Genitourinary system tumors, as a major clinical challenge posing a serious threat to human health, urgently require breakthroughs in the construction of a precision diagnosis and treatment system. The innovative application of molecular imaging technologies, particularly the development of novel molecular probes, is revolutionizing the diagnostic and therapeutic paradigms for urinary tumors. The application of novel molecular probes in the early diagnosis and staging of genitourinary tumors, the role of multimodal molecular imaging probes in guiding precision surgery/radiotherapy, and the clinical translation challenges and strategies for theranostic-integrated probes are systematically reviewed in this article to provide valuable insights and references for related research and clinical practice.

BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

Objective:To compare the efficacy of lateral placement of the intramedullary nail guide pin versus that of median placement of the intramedullary nail guide pin in the closed reduction of metaphyseal fracture of the distal tibia.Methods:A retrospective cohort study was conducted to analyze the clinical data of 48 patients with metaphyseal fracture of the distal tibia who had been admitted to Department of Trauma Orthopaedics, The Second General Hospital of Fuzhou from May 2019 to July 2023. There were 37 males and 11 females, aged (46.0±12.4) years. According to the AO classification, 37 patients were classified as type A1, and 11 ones as type A2. The patients were divided into 2 groups according to the distal positioning of the intramedullary nail guide pins during operation. In the lateral placement group of 26 patients, the distal positioning of the guide pins was located at 1/3 lateral to the articular surface of the distal tibia. In the median placement group of 22 patients, the distal positioning of the guide pins was located at the midpoint of the articular surface of the distal tibia. The operation time, intraoperative blood loss, hospital stay, fracture healing time and fracture reduction were recorded and compared between the 2 groups. Moreover, the visual analogue scale (VAS) pain score, American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, and range of motion of the affected ankle were compared between the 2 groups, as well as within the 2 groups. The complications were compared between the 2 groups at the last follow-up.Results:There were no significant differences in the demographic data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (19.6±4.4) months. The operation time [(81.7±17.3) min], intraoperative blood loss [(78.4±12.2) mL], hospital stay [(5.7±2.1) d] and fracture healing time [(4.3±1.1) months] in the lateral placement group were significantly less than those in the median placement group [(103.0±13.4) min, (111.4±11.7) ml, (8.6±3.5) d, and (6.1±1.3) months] ( P<0.05). There was no significant difference in the VAS pain score between the 2 groups before operation or at the last follow-up ( P>0.05). At the last follow-up, the AOFAS ankle-hindfoot score [(93.6±1.6) points], ankle dorsiflexion (17.9°±1.6°) and plantar flexion (41.9°±1.9°) in the lateral placement group were significantly better than those in the median placement group [(87.8±3.2) points, 15.1°±1.2°, and 38.5°±2.7°] ( P<0.05). In both groups, significant improvements were achieved at the last follow-up in VAS pain score, the AOFAS ankle-hindfoot score, ankle dorsiflexion and plantar flexion compared with the preoperative period ( P<0.05). The incidence of fracture angulation deformity in the lateral placement group (11.5%, 3/26) was lower than that in the median placement group (31.8%, 7/22) ( P>0.05). There was no significant difference in the incidence of complications between the lateral placement group (3.8%, 1/26) and the central placement group (18.2%, 4/22) ( P>0.05). Conclusion:In the closed reduction of metaphyseal fracture of the distal tibia, compared with median placement of the intramedullary nail guide pin, lateral placement of the intramedullary nail guide pin assisted with a Kirschner wire demonstrates advantages of more rapid and effective closed reduction of the fracture, shortened operation time, reduced intraoperative blood loss and promoted postoperative rehabilitation.

To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up.

To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE).

Hedysari radix is the characteristic chi-nese medicine of Gansu Province,with"MiCang Hedysari radix"as the best.Modern pharmacologi-cal research has shown that it has polysaccharides and flavonoids,which have good anti-tumor effects and can inhibit the occurrence and development of various cancers,such as lung cancer,liver cancer,and breast cancer.Cancer is ranked as the second leading cause of death in the world,and the mor-bidity and mortality rates are increasing year by year,seriously affecting the quality of life.At pres-ent,with the modernization of Traditional Chinese Medicine(TCM),there has been a significant break-through in the treatment of malignant tumors with TCM.Based on this,by collating the relevant litera-ture at home and abroad in recent years,the anti-tumor effects and mechanisms of Hedysari radix and its active ingredients are summarized to pro-vide a scientific basis for the study of elucidating the material basis of the anti-tumor effects of He-dysari radix and to promote the development of the Hedysari radix industry.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

Adhering to the guidance of party building is an essential requirement for comprehensively promoting the high-quality development of public hospitals.How to solve the problem of"two skins"of party building and business,further promote the deep integration of the party and business has become an important topic for the party building of public hospitals in the new era.Taking Jieyang People's Hospital as an example,this paper introduces the innovation and exploration experience on the par-ty building work round in the hospital,the working mechanism of which is"1+5+5+4"of"Party building leading,five re-sponsibility coordination,five-step linkage and four-type integration".This approach effectively promotes the deep integration and promotion of the party and business,which further lead the high-quality development of various work in the hospital.It can pro-vide reference for exploring and improving the system and mechanism of the integration of party and business,and further promote party leadership in promoting high-quality development in public hospitals.

Objective:To explore the effect of ginsenoside Rg1 on spermatogenic dysfunction in mice caused by diabetes and its mechanism of action.Methods:Eighteen male C57BL mice were randomly divided into control group, the model group and the ginsenoside Rg1 group by completely random method, with 6 mice in each group. Type 2 diabetes models were established in the model group and the ginsenoside Rg1 group by a high-fat diet combined with intraperitoneal injection of streptozotocin, while control group was injected with the same amount of normal saline. After successful modeling, control group was given a regular diet for 8 weeks, while the model group and ginsenoside Rg1 group were given a high-fat diet for 8 weeks. The ginsenoside Rg1 group was also treated with ginsenoside Rg1 medication. Reproductive hormone levels were detected by enzyme-linked immunosorbent assay test kits, and Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl2 protein, Caspase-3 protein, Bax protein), autophagy-related proteins (P62, LC3Ⅰ, LC3Ⅱ, Beclin1), β-Catenin protein, mTOR protein, LAMP1 protein and transcription factor EB. The body weight, blood glucose levels, testicular index of mice in each group were compared, as well as the testicular injury status.Results:The body weight [(18.77±1.14) g], testosterone level [(141.07±8.47) ng/L], follicle-stimulating hormone level [(9.19±0.74) U/L], and luteinizing hormone level [(1 497.91±99.57) pg/L] of mice in the model group were significantly lower than those in the control [(31.57±2.35) g, P<0.001; (171.50±11.76) ng/L, P<0.001; (12.46±1.54) U/L, P<0.001; (1 807.29±92.76) pg/L, P<0.001]; fasting blood glucose level [(20.82±1.11) mmol/L], glycosylated hemoglobin (12.67%±1.03%), the testis index (0.65%±0.03%) were significantly higher than those in the control [(6.40±1.34) mmol/L, P<0.001; 5.17%±1.17%, P<0.001; 0.48%±0.04%, P<0.001]. Compared with the model group, the body weight [(22.62±0.92) g, P=0.023], testosterone level [(172.63±9.20) ng/L, P<0.001], follicle-stimulating hormone level [(12.37±1.15) U/L, P<0.001], and luteinizing hormone level [(1 847.80±108.80) pg/L, P<0.001] of mice in the ginsenoside Rg1 group increased significantly, fasting blood glucose level [(18.63±1.14) mmol/L, P=0.017], glycosylated hemoglobin (8.50%±1.05%, P<0.001) and testicular index (0.54%±0.02%, P<0.001) decreased significantly. Compared with the control, the expressions of P62 ( P=0.039), LC3Ⅱ/LC3Ⅰ( P<0.001), Beclin1 ( P=0.002) and mTOR ( P=0.036) in the testicular tissue of mice in the model group all increased, the expression of β-Catenin ( P<0.001), LAMP1 ( P=0.005), transcription factor EB ( P<0.001) all decreased. Compared with the model group, the expressions of autophagy-related proteins P62 ( P=0.048), LC3Ⅱ/LC3Ⅰ( P<0.001) , Beclin1 ( P=0.023) and mTOR ( P=0.005) in the ginsenoside Rg1 group all decreased, while the expression of β-Catenin ( P=0.001), LAMP1 ( P=0.011) and transcription factor EB ( P=0.022) all increased. Transmission electron microscopy detected a decrease in the number of autophagosomes in the testicles of mice in the model group, and it improved after drug intervention. The HE staining showed that the testes of mice in the model group exhibited phenotypes such as the shedding and disorganization of spermatogenic cells, while ginsenoside Rg1 was able to improve these phenotypes. Conclusion:Ginsenoside Rg1 can improve testicular injury caused by diabetes in mice by regulating autophagy.

Meniere's disease represents an idiopathic inner ear disorder characterized by endolymphatic hy-drops.Currently,the research methods for identifying genes associated with this disease mainly involve first-genera-tion sequencing and second-generation sequencing.This article reviews research on the genetic study of Meniere's disease,mainly summarizing the candidate genes with repeated pedigree validation in familial Meniere's disease,as well as those frequently reported in sporadic Meniere's disease.