Search

Background: Nurses' competency in pain management is essential for effectively alleviating patients' acute pain, controlling chronic pain, and promoting patient recovery. However, reliable tools for evaluating these competencies across different clinical specialties and healthcare settings are lacking. This study aimed to develop and validate a Pain Management Competency Scale for Nurses (PMCSN) and to assess the pain management competencies of nurses in China through a nationwide survey., Methods: An item pool and a draft scale were developed through literature reviews, semi-structured interviews, and expert panel discussions. This was followed by refinement of the scale via Delphi expert consultations and a pilot test. To validate the scale, 342 nurses were conveniently sampled from six hospitals in Eastern and Central China. The validation process included item analysis, internal consistency reliability assessment, test-retest reliability (with 40 nurses retaking the questionnaire after a 14-day interval), content validity (evaluated by six experts using a 4-point Likert scale), and structural validity (assessed through exploratory and confirmatory factor analyses). The validated scale was then applied in a survey of 1,500 nurses from 15 hospitals across Eastern, Central, and Western China. Statistical analyses included descriptive statistics, analysis of variance (ANOVA), and t-tests., Results: The PMCSN comprised six primary dimensions-Pain Assessment and Monitoring, Pharmacological Pain Management, Non-Pharmacological Pain Management, Management of Analgesic Adverse Effects, Patient/Family Education, and Professional Development-and includes 52 tertiary items. The PMCSN scores ranged from 6 to 120, calculated by summing the standardized scores across the six dimensions, with higher scores indicating greater competency in pain management. The scale's Cronbach's α was 0.974 (dimension-specific values ranging from 0.863 to 0.935) and a test-retest reliability of 0.871. The content validity index (CVI) of the scale was 0.965. Exploratory factor analysis (EFA) showed that the six-factor model explained 67.50% of the variance. Confirmatory factor analysis (CFA) indicated good model fit, with average variance extracted (AVE) values ranging from 0.659 to 0.811 and composite reliability (CR) between 0.909 and 0.973, confirming good convergent validity. The square roots of the AVE values exceeded the inter-factor correlations, indicating good discriminant validity. In the nationwide survey, the average PMCSN score among 1,500 nurses was 101.27 ± 20.97. Nurses with higher education levels scored higher (F = 14.173, p < 0.01), as did those working in Eastern regions (F = 24.632, p < 0.01) and tertiary hospitals (T = -5.476, p < 0.01)., Conclusions: The PMCSN is a valid and reliable tool for assessing nurses' pain management competencies. It provides a standardized approach for evaluation and guides targeted interventions to improve competency. Regional and hospital-level disparities highlight the need for enhanced training in underdeveloped areas and collaboration between hospitals to promote balanced healthcare resources., Competing Interests: Declarations. Ethics approval and consent to participate: This study protocol was approved by the Ethics Committee of the Nursing College of Hangzhou Normal University (2022055). The study was conducted after obtaining written informed consent from the participants. It was also carried out in accordance with the relevant guidelines and regulations of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: The effects of exercise on the health of people with Crohn's disease (CD) remain unclear. This study aimed to explore the perspective of Chinese CD patients on exercise and the quantitative relationship between exercise and patient-reported outcomes., Methods: This study used a mixed methods design consisting of three components. (1) Big data were mined from social media, and latent Dirichlet allocation (LDA) was used to perform cluster analysis on topics related to physical exercise. (2) A seven-step Colaizzi process was used to conduct semistructured interviews to obtain in-depth information about exercise. (3) A cross-sectional study was performed to examine this relationship using the Global Physical Activity Questionnaire (GPAQ) and Patient-reported Outcome Measurement Information System (PROMIS)., Results: LDA yielded a total of 1536 exercise-related posts; eight topics concerning CD patients were obtained through clustering (peer support, exercise therapy, diet, fatigue, exercise type, intestinal symptoms, body constitution and mental health), and 11 patients were interviewed to validate the results of LDA and explore the insight of Chinese CD. We identified two themes: the effects of exercise on people with CD and factors that promote and hinder exercise. A total of 119 patients with CD were surveyed. Considering confounding factors such as disease activity and medication, moderate-intensity recreational PA increased patients' physical function and improved anxiety, depression, fatigue, pain intensity, and pain impact (all p < 0.05). In contrast, high-intensity work may lead to anxiety, depression, fatigue, pain, and pain effects (all p < 0.001). In addition, sedentary behaviour may lead to depression (p = 0.006)., Conclusion: Patients with CD tend to seek guidance on exercise through social media, and they generally believe that exercise is beneficial, especially for their psychological and spiritual health, despite difficulties in exercising. Physical activity may be an important factor affecting patients' psychological health. Crohn's disease has a profound impact on mental and emotional health, reducing patients' quality of life. Exercise is a good habit that can enhance mental, emotional and social health, but there is currently no standard exercise program for patients with Crohn's disease. The exercise experience of Chinese patients with Crohn's disease can be helpful in formulating exercise plans., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the First School of Clinical Medicine, Zhejiang Chinese Medical University (no. 2024-KL-261-01). Informed consent was obtained from all individual participants (Interviews and cross-sectional studies) for study participation. The text data used for LDA come from the public website Baidu Tieba, a publicly available website. According to the statement of Baidu Tieba (browsing and copying data are for the purpose of obtaining information and cannot be used for commercial purposes), ethical approval was not required for the secondary analysis of publicly available data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This in vitro study aimed to evaluate the effect of sodium hypochlorite (NaOCl) and ethylene diamine tetraacetic acid (EDTA) as pretreatments on the resin infiltration efficacy and acid resistance of enamel white spot lesions (WSLs)., Methods: Enamel blocks prepared from the buccal surfaces of sound human premolars were placed in a demineralisation solution for 3 days to establish artificial enamel WSLs. All the blocks with WSLs were randomly divided into four groups (n = 40 per group): RI (Control): resin infiltration only. N/RI: 5.25% NaOCl pretreatment + resin infiltration; E/RI: 17% EDTA pretreatment + resin infiltration; NE/RI: combined pretreatment of 5.25% NaOCl with 17% EDTA + resin infiltration; Enamel pore exposure was measured by using SEM observation and Image J software in each group after pretreatment prior to resin infiltration (n = 8 per group). Resin penetration depth and enamel surface microhardness were assessed after resin infiltration (n = 8 per group for each test) by a confocal laser scanning microscope and a Vickers' microhardness test respectively. The remaining specimens were subjected 7 days of pH cycling after which surface enamel roughness and microhardness were assessed by an atomic force microscope and a microhardness test respectively., Results: Compared to the control group, the enamel surface pore exposure (p = 0.007), resin penetration depth (p = 0.011) and enamel surface microhardness (p < 0.001) were all significantly increased after the pretreatment of 5.25% NaOCl alone or combined with 17% EDTA by one-way ANOVA. After pH cycling, no significant differences were found in enamel surface roughness or microhardness among the four groups (p = 0.55) by two-way ANOVA., Conclusions: Enamel surface pretreatment of 5.25% NaOCl or combined with 17% EDTA improved the efficacy of the resin infiltration of WSLs, but might be useless in enhancing the acid resistance of resin-infiltrated WSLs., Competing Interests: Declarations. Ethics approval and consent to participate: This study complies with all the relevant regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of Xuzhou Central Hospital (No. XZXY-LK-20220805-064). Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Cancer stem-like cells (CSCs) play an important role in initiation and progression of aggressive cancers, including esophageal cancer. Natural killer (NK) cells are key effector lymphocytes of innate immunity that directly attack a wide variety of cancer cells. NK cell-based therapy may provide a new treatment option for targeting CSCs. In this study, we aimed to investigate the sensitivity of human esophageal CSCs to NK cell-mediated cytotoxicity., Methods: CSCs were enriched from human esophageal squamous cell carcinoma cell lines via sphere formation culture. Human NK cells were selectively expanded from the peripheral blood of healthy donors. qRT-PCR, flow cytometry and ELISA assays were performed to examine RNA expression and protein levels, respectively. CFSE-labeled target cells were co-cultured with human activated NK cells to detect the cytotoxicity of NK cells by flow cytometry., Results: We observed that esophageal CSCs were more resistant to NK cell-mediated cytotoxicity compared with adherent counterparts. Consistently, esophageal CSCs showed down-regulated expression of ULBP-1, a ligand for NK cells stimulatory receptor NKG2D. Knockdown of ULBP-1 resulted in significant inhibition of NK cell cytotoxicity against esophageal CSCs, whereas ULBP-1 overexpression led to the opposite effect. Finally, the pro-differentiation agent all-trans retinoic acid was found to enhance the sensitivity of esophageal CSCs to NK cell cytotoxicity., Conclusions: This study reveals that esophageal CSCs are more resistant to NK cells through down-regulation of ULBP-1 and provides a promising approach to promote the activity of NK cells targeting esophageal CSCs., (© 2024. The Author(s).)

Background: Molecular subtyping is expected to enable precise treatment. However, reliable subtyping strategies for clinical application remains defective and controversial. Given the significance of tumor immune dysfunction and exclusion (TIDE), we aimed to develop a novel TIDE-based subtyping strategy to guide personalized immunotherapy in the bladder cancer (BC)., Methods: Transcriptome data of BC was used to evaluate the heterogeneity and the status of TIDE patterns. Subsequently, consensus clustering was applied to classify BC patients based on TIDE marker-genes. Patients' clinicopathological, molecular features and signaling pathways of the different TIDE subtypes were well characterized. We also utilize the deconvolution algorithms to analyze the tumor microenvironment, and further explore the sensitivity and mechanisms of each subtype to immunotherapy. Furthermore, BC patient clinical information, real-world BC samples and urine samples were collected for the validation of our findings, which were used for RNA-seq analysis, H&E staining, immunohistochemistry and immunofluorescence staining, and enzyme-linked immunosorbent assay. Finally, we also explored the conservation of our novel TIDE subtypes in pan-cancers., Results: We identified 69 TIDE biomarker genes and classified BC samples into three subtypes using consensus clustering. Subtype I showed the lowest TIDE status and malignancy with the best prognosis and highest sensitivity to immune checkpoint blockade (ICB) treatment, which was enriched of metabolic related signaling pathways. Subtype III represented the highest TIDE status and malignancy with the poorest prognosis and resistance to ICB treatment, resulting from its inhibitory immune microenvironment and T cell terminal exhaustion. Subtype II was in a transitional state with intermediate TIDE level, malignancy, and prognosis. We further confirmed the existence and characteristics of our novel TIDE subtypes using real-world BC samples and collected patient clinical data. This subtyping method was proved to be more efficient than previous known methods in identifying non-responders to immunotherapy. We also propose that combining our TIDE subtypes with known biomarkers can potentially improve the sensitivity and specificity of these biomarkers. Moreover, besides guiding ICB treatment, this classification approach can assist in selecting the frontline or recommended drugs. Finally, we confirmed that the TIDE subtypes are conserved across the pan-tumors., Conclusions: Our novel TIDE-based subtyping method can serve as a powerful clinical tool for BC and pan-cancer patients, and potentially guiding personalized therapy decisions for selecting potential beneficiaries and excluding resistant patients of ICB therapy., (© 2024. The Author(s).)

Background: Heterogeneity among critically ill patients undergoing invasive mechanical ventilation (IMV) treatment could result in high mortality rates. Currently, there are no well-established indicators to help identify patients with a poor prognosis in advance, which limits physicians' ability to provide personalized treatment. This study aimed to investigate the association of oxygen saturation index (OSI) trajectory phenotypes with intensive care unit (ICU) mortality and ventilation-free days (VFDs) from a dynamic and longitudinal perspective., Methods: A group-based trajectory model was used to identify the OSI-trajectory phenotypes. Associations between the OSI-trajectory phenotypes and ICU mortality were analyzed using doubly robust analyses. Then, a predictive model was constructed to distinguish patients with poor prognosis phenotypes., Results: Four OSI-trajectory phenotypes were identified in 3378 patients: low-level stable, ascending, descending, and high-level stable. Patients with the high-level stable phenotype had the highest mortality and fewest VFDs. The doubly robust estimation, after adjusting for unbalanced covariates in a model using the XGBoost method for generating propensity scores, revealed that both high-level stable and ascending phenotypes were associated with higher mortality rates (odds ratio [OR]: 1.422, 95% confidence interval [CI] 1.246-1.623; OR: 1.097, 95% CI 1.027-1.172, respectively), while the descending phenotype showed similar ICU mortality rates to the low-level stable phenotype (odds ratio [OR] 0.986, 95% confidence interval [CI] 0.940-1.035). The predictive model could help identify patients with ascending or high-level stable phenotypes at an early stage (area under the curve [AUC] in the training dataset: 0.851 [0.827-0.875]; AUC in the validation dataset: 0.743 [0.709-0.777])., Conclusions: Dynamic OSI-trajectory phenotypes were closely related to the mortality of ICU patients requiring IMV treatment and might be a useful prognostic indicator in critically ill patients., (© 2023. The Author(s).)

Background: Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone., Methods: A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups., Results: Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263)., Conclusions: For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Inositol monophosphates (IMP) are key enzymes in the ascorbic acid (AsA) synthesis pathways, which play vital roles in regulating plant growth and development and stresses tolerance. To date, no comprehensive analysis of the expression profile of IMP genes and their functions under abiotic stress in cotton has been reported., Results: In this study, the genetic characteristics, phylogenetic evolution, cis-acting elements and expression patterns of IMP gene family in cotton were systematically analyzed. A total of 28, 27, 13 and 13 IMP genes were identified in Gossypium hirsutum (G. hirsutum), Gossypium barbadense (G. barbadense), Gossypium arboreum (G. arboreum), and Gossypium raimondii (G. raimondii), respectively. Phylogenetic analysis showed that IMP family genes could cluster into 3 clades. Structure analysis of genes showed that GhIMP genes from the same subgroup had similar genetic structure and exon number. And most GhIMP family members contained hormone-related elements (abscisic acid response element, MeJA response element, gibberellin response element) and stress-related elements (low temperature response element, defense and stress response element, wound response element). After exogenous application of abscisic acid (ABA), some GhIMP genes containing ABA response elements positively responded to alkaline stress, indicating that ABA response elements played an important role in response to alkaline stress. qRT-PCR showed that most of GhIMP genes responded positively to alkaline stress, and GhIMP10D significantly upregulated under alkaline stress, with the highest up-regulated expression level. Virus-induced gene silencing (VIGS) experiment showed that compared with 156 plants, MDA content of pYL156:GhIMP10D plants increased significantly, while POD, SOD, chlorophyII and AsA content decreased significantly., Conclusions: This study provides a thorough overview of the IMP gene family and presents a new perspective on the evolution of this gene family. In particular, some IMP genes may be involved in alkaline stress tolerance regulation, and GhIMP10D showed high expression levels in leaves, stems and roots under alkaline stress, and preliminary functional verification of GhIMP10D gene suggested that it may regulate tolerance to alkaline stress by regulating the activity of antioxidant enzymes and the content of AsA. This study contributes to the subsequent broader discussion of the structure and alkaline resistance of IMP genes in cotton., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: This study aimed to investigate the effects of different ferrule heights and crown-to-root ratios on the fracture resistance of endodontically-treated premolars restored with fiber post or cast metal post system., Methods: Eighty extracted human mandibular first premolars with single root canal were treated endodontically and cut from 2.0 mm above the buccal cemento-enamel junction, to create horizontal residual roots. The roots were randomly divided into two groups. The roots in group FP were restored with a fiber post-and-core system, while the roots in group MP were restored with a cast metal post-and-core system. Each group was divided into five subgroups with different ferrule heights (0: no ferrule; 1: 1.0 mm ferrule; 2: 2.0 mm ferrule; 3: 3.0 mm ferrule; 4: 4.0 mm ferrule). All specimens were subsequently restored with metal crowns and embedded in acrylic resin blocks. The crown-to-root ratios of the specimens were controlled at approximately 0.6, 0.8, 0.9, 1.1, and 1.3 of the five subgroups, respectively. Fracture strengths and fracture patterns of the specimens were tested and recorded by a universal mechanical machine., Results: Mean fracture strengths (mean ± standard deviation (kN)) of FP/0 to FP/4 and MP/0 to MP/4 were: 0.54 ± 0.09, 1.03 ± 0.11, 1.06 ± 0.17, 0.85 ± 0.11; 0.57 ± 0.10, 0.55 ± 0.09, 0.88 ± 0.13, 1.08 ± 0.17, 1.05 ± 0.18 and 0.49 ± 0.09, respectively. Two-way ANOVA revealed significant effects of different ferrule heights and crown-to-root ratios on the fracture resistance (P < 0.001), but no difference in fracture resistance between two post-and-core systems (P = 0.973). The highest fracture strengths of the specimen were found with the ferrule length of 1.92 mm in group FP and 2.07 mm in group MP, the crown-to-root ratio of which in 0.90 and 0.92 respectively., there is a significant difference in fracture patterns among the groups(P < 0.05)., Conclusions: When a certain height of ferrule is prepared and a cast metal or fiber post-and-core system is restored for the residual root, the clinical crown-to-root ratio of the tooth after restoration should be kept within 0.90 to 0.92, so as to improve the fracture resistance of endodontically-treated mandibular first premolars., (© 2023. The Author(s).)

Background: Patients with systemic lupus erythematosus (SLE) have autoantibodies against the L1-encoded open-reading frame 1 protein (ORF1p). Here, we report (i) which immune cells ORF1p emanates from, (ii) which L1 loci are transcriptionally active, (iii) whether the cells express L1-dependent interferon and interferon-stimulated genes, and (iv) the effect of inhibition of L1 ORF2p by reverse transcriptase inhibitors., Results: L1 ORF1p was detected by flow cytometry primarily in SLE CD66b + CD15 + regular and low-density granulocytes, but much less in other immune cell lineages. The amount of ORF1p was higher in neutrophils from patients with SLE disease activity index (SLEDAI) > 6 (p = 0.011) compared to patients with inactive disease, SLEDAI < 4. Patient neutrophils transcribed seven to twelve human-specific L1 loci (L1Hs), but only 3 that are full-length and with an intact ORF1. Besides serving as a source of detectable ORF1p, the most abundant transcript encoded a truncated ORF2p reverse transcriptase predicted to remain cytosolic, while the two other encoded an intact full-length ORF2p. A number of genes encoding proteins that influence L1 transcription positively or negatively were altered in patients, particularly those with active disease, compared to healthy controls. Components of nucleic acid sensing and interferon induction were also altered. SLE neutrophils also expressed type I interferon-inducible genes and interferon β, which were substantially reduced after treatment of the cells with drugs known to inhibit ORF2p reverse transcriptase activity., Conclusions: We identified L1Hs loci that are transcriptionally active in SLE neutrophils, and a reduction in the epigenetic silencing mechanisms that normally counteract L1 transcription. SLE neutrophils contained L1-encoded ORF1p protein, as well as activation of the type I interferon system, which was inhibited by treatment with reverse transcriptase inhibitors. Our findings will enable a deeper analysis of L1 dysregulation and its potential role in SLE pathogenesis., (© 2023. The Author(s).)

Background: Cotton is an important industrial crop and a pioneer crop for saline-alkali land restoration. However, the molecular mechanism underlying the cotton response to salt is not completely understood., Methods: Here, we used metabolome data and transcriptome data to analyze the salt tolerance regulatory network of cotton and metabolic biomarkers., Results: In this study, cotton was stressed at 400 m M NaCl for 0 h, 3 h, 24 h and 48 h. NaCl interfered with cotton gene expression, altered metabolite contents and affected plant growth. Metabolome analysis showed that NaCl stress increased the contents of amino acids, sugars and ABA, decreased the amount of vitamin and terpenoids. K-means cluster analysis of differentially expressed genes showed that the continuously up-regulated genes were mainly enriched in metabolic pathways such as flavonoid biosynthesis and amino acid biosynthesis., Conclusion: The four metabolites of cysteine (Cys), ABA(Abscisic acid), turanose, and isopentenyladenine-7-N-glucoside (IP7G) were consistently up-regulated under salt stress, which may indicate that they are potential candidates for cotton under salt stress biomarkers. Combined transcriptome and metabolome analysis revealed accumulation of cysteine, ABA, isopentenyladenine-7-N-glucoside and turanose were important for salt tolerance in cotton mechanism. These results will provide some metabolic insights and key metabolite biomarkers for salt stress tolerance, which may help to understanding of the metabolite response to salt stress in cotton and develop a foundation for cotton to grow better in saline soil., (© 2023. The Author(s).)

Background: 2-oxoglutarate-dependent dioxygenase (2ODD) is the second largest family of oxidases involved in various oxygenation/hydroxylation reactions in plants. Many members in the family regulate gene transcription, nucleic acid modification/repair and secondary metabolic synthesis. The 2ODD family genes also function in the formation of abundant flavonoids during anthocyanin synthesis, thereby modulating plant development and response to diverse stresses., Results: Totally, 379, 336, 205, and 204 2ODD genes were identified in G. barbadense (Gb), G. hirsutum (Gh), G. arboreum (Ga), and G. raimondii (Gb), respectively. The 336 2ODDs in G. hirsutum were divided into 15 subfamilies according to their putative functions. The structural features and functions of the 2ODD members in the same subfamily were similar and evolutionarily conserved. Tandem duplications and segmental duplications served essential roles in the large-scale expansion of the cotton 2ODD family. Ka/Ks values for most of the gene pairs were less than 1, indicating that 2ODD genes undergo strong purifying selection during evolution. Gh2ODDs might act in cotton responses to different abiotic stresses. GhLDOX3 and GhLDOX7, two members of the GhLDOX subfamily from Gh2ODDs, were significantly down-regulated in transcription under alkaline stress. Moreover, the expression of GhLDOX3 in leaves was significantly higher than that in other tissues. These results will provide valuable information for further understanding the evolution mechanisms and functions of the cotton 2ODD genes in the future., Conclusions: Genome-wide identification, structure, and evolution and expression analysis of 2ODD genes in Gossypium were carried out. The 2ODDs were highly conserved during evolutionary. Most Gh2ODDs were involved in the regulation of cotton responses to multiple abiotic stresses including salt, drought, hot, cold and alkali., (© 2023. The Author(s).)

Background: To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method., Methods: The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time., Results: All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into "early phase" and "late phase." In "late phase" cases, there was less time spent on each step of the operation and less EBL., Conclusions: Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique., (© 2023. The Author(s).)

Background: Abscisic acid (ABA) is an important stress hormone, the changes of abscisic acid content can alter plant tolerance to stress, abscisic acid is crucial for studying plant responses to abiotic stress. The abscisic acid aldehyde oxidase (AAO) plays a vital role in the final step in the synthesis of abscisic acid, therefore, understanding the function of AAO gene family is of great significance for plants to response to abiotic stresses., Result: In this study, 6, 8, 4 and 4 AAO genes were identified in four cotton species. According to the structural characteristics of genes and the traits of phylogenetic tree, we divided the AAO gene family into 4 clades. Gene structure analysis showed that the AAO gene family was relatively conservative. The analysis of cis-elements showed that most AAO genes contained cis-elements related to light response and plant hormones. Tissue specificity analysis under NaHCO 3 stress showed that GhAAO2 gene was differentially expressed in both roots and leaves. After GhAAO2 gene silencing, the degree of wilting of seedlings was lighter than that of the control group, indicating that GhAAO2 could respond to NaHCO 3 stress., Conclusions: In this study, the AAO gene family was analyzed by bioinformatics, the response of GhAAO gene to various abiotic stresses was preliminarily verified, and the function of the specifically expressed gene GhAAO2 was further verified. These findings provide valuable information for the study of potential candidate genes related to plant growth and stress., (© 2022. The Author(s).)

Background: We evaluated the prognostic role of deficient mismatch repair (dMMR) systems in stage II and stage III colon cancer patients during different postoperative periods. We also assessed whether patients aged ≥75 could benefit from chemotherapy., Methods: This retrospective study was conducted across three medical centers in China. Kaplan-Meier survival methods and Cox proportional hazards models were used to evaluate the differences in overall survival (OS) and disease-free survival (DFS) rates. Propensity score matching was performed to reduce imbalances in the baseline characteristics of the patients. Landmark analysis was performed to evaluate the role of dMMR during different postoperative periods., Results: The median follow-up time for all patients was 45.0 months (25-75 IQR: 38.0-82.5). There was no significant OS (p = 0.350) or DFS (p = 0.752) benefit associated with dMMR for stage II and III patients during the first postoperative year. However, significant OS (p < 0.001) and DFS (p < 0.001) benefits were observed from the second postoperative year until the end of follow-up. These differences remained after propensity score matching. Moreover, chemotherapy produced no OS (HR = 0.761, 95% CI: 0.43-1.34, p = 0.341) or DFS (HR = 0.98, 95% CI: 0.51-1.88, p = 0.961) benefit for patients aged ≥75 years., Conclusion: The benefits of dMMR in stage III patients were observed from the second postoperative year until the end of follow-up. However, the prognosis of patients with dMMR is not different from that of patients with proficient mismatch repair (pMMR) during the first postoperative year. In addition, elderly patients aged ≥75 years obtained no significant survival benefits from postoperative chemotherapy., (© 2022. The Author(s).)

Background: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear., Methods: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis., Results: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment., Conclusions: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients., (© 2022. The Author(s).)

Background: The burden of healthcare-associated infections (HAIs) and the spread of antimicrobial resistance can be potentially preventable through comprehensive infection prevention and control (IPC) programs. However, information on the current state of IPC implementation is rare in China., Methods: A cross-sectional study was conducted in Zhejiang province, China, from April to June 2021. The Zhejiang nosocomial infection control and quality improvement center (NICQI) cooperated with 11 municipal NICQI centers to introduce the purpose of this study and invite all licensed secondary and tertiary hospitals in Zhejiang province through WeChat group. The questionnaire had three sections, including information about participating hospitals, demographic information about IPs, and the Chinese version of the Infection Prevention and Control Assessment Framework that covered eight core components (CC)., Results: Of the 382 hospitals invited, 222 (58.1% response rate) accepted and completed the online questionnaire. The overall median score of the participating hospitals was 682 (630-723), which corresponded to an advanced level of IPC. There was a significant difference in scores between hospitals types (P < 0.001). Profound differences were revealed regarding the scores of the individual components, with CC2 (IPC guidelines) and CC6 (Monitoring/audit of IPC practices and feedback) having the highest (100) and lowest (65) median scores, respectively. Only 23 (10.4%) hospitals reported assessing facility safety culture., Conclusions: IPC structures are at a relatively high level in acute care hospitals in Eastern China. The identified potential areas for improvement were similar to those identified in developed countries, particularly regarding multimodal strategies for implementation and safety culture construction. Meanwhile, the Chinese government should pay more attention to IPC resources and practices among secondary care hospitals., (© 2022. The Author(s).)

Purposes: In addition to its role in cellular progression and cancer, SIRT6, a member of nicotinamide adenine dinucleotide (NAD + )-dependent class III deacylase sirtuin family, serves a variety of roles in the body's immune system. In this study, we sought to determine the relationship between the expression of SIRT6 and the clinicopathological outcomes of patients with solid tumours by conducting a meta-analysis of the available data., Methods: The databases PubMed and ISI Web of Science were searched for relevant literature, and the results were presented here. Using Stata16.0, a meta-analysis was conducted to determine the impact of SIRT6 on clinicopathological characteristics and prognosis in malignancy patients. The results were published in the journal Cancer Research. The dataset from the Cancer Genome Atlas (TCGA) was used to investigate the prognostic significance of SIRT6 in various types of tumors., Results: The inclusion and exclusion criteria were met by 15 studies. In patients with solid tumours, reduced SIRT6 expression was found to be related with improved overall survival (OS) (HR = 0.66, 95% CI = 0.45-0.97, P < 0.001) as well as improved disease-free survival (DFS) (HR = 0.48, 95% CI = 0.26-0.91, P < 0.001). Low SIRT6 expression was found to be associated with a better OS in breast cancer (HR = 0.49, 95% CI = 0.27-0.89, P = 0.179), but was found to be associated with a worse OS in gastrointestinal cancer (gastric cancer and colon cancer) (HR = 1.83, 95% CI = 1.20-2.79, P = 0.939) after subgroup analysis. In terms of clinicopathological characteristics, SIRT6 expression was found to be linked with distant metastasis (OR = 2.98, 95% CI = 1.59-5.57, P = 0.694). When the data from the TCGA dataset was compared to normal tissue, it was discovered that SIRT6 expression was significantly different in 11 different types of cancers. Meanwhile, reduced SIRT6 expression was shown to be associated with improved OS (P < 0.05), which was consistent with the findings of the meta-analysis. Aside from that, the expression of SIRT6 was found to be associated with both gender and clinical stage., Conclusion: The overall data of the present meta-analysis indicated that low expression of SIRT6 may predict a favorable survival for patients with solid tumors., (© 2022. The Author(s).)

Background: The decoction of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) has been reported as a potential antitumor agent for colorectal cancer (CRC) in experimental and clinical studies, but its underlying mechanism is still unclear., Methods: The current research aims to explore the potential of Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) decoction (AR decoction) in the treatment of CRC and explore the underlying mechanism. SW620 cells were transient transfection to overexpress or knock down wnt 5 or β-Catenin. Astragalus membranaceus (Huangqi) and Rhizoma curcumae (Ezhu) -containing serum (AR-CS) was used to interfere with SW620 cells. Additional AR-CS, Wnt5 inhibitor (IWP-4), and β-Catenin inhibitor (JW55) were used to intervene in SW620 cells. Furthermore, subcutaneously injection of SW620 cells into the right flank of nude mice replicated xenograft mice, which were treated with AR decoction for 21 days., Results: AR-CS significantly reduced the mRNA and protein expression levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in SW620 cells, while inhibiting the proliferation and migration of SW620 cells. In cells overexpressing Wnt5 or β-Catenin, these effects of AR-CS were significantly suppressed. On the contrary, the inhibitory effect of AR-CS on the mRNA and protein levels of ARF6 and N-Cadherin and cell proliferation and migration of SW620 was enhanced, when Wnt5 or β-Catenin were knocked down or suppressed by the inhibitors. Moreover, in the mouse model of xenograft tumors, AR decoction not only reduced the tumor volume and inhibited the mRNA levels and protein levels of Wnt5, β-Catenin, ARF6, and N-Cadherin in the tumor, but also inhibit the protein levels of LRP5, LRP6, TCF-4, and LEF1.The histopathology of mice also showed increased apoptosis in tumor tissues, and AR decoction treatment did not cause pathological damage to the kidney and liver., Conclusions: Our results provide evidence that AR decoction inhibits Wnt5/β-catenin signaling and inhibits the development of CRC, which is a promising traditional medicine in the clinical treatment of CRC., (© 2022. The Author(s).)

Background: Non-small cell lung cancer (NSCLC) is a malignancy with considerable morbidity and mortality. Abnormal metabolism is a hallmark of cancer; however, the mechanism of glycolysis regulation in NSCLC progression is not completely understood. Recent studies suggest that some dysregulated long non-coding RNAs (lncRNAs) play important roles in tumor metabolic reprogramming., Methods: To identify glycolysis-associated-lncRNAs in NSCLC, we compared RNA-sequencing results between high 18 F-fluorodeoxyglucose (FDG)-uptake NSCLC tissues and paired paratumor tissues. The transcript abundance of AL355338 in 80 pairs of clinical samples was evaluated by quantitative real-time PCR assay and fluorescence in situ hybridization. The biological role of AL355338 on NSCLC cells were evaluated by functional experiments in vitro and in vivo. Moreover, RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP) assays were used to identify the protein interacted with AL355338. Co-immunoprecipitation, in situ proximity ligation assays and western blotting were applied to define the potential downstream pathways of AL355338., Results: AL355338 was an upregulated glycolysis-associated lncRNA in NSCLC. Functional assays revealed that AL355338 was critical for promoting aerobic glycolysis and NSCLC progression. Mechanistic investigations showed that AL355338 directly bound with alpha-enolase (ENO1) and enhanced the protein's stability by modulating its degradation and ubiquitination. A positive correlation was observed between AL355338 and ENO1 in NSCLC, and ENO1 was subsequently confirmed to be responsible for the oncogenic role of AL355338. Furthermore, AL355338 was capable of modulating ENO1/EGFR complex interaction and further activating EGFR-AKT signaling., Conclusions: This study indicates that AL355338 confers an aggressive phenotype to NSCLC, and targeting it might be an effective therapeutic strategy., (© 2021. The Author(s).)

Background: There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients., Methods: Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed., Results: Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718-7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789-11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054-13.369; P = .041) in the anti-HBc positive cases., Conclusions: Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients., (© 2021. The Author(s).)

Background: Most patients with systemic lupus erythematosus (SLE) have IgG autoantibodies against the RNA-binding p40 (ORF1p) protein encoded by the L1 retroelement. This study tested if these autoantibodies are also present in children with pediatric SLE (pSLE) and if the p40 protein itself could be detected in immune cells., Methods: Autoantibodies in the plasma of pSLE patients (n = 30), healthy children (n = 37), and disease controls juvenile idiopathic arthritis (JIA) (n = 32) and juvenile dermatomyositis (JDM) (n = 60), were measured by ELISA. Expression of p40 in immune cells was assessed by flow cytometry. Markers of neutrophil activation and death were quantitated by ELISA., Results: IgG and IgA autoantibodies reactive with p40 were detected in the pSLE patients, but were low in healthy controls and in JIA or JDM. pSLE patients with active disease (13 of them newly diagnosed) had higher titers than the same patients after effective therapy (p = 0.0003). IgG titers correlated with SLEDAI (r = 0.65, p = 0.0001), ESR (r = 0.43, p = 0.02), and anti-dsDNA antibodies (r = 0.49, p < 0.03), and inversely with complement C3 (r = -0.55, p = 0.002) and C4 (r = -0.51, p = 0.006). p40 protein was detected in a subpopulation of CD66b + granulocytes in pSLE, as well as in adult SLE patients. Myeloperoxidase and neutrophil elastase complexed with DNA and the neutrophil-derived S100A8/A9 were elevated in plasma from pSLE patients with active disease and correlated with anti-p40 autoantibodies and disease activity., Conclusions: Children with active SLE have elevated IgG and IgA autoantibodies against L1 p40, and this protein can be detected in circulating granulocytes in both pediatric and adult SLE patients. P40 expression and autoantibody levels correlate with disease activity. Markers of neutrophil activation and death also correlate with these autoantibodies and with disease activity, suggesting that neutrophils express L1 and are a source of p40.

Background: In mammals, specification of primordial germ cells (PGCs) is established in the early post-implantation embryo. The bone morphogenetic protein (BMP)-SMAD and WNT3-β-catenin signaling initiate the gene regulatory network for PGC specification. The activation of SOX17-BLIMP1 axis is critical for human PGC program. Moreover, EpCAM and INTEGRINα6 were identified as surface markers of human PGC-like cells (PGCLCs) recently. However, the signaling mechanism for PGC specification in non-rodent mammals remains to be clarified., Methods: We differentiated human induced pluripotent stem cells (hiPSCs) into PGCLCs in vitro in response to Activin A and BMP4. The percentage of EpCAM/INTEGRINα6 double-positive cells (PGCLCs) was analyzed by flow cytometry. The expression of PGC genes was evaluated by qRT-PCR and immunofluorescence. The expression dynamic of multi-lineage genes during the differentiation process was evaluated by qRT-PCR., Results: Under the stimulation for PGCLC induction, the embryoids derived from hiPSCs initiated significant upregulation of the early PGC genes (BLIMP1, TFAP2C, and NANOS3), but maintained low or no levels of DPPA3 and late PGC genes (DAZL and DDX4). The percentage of EpCAM/INTEGRINα6 double-positive PGCLCs reached the highest at day 6 of induction. After pre-induction, the incipient mesoderm-like cells (iMeLCs) upregulated most of the mesoderm genes (EOMES, T, MSXI, RUNX2, and MIXL1). The differentiating embryoids showed high levels of key pluripotency genes, OCT4 and NANOG, but became negative for SOX2. In contrast to iMeLCs, the differentiating embryoids downregulated mesoderm genes RUNX2 and EOMES, and ectoderm gene PAX6, but increased the expression of endoderm gene SOX17., Conclusions: During PGCLC induction process in vitro, the differentiating embryoids not only activated the PGC-related genes, but also displayed complex regulation of pluripotency genes and multi-lineage genes. These results would be meaningful for future research investigating the regulation of human early germ line development.

Background: Lung cancer is one of the most common malignant tumors worldwide. CD36 is a receptor for fatty acids and plays an important role in regulating fatty acid metabolism, which is closely related to tumorigenesis and development. The regulation of miR-21 and its role in tumorigenesis have been extensively studied in recent years. However, the relationship between miR-21 and CD36 regulated fatty acid metabolism in human non-small cell lung cancer remains unknown., Methods: In this study, lentivirus transfection, qRT-PCR, cell migration, immunofluorescence, and western blot were used to examine the relationship between miR-21 and CD36 regulated fatty acid metabolism and the regulation role of miR-21 in human non-small cell lung cancer., Results: This study demonstrated that up-regulation of miR-21 promoted cell migration and cell growth in human non-small cell lung cancer cells. Moreover, the intracellular contents of lipids including cellular content of phospholipids, neutral lipids content, cellular content of triglycerides were significantly increased following miR-21 mimic treatment compared with control, and the levels of key lipid metabolic enzymes FASN, ACC1 and FABP5 were obviously enhanced in human non-small cell lung cancer cells. Furthermore, down-regulation of CD36 suppressed miR-21 regulated cell growth, migration and intracellular contents of lipids in human non-small cell lung cancer cells, which suggested that miR-21 promoted cell growth and migration of human non-small cell lung cancer cells through CD36 mediated fatty acid metabolism. Inhibition of miR-21 was revealed to inhibit cell growth, migration, intracellular contents of lipids, and CD36 protein expression level in human non-small cell lung cancer cells. In addition, PPARGC1B was a direct target of miR-21, and down-regulation of PPARGC1B reversed the inhibition of CD36 expression induced by miR-21 inhibitor., Conclusions: These results explored the mechanism of miR-21 promoted non-small cell lung cancer and might provide a novel therapeutic method in treating non-small cell lung cancer in clinic., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Human adenovirus type 3 (HAdV-3) and 7 (HAdV-7) cause significant morbidity and develop severe complications and long-term pulmonary sequelae in children. However, epidemiologic reports have suggested that nearly all highly severe or fatal adenoviral diseases in children are associated with HAdV-7 rather than HAdV-3. Here, we conduct in-depth investigations to confirm and extend these findings through a comprehensive series of assays in vitro and in vivo as well as clinical correlates., Methods: A total of 8248 nasopharyngeal aspirate (NPA) samples were collected from hospitalized children with acute respiratory infections in Children's Hospital of Chongqing Medical University from June 2009 to May 2015. Among 289 samples that tested positive for HAdVs, clinical data of 258 cases of HAdV-3 (127) and HAdV-7 (131) infections were analyzed. All HAdV-positive samples were classified by sequencing the hexon and fiber genes, and compared with clinical data and virological assays. We also performed in vitro assays of virus quantification, viral growth kinetics, competitive fitness, cytotoxicity and C3a assay of the two strains. Mouse adenovirus model was used to evaluate acute inflammatory responses., Results: Clinical characteristics revealed that HAdV-7 infection caused more severe pneumonia, toxic encephalopathy, respiratory failure, longer mean hospitalization, significantly lower white blood cell (WBC) and platelet counts, compared to those of HAdV-3. In cell culture, HAdV-7 replicated at a higher level than HAdV-3, and viral fitness showed significant differences as well. HAdV-7 also exhibited higher C3a production and cytotoxic effects, and HAdV-7-infected mice showed aggravated pathology and higher pulmonary virus loads, compared to HAdV-3-infected mice. Macrophages in BALF remained markedly high during infection, with concomitant increase in pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ, and IL-6), compared HAdV-3 infection., Conclusions: These results document that HAdV-7 replicates more robustly than HAdV-3, and promotes an exacerbated cytokine response, causing a more severe airway inflammation. The findings merit further mechanistic studies that offer the pediatricians an informed decision to proceed with early diagnosis and treatment of HAdV-7 infection.

Background: To report a first case of lenticule addition and corneal cross-linking for post-LASIK ectasia with associated corneal thinning., Case Presentation: Lenticule addition followed by corneal cross-linking was performed on the left eye of a patient with post-LASIK ectasia. Postoperatively, the corneal power and elevation were stable with a remarkable improvement in corneal thickness, and the lenticule had merged with the adjacent corneal stroma at 30 months follow-up. The patient's corrected distance visual acuity gained two lines., Conclusions: This case provides a potential treatment option for patients with keratectasia and keratoconus in association with thin corneal thickness (less than 400 μm) and may provide the benefit of delaying or avoiding the need for keratoplasty, which has its own associated complications and is limited by the availability of donor corneas.

Background: To report a first case of late-onset diffuse lamellar keratitis (DLK) occurring 4 years after femtosecond laser-assisted small incision lenticule extraction (SMILE)., Case Presentation: A 41-year-old man who underwent SMILE 4 years prior developed DLK in the right eye 1 day after he was struck in the eye by a finger while playing with his son. Slim-lamp microscopy and anterior segment optical coherence tomography (AS-OCT) were used to evaluate the cornea of the right eye. Slit-lamp examination of the right eye revealed epithelial exfoliation and stage 3 DLK with diffuse, dot-like, granular haze in the interface between the cap and stromal bed. After intensive treatment with topical corticosteroids, the DLK resolved and corneal transparency was achieved., Conclusions: This case indicates that DLK can occur several years after SMILE. Ocular trauma may be a risk factor for the development of DLK. The prognosis is usually favorable with early diagnosis and treatment with topical corticosteroids.