Renal cell carcinoma(RCC)is the most common type of malignant kidney tumors,originating from re-nal tubular epithelial cells.The primary treatment options for RCC include surgery and targeted therapy.Despite the notable advancements in RCC research,significant challenges persist,including the high risk of metastasis and recur-rence post-surgery,as well as the low sensitivity to radiotherapy and chemotherapy.Ferroptosis,a form of regulated cell death first identified in 2012,has garnered significant attention due to its involvement in several cellular processes,including redox balance,iron metabolism,and various signaling pathways related to cancer progression.Given its po-tential to be modulated,ferroptosis offers significant promise for the treatment of cancers,ischemic organ damage,and other degenerative diseases associated with lipid peroxidation.This review discusses recent developments in ferroptosis research,with a particular focus on its role in RCC,and explores future research directions in this area.

Percutaneous coronary intervention(PCI),as one of the primary approaches for revascularization,still faces complications such as restenosis,myocardial ischemia-reperfusion injury and no-reflow/slow-flow phenomena,with no currently effective interventions ensuring long-term efficacy.Based on Li Dongyuan's theory that"fire and original qi cannot coexist",this article inherited Academician Chen Keji's academic perspective on"toxin-stasis pathogenesis"and the hemodynamic characteristics of coronary arteries to propose a"four-stage pathological progression"in post-PCI patients,namely spleen-stomach impairment-original qi deficiency-endogenous yin-fire-toxin-stasis accumulation.It emphasized that the heart vessels rely on qi and blood for nourishment and patency for function,elucidated the therapeutic rationale of Danggui Buxue Decoction,and presented the self-formulated Yixin Hemai Prescription,modified through syndrome differentiation,and performed simultaneous reinforcement and dredging,in order to provide diagnosis and treatment ideas for coronary heart disease after PCI treated with TCM.

Background Vascular endothelial damage associated with endothelial progenitor cell dysfunction is considered as an initiating step of hypertension and target organ damage, in which oxidative stress plays a key role. High-intensity intermittent exercise is an effective prevention and treatment method of various chronic diseases; however, little attention has been paid to its effects and mechanisms on endothelial progenitor cells. Objective To observe the effect of high-intensity intermittent exercise on the function of endothelial progenitor cells in patients with hypertension and explore the mechanism of oxidative stress. Methods A total of 60 patients with essential hypertension were randomly divided into a control group and an exercise group. The control group received conventional drug treatment (including diuretics, calcium blockers, and beta-blockers), and the exercise group performed high-intensity intermittent exercise for 8 weeks (3 times·week⁻¹) in addition to the treatment plan of the control group. Before and after intervention, brachial artery flow-mediated vasodilation (FMD) was used to evaluate vascular endothelial function; venous blood was sampled to perfrom circulating endothelial progenitor cell counts; endothelial progenitor cells were cultured in vitro, and the modified Boyden chamber assay and Matrigel lumen formation assay were used to detect their migration and tube formation ability, superoxide fluorescent anion probe method to detect reactive oxygen species levels, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining method to detect cell apoptosis, Western blotting to determine protein expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2, NADPH oxidase 4, and superoxide dismutase. Results Four patients (13.3%) in the control group and 2 patients (6.7%) in the exercise group dropped out; the completion rate of the exercise group's training plan was 94.9%. Compared with the before-intervention indicators, blood pressure decreased, brachial artery FMD increased, number of circulating endothelial progenitor cells increased, their migration and tube formation ability were enhanced, reactive oxygen species levels and cell apoptosis rate were reduced, NADPH oxidase 2 and NADPH oxidase 4 protein expressions were down-regulated, and superoxide dismutase protein expression was up-regulated in the after-intervention exercise group, and the differences were all statistically significant (P < 0.05). There was no significant difference in the above indicators in the control group between before and after intervention (P > 0.05). Conclusion High-intensity intermittent exercise regulates oxidative stress mediated by NADPH oxidase, improves endothelial progenitor cell function, and restores vascular endothelial disorders in patients with essential hypertension.

A 58-year-old female patient presented with red papules, plaques, and scabs on her right foot accompanied by pain and itching for 14 years. Dermatological examination revealed extensive red plaques on her right foot and ankle, with scattered red papules in between; some of the plaques were covered with a moderate amount of yellow-brown crusts, and a small amount of yellow exudate was observed at the junction of the toes and the dorsum of the foot. Histopathological examination of the skin lesions showed hyperkeratosis, parakeratosis, pseudoepitheliomatous hyperplasia, neutrophil aggregation in the epidermis, and mixed inflammatory cell infiltration in the dermis. Three different types of colonies were cultured from the skin lesion tissues: light brown granular colonies, black granular colonies, and white-brown filamentous colonies. Under the microscope, the filamentous colonies appeared as long chains of brown conidia with short cylindrical beaks, while the black and light brown granular colonies appeared as clusters of spores, with single or multiple septa inside, and some budding spores were observed. Electron microscopy further confirmed the above structures. Molecular biological analysis revealed that the three types of colonies were all identified as Alternaria alternata. The patient was diagnosed with cutaneous alternariosis caused by Alternaria alternata with special morphology. After 7 months of treatment with oral itraconazole, the skin lesions healed, and no recurrence was observed during a 3-year follow-up.

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.

BACKGROUND:Formononetin is an isoflavonoid compound widely found in red clover,astragalus,and chickweed,which has the ability to inhibit oxidative stress,inflammatory factor release,and apoptosis. OBJECTIVE:To investigate the effect of formononetin on interleukin-1β-induced chondrocyte injury and its mechanism. METHODS:(1) Cartilage tissues from patients with osteoarthritis and patients with simple meniscus injury were collected,and real-time quantitative PCR was used to detect miR-135b-5p expression. (2) Human chondrocytes were cultured in vitro,and then divided them into nine groups:cells in normal control group were cultured for 48 hours with no treatment;cells in interleukin-1β group were treated with interleukin-1β for 48 hours;cells in interleukin-1β+low-dose formononetin group were treated with 25 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+middle-dose formononetin group were treated with 50 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+high-dose formononetin group were treated with 100 μmol/L formononetin for 24 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+miR NC group were treated with miR NC for 6 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+miR-135b-5p group were treated with miR-135b-5p mimics for 6 hours followed by treatment with interleukin-1β for 48 hours;cells in interleukin-1β+high dose formononetin+anti-miR-NC group were treated with anti-miR-NC for 6 hours,then treated with 100 μmol/L formononetin for 24 hours,and finally treate with interleukin-1β for 48 hours;cells in interleukin-1β+high-dose formononetin+anti-miR-135b-5p group were treated with anti-miR-135b-5p for 6 hours,the treated with 100 μmol/L formononetin for 24 hours,and finally treated with interleukin-1β for 48 hours. Relevant tests are performed after treatment. RESULTS AND CONCLUSION:The expression level of miR-135b-5p in cartilage tissue of patients with osteoarthritis was significantly lower than that of patients with simple meniscus injury (P<0.05). Compared with the normal control group,the expression level of miR-135b-5p,proliferative ability,activity of superoxid dismutase,and expression levels of collagenase Ⅱ protein and Bcl-2 protein in chondrocytes were lower in the interleukin-1β group (P<0.05),while apoptotic rate,lactate dehydrogenase activity,malondialdehyde level,levels of proinflammatory factors,and expression levels of matrix metalloproteinase-13 protein and Bax protein were higher in the interleukin-1β group (P<0.05). Formononetin inhibited chondrocyte damage caused by interleukin-1β in a concentration-dependent manner. Transfection of miR-135b-5p mimics elevated miR-135b-5p expression in the interleukin-1β group and inhibited chondrocyte damage induced by interleukin-1β;transfection of anti-miR-135b-5p decreased miR-135b-5p expression in the interleukin-1β+high-dose formononetin group and inhibited the effect of formononetin on chondrocytes. To conclude,the protective effect of formononetin on chondrocyte injury induced by interleukin-1β may be related to the regulation of miR-135b-5p expression.

Objective To investigate the clinical features,treatment and prognosis of primary testicular lymphoma(PTL),so as to provide reference for the standardized diagnosis and treatment of this disease.Methods Clinical data of 13 PTL cases treated in Xijing Hospital during Jan.2014 and Dec.2024 were retrospectively collected.The patients' diagnosis,treatment methods and prognosis were summarized.Results All 13 patients underwent orchiectomy of the affected side.According to the postoperative pathological results,11 cases were diagnosed as diffuse large B-cell lymphoma and 2 as NK/T-cell lymphoma.Among the 11 cases with diffuse large B-cell lymphoma,10 received immunotherapy and chemotherapy according to the international standardized treatment plan,and 5 received preventive myeloablative injection therapy.Recurrence in the contralateral testis occurred in 3 cases,1 complicated with central nervous system infiltration died,and another 1 refusing chemotherapy had contralateral testicular metastasis.Of the 2 cases with NK/T-cell lymphoma,1 received systemic chemotherapy and died after central nervous system recurrence,and another 1 died 1 month after surgery whithout undergoing chemotherapy.Conclusion Primary testicular lymphoma is highly invasive with poor prognosis.Patients with NK/T-cell lymphoma have extremely poor prognosis,while those with diffuse large B-cell lymphoma have relatively better prognosis.However,even after comprehensive treatment,it is still prone to recurrence in the testis and the central nervous system.

Objective:To investigate the postoperative recurrence-free survival (RFS) and influencing factors of gastrointestinal stromal tumors (GISTs) patients with and without KIT gene exon 11 codon 557 and/or 558 deletion mutations (referred to as 557/558 deletion mutations). Methods:The propensity score matching and retrospective cohort study was conducted. The clinico-pathological data of 337 patients with GISTs who underwent operation at Northern Jiangsu People′s Hospital from January 2006 to December 2022 were collected. There were 198 males and 139 females, aged (59±10)years. Of 337 patients with primary GISTs, 97 cases with KIT gene 557/558 deletion mutations were allocated into 557/558del group, and the rest 240 cases without KIT gene 557/558 deletion mutations were allocated into non-557/558del group. Observation indicators: (1) propen-sity score matching and comparison of clinicopathological data of patients between the two groups after matching; (2) follow-up and RFS; (3) analysis of influencing factors for RFS of patients. Compari-son of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the non parametric rank sum test. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Propensity score matching was done by the 1∶1 nearest neighbor matching method. The caliper value was set as 0.02. Results:(1) Propensity score matching and comparison of clinicopatholo-gical data of patients between the two groups after matching. Of 337 patients, 168 cases were succe-ssfully matched, including 84 cases in the 557/558del group and 84 cases in the non-557/558del group.After propensity score matching, the confounding bias of mitotic index, modified National Institutes of Health risk classification, Armed Forces Institute of Pathology risk classification before matching were eliminated between the two groups, ensuring comparability. (2) Follow-up and RFS. All 337 patients were followed up for 35(range 2?120)months. There were 55 cases of postoperative recurrence or metastasis. After propensity score matching, the 1-, 2-, and 5-year RFS rates in the 557/558 del group were 96.34% [95% confidence interval ( CI) as 89.08%-98.80%], 88.28%(95% CI as 78.63%-93.74%), and 70.54%(95% CI as 55.26%-81.44%), respectively. For the non-557/558 del group, the corresponding rates were 92.78%(95% CI as 84.64%-96.69%), 87.44%(95% CI as 77.86%- 93.06%), and 84.00%(95% CI as 73.33%-90.67%). There was no significant difference in RFS between the two groups ( χ2=2.291, P>0.05).(3) Analysis of influencing factors for RFS of patients. Results of multivariate analysis showed that tumor location, tumor diameter, mitotic index, and muta-tion subtype were independent factors influencing postoperative RFS of GISTs patients before pro-pensity score matching ( hazard ratio=3.262, 1.110, 3.041, 7.082, 2.945, 95% CI as 1.874-5.680, 1.039-1.186, 1.681-5.503, 3.304-15.180, 1.681-5.158, P<0.05). Conclusions:There is no significant difference in postoperative RFS of GISTs patients with and without KIT gene 557/558 deletion muta-tions. Tumor location, tumor diameter, mitotic index and mutation subtype are independent factors influencing postoperative RFS in GISTs patients.

A 58-year-old female patient presented with red papules, plaques, and scabs on her right foot accompanied by pain and itching for 14 years. Dermatological examination revealed extensive red plaques on her right foot and ankle, with scattered red papules in between; some of the plaques were covered with a moderate amount of yellow-brown crusts, and a small amount of yellow exudate was observed at the junction of the toes and the dorsum of the foot. Histopathological examination of the skin lesions showed hyperkeratosis, parakeratosis, pseudoepitheliomatous hyperplasia, neutrophil aggregation in the epidermis, and mixed inflammatory cell infiltration in the dermis. Three different types of colonies were cultured from the skin lesion tissues: light brown granular colonies, black granular colonies, and white-brown filamentous colonies. Under the microscope, the filamentous colonies appeared as long chains of brown conidia with short cylindrical beaks, while the black and light brown granular colonies appeared as clusters of spores, with single or multiple septa inside, and some budding spores were observed. Electron microscopy further confirmed the above structures. Molecular biological analysis revealed that the three types of colonies were all identified as Alternaria alternata. The patient was diagnosed with cutaneous alternariosis caused by Alternaria alternata with special morphology. After 7 months of treatment with oral itraconazole, the skin lesions healed, and no recurrence was observed during a 3-year follow-up.