AIM:To assess the efficacy of intravitreal conbercept for treating neovascular age-related macular degeneration(nAMD)under a treat-and-extend(T & E)regimen.METHODS: A retrospective analysis was conducted on nAMD patients followed over a 2-year period(May 2020 to May 2022). All eyes received three monthly loading intravitreal injections of conbercept, followed by a T& E regimen in which the injection interval was extended by 2 or 4 wk according to disease activity, up to a maximum of 16 wk. When disease activity recurred, the interval was shortened. Patients were divided into initial and non-initial treatment groups based on treatment history. Best-corrected visual acuity(BCVA), central macular thickness(CMT), injection frequency, and intervals between injections over the 24-month follow-up were compared.RESULTS:Totally 27 patients(15 males and 12 females, 33 eyes)were enrolled. In the initial treatment group(18 eyes, mean age 65.72±12.32 y), BCVA significantly improved at 1, 3, and 6 mo(P<0.05), and CMT significantly improved at 1 and 3 mo(P<0.05). In the non-initial treatment group(15 eyes, mean age 69.00±9.21 y), BCVA improved significantly at 3 mo(P<0.05), whereas CMT remained stable(P >0.05). Baseline CMT was similar between the groups(P>0.05). However, significant differences were observed at multiple post-injection time points(P<0.05). The total number of injections did not differ between the groups(P>0.05). Intervals between injections varied, with the majority at 4 and 3-4 mo in the initial and non-initial treatment groups, respectively.CONCLUSION:Initiating intravitreal conbercept therapy under a T & E regimen results in superior visual and anatomical outcomes compared with non-initial treatment.

Objective:To evaluate the clinical efficacy and safety of sulodexide soft capsules in treating proteinuria after renal transplantation, as well as its impact on graft function.Methods:The clinical data from 80 recipients who developed proteinuria after renal transplantation and were treated with sulodexide soft capsules during regular follow-up at the outpatient department of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 1, 2019, to March 1, 2023, were retrospectively analyzed. Proteinuria levels, graft function, safety-related indicators (coagulation function), and adverse events were compared before treatment and at 1, 2, 3, 6, and 12 months after treatment. Based on efficacy, recipients were divided into a satisfactory efficacy group (67 cases) and a general efficacy group (13 cases). Univariate and multivariate logistic regression analyses were conducted to stratify baseline data and explore factors influencing efficacy.Results:Among the 80 recipients, 63 (78.75%) had mild proteinuria and 17 (21.25%) had moderate proteinuria. The overall treatment response rate was 91.25% (73/80). Drug-related adverse events occurred in 12 patients (15.0%). Median urinary protein excretion at 1, 2, 3, 6, and 12 months post-treatment was 0.35 (0.20, 0.55) g/24 h, 0.30 (0.17, 0.44) g/24 h, 0.23 (0.15, 0.39) g/24 h, 0.21 (0.13, 0.32) g/24 h, and 0.15 (0.10, 0.23) g/24 h, respectively, all significantly lower than the pre-treatment level of 0.52 (0.43, 0.90) g/24 h (all P<0.001). The median urinary albumin-to-creatinine ratios at the corresponding time points were 99.15 (45.33, 201.13) μg/mg, 77.20 (43.30, 176.20) μg/mg, 57.50 (31.35, 173.75) μg/mg, 53.55 (25.90, 142.00) μg/mg, and 39.05 (20.53, 103.60) μg/mg, also significantly reduced compared to the pre-treatment value of 152.05 (71.90, 271.23) μg/mg ( P=0.012, P=0.003, P<0.001, P<0.001, P<0.001, respectively). At 12 months post-treatment, the serum creatinine level (132.86±36.86 μmol/L) showed a statistically significant improvement compared to the pre-treatment level (146.60±48.42 μmol/L) ( P=0.045). Univariate analysis indicated that satisfactory efficacy was associated with the time of proteinuria onset post-transplantation, the interval between proteinuria onset and treatment initiation, and recipient age ( HR= 1.001, 95% CI: 1.001-1.020, P=0.043; HR = 1.034, 95% CI: 1.009-1.058, P=0.006; HR=1.058, 95% CI: 1.003-1.116, P=0.040). Stratified univariate analysis revealed that proteinuria onset within 2 years post-transplantation, treatment initiation within 2 years of proteinuria onset, and age younger than 45 years were significantly associated with satisfactory efficacy ( HR=5.524, 95% CI: 1.510-20.207, P=0.010; HR= 7.800, 95% CI: 2.104-28.920, P=0.002; HR=5.972, 95% CI: 1.497-23.822, P=0.011). Multivariate analysis identified the interval between proteinuria onset and treatment initiation as an independent factor influencing satisfactory efficacy ( HR=1.025, 95% CI: 1.010-1.093, P=0.015). Conclusions:Sulodexide effectively reduces proteinuria after renal transplantation, particularly in mild-to-moderate or early-onset cases, while maintaining stable allograft function without significant adverse effects

Ulcerative colitis （UC） is an idiopathic，chronic inflammatory disease of the colonic mucosa that originates in the rectum and is an important contributing factor in the development of clinical conditions such as small bowel obstruction and rectal cancer. In modern clinical treatment of UC，equal emphasis is placed on both Chinese and Western medicine，demonstrating certain advantages in inducing remission and preventing recurrence. Wumeiwan （WMW） originates from Article 338 of the Jueyin section in Zhang Zhongjing's Treatise on Cold Damage and Miscellaneous Diseases during the Han Dynasty. The original text states that "for roundworm reversal，WMW is indicated. It is also used for chronic diarrhea". It is a well-established prescription for treating prolonged diarrhea and dysentery，with functions of regulating Qi and blood，unblocking the triple energizers，and clearing heat in the upper while warming the lower body. Studies have shown that WMW has favorable effects in the prevention and treatment of UC. This review summarizes research on the indications and pharmacological basis of WMW in treating UC，as well as its clinical applications and underlying mechanisms. Findings indicate that WMW，whether used as the original formula，modified，or in combination with chemical drugs，compound prescriptions，or acupuncture and moxibustion，can exert therapeutic effects by resisting oxidative stress，reducing inflammatory factor levels，inhibiting apoptosis，enhancing immune responses，regulating the intestinal microbiota，and suppressing signaling pathways such as Toll-like receptor 4 （TLR4）/nuclear factor-kappa B （NF-κB）/myeloid differentiation factor 88 （MyD88），Janus kinase （JAK）/signal transducer and activator of transcription （STAT），and Notch. These mechanisms provide a theoretical basis for the clinical application of WMW in the treatment of UC.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.

Objective:To investigate the predictive value of machine learning-based CT radiomics model for radioresistance in patients with esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of 185 patients with ESCC treated with radical radiotherapy in the First Affiliated Hospital of Anhui Medical University from December 2015 to July 2022 were retrospectively analyzed, and all patients were randomly divided into a training set ( n=129) and a validation set ( n=56) at a ratio of 7 : 3. The radiomics parameters of the primary lesion of esophageal cancer and the surrounding 5 cm region in the patients' CT arterial phase images were extracted, and 6 machine learning methods were used to screen the optimal radiomics model to obtain the optimal radiomics score (Radscore). Independent prognostic predictors of radioresistance in ESCC were obtained by univariate and multivariate logistic regression analyses, which was used as the basis for constructing the nomogram. The predictive performance of different models was compared by the area under the receiver operating characteristic (ROC) curve (AUC). The predictive efficacy and clinical value of the combined model were evaluated using calibration curve, decision curve analysis and clinical impact curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results:The combined intratumoral and peritumoral radiomics model based on naive Bayesian classifier yielded the optimal prediction performance, with AUC of 0.859 and 0.936 in the training set and validation set, respectively. Multivariate logistic regression analysis showed that Radscore and T stage were the independent prognostic predictors of radioresistance in ESCC patients, and the AUC of the combined model constructed based on these predictors in the training and validation sets were 0.942 and 0.959, respectively. Calibration curve, decision curve analysis and clinical impact curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) all indicated higher clinical benefit and more consistent predictive efficacy of the combined model.Conclusions:Machine learning-based CT radiomics model is useful for the prediction of radioresistance in ESCC. The nomogram of radiomics and clinical parameters can further improve the prediction accuracy and provide novel reference for individualized treatment of patients with ESCC.

Objective:To investigate the predictive value of machine learning-based CT radiomics model for radioresistance in patients with esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of 185 patients with ESCC treated with radical radiotherapy in the First Affiliated Hospital of Anhui Medical University from December 2015 to July 2022 were retrospectively analyzed, and all patients were randomly divided into a training set ( n=129) and a validation set ( n=56) at a ratio of 7 : 3. The radiomics parameters of the primary lesion of esophageal cancer and the surrounding 5 cm region in the patients' CT arterial phase images were extracted, and 6 machine learning methods were used to screen the optimal radiomics model to obtain the optimal radiomics score (Radscore). Independent prognostic predictors of radioresistance in ESCC were obtained by univariate and multivariate logistic regression analyses, which was used as the basis for constructing the nomogram. The predictive performance of different models was compared by the area under the receiver operating characteristic (ROC) curve (AUC). The predictive efficacy and clinical value of the combined model were evaluated using calibration curve, decision curve analysis and clinical impact curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results:The combined intratumoral and peritumoral radiomics model based on naive Bayesian classifier yielded the optimal prediction performance, with AUC of 0.859 and 0.936 in the training set and validation set, respectively. Multivariate logistic regression analysis showed that Radscore and T stage were the independent prognostic predictors of radioresistance in ESCC patients, and the AUC of the combined model constructed based on these predictors in the training and validation sets were 0.942 and 0.959, respectively. Calibration curve, decision curve analysis and clinical impact curve, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) all indicated higher clinical benefit and more consistent predictive efficacy of the combined model.Conclusions:Machine learning-based CT radiomics model is useful for the prediction of radioresistance in ESCC. The nomogram of radiomics and clinical parameters can further improve the prediction accuracy and provide novel reference for individualized treatment of patients with ESCC.

Objective:To evaluate the clinical efficacy and safety of sulodexide soft capsules in treating proteinuria after renal transplantation, as well as its impact on graft function.Methods:The clinical data from 80 recipients who developed proteinuria after renal transplantation and were treated with sulodexide soft capsules during regular follow-up at the outpatient department of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 1, 2019, to March 1, 2023, were retrospectively analyzed. Proteinuria levels, graft function, safety-related indicators (coagulation function), and adverse events were compared before treatment and at 1, 2, 3, 6, and 12 months after treatment. Based on efficacy, recipients were divided into a satisfactory efficacy group (67 cases) and a general efficacy group (13 cases). Univariate and multivariate logistic regression analyses were conducted to stratify baseline data and explore factors influencing efficacy.Results:Among the 80 recipients, 63 (78.75%) had mild proteinuria and 17 (21.25%) had moderate proteinuria. The overall treatment response rate was 91.25% (73/80). Drug-related adverse events occurred in 12 patients (15.0%). Median urinary protein excretion at 1, 2, 3, 6, and 12 months post-treatment was 0.35 (0.20, 0.55) g/24 h, 0.30 (0.17, 0.44) g/24 h, 0.23 (0.15, 0.39) g/24 h, 0.21 (0.13, 0.32) g/24 h, and 0.15 (0.10, 0.23) g/24 h, respectively, all significantly lower than the pre-treatment level of 0.52 (0.43, 0.90) g/24 h (all P<0.001). The median urinary albumin-to-creatinine ratios at the corresponding time points were 99.15 (45.33, 201.13) μg/mg, 77.20 (43.30, 176.20) μg/mg, 57.50 (31.35, 173.75) μg/mg, 53.55 (25.90, 142.00) μg/mg, and 39.05 (20.53, 103.60) μg/mg, also significantly reduced compared to the pre-treatment value of 152.05 (71.90, 271.23) μg/mg ( P=0.012, P=0.003, P<0.001, P<0.001, P<0.001, respectively). At 12 months post-treatment, the serum creatinine level (132.86±36.86 μmol/L) showed a statistically significant improvement compared to the pre-treatment level (146.60±48.42 μmol/L) ( P=0.045). Univariate analysis indicated that satisfactory efficacy was associated with the time of proteinuria onset post-transplantation, the interval between proteinuria onset and treatment initiation, and recipient age ( HR= 1.001, 95% CI: 1.001-1.020, P=0.043; HR = 1.034, 95% CI: 1.009-1.058, P=0.006; HR=1.058, 95% CI: 1.003-1.116, P=0.040). Stratified univariate analysis revealed that proteinuria onset within 2 years post-transplantation, treatment initiation within 2 years of proteinuria onset, and age younger than 45 years were significantly associated with satisfactory efficacy ( HR=5.524, 95% CI: 1.510-20.207, P=0.010; HR= 7.800, 95% CI: 2.104-28.920, P=0.002; HR=5.972, 95% CI: 1.497-23.822, P=0.011). Multivariate analysis identified the interval between proteinuria onset and treatment initiation as an independent factor influencing satisfactory efficacy ( HR=1.025, 95% CI: 1.010-1.093, P=0.015). Conclusions:Sulodexide effectively reduces proteinuria after renal transplantation, particularly in mild-to-moderate or early-onset cases, while maintaining stable allograft function without significant adverse effects

Purpose To study the relationshiPbetween CD88 expression and clinicopathologic features and epithelial-mesenchymal transition(EMT)in esophageal squamous cell carcinoma.Methods TCGA and TIMER database were used to analyze the expression level of CD88 in esophageal squamous cell carcinoma and adjaecnt esophageal squamous cell epithelium and its relationship with epithelial-mesenchymal transition.Par-affin specimens were collected from 199 patients with clinically diagnosed esophageal squamous cell carcinoma.Immunohisto-chemical EnVision method was used to detect the expression of CD88 and EMT-related proteins in esophageal squamous cell carcinoma and adjacent tissues,the relationship between CD88 expression and clinicopathological features,prognosis and EMT in ESCC tumors was analyzed.Results There were 86 cases with high CD88 expression and 113 cases with low CD88 expres-sion.The expression level of CD88 in esophageal squamous cell carcinoma was significantly higher than that of paracancerous tis-sue(P＜0.001).The group with high CD88 expression had lower ESCC differentiation level(P＜0.001)and higher T stage(P=0.03).The 5-year survival of patients with high CD88 ex-pression was significantly lower than that of patients with low CD88 expression(P=0.002).Cox univariate and multivariate analysis showed that CD88 expression was an independent prog-nostic factor for overall survival of patients with esophageal squa-mous cell carcinoma(P=0.013).The high expression of CD88 was negatively correlated with E-cadherin(r=-0.146,P=0.039),and positively correlated with vimentin(r=0.387,P=1.61e-08)and N-cadherin(r=0.304,P=1.3e-05).Con-clusion CD88 is highly expressed in esophageal squamous cell carcinoma.CD88 may affect the occurrence,development,in-vasion and metastasis of esophageal squamous cell carcinoma through EMT,and it might be used as a prognostic marker for e-sophageal squamous cell carcinoma patients.

Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m²) vs. (60±15) mL/(min·1.73 m²), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.