Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.
Humans ; Immunoglobulin G4-Related Disease/metabolism* ; Immunoglobulin G/metabolism* ; Machine Learning ; Animals ; Proteomics/methods*

Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Objective:To develop a simplified confocal laser endomicroscopy (CLE)-based healing scoring system for assistant diagnosis of deep remission in ulcerative colitis (UC).Methods:CLE images from consecutive UC patients in clinical remission or mild activity and healthy controls undergoing CLE at Peking University First Hospital from January 2017 to December 2019 were retrospectively analyzed. According to the diagnosis of inflammation in intestinal segments in the medical records of UC patients, CLE images were divided into two groups, the involved group (inflamed UC segment) and the control group (segments from healthy individuals and non-inflamed UC segments). CLE features differentiating the groups were identified, and univariable regression analysis was used to obtain indicators related to unhealed histological inflammation (Geboes score>2.0), forming a simplified CLE healing score using the significant indicators, and receiver operator characteristic (ROC) curve was drawn.Results:The study included 53 UC patients and 14 healthy controls, yielding 201 CLE segments (42 healthy, 69 non-inflamed, 90 inflamed). Eight CLE features differed significantly between the involved and the control groups ( P<0.001), including crypt distortion, crypt lumen irregularity, crypt proximity, crypt sparsity, crypt lumen fluorescein leakage, vascular fluorescein leakage, increased vessel diameter, and cellular infiltration. Univariable regression analysis indicated there were 4 indicators related to histological inflammation, including crypt distortion ( P=0.025, OR=3.613, 95% CI:1.174-11.114), crypt lumen irregularity ( P=0.021, OR=4.081, 95% CI: 1.233-13.511), crypt fluorescein leakage ( P=0.011, OR=5.486, 95% CI: 1.468-20.494) and increased vessel diameter ( P=0.002, OR=7.724, 95% CI: 2.062-28.938). These 4 indicators were combined to form a simplified CLE healing score and a ROC curve was plotted with AUC of 0.769 (95% CI:0.654-0.833). The optimal threshold for histological healing was the absence of all four features (score=0), with sensitivity and specificity of 83.1% (59/71) and 42.1% (8/19), respectively. Conclusion:The simplified CLE score demonstrates high sensitivity and correlates positively with histological healing, supporting its utility as an adjunct tool for assessing deep remission in UC.

Objective:To evaluate the clinical efficacy of endoscopic treatment of superficial non-ampullary duodenal adenoma.Methods:A retrospective analysis was performed on the clinical data and follow-up information of patients diagnosed with superficial duodenal non-ampullary adenomas via preoperative endoscopy and treated endoscopically at Peking University First Hospital between January 2013 and January 2024. The overall en bloc resection rate, complete resection rate of the lesion, perioperative complications, and recurrence rates were evaluated. Patients were categorized into three groups based on their treatment modality: endoscopic mucosal resection (EMR)（ n=46）, endoscopic submucosal dissection (ESD)（ n=16）, and modified ESD (ESD with snare, ESD-S)（ n=24）. Comparative analyses were conducted to evaluate operative time, en bloc resection rate, and complete resection rate among the three groups. Results:Among 86 patients, the overall en bloc and complete resection rates were 87.2% (75/86) and 86.0% (74/86), respectively. No case of delayed bleeding was observed during the perioperative period. Intraoperative perforation occurred in two patients, both of whom improved following conservative management. Delayed perforation was noted in four patients, and three of them were successfully managed with surgical intervention, while one case was resolved after conservative treatment. During the follow-up period, local recurrence was identified in two patients. Following re-treatment with endoscopy and continuous surveillance, no further recurrence was observed. The operative times for the EMR group, ESD-S group, and ESD group were 4 (1-36) minutes, 25 (5-190) minutes, and 46 (5-150) minutes, respectively. Significant differences were observed in operative times among the three groups ( Hc=49.892, P<0.001). The en bloc resection rates for the EMR, ESD-S, and ESD groups were 80.4% (37/46), 91.7% (22/24), and 100.0% (16/16), respectively. The complete resection rates were 80.4% (37/46), 91.7% (22/24), and 93.8% (15/16) for the respective groups. Conclusion:Endoscopic treatment demonstrates favorable efficacy and safety for superficial non-ampullary duodenal adenoma. In addition to traditional EMR and ESD, ESD-S is also an effective procedure for endoscopic treatment of non-ampullary duodenal adenoma.

Intracranial atherosclerotic stenosis (ICAS) is a common cause of ischemic stroke. The evaluation of its structure and function is of great significance for formulating clinical intervention strategies. The indications for endovascular treatment of ICAS lesions in the past were mainly based on the degree of luminal stenosis showed by cerebral angiography, which had certain limitations. The translesional pressure ratio (PR), as an important indicator for functional assessment after arterial stenosis, has gradually received attention in the evaluation of ICAS lesions in recent years. This article reviews the evaluation methods and clinical significance of PR in ICAS lesions.

Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Objective:To develop a simplified confocal laser endomicroscopy (CLE)-based healing scoring system for assistant diagnosis of deep remission in ulcerative colitis (UC).Methods:CLE images from consecutive UC patients in clinical remission or mild activity and healthy controls undergoing CLE at Peking University First Hospital from January 2017 to December 2019 were retrospectively analyzed. According to the diagnosis of inflammation in intestinal segments in the medical records of UC patients, CLE images were divided into two groups, the involved group (inflamed UC segment) and the control group (segments from healthy individuals and non-inflamed UC segments). CLE features differentiating the groups were identified, and univariable regression analysis was used to obtain indicators related to unhealed histological inflammation (Geboes score>2.0), forming a simplified CLE healing score using the significant indicators, and receiver operator characteristic (ROC) curve was drawn.Results:The study included 53 UC patients and 14 healthy controls, yielding 201 CLE segments (42 healthy, 69 non-inflamed, 90 inflamed). Eight CLE features differed significantly between the involved and the control groups ( P<0.001), including crypt distortion, crypt lumen irregularity, crypt proximity, crypt sparsity, crypt lumen fluorescein leakage, vascular fluorescein leakage, increased vessel diameter, and cellular infiltration. Univariable regression analysis indicated there were 4 indicators related to histological inflammation, including crypt distortion ( P=0.025, OR=3.613, 95% CI:1.174-11.114), crypt lumen irregularity ( P=0.021, OR=4.081, 95% CI: 1.233-13.511), crypt fluorescein leakage ( P=0.011, OR=5.486, 95% CI: 1.468-20.494) and increased vessel diameter ( P=0.002, OR=7.724, 95% CI: 2.062-28.938). These 4 indicators were combined to form a simplified CLE healing score and a ROC curve was plotted with AUC of 0.769 (95% CI:0.654-0.833). The optimal threshold for histological healing was the absence of all four features (score=0), with sensitivity and specificity of 83.1% (59/71) and 42.1% (8/19), respectively. Conclusion:The simplified CLE score demonstrates high sensitivity and correlates positively with histological healing, supporting its utility as an adjunct tool for assessing deep remission in UC.

Objective:To evaluate the clinical efficacy of endoscopic treatment of superficial non-ampullary duodenal adenoma.Methods:A retrospective analysis was performed on the clinical data and follow-up information of patients diagnosed with superficial duodenal non-ampullary adenomas via preoperative endoscopy and treated endoscopically at Peking University First Hospital between January 2013 and January 2024. The overall en bloc resection rate, complete resection rate of the lesion, perioperative complications, and recurrence rates were evaluated. Patients were categorized into three groups based on their treatment modality: endoscopic mucosal resection (EMR)（ n=46）, endoscopic submucosal dissection (ESD)（ n=16）, and modified ESD (ESD with snare, ESD-S)（ n=24）. Comparative analyses were conducted to evaluate operative time, en bloc resection rate, and complete resection rate among the three groups. Results:Among 86 patients, the overall en bloc and complete resection rates were 87.2% (75/86) and 86.0% (74/86), respectively. No case of delayed bleeding was observed during the perioperative period. Intraoperative perforation occurred in two patients, both of whom improved following conservative management. Delayed perforation was noted in four patients, and three of them were successfully managed with surgical intervention, while one case was resolved after conservative treatment. During the follow-up period, local recurrence was identified in two patients. Following re-treatment with endoscopy and continuous surveillance, no further recurrence was observed. The operative times for the EMR group, ESD-S group, and ESD group were 4 (1-36) minutes, 25 (5-190) minutes, and 46 (5-150) minutes, respectively. Significant differences were observed in operative times among the three groups ( Hc=49.892, P<0.001). The en bloc resection rates for the EMR, ESD-S, and ESD groups were 80.4% (37/46), 91.7% (22/24), and 100.0% (16/16), respectively. The complete resection rates were 80.4% (37/46), 91.7% (22/24), and 93.8% (15/16) for the respective groups. Conclusion:Endoscopic treatment demonstrates favorable efficacy and safety for superficial non-ampullary duodenal adenoma. In addition to traditional EMR and ESD, ESD-S is also an effective procedure for endoscopic treatment of non-ampullary duodenal adenoma.

OBJECTIVE To conduct a reevaluation of the systematic review(SR)/meta-analysis on the use of Xianling gubao capsules(XLGBC)for knee osteoarthritis(KOA),and provide evidence-based support for the clinical use of the drugs.METHODS Computerized searches including CNKI,Wanfang Data,VIP,China Biomedical Literature Database,the Cochrane Library,PubMed,Embase and Web of Science were conducted to collect systematic reviews(SR)or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st,2024.The report quality,methodological quality,risk of bias and evidence quality were assessed using the PRISMA 2020 statement,AMSTAR 2 scale,ROBIS tool and GRADE tool,respectively.A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed.RESULTS A total of five SR/meta-analyses were included.The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete(21 points),while four studies had deficiencies(18-20 points).The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low.According to the ROBIS tool evaluation,the risk of comprehensive bias in all five studies was classified as high.GRADE tool evaluation revealed that among 49 outcome indicators,5(10.2％)were rated as moderate-quality evidence(10.2％),12 as low-quality evidence(24.5％),and 32 as very low-qualitv evidence(65.3％).The results of comprehensive quality analysis showed that the clinical efficacy,visual analogue scale score,pain relief time,comprehensive indexes of knee joint function,the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone(P＜0.05).CONCLUSIONS Compared with conventional treatment,XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages.However,due to the low quality of evidence for the outcome indicators included in the studies,the conclusions should be interpreted with caution.