BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective To investigate the effect of bone metastasis on the efficacy of immune check-point inhibitors(ICI)in treatment of advanced non-small cell lung cancer(NSCLC).Methods A retro-spective analysis was conducted in 248 patients with advanced NSCLC who received ICI therapy.The patients were divided into bone metastasis group(110 cases)and non-bone metastasis group(138 ca-ses)based on the presence of bone metastasis.Clinical characteristics,objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.The correlations of factors such as bone metastasis with the survival prognosis of NSCLC patients were analyzed using the Cox proportional hazards regression mod-el.A total of 60 treatment-naive NSCLC patients with bone metastasis were selected from research ob-jects,with 30 patients receiving ICI combined with conventional chemotherapy(combination group)and 30 patients receiving conventional chemotherapy alone(chemotherapy group).The therapeutic effects and incidence of treatment emergent adverse events(TEAE)were compared between the two groups.Results There were no statistically significant differences in ORR and DCR between the bone metastasis and non-bone metastasis groups(P＞0.05).The PFS of the bone metastasis group(5.53 months)was shorter than that of the non-bone metastasis group(7.72 months)(x2=3.674,P=0.045).However,there was no statistically significant difference in OS between the bone me-tastasis group and the non-bone metastasis group(16.98 versus 17.56 months,x2=1.333,P=0.248).Multivariate Cox regression analysis showed that bone metastasis was an independent prog-nostic factor for PFS in NSCLC patients(HR=1.52,95％CI,1.10 to 1.98,P=0.003),but not a prognostic factor for OS(P＞0.05).The ORR and DCR in the combination group were 43.33％and 93.33％,respectively,which were higher than 26.67％and 76.67％in the chemotherapy group(P＜0.05).The PFS in the combination group was longer than that in the chemotherapy group(x2=4.023,P=0.036).However,there was no statistically significant difference in OS be-tween the two groups(x2=1.235,P=0.267).There were no statistically significant differences in the overall incidence of TEAEs or the incidence of≥grade 3 TEAE between the two groups(P＞0.05).Conclusion Although the occurrence of bone metastasis has an adverse effect on the effica-cy of ICI therapy in advanced NSCLC,patients with bone metastasis can still achieve better thera-peutic effects through ICI combined with chemotherapy compared with chemotherapy alone.

This article explores the technological innovations and clinical prospects of robot-assisted hiatal hernia repair (RAHHR). RAHHR demonstrates outstanding performance in hiatal hernia repair, particularly for complex hernias, owing to its advantages such as 3D visualization and 7-degree-of-freedom robotic arms, which contribute to reduced recurrence rates and accelerated recovery. However, challenges remain, including high costs and limited operative space. Future directions include the development of single-port robotic systems, force feedback technology, and AI-powered surgical navigation. Standardized training and technological innovations are expected to promote its widespread application.

Objective To investigate the damage mechanism of extracellular vesicles(EVs)derived from ves-tibular schwannoma(VS)on HEI-OC1 cells and the protective effect of the ferroptosis inhibitor ferrostatin-1(Fer-1).Methods Tumor tissues and clinical data were collected from four patients with stage Ⅱ or Ⅲ VS,classified as grade D according to the AAO-HNS hearing classification.Primary VS cells were extracted,and their conditioned supernatant was collected.EVs were isolated using ultracentrifugation and identified.HEI-OC1 cells were cultured in vitro and divided into three groups:the control group(no treatment),the EVs group(treated with 3000 parti-cles/cell VS-EVs for 24 hours),and the EVs+Fer-1 group(pretreated with 20 μmol/L Fer-1 for 2 hours followed by co-culture with 3000 particles/cell VS-EVs for 24 hours).Cell viability was assessed using the CCK-8 assay,re-active oxygen species(ROS)levels were quantified using the DCFH-DA fluorescent probe,and lipid peroxidation was evaluated using the BODIPY 581/591 C11 probe.Results Compared with the control group,the EVs group showed significantly reduced cell viability(P＜0.001)and increased levels of ROS(P＜0.001)and lipid peroxides(P＜0.001).However,the EVs+Fer-1 group exhibited significantly restored cell viability(P＜0.001)and re-duced levels of ROS and lipid peroxidation(P＜0.001).Conclusion VS-derived EVs disrupts redox homeostasis,promotes intracellular accumulation of lipid peroxides and ROS,and induces ferroptosis in HEI-OC1 cells.Fer-1 significantly alleviates VS-EVs-induced ferroptosis,thereby protecting HEI-OC1 cells from damage.

Glioblastoma (GBM) is the most aggressive malignant tumor of the adult central nervous system, with limited treatment options and poor prognosis. Radiotherapy (RT) remains a cornerstone of GBM treatment; however, tumor cell resistance to RT severely limits its efficacy. Recently, metabolic reprogramming (MR) has gained widespread attention as a critical mechanism enabling GBM cells to evade RT‐induced stress. In this review, the central roles of glucose, lipid, and amino acid metabolic reprogramming in GBM's resistance to RT were outlined, highlighting how GBM remodels metabolic pathways to enhance DNA damage repair, antioxidant defenses, and immune evasion after RT. Although combining metabolic inhibitors with RT has shown potential in improving GBM treatment outcomes, challenges such as overcoming the blood‐brain barrier and addressing tumor heterogeneity remain. The integration of nanomedicine‐based delivery systems and immunotherapy offers new hope for GBM treatment. Future research should focus on developing multidimensional, personalized metabolic targeting strategies, combined with immunotherapy and emerging technologies, to further improve therapeutic outcomes and survival rates for GBM patients.

To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

[Purpose]To analyze the survival of lung cancer,liver cancer and stomach cancer in Jiashan County,Zhejiang Province from 2006 to 2020.[Methods]From January 1,2006 to De-cember 31,2020,new cases of lung cancer,liver cancer and stomach cancer were collected in Jiashan County,Zhejiang Province.The 5-year observed survival rate(OSR),relative survival rate(RSR)and age-standardized relative survival rate(ARSR)by sex and age were calculated from 2006-2010,2011-2015 and 2016-2020.The observed and relative survivals were calculated using the lifetime table and Ederer Ⅱ methods,respectively,and age standardized using the Inter-national Cancer Survival Standard.Joinpoint software was utilized to compute the average annual percentage change(AAPC)for analyzing trends in various survival rates from 2006 to 2020.[Re-sults]The 5-year RSR of lung cancer,liver cancer and stomach cancer increased from 8.1％,4.8％and 23.2％(2006-2010)to 36.0％,17.6％and 48.2％(2016-2020),showing an increasing trend(AAPC=14.4％,AAPC=11.4％,AAPC=6.4％,respectively,all P＜0.05).Accordingly,the 5-year RSR of three types of malignant tumors showed an increasing trend in both men and women(all P＜0.05)except liver cancer in women(P＞0.05).The 5-year RSR of three types of malignant tu-mors in the age groups of 0～64 and 65+years old showed a significant increasing trend(all P＜0.05).The increase of lung cancer and liver cancer was greater in the age group of 0～64 years old,and the increase of gastric cancer was greater in the age group of 65+years old.[Conclusion]The 5-year survival rates of the three types of malignant tumors with the highest mortality risk in Jiashan County,Zhejiang Province all increased significantly from 2006 to 2020,indicating that the pre-vention and treatment effect of malignant tumors is significant,but the survival rate of malignant tumors varied significantly among different populations,so targeted intervention should be carried out.

China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.

This study aimed to identify mutations in the human insulin receptor gene (INSR) and investigate their role in the pathogenesis of severe insulin resistance syndrome. Sanger sequencing of the INSR gene was performed on a patient clinically suspected of having type A insulin resistance syndrome admitted to the Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital. Upon identifying mutations, relevant exons were sequenced in her first-degree relatives. Additionally, control groups consisting of individuals with type 2 diabetes and those with normal glucose tolerance were screened for the mutation detected in the patient. Functional predictions of the INSR protein were made using MutationTaster, SIFT, and PolyPhen2 software. A previously unreported heterozygous missense mutation, c.3652G/A (Asp1218Asn), in exon 20 was identified in both the proband and her father. This mutation was not present in any of the control individuals. Multiple prediction tools indicate that this mutation likely disrupts gene/protein structure or function. The c.3652G/A (Asp1218Asn) heterozygous mutation in INSR is a novel variant that plays a significant role in the pathogenesis of severe insulin resistance in this Chinese family.

Objective:To investigate multi-system involvement in Kennedy′s disease and its association with disease progression.Methods:We retrospectively reviewed the clinical, laboratory, and electrophysiological data from 48 genetically confirmed patients with Kennedy′s disease at the Department of Neurology, First Medical Center of the Chinese PLA General Hospital, between February 2016 and February 2024. The disease progression rate was calculated based on the functional scores at baseline and follow-up. Correlation analyses and multiple linear regression models were employed to assess the relationships among clinical variables and to identify potential predictors of disease progression.Results:The age of muscle weakness onset ranged from 16 to 66 years (mean 42±11 years), with a diagnostic delay of 5.0 (3.0, 9.8) years. Lower limb weakness was the most common initial symptom in 72.9% (35/48) of patients, and 37.5% (18/48) exhibited non-motor manifestations prior to the onset of weakness. Core motor manifestations included bulbar weakness (89.6%, 43/48) and symmetric proximal limb weakness (83.3%, 40/48), frequently accompanied by gynecomastia (74.2%, 23/31) and sexual dysfunction (64.6%, 31/48). The median CAG repeat length was 43 (42, 46), which showed a significant negative correlation with the age at onset ( r=-0.406, P=0.004). Patients with CAG repeats > 43 had a higher prevalence of sexual dysfunction. Elevated serum muscle enzymes were observed in 97.9% (47/48), and abnormal sex hormone levels were detected in 81.2% (39/48). Sensory neuropathy was present in 68.1% (32/47), with CAG repeat length inversely correlating with compound muscle action potential (CMAP) amplitudes in the median ( β=-0.29; t=-2.27, P=0.029) and ulnar ( β=-0.22; t=-2.23, P=0.031) nerves. Low-frequency repetitive nerve stimulation (RNS) revealed a decrement in 43.3% (13/30) of patients, most commonly affecting the axillary and spinal accessory nerves. The disease progression rate was 1.3±0.3 (range: 0.5-2.0). Furthermore, serum creatine kinase-MB (CK-MB) levels were negatively correlated with disease progression rate ( r=-0.303, P=0.036). Conclusions:Kennedy′s disease presents with diverse initial manifestations and frequent multi-system involvement. Non-motor manifestations may precede muscle weakness, serving as valuable clues for early diagnosis. Widespread sex hormone abnormalities (particularly testosterone/luteinizing hormone dysregulation) support the role of androgen insensitivity in disease pathogenesis. Sensory neuropathies are frequent and not length-dependent. The presence of decremental responses on low-frequency RNS suggests neuromuscular junction dysfunction, which may underlie motor impairment in patients with Kennedy′s disease. Finally, serum CK-MB may serve as a potential biomarker for disease progression.