Intravitreal anti-vascular endothelial growth factor(anti-VEGF)therapy has been widely used, but the variability in its therapeutic efficacy limits individualized treatment. In recent years, the application of artificial intelligence(AI)has opened up new avenues for personalized treatment response prediction, and its core branches include machine learning(ML)and deep learning(DL). This review systematically retrieved and analyzed 41 relevant studies published up to April 2025. Comprehensive analysis reveals that AI predictive models are evolving from forecasting single endpoints(such as visual acuity or central retinal thickness)to integrating multi-dimensional endpoints(encompassing anatomical, functional, and treatment demand parameters)and generating predictive imaging outputs. In terms of technical approaches, DL models(28 studies, accounting for 68.3%)dominate this field due to their robust image interpretation capabilities, while ML models(10 studies, 24.4%)retain significant value in the analysis of structured clinical data. Cross-disease comparisons indicate that research efforts are most concentrated on age-related macular degeneration(ARMD)and diabetic macular edema(DME), with shared conceptual frameworks for model construction, yet distinct anatomical and functional indicators are prioritized for each disease. Currently, the field confronts several key challenges, including insufficient prospective clinical validation, limited model interpretability(the “black box problem”), and a scarcity of high-quality multi-center datasets. Moving forward, it is imperative to advance real-world validation and develop explainable AI techniques to expedite the clinical translation of these predictive models.

OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ （AS- Ⅳ ） on lipopolysaccharide （LPS）-induced neuroinflammation. METHODS BV2 cells were divided into control group， LPS group， AS-Ⅳ groups at concentrations of 20 and 40 μmol/L， and dexamethasone group （2 μmol/L）. Except for control group， neuroinflammation model was established with LPS （1 μg/mL） in other groups after medication. The levels of inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and nitric oxide （NO）] in cell supernatant were measured in each group. Mice were randomly divided into normal group， model group， positive control group （Aspirin enteric-coated tablet， 20 mg/kg）， AS-Ⅳ low- and high-dose groups （10， 20 mg/kg）， with 6 mice in each group. Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection， once a day， for 14 consecutive days. Except for normal group， other groups were intraperitoneally injected with LPS （250 μg/kg） 1 hour after daily administration of the drug/normal saline to establish neuroinflammation model. Serum levels of IL-6 and TNF-α were measured 2 h after the last medication； histopathological morphology of cerebral tissue in mice were observed； the co-localization of inducible nitric oxide synthase （iNOS）/ionized calcium binding adapter molecule 1 （Iba1） and CD206/Iba1 in the cerebral cortex region of mice was observed； the expressions of proteins related to the nuclear factor-κB （NF-κB）/mitogen-activated protein kinase （MAPK） signaling pathway in brain tissue of mice were also determined， including NF-κB p65， phosphorylated NF-κB p65（p-NF-κB p65）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， extracellular signal-regulated kinase （ERK）， and phosphorylated ERK （p-ERK）. RESULTS In the cell experiments， compared with control group， the levels of IL-6， TNF- α and NO in the cell supernatant of the LPS group were increased significantly （P＜0.05）； compared with LPS group， the levels of IL-6， TNF-α and NO were decreased significantly in the administration groups （P＜0.05）. In the animal experiments， compared with the normal group， the serum levels of IL-6 and TNF- α， the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex， and the phosphorylation levels of p38 MAPK， NF- κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group （P＜0.05）； the number of CD206/ Iba1 co-localization positive cells in the cerebral cortex region significantly decreased （P＜0.05）. The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement. Compared with model group， above quantitative indexes of mice were all reversed significantly in administration groups （P＜0.05）； the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement. CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway， promote the M2-type polarization of microglia， and thereby suppress neuroinflammatory responses.

Objective To explore the bioactive components in Jiawei Xiaoyao Pills(JWXYP)and their mechanisms for alleviating depression-like behaviors.Methods The active compounds,key targets,and pathways of JWXYP were identified using TCMSP and TCMIP databases.Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress(CUMS)-induced depression groups.After modeling,the 5 model groups were treated with daily gavage of normal saline,1.8 mg/kg fluoxetine hydrochloride(positive control drug),or JWXYP at 1.44,2.88,and 4.32 g/kg.The depression-like behaviors of the rats were evaluated using behavioral tests,and pathological changes in the liver and hippocampus were examined with HE staining.The biochemical indicators in the serum and brain tissues were detected using ELISA.Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA,and gut microbiota changes were analyzed using 16S rDNA sequencing.Results Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system.In the rat models subjected to CUMS,treatment with JWXYP significantly improved body weight loss,sucrose preference and open field activities,reduced liver inflammation,alleviated structural changes in the hippocampal neurons,decreased serum levels of TNF-α,IL-1β,IL-6 and LBP,and increased 5-HT and VIP concentrations in the serum and brain tissue,and these effects were the most pronounced in the high-dose group.Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats,involving the pathways for bile acid biosynthesis and amino acid metabolism.16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.Conclusion JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters,inhibiting inflammation and oxidation,and modulating gut microbiota.

Objective:To compare the efficacy of robot-assisted percutaneous reduction and screw fixation versus open reduction and plate fixation via the sinus tarsi approach in the treatment of Sanders types II and III calcaneal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 82 patients (90 feet) with calcaneal fractures admitted to the Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University from January 2020 to April 2024, including 74 males and 8 females, aged 24-87 years [(46.4±12.1)years]. According to Essex-Lopresti classification, the fractures were classified as tongue-type in 43 patients and joint-collapse-type in 47. According to Sanders classification, 69 feet were classified as type II and 21 as type III. Forty-seven patients (52 feet) were treated with robot-assisted percutaneous reduction and screw fixation (screw fixation group) and 35 (38 feet) with open reduction and plate fixation via the sinus tarsi approach (plate fixation group). The two groups were compared in terms of the operation duration, intraoperative blood loss, length of hospital stay and time to weight-bearing. The width, height, length, B?hler angle and Gissane angle of the calcaneus before surgery and at 1 day after surgery were compared. The Maryland foot and ankle function score, American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot function score, and visual analogue scale (VAS) score at 1, 3 months postoperatively, and at the last follow-up were compared. The incidence of postoperative complications and removal rate of internal fixation were also detected in the two groups.Results:All the patients were followed up for 9-60 months [(30.0±14.5)months]. There was no significant difference in the operation duration between the two groups ( P>0.05). The intraoperative blood loss, length of hospital stay and time to weight-bearing in the screw fixation group were 10.0(10.0, 20.0)ml, 7.0(5.0, 8.0)days and (5.0±0.8)weeks, which were significantly less or shorter than 30.0(20.0, 50.0)ml, 8.0(6.0, 11.0)days and (6.9±0.7)weeks in the plate fixation group ( P<0.05). The width, height, length, B?hler angle and Gissane angle of the calcaneus at 1 day after surgery were (43.4±4.2)mm, (46.2±4.0)mm, (81.6±5.1)mm, 27.1(20.4, 30.4)° and (113.4±10.1)° in the screw fixation group, which were all improved compared with those before surgery [(47.8±4.6)mm, (39.3±4.8)mm, (79.2±5.9)mm, 9.5(0.0,16.5)° and (119.3±13.4)°] ( P<0.01). The width, height, length and B?hler angle of the calcaneus at 1 day after surgery were (41.6±5.7)mm, (48.4±4.8)mm, (83.1±5.7)mm and 27.3(21.3, 31.6)° in the plate fixation group, which were all improved compared with those before surgery [(47.8±5.0)mm, (41.7±5.1)mm, (80.1±5.9)mm and 12.9(7.2,19.8)°] ( P<0.01), with no significant difference in the Gissane angle ( P>0.05). Before surgery and at 1 day postoperatively, no significant differences were found in the width, length, B?hler angle or Gissane angle of the calcaneus between the two groups ( P>0.05), while the height of the calcaneus in the screw fixation group was lower than that in the plate fixation group ( P<0.05). At 1 month after surgery and at the last follow-up, there were no significant differences in the Maryland foot and ankle function score, AOFAS ankle and hindfoot function score, and VAS score between the two groups ( P>0.05). At 3 months after surgery in the screw fixation group, the Maryland foot and ankle function score was (79.7±3.8)points, significantly higher than (74.7±2.8)points in the plate fixation group ( P<0.01); the AOFAS ankle and hindfoot function score was (77.1±5.0)points, significantly higher than (70.1±3.6)points in the plate fixation group ( P<0.01); the VAS score was 1.0(1.0, 2.0)points, significantly lower than 2.5(2.0, 3.0)points in the plate fixation group ( P<0.01). No significant difference was detected in the incidence of postoperative complications between the two groups ( P>0.05). The removal rate of internal fixation was 10% (5/52) in the screw fixation group, significantly lower than 29% (11/38) in the plate fixation group ( P<0.05). Conclusion:Compared with open reduction and plate fixation via the sinus tarsi approach, robot-assisted percutaneous reduction and screw fixation has the advantages of less intraoperative blood loss, shorter hospital stay, earlier weight-bearing exercises, better early functional recovery and pain relief, and lower internal fixation removal rate in the treatment of Sanders types II and III calcaneal fractures.

Objectives:To explore the therapeutic efficacy of balloon stent kissing technique(BSKT)and jailing wire technique(JWT)in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch of the coronary artery,and to observe the impact of these two interventional procedures on the lumen area,angina symptoms,cardiac function,myocardial injury,and myocardial perfusion of patients.Methods:A retrospective analysis was conducted in 203 patients with true bifurcation lesions of the left anterior descending branch-diagonal branch who underwent BSKT and JWT procedures and completed a 6-month follow-up in the Department of Cardiovascular Medicine at Shijiazhuang People's Hospital from January 2022 to January 2024.Patients were randomly assigned to the BSKT group(n=107)or the JWT group(n=96).The safety,efficacy,and myocardial perfusion indicators of the two groups were compared.Results:The minimum lumen area measured by intravascular ultrasound immediately after procedure,the Canadian Cardiovascular Society angina classification at 6 months post-intervention,the total score of resting+stress myocardial perfusion at 6 months post-intervention,the total number of segments with resting+stress myocardial ischemia,and the abnormal myocardial perfusion area in both the BSKT group and JWT group were significantly improved compared to baseline values(all P<0.05).In the BSKT group,87 cases(81.3%)achieved immediate success in stent placement,whereas in the JWT group,64 cases(66.7%)achieved immediate success in stent placement.The BSKT group significantly outperformed the JWT group.In terms of the myocardial injury and cardiac function indicators assessed on postoperative day 1,the cardiac troponin I level([0.22±0.13]ng/ml vs.[0.45±0.27]ng/ml,P<0.001),creatine kinase MB([35.24±13.15]U/L vs.[42.39±21.66]U/L,P=0.004),and B-type natriuretic peptide([133.52±25.62]pg/ml vs.[167.22±22.04]pg/ml,P<0.001)were all significantly lower in the BSKT group than in the JWT group.In terms of the myocardial perfusion indicators at 6 months post-intervention,the number of ischemic segments under stress(3.23±1.54 vs.3.87±1.62,P=0.004),the total score of stress perfusion(4.18±2.21 vs.4.97±2.96,P=0.031),and the abnormal myocardial perfusion area([7.04±3.27]%vs.[8.24±3.69]%,P=0.014)were all significantly lower in the BSKT group than in the JWT group.Conclusions:Both BSKT and JWT procedures can significantly improve the lumen area of the left anterior descending branch,angina symptoms,and myocardial perfusion in patients with true bifurcation lesions of the left anterior descending branch-diagonal branch.The BSKT procedure provides more adequate protection for the bifurcation vessels compared to the JWT procedure.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

Standardized clinical trial reporting is crucial for ensuring the scientific validity,reproducibility,and clinical translational value of reported results.The Consolidated Standards of Reporting Trials(CONSORT)statement,an internationally recognized guideline for randomized controlled trials(RCTs),has become an important reference standard for writing research papers in medicine since the 2010 version of CONSORT was published.With advancements in scientific research methodologies and the emergence of new forms of clinical trials,the CONSORT working group released an updated version in April 2025,published in journals such as The BMJ.Herein,we provide a systematic interpretation of the core revisions of CONSORT 2025,as well as a comparison with CONSORT 2010 to highlight the key differences.By providing practical,example-based recommendations,we aim to help domestic researchers apply the new guidelines efficiently,thereby improving the quality of clinical trial reports authored by domestic researchers.

A high-quality clinical trial protocol is the cornerstone for ensuring the scientific integrity and ethical compliance of a study.The Standard Protocol Items:Recommendations for Interventional Trials(SPIRIT)has become the international benchmark for developing clinical trial protocols since its release in 2013.To adapt to the developing trends of open science and patient-centered principles,the SPIRIT group completed a comprehensive update in 2025.While retaining its core structure,this updated guideline introduces a new open science module and incorporates several new elements,including patient and public involvement,trial monitoring,and data sharing,alongside substantial revisions of five pre-existing items.In this article,we critically examine the core revisions in SPIRIT 2025 and,through analysis of representative case studies,illustrate the practical application of the new reporting guideline in drafting trial protocols.Our goal is to to provide Chinese researchers with a valuable reference for understanding and implementing this new reporting guideline,thereby enhancing the quality and rigor of clinical trial protocols developed in the country.

Objective:To investigate the clinical characteristics and prognosis of follicular lymphoma (FL) patients with different primary sites using the Surveillance, Epidemiology, and End Results (SEER) database.Methods:Clinical data of 7167 patients with early-stage FL (stage I-II) from the SEER database between 2000 and 2015 were respectively analyzed. Primary sites were divided into intranodal and extranodal types. Intranodal primary sites included supradiaphragmatic lymph nodes (LN), subphrenic lymph nodes and Waldeyer's ring. Extranodal primary sites consisted of skin, gastrointestinal tract, duodenum, head and neck, other sites. Prognostic factors and overall survival (OS) in patients with different primary sites were analyzed. OS rate was evaluated using Kaplan-Meier method and survival difference between primary sites was compared with log-rank test. Inverse probability treatment weighting (IPTW) and multi-variable analysis were applied to adjust for confounding factors. Multivariate Cox regression analysis of influencing factors of OS was performed.Results:The median age was 63 years old, with the median follow-up time of 63 months. There was no difference in prognosis among the intranodal groups or between the intranodal and extranodal groups. The 10-year OS rates of the supradiaphragmatic lymph LN ( n=2146), subdiaphragmatic LN ( n=2811), and the Waldeyer's ring ( n=151) groups were 70.7%, 69.9% and 73.4%, respectively ( P=0.422 for infradiaphragmatic LN vs. supradiaphragmatic LN, P=1.000 for Waldeyer's ring vs. supradiaphragmatic LN), and 70.3% and 68.9% for intranodal ( n=5108) and extranodal ( n=2059), respectively. There was no significant difference in OS between the groups ( P=0.581) after IPTW adjustment. The most common primary sites in extranodal disease were skin, gastrointestinal tract, head and neck, and duodenum. The 10-year OS for skin, gastrointestinal tract, and cutaneous was 74.2%, 74.7%, and 87.3%, respectively, significantly higher than 55.6% for other sites (duodenum vs. others sites, gastrointestinal vs. others sites, skin vs. others sites: all P<0.001). Multivariate Cox regression analysis revealed that difference in OS was not significant among the intranodal groups or between the intranodal and extranodal groups. However, different extranodal primary site was an independent prognostic factor for OS. Conclusions:Early FL patients with supradiaphragmatic LN, subdiaphragmatic LN and Waldeyer's ring, and between the intranodal and extranodal primary sites obtain similar prognosis. However, early-stage FL patients with different extranodal primary sites have prognostic differences. The prognosis of primary skin, gastrointestinal tract and duodenum is significantly better than that of other extranodal primary sites.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.