotype concerning sagittal and vertical positions of maxillofacial hard and soft tissues., (© 2024. The Author(s).)

Microsatellite instability (MSI) has been widely acknowledged as an important factor regulating tumor intrinsic biological behavior and affecting the survival of gastric cancer patients. Here, we firstly identified the RARB as a gene associated with MSI gastric cancer. RARB was downregulated in human gastric cancer tissues compared to paired paracancerous tissues, Knockdown of RARB accelerated the proliferation, invasion and migration of cancer cells in vitro. Mechanismly, RARB knockdown promoted epithelial-mesenchymal transition (EMT) process of gastric cancer. However, RARB Low patients exhibited better survival compared to RARB High patients. Further study revealed that RARB expression was inversely correlated with MSI status and immune infiltrates in vivo. Thus, RARB may be a potential target for the treatment of gastric cancer., (© 2024. The Author(s).)

Background: Small songbirds respond and adapt to various geographical barriers during their annual migration. Global flyways reveal the diverse migration strategies in response to different geographical barriers, among which are high-elevation plateaus. However, few studies have been focused on the largest and highest plateau in the world, the Qinghai-Tibet Plateau (QTP) which poses a significant barrier to migratory passerines. The present study explored the annual migration routes and strategies of a population of Siberian Rubythroats (Calliope calliope) that breed on the north-eastern edge of the QTP., Methods: Over the period from 2021 to 2023, we applied light-level geolocators (13 deployed, seven recollected), archival GPS tags (45 deployed, 17 recollected), and CAnMove multi-sensor loggers (with barometer, accelerometer, thermometer, and light sensor, 20 deployed, six recollected) to adult males from the breeding population of Siberian Rubythroat on the QTP. Here we describe the migratory routes and phenology extracted or inferred from the GPS and multi-sensor logger data, and used a combination of accelerometric and barometric data to describe the elevational migration pattern, flight altitude, and flight duration. All light-level geolocators failed to collect suitable data., Results: Both GPS locations and positions derived from pressure-based inference revealed that during autumn, the migration route detoured from the bee-line between breeding and wintering grounds, leading to a gradual elevational decrease. The spring route was more direct, with more flights over mountainous areas in western China. This different migration route during spring probably reflects a strategy for faster migration, which corresponds with more frequent long nocturnal migration flights and shorter stopovers during spring migration than in autumn. The average flight altitude (1856 ± 781 m above sea level) was correlated with ground elevation but did not differ between the seasons., Conclusions: Our finding indicates strong, season-dependent impact of the Qinghai-Tibet Plateau on shaping passerine migration strategies. We hereby call for more attention to the unexplored central-China flyway to extend our knowledge on the environment-migration interaction among small passerines., (© 2024. The Author(s).)

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC., (© 2024. The Author(s).)

Backgrounds: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD., Methods: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices., Results: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [ TyG adjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WC aHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtR aHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WC aHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtR aHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices., Conclusion: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD., (© 2024. The Author(s).)

Background: Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading., Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI)., Results: Multi-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17 + GBC cells, neutrophils, and surrounding fibroblasts, which may help cultivate the oxLDL-absorbing neutrophils., Conclusions: Our study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17 + GBC cells in GBC-LI., (© 2024. The Author(s).)

Background: To investigate the association between the Dietary Inflammatory Index (DII) and all-cause mortality in patients with osteoarthritis (OA)., Methods: In this retrospective cohort study, data on OA patients were obtained from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. OA diagnosis was self-reported. The study population was divided into low and high DII groups based on the DII's median. All-cause mortality was the outcome, which was determined via linkage to the National Death Index (NDI) until 31 December 2019. Multivariable Cox regression analyses were employed to investigate the association between the DII and all-cause mortality. The survival of the low and high DII groups was exhibited by Kaplan-Meier curves. Furthermore, subgroup analyses were carried out in terms of age and comorbidity., Results: A total of 3804 patients with OA were included, with 1902 (50%) in the low DII group and 1902 (50%) in the high DII group. Patients with a high DII had a significantly greater risk of all-cause mortality than those with a low DII (HR = 1.21, 95%CI: 1.02-1.44, P = 0.025). A high DII was associated with a significantly increased risk of all-cause mortality compared with a low DII in patients aged ≥ 65 years [hazard ratio (HR) = 1.28, 95% confidence level (CI): 1.07-1.53, P = 0.006). Hypertensive patients with a high DII had a significantly greater risk of all-cause mortality than those with a low DII (HR = 1.25, 95%CI: 1.03-1.52, P = 0.025). For patients with cardiovascular disease (CVD), a high DII was associated with a significantly higher risk of all-cause mortality than a low DII (HR = 1.43, 95%CI: 1.17-1.75, P < 0.001). A high DII was associated with a significantly greater risk of all-cause mortality, as compared with a low DII in patients with chronic kidney disease (CKD) (HR = 1.22, 95%CI: 1.02-1.45, P = 0.026)., Conclusion: The DII was positively associated with the risk of all-cause mortality in patients with OA. This association differed by age, hypertension, CVD, and CKD. Adherence to diet with a low DII may be beneficial in prognosis improvement., (© 2024. The Author(s).)

Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A., (© 2024. The Author(s).)

Background: Triglyceride-glucose (TyG) index has been determined to play a role in the onset of metabolic syndrome (MetS). Whether the TyG index and TyG with the combination of obesity indicators are associated with the clinical outcomes of the MetS population remains unknown., Method: Participants were extracted from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 years. Three indicators were constructed including TyG index, TyG combining with waist circumference (TyG-WC), and TyG combining with waist-to-height ratio (TyG-WHtR). The MetS was defined according to the National Cholesterol Education Program (NCPE) Adult Treatment Panel III. Kaplan-Meier (KM) curves, restricted cubic splines (RCS), and the Cox proportional hazard model were used to evaluate the associations between TyG-related indices and mortality of the MetS population. The sensitive analyses were performed to check the robustness of the main findings., Results: There were 10,734 participants with MetS included in this study, with 5,570 females and 5,164 males. The median age of the study population was 59 years old. The multivariate Cox regression analyses showed high levels of TyG-related indices were significantly associated with the all-cause mortality of MetS population [TyG index: adjusted hazard ratio (aHR): 1.36, 95%confidence interval (CI): 1.18-1.56, p < 0.001; TyG-WHtR index: aHR = 1.29, 95%CI: 1.13-1.47, p < 0.001]. Meanwhile, the TyG-WC and TyG-WHtR index were associated with cardiovascular mortality of the MetS population (TyG-WC: aHR = 1.45, 95%CI: 1.13-1.85, p = 0.004; TyG-WHtR: aHR = 1.50 95%CI: 1.17-1.92, p = 0.002). Three TyG-related indices showed consistent significant correlations with diabetes mortality (TyG: aHR = 4.06, 95%CI: 2.81-5.87, p < 0.001; TyG-WC: aHR = 2.55, 95%CI: 1.82-3.58, p < 0.001; TyG-WHtR: aHR = 2.53 95%CI: 1.81-3.54, p < 0.001). The RCS curves showed a non-linear trend between TyG and TyG-WC indices with all-cause mortality (p for nonlinearity = 0.004 and 0.001, respectively). The sensitive analyses supported the positive correlations between TyG-related indices with mortality of the MetS population., Conclusion: Our study highlights the clinical value of TyG-related indices in predicting the survival of the MetS population. TyG-related indices would be the surrogate biomarkers for the follow-up of the MetS population., (© 2024. The Author(s).)

Background: Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH., Results: Liver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1β, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis. Mitochondrial dysfunction was assessed through various parameters including mitochondrial DNA (mtDNA) levels, ROS generation, mitochondrial membrane potential, ATP contents, levels of mitochondrial function-related proteins and morphological changes of mitochondria. AH induced gasdermin D (GSDMD) activation, leading to increased protein expression of N-terminal GSDMD (GSDMD-N), NLRP3, and Caspase 11 in liver tissues. Downregulation of GSDMD alleviated alcohol-induced hepatocyte pyroptosis. Alcohol also causes mitochondrial dysfunction in hepatocytes in AH, which was improved by inhibiting GSDMD. Furthermore, enhancing mitochondrial function suppressed alcohol-induced hepatocyte pyroptosis. Further, knockdown of GSDMD or dynamin-related protein 1 (Drp1) improved AH-induced liver injury, accompanied by a decrease in hepatocyte pyroptosis., Conclusion: GSDMD induces hepatocyte pyroptosis by modulating mitochondrial dysfunction during AH-induced inflammation and liver injury. These findings may pave the way to develop new therapeutic treatments for AH., (© 2024. The Author(s).)

Background: Multimorbidity is becoming an increasingly serious public health challenge in the aging population. The impact of nutrients on multimorbidity remains to be determined and was explored using data from a UK cohort study., Method: Our research analysis is mainly based on the data collected by the United Kingdom Women's Cohort Study (UKWCS), which recruited 35,372 women aged 35-69 years at baseline (1995 to 1998), aiming to explore potential associations between diet and chronic diseases. Daily intakes of energy and nutrients were estimated using a validated 217-item food frequency questionnaire at recruitment. Multimorbidity was assessed using the Charlson comorbidity index (CCI) through electronic linkages to Hospital Episode Statistics up to March 2019. Cox's proportional hazards models were used to estimate associations between daily intakes of nutrients and risk of multimorbidity. Those associations were also analyzed in multinomial logistic regression as a sensitivity analysis. In addition, a stratified analysis was conducted with age 60 as the cutoff point., Results: Among the 25,389 participants, 7,799 subjects (30.7%) were confirmed with multimorbidity over a median follow-up of 22 years. Compared with the lowest quintile, the highest quintile of daily intakes of energy and protein were associated with 8% and 12% increased risk of multimorbidity respectively (HR 1.08 (95% CI 1.01, 1.16), p-linearity = 0.022 for energy; 1.12 (1.04, 1.21), p-linearity = 0.003 for protein). Higher quintiles of daily intakes of vitamin C and iron had a slightly lowered risk of multimorbidity, compared to the lowest quintile. A significantly higher risk of multimorbidity was found to be linearly associated with higher intake quintiles of vitamin B12 and vitamin D (p-linearity = 0.001 and 0.002, respectively) in Cox models, which became insignificant in multinomial logistic regression. There was some evidence of effect modification by age in intakes of iron and vitamin B1 associated with the risk of multimorbidity (p-interaction = 0.006 and 0.025, respectively)., Conclusions: Our findings highlight a link between nutrient intake and multimorbidity risk. However, there is uncertainty in our results, and more research is needed before definite conclusions can be reached., (© 2024. The Author(s).)

Background: Early childhood caries (ECC) causes severe, widespread oral health issues in children. Dental undergraduates and residents are expected to have a solid understanding of ECC for children's oral health promotion. This study aimed to evaluate the knowledge, attitude, and clinical practice on ECC among dental undergraduates and residents in China., Methods: A 23-item electronic questionnaire was distributed to 598 dental undergraduates (4th- and 5th-year undergraduates) and residents (1st-, 2nd-, and 3rd-year residents) at the School of Stomatology, Wuhan University, China (in April-May 2023). SPSS Statistics was used to analyze the data using the Chi-square test at a significance level of 0.05., Results: A total of 422 questionnaires were completed by participants (recovery rate: 70.6%) from various academic levels. Around 77.3% of participants had heard of ECC (mainly from textbooks), and only 27.5% considered themselves familiar with it. Residents (79.8%) had higher risk awareness of ECC on children's overall health than undergraduates (58.3%) (p < 0.05), but only 54.0% of participants correctly defined ECC. Most participants had a positive understanding of ECC's pathogenic factors and preventive measures, including feeding patterns (71.6%), fluoride application (93.4%), and teeth cleaning (93.1%). Furthermore, only 50.2% of participants encountered ECC cases in clinic., Conclusions: Despite having a suboptimal level of ECC-related knowledge and practice, dental undergraduates and residents in China demonstrated a more positive attitude towards its etiology-based prevention. Strengthening ECC education, guidance, and practice may enable them to gain a better understanding of ECC learning, which would benefit children's oral health., (© 2024. The Author(s).)

Background: Aeromonas hydrophila infections can cause gastrointestinal symptoms such as diarrhea; however, deep infections are rarely reported. Outbreaks of A. hydrophila are reported more frequently in fish, poultry, and snakes than in humans. This study aimed to track clonal relatedness of deep infections caused by A. hydrophila using whole genome sequencing (WGS)., Methods: We collected three isolates of A. hydrophila in July 19 to August 29, 2019, from patients that underwent spine surgery. Accurate species identification was performed using whole-genome average nucleotide identity (ANI). Antimicrobial susceptibility testing was performed using a VITEK 2 automated AST-N334 Gram-negative susceptibility card system. Antimicrobial resistance and virulence genes were identified using the Comprehensive Antibiotic Resistance Database and Virulence Factor Database VFanalyzer., Results: All three isolates were identified as A. hydrophila based on ANI and multilocus sequence typing analysis revealed that A. hydrophila belonged to a novel sequence type (ST1172). All three isolates were susceptible to amikacin and levofloxacin; however, they were resistant to piperacillin/tazobactam, ceftriaxone, cefuroxime, cefoxitin, and imipenem. Isolate 19W05620 (patient 3) showed increased ceftazidime resistance (minimum inhibitory concentration ≥ 64 µg/mL). All three isolates possessed the same chromosomally encoded β-lactamases, including bla OXA-724 (β-lactamase), imiH (metallo-β-lactamase), and bla MOX-13 (AmpC) in plasmids., Conclusions: Our study validated the transmission of a novel carbapenem-resistant A. hydrophila sequence type (ST1172) in patients that underwent spine surgery. Control measures should be developed to prevent dissemination of A. hydrophila in the hospital setting., (© 2024. The Author(s).)

Background: Resolving the phylogeny of rapidly radiating lineages presents a challenge when building the Tree of Life. An Old World avian family Prunellidae (Accentors) comprises twelve species that rapidly diversified at the Pliocene-Pleistocene boundary., Results: Here we investigate the phylogenetic relationships of all species of Prunellidae using a chromosome-level de novo assembly of Prunella strophiata and 36 high-coverage resequenced genomes. We use homologous alignments of thousands of exonic and intronic loci to build the coalescent and concatenated phylogenies and recover four different species trees. Topology tests show a large degree of gene tree-species tree discordance but only 40-54% of intronic gene trees and 36-75% of exonic genic trees can be explained by incomplete lineage sorting and gene tree estimation errors. Estimated branch lengths for three successive internal branches in the inferred species trees suggest the existence of an empirical anomaly zone. The most common topology recovered for species in this anomaly zone was not similar to any coalescent or concatenated inference phylogenies, suggesting presence of anomalous gene trees. However, this interpretation is complicated by the presence of gene flow because extensive introgression was detected among these species. When exploring tree topology distributions, introgression, and regional variation in recombination rate, we find that many autosomal regions contain signatures of introgression and thus may mislead phylogenetic inference. Conversely, the phylogenetic signal is concentrated to regions with low-recombination rate, such as the Z chromosome, which are also more resistant to interspecific introgression., Conclusions: Collectively, our results suggest that phylogenomic inference should consider the underlying genomic architecture to maximize the consistency of phylogenomic signal., (© 2024. The Author(s).)

Background: Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment, and the underlying mechanism has not been fully elucidated. This study aimed to clarify the role and mechanism of Human antigen R (HuR) as a therapeutic target for CRPC progression., Methods: HuR was knocked out by Cas9 or inhibited by the HuR-specific inhibitor KH-3 in CRPC cell lines and in a mouse xenograft model. The effects of HuR inhibition on tumour cell behaviors and signal transduction were examined by proliferation, transwell, and tumour xenograft assays. Posttranscriptional regulation of BCAT1 by HuR was determined by half-life and RIP assays., Results: HuR knockout attenuated the proliferation, migration, and invasion of PC3 and DU145 cells in vitro and inhibited tumour progression in vivo. Moreover, BCAT1 was a direct target gene of HuR and mediated the oncogenic effect of HuR on CRPC. Mechanistically, HuR directly interacted with BCAT1 mRNA and upregulated BCAT1 expression by increasing the stability and translation of BCAT1, which activated ERK5 signalling. Additionally, the HuR-specific inhibitor KH-3 attenuated CRPC progression by disrupting the HuR-BCAT1 interaction., Conclusions: We confirmed that the HuR/BCAT1 axis plays a crucial role in CRPC progression and suggest that inhibiting the HuR/BCAT1 axis is a promising therapeutic approach for suppressing CRPC progression., (© 2024. The Author(s).)

Background: Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state., Aim: To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs., Methods: PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality., Results: Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions., Conclusion: Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary., (© 2024. The Author(s).)

Background: Ovarian cancer is one of the most common gynecological malignancies due to the lack of early symptoms, early diagnosis and limited screening. Therefore, it is necessary to understand the molecular mechanism underlying the occurrence and progression of ovarian cancer and to identify a basic biomarker for the early diagnosis and clinical treatment of ovarian cancer., Methods: The association between FBXO28 and ovarian cancer prognosis was analyzed using Kaplan‒Meier survival analysis. The difference in FBXO28 mRNA expression between normal ovarian tissues and ovarian tumor tissues was obtained from The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) cohorts. The expression levels of the FBXO28 protein in ovarian cancer tissues and normal ovarian tissues were measured via immunohistochemical staining. Western blotting was used to determine the level of FBXO28 expression in ovarian cancer cells. The CCK-8, the colony formation, Transwell migration and invasion assays were performed to evaluate cell proliferation and motility., Results: We found that a higher expression level of FBXO28 was associated with poor prognosis in ovarian cancer patients. Analysis of the TCGA and GTEx cohorts showed that the FBXO28 mRNA level was lower in normal ovarian tissue samples than in ovarian cancer tissue samples. Compared with that in normal ovarian tissues or cell lines, the expression of FBXO28 was greater in ovarian tumor tissues or tumor cells. The upregulation of FBXO28 promoted the viability, proliferation, migration and invasion of ovarian cancer cells. Finally, we demonstrated that FBXO28 activated the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer., Conclusions: In conclusion, FBXO28 enhanced oncogenic function via upregulation of the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer., (© 2024. The Author(s).)

Background: The outcomes of patients with tumors of the thoracolumbar spine treated with en bloc resection (EBR) using three-dimensional (3D)-printed endoprostheses are underreported., Methods: We retrospectively evaluated patients with thoracolumbar tumors who underwent surgery at our institution. Logistic regression analysis was performed to identify the potential risk factors for surgical complications. Nomograms to predict complications were constructed and validated., Results: A total of 53 patients with spinal tumors underwent EBR at our hospital; of these, 2 were lost to follow-up, 45 underwent total en bloc spondylectomy, and 6 were treated with sagittal en bloc spondylectomy. The anterior reconstruction materials included a customized 3D-printed artificial vertebral body (AVB) in 10 cases and an off-the-shelf 3D-printed AVB in 41 cases, and prosthesis mismatch occurred in 2 patients reconstructed with the off-the-shelf 3D-printed AVB. The median follow-up period was 21 months (range, 7-57 months). Three patients experienced local recurrence, and 5 patients died at the final follow-up. A total of 50 perioperative complications were encountered in 29 patients, including 25 major and 25 minor complications. Instrumentation failure occurred in 1 patient, and no prosthesis subsidence was observed. Using a combined surgical approach was a dependent predictor of overall complications, while Karnofsky performance status score, lumbar spine lesion, and intraoperative blood loss ≥ 2000 mL were predictors of major complications. Nomograms for the overall and major complications were constructed using these factors, with C-indices of 0.850 and 0.891, respectively., Conclusions: EBR is essential for the management of thoracolumbar tumors; however, EBR has a steep learning curve and a high complication rate. A 3D-printed AVB is an effective and feasible reconstruction option for patients treated with EBR., (© 2023. The Author(s).)

Background: MicroRNA (miRNA) which can act as post-transcriptional regulators of mRNAs via base-pairing with complementary sequences within mRNAs is involved in processes of the complex interaction between immune system and tumors. In this research, we elucidated the profiles of miRNAs and target mRNAs expression and their associations with the phenotypic hallmarks of colorectal cancers (CRC) by integrating transcriptomic, immunophenotype, methylation, mutation and survival data., Results: We conducted the analysis of differential miRNA/mRNA expression profile by GEO, TCGA and GTEx databases and the correlation between miRNA and targeted mRNA by miRTarBase and TarBase. Then we detected using qRT-PCR and validated the diagnostic value of miRNA-mRNA regulator pairs by the ROC, calibration curve and DCA. Phenotypic hallmarks of regulatory pairs including tumor-infiltrating lymphocytes, tumor microenvironment, tumor mutation burden, global methylation and gene mutation were also described. The expression levels of miRNAs and target mRNAs were detected in 80 paired colon tissue samples. Ultimately, we picked up two pivotal regulatory pairs (miR-139-5p/ STC1 and miR-20a-5p/ FGL2) and verified the diagnostic value of the complex model which is the combination of 4 signatures above-mentioned in 3 testing GEO datasets and an external validation cohort., Conclusions: We found that 2 miRNAs by targeting 2 metastasis-related mRNAs were correlated with tumor-infiltrating macrophages, HRAS, and BRAF gene mutation status. Our results established the diagnostic model containing 2 miRNAs and their respective targeted mRNAs to distinguish CRCs and normal controls and displayed their complex roles in CRC pathogenesis especially tumor immunity., (© 2023. The Author(s).)

Background and Objective: Calcaneal Sanders type II or III fractures are highly disabling with significant burden. Surgical treatment modalities include open reduction and internal fixation (ORIF) techniques and a variety of minimally invasive surgical (MIS) approaches. ORIF techniques are associated with complications and traditional MIS techniques need extensive intraoperative fluoroscopic procedures. The present study aims to investigate the effects of three different minimally invasive internal fixation (MIIF) techniques used to treat Sanders type II intra-articular calcaneal fractures using finite element analyses., Methods: A 64-row spiral computed tomography scan was used to observe the calcaneus of a healthy adult. The scanning data were imported into Mimics in a DICOM format. Using a new model of a Sanders type II-B intra-articular calcaneal fracture, three minimally invasive techniques were simulated. Technique A involved fixation using an isolated minimally invasive locking plate; Technique B used a minimally invasive locking plate with one medial support screw; and Technique C simulated a screw fixation technique using four 4.0-mm screws. After simulating a 640-N load on the subtalar facet, the maximum displacement and von Mises stress of fragments and implants were recorded to evaluate the biomechanical stability of different fixation techniques using finite element analyses., Results: After stress loading, the maximum displacements of the fragments and implants were located at the sustentaculum tali and the tip of sustentaculum tali screw, respectively, in the three techniques; however, among the three techniques, Technique B had better results for displacement of both. The maximum von Mises stress on the fragments was < 56 Mpa, and stress on the implants using the three techniques was less than the yield strength, with Technique C having the least stress., Conclusion: All three techniques were successful in providing a stable fixation for Sanders type II intra-articular calcaneal fractures, while the minimally invasive calcaneal locking plate with medial support screw fixation approach exhibited greater stability, leading to improved enhancement for the facet fragment; however, screw fixation dispersed the stress more effectively than the other two techniques., (© 2023. The Author(s).)

Background: Aptamers, which are biomaterials comprised of single-stranded DNA/RNA that form tertiary structures, have significant potential as next-generation materials, particularly for drug discovery. The systematic evolution of ligands by exponential enrichment (SELEX) method is a critical in vitro technique employed to identify aptamers that bind specifically to target proteins. While advanced SELEX-based methods such as Cell- and HT-SELEX are available, they often encounter issues such as extended time consumption and suboptimal accuracy. Several In silico aptamer discovery methods have been proposed to address these challenges. These methods are specifically designed to predict aptamer-protein interaction (API) using benchmark datasets. However, these methods often fail to consider the physicochemical interactions between aptamers and proteins within tertiary structures., Results: In this study, we propose AptaTrans, a pipeline for predicting API using deep learning techniques. AptaTrans uses transformer-based encoders to handle aptamer and protein sequences at the monomer level. Furthermore, pretrained encoders are utilized for the structural representation. After validation with a benchmark dataset, AptaTrans has been integrated into a comprehensive toolset. This pipeline synergistically combines with Apta-MCTS, a generative algorithm for recommending aptamer candidates., Conclusion: The results show that AptaTrans outperforms existing models for predicting API, and the efficacy of the AptaTrans pipeline has been confirmed through various experimental tools. We expect AptaTrans will enhance the cost-effectiveness and efficiency of SELEX in drug discovery. The source code and benchmark dataset for AptaTrans are available at https://github.com/pnumlb/AptaTrans ., (© 2023. The Author(s).)

Background: Caring behavior among nurses would have an impact on patient outcomes. External organizational job resources and personal internal psychological resources are correlated to nurses' caring behavior. Authentic leadership and psychological capital were shown to be correlated with nurses' caring behavior in previous studies. However, the relationships among the three are nevertheless unclear. This study aimed to examine if psychological capital could act as a mediator between nursing managers' authentic leadership and nurses' caring behavior., Methods: In December 2021, a total of 3,662 nurses were recruited from 37 hospitals in Anhui Province, China. They filled out online surveys, including general demographic information, the Authentic Leadership Questionnaire, the Psychological Capital Questionnaire, and the Caring Behavior Inventory. Structural Equation Modeling and the bootstrapping procedure were used to examine the mediating role of psychological capital., Results: The scores of authentic leadership, psychological capital, and caring behavior of 3,495 nurses were 52.04 ± 13.24, 96.89 ± 17.78, and 104.28 ± 17.01, respectively. Psychological capital significantly mediated the relationship between authentic leadership and nurses' caring behavior (β = 0.378, p < 0.001, 95% confidence interval: 0.350 ~ 0.402), which made up 78.75% of the total impact (0.480)., Conclusion: The findings of this study suggested that nursing managers should develop an authentic leadership style, which can effectively improve nurses' caring behaviors toward patients in clinical practice. Meanwhile, nursing leaders should strengthen nurses' psychological evaluation and training, and promote nurses' caring behavior in clinical settings., (© 2023. The Author(s).)

Manganese-based nanomaterials (Mn-nanomaterials) hold immense potential in cancer diagnosis and therapies. However, most Mn-nanomaterials are limited by the low sensitivity and low efficiency toward mild weak acidity (pH 6.4-6.8) of the tumor microenvironment, resulting in unsatisfactory therapeutic effect and poor magnetic resonance imaging (MRI) performance. This study introduces pH-ultrasensitive PtMn nanoparticles as a novel platform for enhanced ferroptosis-based cancer theranostics. The PtMn nanoparticles were synthesized with different diameters from 5.3 to 2.7 nm with size-dominant catalytic activity and magnetic relaxation, and modified with an acidity-responsive polymer to create pH-sensitive agents. Importantly, R-PtMn-1 (3 nm core) presents "turn-on" oxidase-like activity, affording a significant enhancement ratio (pH 6.0/pH 7.4) in catalytic activity (6.7 folds), compared with R-PtMn-2 (4.2 nm core, 3.7 folds) or R-PtMn-3 (5.3 nm core, 2.1 folds), respectively. Moreover, R-PtMn-1 exhibits dual-mode contrast in high-field MRI. R-PtMn-1 possesses a good enhancement ratio (pH 6.4/pH 7.4) that is 3 or 3.2 folds for T 1 - or T 2 -MRI, respectively, which is higher than that of R-PtMn-2 (1.4 or 1.5 folds) or R-PtMn-3 (1.1 or 1.2 folds). Moreover, their pH-ultrasensitivity enabled activation specifically within the tumor microenvironment, avoiding off-target toxicity in normal tissues during delivery. In vitro studies demonstrated elevated intracellular reactive oxygen species production, lipid peroxidation, mitochondrial membrane potential changes, malondialdehyde content, and glutathione depletion, leading to enhanced ferroptosis in cancer cells. Meanwhile, normal cells remained unaffected by the nanoparticles. Overall, the pH-ultrasensitive PtMn nanoparticles offer a promising strategy for accurate cancer diagnosis and ferroptosis-based therapy., (© 2023. The Author(s).)

Background: This study used an atrial septal shunt to compare the treatment progress and prognosis for patients with heart failure (HF) who have different ejection fractions., Methods: Twenty HF patients with pulmonary hypertension, who required atrial septal shunt therapy, were included in this study. The patients underwent surgery between December 2012 and December 2020. They were divided into two groups based on their ejection fraction: a group with reduced ejection fraction (HFrEF) and a group with preserved ejection fraction(HFpEF) + mid-range ejection fraction (HfmrEF). Echocardiography was utilized to evaluate parameters such as left ventricular dimension (LVD), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume (LVEDV). Hemodynamic parameters were measured using cardiac catheterization. The patient's cardiac function was assessed using the six-minute walking test (6MWT), KCCQ score, NYHA classification, and the degree of functional mitral regurgitation (FMR). Followed-up visits were conducted at 1, 3, and 6 months, and any adverse effects were recorded., Results: The LVEF values were consistently higher in the HFpEF+HFmrEF group than HFrEF group at all periods (P < 0.05). Differences in LVD were observed between the two groups before the surgery. Statistically, significant differences were found at the preoperative stage, 1 month, and 3 months (P < 0.05, respectively). However, the LVEDV showed a significant difference between the two groups only at 3 months (P = 0.049). Notably, there were notable variations in LAPm, LAPs, and the pressure gradient between the LA-RA gradient at baeline, after implantation, and during the 6 months follow-up (all P < 0.05)., Conclusion: Following treatment, the HFpEF+HFmrEF group exhibited more significant improvements in echocardiographic and cardiac catheterization indices than the HFrEF group. However, there was no statistically significant difference between the two groups regarding the 6MWT and KCCQ scores. It is important to note that the findings of this study still require further investigation in a large sample size of patients., (© 2023. The Author(s).)

Background: Previous studies have indicated that HBV pregenome RNA (HBV pgRNA) could predict HBeAg seroconversion among the chronic hapatitis B (CHB) patients treated with pegylated interferon (Peg-IFN) or nucleos(t)ide analogues (NAs). However, the data about the prediction of HBV pgRNA for spontaneous HBeAg seroconversion is limited., Methods: One hundred thirteen CHB patients with HBeAg-positive in the immune active phase were followed up for 76 weeks without antiviral treatment. Based on the laboratory test results of liver function, HBeAg, anti-HBe, and HBV DNA at week 76, patients were assigned to two groups: spontaneous HBeAg seroconversion (group A, n = 18) and non-spontaneous HBeAg seroconversion group. Among the latter group, 36 patients were selected as controls (group B, n = 36)., Results: At week 12, between group A and group B, there was a significant difference in the level of HBV pgRNA (group A 6.35 ± 1.24 log 10 copies/ml and group B 7.52 ± 0.79 log 10 copies/ml, P = 0.001), and the difference enlarged at week 28. The receiver operating characteristic curves (AUROCs) of the HBV pgRNA level and the ∆HBV pgRNA at week 28 were 0.912 (P = 0.001, 95% CI: 0.830-0.994), and 0.934 (P = 0.001, 95% CI: 0.872-0.996), respectively. The optimal cutoffs of HBV pgRNA and the reduction from baseline (∆HBV pgRNA) at week 28 for spontaneous HBeAg seroconversion prediction were 5.63 log 10 copies/ml and 1.85 log 10 copies/ml, respectively. The positive predictive value and negative predictive value of HBV pgRNA and ∆HBV pgRNA at week 28 were 86.7% and 87.2%, 87.5% and 89.5%, respectively. And the combination of the HBV pgRNA level and the HBV pgRNA decreased could provide better prediction., Conclusions: HBV pgRNA is a sound predictor for spontaneous HBeAg seroconversion among the CHB patients in immune active phase. Dynamic monitoring of HBV pgRNA is helpful for clinical treatment decision., (© 2023. The Author(s).)

Background: Although non-pharmacological smoking cessation measures have been widely used among smokers, current research evidence on the effects of smoking cessation is inconsistent and of mixed quality. Moreover, there is a lack of comprehensive evidence synthesis. This study seeks to systematically identify, describe, and evaluate the available evidence for non-pharmacological interventions in smoking populations through evidence mapping (EM), and to search for best-practice smoking cessation programs., Methods: A comprehensive search for relevant studies published from the establishment of the library to January 8, 2023, was conducted in PubMed, Web of Science, Embase, the Cochrane Library, CNKI, CBM, Wan Fang, and VIP. Two authors independently assessed eligibility and extracted data. The PRISMA statement and AMSTAR 2 tool were used to evaluate the report quality and methodology quality of systematic reviews/meta-analyses (SRs/MAs), respectively. Bubble plots were utilized to display information, such as the study population, intervention type, evidence quality, and original study sample size., Results: A total of 145 SRs/MAs regarding non-pharmacological interventions for smoking cessation were investigated, with 20 types of interventions identified. The most commonly used interventions were cognitive behaviour education (n = 32, 22.07%), professional counselling (n = 20, 13.79%), and non-nicotine electronic cigarettes (e-cigarettes) (n = 13, 8.97%). Among them, counselling and behavioural support can improve smoking cessation rates, but the effect varies depending on the characteristics of the support provided. These findings are consistent with previous SRs/MAs. The general population (n = 108, 74.48%) was the main cohort included in the SRs/MAs. The total score of PRISMA for the quality of the reports ranged from 8 to 27, and 13 studies (8.97%) were rated as high confidence, and nine studies (6.21%) as moderate confidence, in the AMSTAR 2 confidence rating., Conclusions: The abstinence effect of cognitive behaviour education and money incentive intervention has advantages, and non-nicotine e-cigarettes appear to help some smokers transition to less harmful replacement tools. However, the methodological shortcomings of SRs/MAs should be considered. Therefore, to better guide future practice in the field of non-pharmacological smoking cessation, it is essential to improve the methodological quality of SRs and carry out high-quality randomized controlled trials (RCTs)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Increasing evidence suggests that hepatocellular carcinoma (HCC) stem cells (LCSCs) play an essential part in HCC recurrence, metastasis, and chemotherapy and radiotherapy resistance. Multiple studies have demonstrated that stemness-related genes facilitate the progression of tumors. However, the mechanism by which stemness-related genes contribute to HCC is not well understood. Here, we aim to construct a stemness-related score (SRscores) model for deeper analysis of stemness-related genes, assisting with the prognosis and individualized treatment of HCC patients.Further, we found that the gene LPCAT1 was highly expressed in tumor tissues by immunohistochemistry, and sphere-forming assay revealed that knockdown of LPCAT1 inhibited the sphere-forming ability of hepatocellular carcinoma cells., Methods: We used the TCGA-LIHC dataset to screen stemness-related genes of HCC from the MSigDB database. Prognosis, tumor microenvironment, immunological checkpoints, tumor immune dysfunction, rejection, treatment sensitivity, and putative biological pathways were examined. Random forest created the SRscores model. The anti-PD-1/anti-CTLA4 immunotherapy, tumor mutational burden, medication sensitivity, and cancer stem cell index were compared between the high- and low-risk score groups. We also examined risk scores for different cell types using single-cell RNA sequencing data and correlated transcription factor activity in cancer stem cells with SRscores genes. Finally, we tested core marker expression and biological functions., Results: Patients can be divided into two subtypes (Cluster1 and Cluster2) based on the TCGA-LIHC dataset's identification of 11 stemness-related genes. Additionally, a SRscores was developed based on subtypes. Cluster2 and the group with the lowest SRscores had superior survival and immunotherapy response than Cluster1 and the group with the highest SRscores. The group with a high SRscores was significantly more enriched in classical tumor pathways than the group with a low SRscores. Multiple transcription factors and SRscores genes are correlated. The core gene LPCAT1 is highly expressed in rat liver cancer tissues and promotes tumor cell sphere formation., Conclusion: A SRscores model can be utilized to predict the prognosis of HCC patients as well as their response to immunotherapy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The glyoxalase system includes glyoxalase I (GLXI), glyoxalase II (GLXII) and glyoxalase III (GLXIII), which are responsible for methylglyoxal (MG) detoxification and involved in abiotic stress responses such as drought, salinity and heavy metal., Results: In this study, a total of 620 GLX family genes were identified from 21 different plant species. The results of evolutionary analysis showed that GLX genes exist in all species from lower plants to higher plants, inferring that GLX genes might be important for plants, and GLXI and GLXII account for the majority. In addition, motif showed an expanding trend in the process of evolution. The analysis of cis-acting elements in 21 different plant species showed that the promoter region of the GLX genes were rich in phytohormones and biotic and abiotic stress-related elements, indicating that GLX genes can participate in a variety of life processes. In cotton, GLXs could be divided into two groups and most GLXIs distributed in group I, GLXIIs and GLXIIIs mainly belonged to group II, indicating that there are more similarities between GLXII and GLXIII in cotton evolution. The transcriptome data analysis and quantitative real-time PCR analysis (qRT-PCR) show that some members of GLX family would respond to high temperature treatment in G.hirsutum. The protein interaction network of GLXs in G.hirsutum implied that most members can participate in various life processes through protein interactions., Conclusions: The results elucidated the evolutionary history of GLX family genes in plants and lay the foundation for their functions analysis in cotton., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Studies have shown that microRNA-191 (miR-191) is involved in the development and progression of a variety of tumors. However, the function and mechanism of miR-191 in oral squamous cell carcinoma (OSCC) have not been clarified., Methods: The expression level of miR-191 in tumor tissues of patients with primary OSCC and OSCC cell lines were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. OSCC cells were treated with miR-191 enhancers and inhibitors to investigate the effects of elevated or decreased miR-191 expression on OSCC cells proliferation, migration, cell cycle, and tumorigenesis. The target gene of miR-191 in OSCC cells were analyzed by dual-Luciferase assay, and the downstream signaling pathway of the target genes was detected using western blot assay., Results: The expression of miR-191 was significantly upregulated in OSCC tissues and cell lines. Upregulation of miR-191 promoted proliferation, migration, invasion, and cell cycle progression of OSCC cells, as well as tumor growth in nude mice. Meanwhile, reduced expression of miR-191 inhibited these processes. Phospholipase C delta1 (PLCD1) expression was significantly downregulated, and negatively correlated with the expression of miR-191 in OSCC tissues. Dual-Luciferase assays showed that miR-191-5p could bind to PLCD1 mRNA and regulate PLCD1 protein expression. Western blot assay showed that the miR-191 regulated the expression of β-catenin and its downstream gene through targeting PLCD1., Conclusion: MicroRNA-191 regulates oral squamous cell carcinoma cells growth by targeting PLCD1 via the Wnt/β-catenin signaling pathway. Thus, miR-191 may serve as a potential target for the treatment of OSCC., (© 2023. The Author(s).)

Background: Oral lichen planus (OLP) is a local autoimmune disease induced by T-cell dysfunction that frequently affects middle-aged or elderly people, with a higher prevalence in women. CD8 + T cells, also known as killer T cells, play an important role in the progression and persistence of OLP. In order to identify different OLP subtypes associated with CD8 + T cell pathogenesis, consensus clustering was used., Methods: In this study, we preprocessed and downscaled the OLP single-cell dataset GSE211630 cohort downloaded from Gene Expression Omnibus (GEO) to finally obtain the marker genes of CD8 + T cells. Based on the expression of marker genes, we classified OLP patients into CMGs subtypes using unsupervised clustering analysis. The gene expression profiles were analyzed by WGCNA using the "WGCNA" R package based on the clinical disease traits and typing results, and 108 CD8 + T-cell related OLP pathogenicity-related genes were obtained from the intersection. Patients were once again classified into gene subtypes based on intersection gene expression using unsupervised clustering analysis., Results: After obtaining the intersecting genes of CD8 + T cells related to pathogenesis, OLP patients can be precisely classified into two different subtypes based on unsupervised clustering analysis, and subtype B has better immune infiltration results, providing clinicians with a reference for personalized treatment., Conclusions: Classification of OLP into different subtypes improve our current understanding of the underlying pathogenesis of OLP and provides new insights for future studies., (© 2023. The Author(s).)

Background: The prognosis of patients with colorectal cancer is related to early detection. However, commonly used screening markers lack sensitivity and specificity. In this study, we identified diagnostic methylation sites for colorectal cancer., Methods: After screening the colorectal cancer methylation dataset, diagnostic sites were identified via survival analysis, difference analysis, and ridge regression dimensionality reduction. The correlation between the selected methylation sites and the estimation of immune cell infiltration was analyzed. The accuracy of the diagnosis was verified using different datasets and the 10-fold crossover method., Results: According to Gene Ontology, the main enrichment pathways of genes with hypermethylation sites are axon development, axonogenesis, and pattern specification processes. However, the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggests the following main enrichment pathways: neuroactive ligand-receptor interaction, calcium signaling, and cAMP signaling. In The Cancer Genome Atlas (TCGA) and GSE131013 datasets, the area under the curve of cg07628404 was > 0.95. For the NaiveBayes machine model of cg02604524, cg07628404, and cg27364741, the accuracies of 10-fold cross-validation in the GSE131013 and TCGA datasets were 95% and 99.4%, respectively. The survival prognosis of the hypomethylated group (cg02604524, cg07628404, and cg27364741) was better than that of the hypermethylated group. The mutation risk did not differ between the hypermethylated and hypomethylated groups. The correlation coefficient between the three loci and CD4 central memory T cells, hematological stem cells, and other immune cells was not high (p < 0.05)., Conclusion: In cases of colorectal cancer, the main enrichment pathway of genes with hypermethylated sites was axon and nerve development. In the biopsy tissues, the hypermethylation sites were diagnostic for colorectal cancer, and the NaiveBayes machine model of the three loci showed good diagnostic performance. Site (cg02604524, cg07628404, and cg27364741) hypermethylation predicts poor survival for colorectal cancer. Three methylation sites were weakly correlated with individual immune cell infiltration. Hypermethylation sites may be a useful repository for diagnosing colorectal cancer., (© 2023. The Author(s).)

Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease of the pancreas. Reactive oxygen species (ROS) play a key role in the occurrence and development of AP. With increasing ROS levels, the degree of oxidative stress and the severity of AP increase. However, diagnosing AP still has many drawbacks, including difficulties with early diagnosis and undesirable sensitivity and accuracy. Herein, we synthesized a semiconducting polymer nanoplatform (SPN) that can emit ROS-correlated chemiluminescence (CL) signals. The CL intensity increased in solution after optimization of the SPN. The biosafety of the SPN was verified in vitro and in vivo. The mechanism and sensitivity of the SPN for AP early diagnosis and severity assessment were evaluated in three groups of mice using CL intensity, serum marker evaluations and hematoxylin and eosin staining assessments. The synthetic SPN can be sensitively combined with different concentrations of ROS to produce different degrees of high-intensity CL in vitro and in vivo. Notably, the SPN shows an excellent correlation between CL intensity and AP severity. This nanoplatform represents a superior method to assess the severity of AP accurately and sensitively according to ROS related chemiluminescence signals. This research overcomes the shortcomings of AP diagnosis in clinical practice and provides a novel method for the clinical diagnosis of pancreatitis in the future., (© 2023. The Author(s).)

Background: Post-dural puncture headache (PDPH) is a major complication of neuraxial anesthesia. PDPH usually occurs after Caesarean section in obstetric patients. The efficacy of prophylactic pharmacological therapies remains controversial., Methods: Seven pharmacological therapies (aminophylline (AMP), dexamethasone, gabapentin/pregabalin (GBP/PGB), hydrocortisone, magnesium, ondansetron (OND), and propofol (PPF)), were studied in this Bayesian network meta-analysis. The primary outcome was the cumulative incidence of PDPH within 7 days. Secondary outcomes included the incidence of PDPH at 24 and 48 h postoperatively, the severity of headache in PDPH patients (24, 48, and 72 h postoperatively), and postoperative nausea and vomiting (PONV)., Results: Twenty-two randomized controlled trials with 4,921 pregnant women (2,723 parturients received prophylactic pharmacological therapies) were included. The analyses demonstrated that PPF, OND, and AMP were efficient in decreasing the cumulative incidence of PDPH during the follow-up period compared to the placebo group (OR = 0.19, 95% CI: 0.05 to 0.70; OR = 0.37, 95% CI: 0.16 to 0.87; OR = 0.40, 95% CI: 0.18 to 0.84, respectively). PPF and OND had the lower incidence of PONV compared to the placebo group (OR = 0.07, 95% CI: 0.01 to 0.30; and OR = 0.12, 95% CI: 0.02 to 0.63). No significant difference in other outcomes was found among different therapies., Conclusions: Based on available data, PPF, OND, and AMP may have better efficacy in decreasing the incidence of PDPH compared to the placebo group. No significant side effects were revealed. Better-designed studies are requested to verify these conclusions., (© 2023. The Author(s).)

Demyelination occurs in multiple central nervous system (CNS) disorders and is tightly associated with neuroinflammation. Pyroptosis is a form of pro-inflammatory and lytic cell death which has been observed in CNS diseases recently. Regulatory T cells (Tregs) have exhibited immunoregulatory and protective effects in CNS diseases. However, the roles of Tregs in pyroptosis and their involvement in LPC-induced demyelination have not been explicated. In our study, Foxp3-diphtheria toxin receptor (DTR) mice treated with diphtheria toxin (DT) or PBS were subjected to two-site lysophosphatidylcholine (LPC) injection. Immunofluorescence, western blot, Luxol fast blue (LFB) staining, quantitative real-time PCR (qRT-PCR) and neurobehavior assessments were performed to evaluate the severity of demyelination, neuroinflammation and pyroptosis. Pyroptosis inhibitor was further used to investigate the role of pyroptosis in LPC-induced demyelination. RNA-sequencing was applied to explore the potential regulatory mechanism underlying the involvement of Tregs in LPC-induced demyelination and pyroptosis. Our results showed that depletion of Tregs aggravated microgliosis, inflammatory responses, immune cells infiltration and led to exacerbated myelin injury as well as cognitive defects in LPC-induced demyelination. Microglial pyroptosis was observed after LPC-induced demyelination, which was aggravated by Tregs depletion. Inhibition of pyroptosis by VX765 reversed myelin injury and cognitive function exacerbated by Tregs depletion. RNA-sequencing showed TLR4/myeloid differentiation marker 88 (MyD88) as the central molecules in Tregs-pyroptosis pathway, and refraining TLR4/MyD88/NF-κB pathway alleviated the aggravated pyroptosis induced by Tregs depletion. In conclusion, our findings for the first time indicate that Tregs alleviate myelin loss and improve cognitive function by inhibiting pyroptosis in microglia via TLR4/MyD88/NF-κB pathway in LPC-induced demyelination., (© 2023. The Author(s).)

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood., Methods: We sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro., Results: Using expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group., Conclusion: Our findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer., (© 2023. The Author(s).)

Purpose: Retinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD., Methods: A meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases., Results: In this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11-0.46, I 2 : 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10-0.47, I 2 : 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression., Conclusion: The findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed., (© 2023. The Author(s).)

Objective: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH., Methods: Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves., Results: In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490-9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014-1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002-1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969-0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037-1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069-1.141; P < 0.001) were independent risk factors. Based on these 6 factors, the nomogram can be employed to predict early functional prognosis with high accuracy (AUC 0.791). Decision curve analysis and clinical impact curves showed an increased net benefit for utilizing the nomogram., Conclusion: The haemoglobin level at admission may be an easily overlooked factor in clinical work. This new nomogram model could be a promising and convenient tool to predict the early functional prognosis of adults with ICH. More prospective multicentre studies are needed to validate these findings., (© 2023. The Author(s).)

Background: Total removal of the vestibular schwannoma when preserving the function of the facial nerve is difficult. The objective of the current study was to investigate the short-term clinical outcome of vestibular schwannoma removal via retro-sigmoid approach., Methods: One-hundred consecutive patients diagnosed with vestibular schwannoma were surgically treated between December 2018 and August 2019 in Xuanwu Hospital, Capital Medical University. The clinical classification, surgical position, gross total removal rate, the anatomical and functional preservation rates of facial nerve, and the postoperative complications were retrospectively analyzed., Results: All 100 patients including 34 males and 66 females were operated on via retro-sigmoid approach. According to Koos vestibular schwannoma grading system, 18 cases were grade 2, 34 cases were grade 3, and 48 cases were grade 4. According to Hannover vestibular schwannoma grading system, 5 cases were T2, 6 cases were T3a, 8 cases were T3b, 30 cases were T4a, and 51 cases were T4b. Seventy-three surgeries were performed under lateral position, and 27 cases were operated under semi-sitting position. The gross total removal rate was 90.0%; the anatomic reservation rate of the facial nerve was 96.0%. According to the House-Brackman system, the facial nerve function was grades 1-2 in 78.0% cases, grade 3 in 7.0% cases, and grades 4-5 in 15% cases. For patients with effective hearing before operation, the hearing reservation rate was 19.0%. Two patients (2.0%) developed intracranial hematoma after operation., Conclusion: Most vestibular schwannoma could be completely removed with good postoperative facial nerve function. If total removal of tumor is difficult, we should give priority to the functional preservation of the nerve function., (© 2022. The Author(s).)

Background: Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal cancers worldwide accompany with an extremely poor prognosis. Therefore, this study aims to screen for new molecules affecting ESCC and explore their mechanisms of action to provide ideas for targeted therapies for ESCC., Methods: Firstly, we screened out the membrane protein SCARA5 by high-throughput sequencing of the ESCC patient tissues, and RT-qPCR and WB were used to verify the differential expression of SCARA5 in esophageal cell lines, and IHC analyzed the expression localization of SCARA5 in ESCC tissue. Then, flow cytometry, wound healing assay, Transwell assay and CCK-8 assay were used to explore the effects of SCARA5 on cell cycle, migration and invasion as well as cell proliferation activity of esophageal squamous carcinoma cells. Meanwhile, transmission electron microscopy was used to detect changes in cellular mitochondrial morphology, and flow cytometry were used to detect changes in intracellular reactive oxygen metabolism, and immunofluorescence and flow cytometry were used to detect changes in intracellular Fe 2+ . Mechanistically, co-immunoprecipitation was used to detect whether SCARA5 binds to ferritin light chain, and ferroptosis-related protein expression was detected by WB. Finally, the tumor xenograft model was applied to validation the role of SCARA5 tumor growth inhibition in vivo., Results: We found that SCARA5 was aberrantly decreased in ESCC tissues and cell lines. Furthermore, we confirmed that SCARA5 suppressed the cell cycle, metastasis and invasion of ESCC cells. Meanwhile, we also found that overexpression of SCARA5 caused changes in mitochondrial morphology, accumulation of intracellular reactive oxygen species and increased intracellular Fe 2+ in ESCC cells, which induced ferroptosis in ESCC cells. Mechanically, we validated that SCARA5 combined with ferritin light chain and increased intracellular Fe 2+ . As well as, overexpression SCARA5 induced ferroptosis by increasing ferritin light chain in nude mice subcutaneous tumors and inhibited the growth of nude mice subcutaneous tumors., Conclusion: Collectively, our findings demonstrated that SCARA5 suppressed the proliferation and metastasis of ESCC by triggering ferroptosis through combining with ferritin light chain., (© 2022. The Author(s).)

Background: Inhibitors of ornithine decarboxylase (ODC) are effective at preventing colorectal cancer (CRC). However, their high toxicity limits their clinical application. This study was aimed to explore the potential of microRNAs (miRNAs) as an inhibitor of ODC., Methods: miRNA array was used to identify dysregulated miRNAs in CRC tumors of mice and patients. Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) were used to induce CRC in mice. miRNA function in carcinogenesis was determined by soft-agar colony formation, flow cytometry, and wound healing of CRC cells. Mini-circle was used to deliver miRNA into colons., Results: MiRNA profiling identified miR-378a-3p (miR-378a) as the most reduced miRNA in CRC tumors of patients and mice treated with AOM/DSS. Pathway array analysis revealed that miR-378a impaired c-MYC and ODC1 pathways. Further studies identified FOXQ1 (forkhead box Q1) and ODC1 as two direct targets of miR-378a. FOXQ1 activated transcription of c-MYC, a transcription activator of ODC1. In addition to directly targeting ODC1, miR-378a also inhibited expression of ODC1 via the FOXQ1-cMYC axis, thereby inhibiting polyamine synthesis in human CRC cells. Phenotypically, by reducing polyamine synthesis, miR-378a induced apoptosis and inhibited proliferation and migration of CRC cells, while disrupting the association of miR-378a with FOXQ1 and ODC1 offset the effects of miR-378a, suggesting that FOXQ1 and ODC1 were required for miR-378a to inhibit CRC cell growth. MiR-378a treatment robustly prevented growth of HCC by inhibiting polyamine synthesis in AOM/DSS mice., Conclusion: MiR-378a prevents CRC by inhibiting polyamine synthesis, suggesting its use as a novel ODC inhibitor against CRC., (© 2022. The Author(s).)

Background: Prostate cancer (PCa) is currently the major malignancy in men. It is becoming increasingly clear that competitive endogenous RNA (ceRNA) regulation networks are important in a wide variety of cancers. Nevertheless, there is still much to learn about the biological functions of the ceRNA network in prostate cancer., Methods: The ceRNA network was constructed using the "GDCRNATools" package. Based on survival analysis, we obtained AC005154.6/hsa-miR-29c-3p/CCNL2 for further analysis. The prognostic model based on this ceRNA network was constructed by univariate and multivariate Cox regression methods. Furthermore, functional enrichment analysis, mutation landscape analysis, immune infiltration analysis, drug sensitivity analysis, methylation analysis, pan-cancer analysis, and molecular experiments of CCNL2 were carried out to investigate the role of CCNL2 in tumorigenesis., Results: We identified the AC005154.6/CCNL2 axis as a risk factor that can promote the progression of prostate cancer by bioinformatics analysis and molecular experiments. Immune infiltration analysis suggested that CCNL2 may act as a novel biomarker for treatment decisions. The methylation level of CCNL2 was significantly decreased in tumor samples, possibly contributing to the upregulation of CCNL2 in prostate cancer. Moreover, CCNL2 is differentially expressed in multiple cancers and is tightly correlated with immune infiltration., Conclusion: The current study constructed a ceRNA network, AC005154.6/hsa-miR-29c-3p/CCNL2. Potentially, this biomarker can be used for early diagnosis and decision-making about prostate cancer treatment., (© 2022. The Author(s).)

Background: The mesenchymal stem cells (MSCs) were used to repair tissue injury. However, the treatment effect was not satisfactory. We investigated whether lncRNA MIR155HG could promote survival and migration of MSCs under oxidative stress, which mimics in vivo environments. Furthermore, we studied the protective effect of exosomes secreted by MSCs transfected with MIR155HG on endothelial cells. This study aimed to determine whether exploiting MSCs and exosomes modified with lncRNA MIR155HG would exert synergistic therapeutic effect to attenuate vein graft intimal hyperplasia more effectively., Methods: Lentivirus containing lncRNA MIR155HG overexpressing vector was packaged and used to infect MSCs. Then, CCK-8 assay, flow cytometry, Transwell assay, and Elisa assay were used to assess the functional changes of MSCs with overexpressed MIR155HG (OE-MSCs). Furthermore, the associated pathways were screened by Western blot. MIR155HG-MSCs-derived exosomes (OE-exo) were collected and co-cultured with human umbilicus vein endothelial cell (HUVEC). We validated the protective effect of OE-exo on HUVEC. In vivo, both MSCs and exosomes modified with MIR155HG were injected into a vein graft rat model via tail vein. We observed MSCs homing and intimal hyperplasia of vein graft using a fluorescent microscope and histological stain., Results: Our study found that lncRNA MIR155HG promoted proliferation, migration, and anti-apoptosis of MSCs. NF-κB pathway took part in the regulation process induced by MIR155HG. OE-exo could enhance the activity and healing ability of HUVEC and reduce apoptosis. In vivo, OE-MSCs had a higher rate of homing to vascular endothelium. The combined treatment with OE-MSCs and OE-exo protected vascular endothelial integrity, reduced inflammatory cell proliferation, and significantly attenuated intimal hyperplasia of vein graft., Conclusion: LncRNA MIR155HG could promote the survival and activity of MSCs, and reduce the apoptosis of HUVECs using exosome delivery. Exploiting MSCs and exosomes modified with MIR155HG could attenuate vein graft intimal hyperplasia more effectively and maximize the surgical effect., (© 2022. The Author(s).)

Background: The use of donated oocytes (DO) for in vitro fertilization(IVF) treatment in patients with infertility is generally recognized, and females with polycystic ovarian syndrome (PCOS) can participate in oocyte donation programs as donor patients. However, the pregnancy outcomes and offspring follow-up in patients with PCOS as the recipients are unclear. This study was to compare the pregnancy outcomes and follow-up of offspring in PCOS and non-PCOS receptor., Methods: This was a retrospective cohort study of 62 patients undergoing the oocyte reception program were separated into 2 groups: Group I, PCOS oocyte recipients (n = 30); Group II, non-PCOS recipients (n = 32). Medical records were reviewed, and rates of fertilization, cleavage, high-quality embryos and blastocysts were compared between PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, multiple pregnancies, and offspring outcomes were calculated using the first single vitrified-warmed blastocyst transfer (SVBT) analysis between the groups., Results: The average recipient age and body mass index (BMI) of PCOS and non-PCOS patients was (36.3 ± 2.6 vs. 36.2 ± 2.8, and 23.4 ± 3.9 vs. 23.7 ± 4.0), respectively (P > 0.05). The fertilization, cleavage, high-quality embryos and blastocyst rates were not significantly different between the PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, and multiple pregnancies were not significantly different in SVBT between the PCOS and non-PCOS groups. The incidence of complications, such as pre-eclampsia or gestational diabetes, between PCOS and non-PCOS groups was similar (11.8% vs.11.1%, 5.9% vs.5.5%; P > 0.05). Preterm births were also similar (11.8% vs.16.7%, P > 0.05). Donor oocytes are more likely to be delivered via cesarean Sect. (80.0% vs. 86.7%: P > 0.05). The mean gestational age, birth weight, and height were comparable between the 2 groups during full-term delivery., Conclusion: There was no difference in the pregnancy outcomes and follow-up of the offspring between the PCOS and non-PCOS groups., (© 2022. The Author(s).)

Background: Various methods are used for cervical ripening during the induction of labor. Mechanical and pharmacological methods are commonly used for cervical ripening. A double-balloon catheter was specifically developed to ripen the cervix and induce labor; however, the efficacy of the double-balloon catheter in cervical ripening compared to other methods is unknown., Methods: We searched five databases and performed a Bayesian network meta-analysis. Six interventions (double-balloon catheter, Foley catheter, oral misoprostol, vaginal misoprostol, dinoprostone, and double-balloon catheter combined with oral misoprostol) were included in the search. The primary outcomes were cesarean delivery rate and time from intervention-to-birth. The secondary outcomes were as follows: Bishop score increment; achieving a vaginal delivery within 24 h; uterine hyperstimulation with fetal heart rate changes; need for oxytocin augmentation; instrumental delivery; meconium staining; chorioamnionitis; postpartum hemorrhage; low Apgar score; neonatal intensive care unit admission; and arterial pH., Results: Forty-eight randomized controlled trials involving 11,482 pregnant women were identified. The cesarean delivery rates of the cervical ripening with a double-balloon catheter and oral misoprostol, oral misoprostol, and vaginal misoprostol were significantly lower than cervical ripening with a Foley catheter (OR = 0.48, 95% CI: 0.23-0.96; OR = 0.74, 95% CI: 0.58-0.93; and OR = 0.79, 95% CI: 0.64-0.97, respectively; all P < 0.05). The time from intervention-to-birth of vaginal misoprostol was significantly shorter than the other five cervical ripening methods. Vaginal misoprostol and oral misoprostol increased the risk of uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter. A double-balloon catheter with or without oral misoprostol had similar outcomes, including uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter., Conclusion: Double-balloon catheter did not show superiority when compared with other single method in primary and secondary outcomes of labor induction. The combination of double-balloon catheter with oral misoprostol was significantly reduced the rate of cesarean section compared to Foley catheter without increased risk of uterine hyperstimulation with fetal heart rate changes, which was shown in oral or vaginal misoprostol., (© 2022. The Author(s).)

Background: Apoptin, as a tumor-specific pro-apoptotic protein, plays an important anti-tumoral role, but its mechanism of autophagy activation and the interaction between autophagy and apoptosis have not been accurately elucidated. Here, we studied the mechanism of apoptin-induced apoptosis and autophagy and the interaction between two processes., Methods: Using crystal violet staining and the CCK-8 assay, we analyzed the effect of apoptin in the inhibition of liver cancer cells in vitro and analyzed the effect of inhibiting liver cancer in vivo by establishing a nude mouse tumor model. Flow cytometry and fluorescence staining were used to analyze the main types of apoptin-induced apoptosis and autophagy. Subsequently, the relationship between the two events was also analyzed. Flow cytometry was used to analyze the effect of ROS on apoptin-mediated apoptosis and autophagy mediated by apoptin. The effect of ROS on two phenomena was analyzed. Finally, the role of key genes involved in autophagy was analyzed using gene silencing., Results: The results showed that apoptin can significantly increase the apoptosis and autophagy of liver cancer cells, and that apoptin can cause mitophagy through the increase in the expression of NIX protein. Apoptin can also significantly increase the level of cellular ROS, involved in apoptin-mediated autophagy and apoptosis of liver cancer cells. The change of ROS may be a key factor causing apoptosis and autophagy., Conclusion: The above results indicate that the increase in ROS levels after apoptin treatment of liver cancer cells leads to the loss of mitochondrial transmembrane potential, resulting in endogenous apoptosis and mitophagy through the recruitment of NIX. Therefore, ROS may be a key factor connecting endogenous apoptosis and autophagy induced by apoptin in liver cancer cells. Video abstract., (© 2022. The Author(s).)

Background: Implicit absenteeism is very common among clinical nurses. We aimed to evaluate the role of psychological coherence in the inclusive leadership and implicit absenteeism among obstetrics and gynecology nurses, to provide evidence to the clinical management of nurses., Methods: Through the convenience sampling method, a survey of gynecology nurses in tertiary hospitals in 16 cities of Anhui Province, China was conducted using the General Information Questionnaire, the Stanford Implicit Absence Scale, the Inclusive Leadership Scale and the Sense of Coherence Scale. Statistical analysis was performed by SPSS 20., Results: A total of 1080 nurses were included with an effective response rate of 93.5%. The average score of nurses' recessive absenteeism in this study was (16.8 ± 0.15). The average of inclusive leadership score was (34.25 ± 7.23). The average score of psychological coherence score of obstetrics and gynecology nurses was (55.79 ± 8.28). Pearson correlation analysis showed that there was a relationship between implicit absenteeism behavior, inclusive leadership, and the level of psychological coherence in obstetrics and gynecology nurses (all P < 0.05). Linear regression analysis indicated that psychological coherence played a partial mediating role between inclusive leadership and obstetrics and gynecology nurses' implicit absenteeism (all P < 0.05)., Conclusions: Obstetrics and gynecology nurses have serious recessive absenteeism with low sense of psychological coherence and inclusive leadership. Nursing managers should improve the psychological coherence through effective interventions, thereby reducing the incidence of implicit absenteeism., (© 2022. The Author(s).)