AIM:To investigate the short-term efficacy of autologous serum eye drops combined with prednisolone acetate in the treatment of severe dry eye with grade II-III corneal injury.METHODS:Prospective, randomized, controlled single center study. Totally 122 patients(122 eyes, all enrolled patients had bilateral disease, with the more severely affected eye selected as the study eye; if the severity was similar between both eyes, the right eye was chosen as the study eye)with severe dry eye and grade II-III corneal injury who were treated at Wuhan University Affiliated Aier Eye Hospital from March 2023 to March 2025 were randomly divided into a control group(treated with sodium hyaluronate eye drops combined with autologous serum eye drops)and an observation group(treated with sodium hyaluronate eye drops, autologous serum eye drops combined with prednisolone acetate eye drops)using a random number table method. After continuous administration for 2 wk, the tear inflammatory reaction [interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)], subjective symptoms [ocular surface disease index(OSDI)score], lacrimal gland function [tear film break-up time(TBUT)and Schirmer tear secretion test(SⅠt)], corneal injury degree [corneal fluorescein staining(CFS)score] and corneal nerve function [total number and density of corneal subepithelial nerve(SBN)] before and after treatment were compared between the two groups, and the occurrence of adverse reactions during treatment was recorded. RESULTS:All patients have completed follow-up. The control group consisted of 61 cases and 61 eyes, with 24 males and 37 females, with an average age of 43.87±5.12y. There were 61 cases and 61 eyes in the observation group, including 21 males and 40 females, with an average age of 42.15±4.76y. At 1 and 2 wk after treatment, the levels of IL-6 and TNF-α in tears, OSDI score, and CFS score of the two groups were significantly lower than those before treatment, and those in the observation group were lower than those in the control group(all P<0.05). The total number of TBUT, SⅠt, SBN, and SBN density in both groups of patients increased significantly compared to before treatment, and the observation group was higher than the control group(all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups of patients during treatment(P=0.717).CONCLUSION:The combination of autologous serum eye drops and prednisolone acetate is effective in treating severe dry eye with grade II-III corneal injury. It can reduce patients' inflammatory reactions, subjective symptoms, and degree of corneal injury, promote the improvement of lacrimal gland function and corneal nerve function, providing a new strategy for corneal nerve repair. Furthermore, the combination therapy does not increase the risk of adverse reactions and shows good safety in short-term application.

OBJECTIVE: To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance. METHODS: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated. RESULTS: Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818]. CONCLUSION Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans ; Female ; Tongue/diagnostic imaging* ; Adult ; Anemia/diagnosis* ; Middle Aged ; Face/diagnostic imaging* ; Young Adult ; Machine Learning

To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.

Background and Aims:Laparoscopic transcystic bile duct exploration(LTCBDE)has become the preferred method for treating secondary bile duct stones due to its advantages of minimal trauma,fast recovery,and low complication rates.However,challenges remain in the dilation of the cystic duct,the insertion of the choledochoscope,and the exploration of the common hepatic duct and intrahepatic bile ducts.This study was performed to explore the clinical application and effectiveness of the programmed modified LTCBDE in the treatment of gallbladder stones combined with common bile duct stones.Methods:A retrospective analysis was conducted on the clinical data of 248 patients who underwent programmed modified LTCBDE at the Affiliated Suzhou Ninth Hospital of Soochow University from January 2018 to January 2024.The surgical strategies and treatment outcomes were summarized.Data from 913 patients who underwent laparoscopic common bile duct exploration(LCBDE)during the same period were also collected to compare surgical outcomes and postoperative complications between the two groups.Results:Through programmed surgical steps,the innovative"diaphragm"incision technique,and improved bile duct probe application,244 patients(98.4%)successfully underwent LTCBDE,while 4 patients were converted to LCBDE due to failure to insert a 4.9 mm choledochoscope through the cystic duct.After operation,1 patient(0.4%)had residual bile duct stones,which were successfully removed through T-tube tract stone extraction(this patient was converted to LCBDE during the procedure).Additionally,1 case of bile leakage and 1 case of abdominal infection(each 0.4%)occurred,both of which resolved with conservative treatment.No cases of intra-abdominal bleeding,bile duct stenosis,or bile duct injury were reported.The average operative time in the programmed modified LTCBDE group was comparable to that of the LCBDE group(85.2 min vs.88.0 min,P=0.398),but the postoperative hospital stay was significantly shorter(6.2 d vs.8.3 d,P<0.001),and the incidence of complications was lower(1.6%vs.4.7%,P=0.044).Conclusion:The programmed modified LTCBDE is a standardized,safe,and effective procedure with a low complication rate.It is worthy of further clinical promotion and application.

Objective To generalize and summarize the types,content elements,outcome measures,application effects,and safety monitoring of the infant-cued behavior-based feeding,so as to provide guidance for the clinical application and research in the future.Methods The literature was retrieved from PubMed,CINAHL,CNKI,and Wanfang Data-base,with a retrieval timeframe from database establishment to August 20,2024.The included literature was sum-marized and analyzed.Results A total of 28 studies were included,of which 15 were randomized controlled trials,7 were quasi-experimental studies,and 6 were observational studies.The infant-cued behavior-based feeding pattern could be categorized as ad libitum feeding,demand feeding,semi-demand feeding,and behavioral cue-based feeding.The content elements included assessment,supporting strategies,and advancement of oral feeding.The infant-cued behavior-based feeding pattern had a positive impact on feeding and developmental outcomes,immune function,rate of complications and length of hospital stay in preterm infants.The safety monitoring consisted of heart rate,blood oxygen saturation,blood sugar,and daily weight gain.Conclusion It is beneficial to implement the infant-cued behavior-based feeding pattern in preterm infants,which leads to better clinical outcomes.To support its implementation in clinical practice,we need to validate and enhance the application value of the feeding pattern in the future by concentrating on clinically individual differences,refining feeding intervention programs,improving effect evaluation and safety monitoring.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Objective To investigate the predictive value of preoperative systemic inflammatory response index(SIRI)combined with clinicopathological parameters for postoperative recurrence in cervical cancer and to construct a prognostic model in order to optimize recurrence risk assessment.Methods Patients with cervical cancer who underwent standard surgical treatment at the First Affiliated Hospital of Chongqing Medical University(training cohort,n=996)and Chongqing Maternal and Child Health Hospital(validation cohort,n=496)between January 2017 and January 2022 were retrospectively enrolled based on our strict inclusion and exclusion criteria.Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for recurrence-free survival(RFS),and then a nomogram was constructed.Receiver operating characteristic(ROC)curve was plotted to assess the predictive performance of the model,and the area under the curve(AUC)and calibration curve were employed to evaluate the model.Kaplan-Meier survival analysis was performed to determine the clinical application.Results Cox regression analysis demonstrated that International Federation of Gynecology and Obstetrics(FIGO)stage(P<0.001),tumor size(P<0.001),pathological type(P<0.001),tumor grade(P=0.007),parametrial invasion(P<0.001),depth of myometrial invasion(P=0.019),lymphovascular space invasion(P=0.019),vaginal margin involvement(P=0.010),adjuvant therapy(P=0.012),and SIRI(P<0.001)were independent prognostic factors for RFS.Our nomogram model based on above prognostic factors exhibited superior predictive performance for 1-,3-,and 5-year RFS,with a significantly higher AUC value(0.886)than those of single-parameter models.Conclusion Our nomogram model demonstrated good accuracy in predicting RFS in cervical cancer patients,providing a potential tool for personalized clinical decision-making in recurrence risk management.

Objective To determine the median effective concentration(EC50)of ropivacaine at the volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block in children aged 6 to 10 years.Methods A prospective dose-finding trial was conducted based a sequential Dixon up-and-down allocation.We recruited children aged 6 to 10 years who were scheduled for unilateral surgery on upper extremity regions in our hospital from April to December 2022.All of them were subjected to general intravenous anaesthesia combined with ultrasound-guided interscalene brachial plexus block.The ropivacaine volume for each patient was 0.5 mL/kg.The concentration of 0.2%for the first patient,subsequent concentrations were adjusted based on the block effect of previous patient,increase or decrease by 0.02%.The trial was stopped when there were 7 turning points.Isotonic regression and Bootstrap were used to calculate the values of EC50 and 95%effective concentration(EC95),along with their 95%confidence intervals(CI).General data,incidence of adverse events,and score of postoperative pain were recorded.Results A total of 26 children aged 6 to 10 years were included.The EC50 of ultrasound-guided interscalene brachial plexus block was determined to be 0.091%(95%CI:0.077%～0.105%),and the EC95 was estimated to be 0.117%(95%CI:0.110%～0.118%).Successful blockade was achieved in 16 cases(61.5%),while 10 cases(38.5%)failed.No statistical differences existed between successful and failed cases regarding sex,age,body weight,surgical site,surgical laterality,operative time,or anesthesia duration.None of the patients experienced adverse events such as pneumothorax,vascular injury,or Horner's syndrome,and the score of postoperative pain were all<6 by modified Children's Hospital of Eastern Ontario Pain Scale.Conclusion In children aged 6 to 10 years,the EC50 of ropivacaine is 0.091%at a volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block,and this low dose of regional anesthetic can reduce the risks such as systemic toxicity and direct neurotoxicity.

Fecal microbiota transplantation (FMT) technology originated in China during the Eastern Jin Dynasty and has rapidly developed over the past two decades, becoming a primary method for studying the causal relationship between gut microbiota and the occurrence and progression of diseases. At the same time, the therapeutic effects of FMT in the field of gastrointestinal diseases have gained widespread recognition and are gradually expanding into other disease areas. The FMT procedure is relatively complex, and there is currently no standardized method; its success is influenced by various factors, including the donor, recipient, processing of the fecal material, and the method of implantation. Given the increasingly recognized relationship between gut microbiota and various diseases, FMT has become a research hotspot in both scientific studies and clinical applications, achieving a series of significant advancements. To help researchers better understand this technology, this paper will outline the development history of FMT, summarize common operational methods in research and clinical settings, review its application progress, and look forward to future development directions.