Objective:To explore the effects of ubiquitin-conjugating enzyme E2L3 (UBE2L3) on the proliferation and apoptosis of head and neck squamous cell carcinoma (HNSCC) cell line UMSCC-1 in vitro and its potential mechanisms, and to investigate the relationship between UBE2L3 and immune cell infiltration in the HNSCC tumor microenvironment.Methods:The plasmid carrying UBE2L3 gene sequence was transfected into UMSCC-1 cells by using liposome transfection technology (UBE2L3 overexpression group), and UMSCC-1 cells transfected with the empty plasmid was treated as the control group. The quantitative polymerase chain reaction (qPCR) was used to detect the expression level of UBE2L3 mRNA after transfection, and the transfection efficiency was evaluated. The proliferation levels of the 2 groups of cells were detected by using CCK-8 assay and the cell proliferation rate was calculated. The apoptosis rates of the 2 groups of cells after etoposide induced apoptosis for 24 h were detected by using flow cytometry. The expression levels of Cyclin D1, apoptosis-related proteins bcl-2, and Bax in the 2 groups of cells were detected by using Western blotting. The samples of 504 HNSCC tissues in the Cancer Genome Atlas (TCGA) were analyzed by using the single-sample gene set enrichment analysis (ssGSEA) database. The median expression level of UBE2L3 was used to distinguish between high and low expression of UBE2L3 transcriptional level. The differences in immune cell enrichment score between high and low expression samples were compared, and the relationship between UBE2L3 expression level and immune cell number was analyzed.Results:qPCR results showed that the relative expression level of UBE2L3 mRNA in UMSCC-1 cells carrying UBE2L3 gene sequence plasmid was higher than that in UMSCC-1 cells transfected with the empty plasmid (9.32±1.15 vs. 1.00±0.02), and the difference was statistically significant ( t = 7.23, P < 0.001), indicating successful transfection. The CCK-8 assay showed that the cell proliferation rate of UMSCC-1 cells in the UBE2L3 overexpression group for 24 h and 48 h of culture was higher than that in the control group [24 h: (184.0±7.9)% vs. (100.0±5.6)%; 48 h: (165.5±5.3)% vs. (100.0±5.3)%], and the differences were statistically significant (both P < 0.001). Flow cytometry showed that the apoptosis rate of UMSCC-1 cells in the UBE2L3 overexpression group was lower than that in the control group [(9.9±1.3)% vs. (15.6±1.3)%], and the difference was statistically significant ( t = 2.78, P = 0.005). Western blotting showed that the relative expression levels of Cyclin D1 and bcl-2 proteins in UMSCC-1 cells of the UBE2L3 overexpression group were higher than those in the control group, while the relative expression level of Bax protein was lower than that in the control group, and the differences were statistically significant (all P < 0.05). The ssGSEA analysis showed that the enrichment scores of B cells, CD8 + T cells, neutrophils, T cells, T helper 17 (Th17) cells, and regulatory T cells (Treg) in 252 HNSCC tissues samples with low UBE2L3 transcriptional expression level were higher than in 252 samples with high UBE2L3 transcriptional expression level in the TCGA database, while the enrichment scores of natural killer (NK) cells and T helper 2 (Th2) cells in patients with low UBE2L3 expression were lower than those in those with high UBE2L3 expression, and the differences were statistically significant (all P < 0.05). Correlation analysis showed that the expression level of UBE2L3 in HNSCC tissues was positively correlated with the number of Th2 cells ( R = 0.182) and NK cells ( R = 0.172), and negatively correlated with the number of Treg cells ( R = -0.095), dendritic cells ( R = -0.099), Th17 cells ( R = -0.129), CD8 + T cells ( R = -0.146), mast cells ( R = -0.161), T cells ( R = -0.171), and B cells ( R = -0.188), and the differences were statistically significant (all P > 0.05). Conclusions:UBE2L3 can promote the proliferation and inhibit the apoptosis of HNSCC cells probably by regulating the cell cycle and apoptosis signaling pathways through Cyclin D1, bcl-2, and Bax. UBE2L3 may be associated with immune cell infiltration in the HNSCC microenvironment.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, which not only affects the digestive tract, but also involves extraintestinal organs and tissues such as joints and eyes, and ultimately endangers human health and affects the quality of life of patients. With the development of information technology, there is an increasing application of digital therapeutics in the management of IBD. This article aims to comprehensively analyze the characteristics, use, and challenges of digital therapeutics in the management of IBD, and explore its potential to improve treatment adherence, disease surveillance, and improve patients' quality of life.

Objective:To investigate the association between anti-rituximab antibodies (ARA) and relapse after rituximab (RTX) therapy in children with frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS).Methods:A retrospective cohort study was conducted. Clinical and laboratory data were collected from 48 FRNS or SDNS children treated with RTX in the Department of Pediatrics, General Hospital of Eastern Theater Command, between April 2024 and October 2024. Data included RTX dosing frequency, relapse events, peripheral CD20? B-cell counts, and ARA levels. With a 6-month observation period after the last RTX therapy, the children were divided into an ARA-positive group and an ARA-negative group based on ARA test results. Chi-square test, independent sample t-test, or Mann-Whitney U test were used to compare relapse rates and laboratory indicators between the two groups. The predictive value of ARA levels for relapse was evaluated using univariate receiver operating characteristic (ROC) curve analysis. Results:Among the 48 children (36 males, 12 females), the age of disease onset was 3.5 (2.0, 6.0) years, the ages at the first and last RTX treatments were 7.0 (5.0, 12.0) years and 9.5 (7.0, 13.0) years, respectively. The overall ARA positive rate was 29% (14/48). The relapse rate in the ARA-positive group was significantly higher than that in the negative group ( P<0.05). The ARA level was 0.01 (0.01, 5.88) μg/L, and all 12 children with ARA levels >5.88 μg/L relapsed. ROC curve analysis showed that ARA levels predicted relapse after RTX treatment in FRNS or SDNS children with an area under the curve (AUC) of 0.73, sensitivity of 0.50, specificity of 1.00, and an optimal cut-off value of 5.02 μg/L. All children received single-dose RTX therapy, with no significant difference in treatment frequency between the two groups ( P>0.05). At 3 months after the last rituximab therapy, CD20? B cell counts were significantly higher in the ARA-positive group ( P<0.05). During follow-up, 15% (7/48) of the children experienced infusion-related adverse reactions, with no significant difference in incidence between the two groups ( P>0.05). Conclusion:ARA is significantly associated with relapse in FRNS or SDNS children after RTX therapy.

Objective:To provide reference for improving the ability of Investigator-Initiated Trials (IIT) research ethics review in the new era by analyzing the situation of clinical research projects and ethical review in hospitals under the increasingly standardized management requirements of clinical research.Methods:Taking the IIT projects reviewed by the Ethics Committee of our Institute from 2012 to 2023 as examples, the development trend, types, characteristics and the situation of ethical review were comprehensively compared and analyzed.Results:From 2012 to 2023, the number of IIT projects in our hospital increased rapidly, especially the multi-center and high-risk projects. IIT researches in the field of oncology and neurology are hot topics at present. After the addition of scientific review, the passing rate of ethical review increased. After the promulgation of the new regulations, the application rate of follow-up examination increased to a certain extent.Conclusions:In view of the current types and distribution characteristics of IIT, as well as key weaknesses in ethical review, the ethics Committee should strengthen the qualification management of main researchers and research teams, standardize the annual follow-up review of IIT research through multiple channels such as research ethics education and information platform, promote the establishment of the responsibility system of research liaison officers, and improve the review process of off-label drug use research. High-risk IIT projects should strengthen ethical supervision, case-by-case reporting and tracking system, and vulnerable groups projects should strengthen ethical review and supervision of informed consent process, and explore the establishment of a high-quality ethical management system from the above aspects.

OBJECTIVE To explore the distribution of pathogens isolated from the cervical cancer(CC)patients with postoperative urinary catheter-associated urinary tract infection(UTI)and analyze the predictive values of se-rum high mobility group protein B1(HMGB1),Toll-like receptor 4(TLR4)and nuclear factor kappa B(NF-κB).METHODS Totally 116 patients with CC who underwent radical resection in the First Affiliated Hospital of Henan University of Science and Technology from Jan.2021 to Jan.2024 were enrolled in the study and were divided into the infection group with 31 cases and the non-infection group with 85 cases according to the status of complication with UTI after urinary catheterization.The midstream urine specimens were collected by aseptic method,the pathogens were isolated and identified.The serum HMGB1 level was detected by means of enzyme-linked immu-nosorbent assay,the relative expression levels of peripheral blood TLR4 and NF-κB proteins were detected by Western blot.The efficiencies of serum HMGB1,TLR4 and NF-κB in prediction of postoperative urinary catheter-associated UTI in the CC patients were analyzed by means of receiver operating characteristic(ROC)curves.RESULTS Totally 49 strains of pathogens were isolated from 31 CC patients with postoperative urinary catheter-associated UTI,and the patients who had infection of single species were dominant.Gram-negative bacteria were the most common pathogens,accounting for 61.22％.There were significant differences in the age,complication with diabetes mellitus,duration of urinary catheter indwelling,postoperative uroschesis and previous history of UTI between the infection group and the non-infection group(P＜0.05);there were significant differences in the levels of serum HMGB1,TLR4 and NF-κB between the two groups(P＜0.05).The area under the curve(AUC)of the joint detection of serum HMGB1,TLR4 and NF-κB was 0.906 in prediction of the postoperative urinary catheter-associated UTI in the CC patients,with the sensitivity 83.87％;the predictive efficiencies of the joint de-tection of the indexes were better than those of the single detection(P＜0.05).CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the CC patients with postoperative urinary catheter-asso-ciated UTI.The joint detection of the serum HMGB1,TLR4 and NF-κB has the highest value in prediction of postoperative urinary catheter-associated UTI in the CC patients.

Objective:To establish and explore a novel model and its clinical application value based on abnormal des-gamma-carboxy prothrombin (DCP) for the early-stage diagnosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Methods:A total of 420 cases with chronic HBV infection with nodular liver lesions examined by imaging at the Third Hospital of Hebei Medical University from January 2021 to June 2024 were retrospectively selected. They were divided into the HBV-HCC group (182 cases) and the control group (238 cases) according to the current HCC diagnostic criteria. The basic information of patients, liver-related biochemical indicators, serum DCP, alpha-fetoprotein (AFP) levels, and the efficacy of combined detection in diagnosing early-stage HCC were collected and analyzed. A DSGAA model based on DCP (D) combined with gender (S), γ-glutamyl transferase (GGT, G), AFP (A) and age (A) as independent variables was constructed. The diagnostic performance of the novel model was compared with that of the traditional model through nomogram visualization output and calibration curve.Results:The age, sex, hemoglobin, albumin, alanine aminotransferase, alkaline phosphatase, and GGT levels were significantly higher in patients with HCC than those of the control group ( P<0.05). The positivity detection rate in patients with HBV-HCC was significantly higher in DCP than that of AFP (85.71% vs. 59.89%, P<0.05). The abnormal detection rate of DCP in patients with AFP-negative was 76.7%. The sensitivity for diagnosing HCC was significantly higher in DCP than AFP (73.63% vs. 64.29%, P<0.05), with specificity of 83.6% in all. The specificity for diagnosing early-stage HCC was 89.09%, surpassing that of AFP at 68.06% ( P<0.05). The area under the receiver operating characteristic curve (AUC) for the constructed DSGAA diagnostic model was 0.8841, with an optimal cutoff value of 0.377, a sensitivity of 80.22%, and a specificity of 86.13%. The AUC for diagnosing early-stage HCC was 0.8122, with a sensitivity of 66.18%, and a specificity of 86.13%, and the diagnostic efficacy was higher than other models ( P<0.05). Conclusion:DCP has superior diagnostic efficacy for HBV-related HCC, and the DSGAA model is expected to be used as a new method for screening and diagnosing early-stage HBV-related HCC.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To evaluate the diagnostic value of intestinal tissue metagenomic next-generation sequencing (mNGS) in severe diarrhea following haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Sixteen patients who developed severe diarrhea or hematochezia after haploidentical allo-HSCT at the First Affiliated Hospital of Fujian Medical University (June 2023–August 2024) were enrolled. All underwent gastrointestinal endoscopy and mNGS for microbial detection. Clinical, endoscopic, pathological, and microbiological data were analyzed to evaluate the diagnostic value of mNGS and treatment outcomes following targeted therapy.Results:The study included 16 patients (12 males, 4 females; median age 32.5 years, range 3–60 years). Diarrhea occurred a median of 3.93 months post-transplant (range 1.63–10.40 months). Stool cultures were negative except for one case with Candida. One patient tested positive for Clostridium difficile antigen. Endoscopy revealed mucosal congestion, edema, erosion, and bleeding, with focal inflammation on pathology. mNGS detected pathogens in 87.5% (14/16) of cases, including mixed infections in 78.5% (11/14). Common pathogens were Klebsiella pneumoniae, Enterococcus faecium, Escherichia coli, Rhizopus microsporus, EBV, and CMV. Targeted treatment adjustments led to symptom improvement in 87.5% of patients.Conclusion:Allo-HSCT patients are prone to infectious diarrhea due to immunosuppression. Molecular analysis of endoscopic biopsy tissues using mNGS can accurately identify pathogens, guide targeted therapy, and improve clinical outcomes.

Objective To compare the efficacy and safety of computed tomography (CT)-guided percutaneous versus electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation (MWA) for the treatment of pulmonary nodules. Methods A retrospective analysis was conducted on the data of high-risk pulmonary nodule patients who underwent MWA at the Nanjing Drum Tower Hospital between 2022 and 2023. The pathological diagnosis rate, complications, and progression-free survival (PFS) rate were compared between the CT group and the ENB group. Results There were 61 patients in the CT group, including 30 males and 31 females, with an average age of (67.22±9.13) years. There were 53 patients in the ENB group, including 29 males and 24 females, with an average age of (65.29±13.76) years. The pathological diagnosis rate in the CT group was slightly higher than that in the ENB group (88.52% vs. 71.69%, P=0.03). However, the ENB group exhibited a lower incidence of perioperative complications, including pneumothorax (16.39% vs. 3.77%, P=0.03), hemoptysis (19.67% vs. 5.66%, P=0.05), and pain (22.95% vs. 7.55%, P=0.03). There was no statistically significant difference in PFS rate between the two groups [HR=1.17, 95%CI (0.23, 5.81), P=0.85]. Conclusion Both CT-guided and ENB-guided MWA are effective treatment modalities for high-risk pulmonary nodules.

Epidemiological investigations and clinical studies have shown that inappropriate ambient temperatures (high and low temperatures) are the independent risk factors for ischemic stroke, but their underlying physiological mechanisms are not fully understood. This article systematically reviews the potential mechanisms by which inappropriate ambient temperatures promote the occurrence of ischemic stroke through multiple pathways, such as activating the sympathetic-renin-angiotensin system, inducing systemic inflammation and oxidative stress, damaging the integrity of the intestinal barrier and blood-brain barrier, and disrupting coagulation-fibrinolysis balance.