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).

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Objective To summarize the clinicopathological characteristics,diagnostic and therapeutic process and aeromedical evaluation of 17 cases of thyroid cancer in Chinese military pilots in order to provide a reference for the diagnosis and treatment of disease and aeromedical evaluation of patients with thyroid cancer in military pilots in the future.Methods A retrospective analysis was conducted on the clinicopathological characteristics,treatment methods and aerospace medical evaluation conclusions of 17 military pilots with thyroid cancer who were hospitalized and underwent diagnosis,treatment and aeromedical evaluation at the Department of Aviation Medicine of Xijing Hospital from March 2021 to March 2025.Results All 17 pilots with thyroid cancer were male,and the age of onset ranged from 22 to 51 years old(with a median age of 40 years old).All patients underwent fine-needle aspiration biopsy of thyroid nodules or enlarged cervical lymph nodes before the operation.The postoperative pathological types were all papillary thyroid carcinoma.Among them,16 cases were papillary thyroid microcarcinoma,9 cases were combined with regional lymph node metastasis,and 1 case with postoperative complications of Horner's syndrome recovered after treatmentwas.14 patients underwent unilateral glandular lobe and isthectomy of the thyroid,3 patients underwent total/near-total thyroidectomy,2 patients received radioactive 131I treatment after the operation,and 17 patients received thyroid stimulating hormone(TSH)suppression therapy after the operation.After aerospace medical evaluation,15 cases were qualified for flight duties,the observation time was 3 to 6 months(with an average observation time of 4.2 months),1 case reached the age limit,and 1 case was temporarily unqualified for failure to achieve TSH suppression.After 0.5 to 4.0 years of follow-up,no patient showed signs of recurrence or metastasis.Conclusion For thyroid cancer in military pilots,universal screeningprotocols and earlydetection,as well as standardized therapeutic regimensshould be carried out.Evidence-based aeromedical evaluations and long-term monitoring should be conducted based on the aircraft type,jobs,and flight experience to preserve military combat effectiveness to the greatest extent.

Objective To investigate the expression of EIF5A1 in intrahepatic cholangiocarcinoma cell lines and human hepatobiliary duct epithelia,and its effect on the proliferation,migration and invasion ability and Wnt/β-Catenin signaling pathway in HUCCT1 cells.Methods Western blot was used to detect the basal expression level of EIF5A1 in intrahepatic cholangiocarcinoma cell lines and human intrahepatic cholangiocarcinoma epithelial cells.Transient transfection of siRNA was used to silence the expression of EIF5A1 in intrahepatic cholangiocarcinoma cell HUCCT1.The experimental groups were divided into blank control group(Con),siRNA1 group,and siRNA2 group.The most effective siRNA was screened by Western blot.The effects of EIF5A1 silencing on the proliferation,migration and invasion ability of HUCCT1 cells were detected by CCK-8,EdU cell proliferation assay and Transwell assay.The effect of EIF5A1 silencing on the Wnt/β-Catenin signaling pathway in HUCCT1 cells was detected by Western blot.Results The results of CCK-8 and EdU cell proliferation experiments showed that the proliferation ability of HUCCT1 cells decreased after EIF5A1 silencing(P<0.05),and Transwell migration and invasion experiments showed that the migration and invasion ability of Hucct1 cells decreased after EIF5A1 silencing(P<0.05).Western blot analysis revealed decreased expression of β-Catenin,Cyclin D1,MMP-2 and Survivin in Wnt/β-Catenin signaling pathway after EIF5A1 silencing(P<0.05).Conclusion EIF5A1 may promote the proliferation,migration and invasion of intrahepatic bile duct cancer cells through Wnt/β-Catenin signaling pathway.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective:To investigate the effectiveness and safety of ultrasound-guided endovascular therapy for autogenous arteriovenous fistula (AVF) thrombosis.Methods:It was a single-center retrospective cohort study. Data of patients undergoing ultrasound-guided intravascular therapy due to AVF thrombosis in the First Hospital of Hebei Medical University from August 2018 to June 2021 were analyzed. According to different surgical procedures, the patients were divided into two groups. Patients treated with percutaneous transluminal angioplasty (PTA) + drilling thrombectomy were in group A, and patients treated with PTA only were in group B. After 1 year of follow-up, the surgical technique success rate, primary patency rate, secondary patency rate and complications were compared between the two groups.Results:A total of 152 patients were enrolled, including 74 in group A and 78 in group B. There were no significant differences in gender, age, proportion of patients with diabetes and hypertension, and thrombosis time of AVF between the two groups (all P>0.05). Compared with group B, the diameter and length of thrombus in group A were larger [13.0(9.0, 16.0) mm vs. 6.0(5.0, 6.5) mm, Z=-9.362, P<0.001; 12(8, 15) cm vs. 3(3, 4) cm, Z=-10.061, P<0.001], and the establishment time of AVF was longer [5(2, 7) years vs. 2(1, 5) years, Z=-2.698, P=0.007]. Among the overall patients, the success rate of surgery was 96.7% (147/152), and the success rate of surgery was 95.9% (71/74) in group A and 97.4% (76/78) in group B respectively, with no statistical difference ( χ2=0.004, P=0.952). Kaplan-Meier survival analysis showed that, overall, the primary patency rate at 3rd, 6th and 12th month after operation was 87.1%, 71.4% and 56.6%, and the secondary patency rate was 97.1%, 96.4% and 94.1%, respectively. The primary patency rate of group A at 3rd, 6th and 12th month was 82.4%, 66.7% and 53.6%, and the secondary patency rate was 95.7%, 94.2% and 89.7%, respectively. The primary patency rate of group B at 3rd, 6th and 12th month was 91.5%, 73.2% and 59.7%, and the secondary patency rate was 98.6%, 98.6% and 98.5%, respectively. There was no significant difference in the primary and secondary patency rate between group A and group B at 3rd, 6th and 12th month (all P>0.05). The duration of operation in group A was longer than that in group B [2.0(1.9, 2.0) h vs. 2.0(1.0, 2.0) h, Z=-5.181, P<0.001], but no serious complications occurred in both groups. Conclusion:The two surgical methods are effective, safe and reliable in the treatment of AVF thrombosis, and have high clinical application value.

Objective:To analyze the epidemic characteristics of brucellosis in China from 2004 to 2018, in order to understand the development trend of brucellosis.Methods:The surveillance data of brucellosis in China from 2004 to 2018 were collected from National Public Health Science Data Center. Joinpoint regression was used to analyze the trend of brucellosis incidence in China and various provinces. Overall trends were estimated by the average annual percentage change (AAPC). Seasonal and trend decomposition using loess (STL) was used to analyze the seasonal characteristics of brucellosis in China and various provinces. The age-related thermodynamic diagram of incidence rate was used to analyze the characteristics of age-onset changes.Results:From 2004 to 2018, a total of 524 980 brucellosis cases and 16 deaths were reported nationwide, with a incidence rate of 2.61/100 000 and a case fatality rate of (3.05 × 10 -3)%. The incidence of brucellosis in China was on the rise (AAPC = 11.58%, 95% CI: 7.91% - 15.25%, P < 0.001). There was no significant trend of change in Inner Mongolia Autonomous Region, Shanxi and Shaanxi provinces ( P > 0.05). Tibet Autonomous Region showed a downward trend (AAPC = - 55.19%, P < 0.001). All other provinces were showing an upward trend (AAPC > 0, P < 0.05). The peak incidence in China occurred from April to June. In terms of provinces, the peak incidence in Hainan, Sichuan, Guizhou, Fujian and Anhui provinces occurred from April to August, the peak incidence in Chongqing and Shanghai cities occurred from June to August, and the peak incidence in other provinces was generally from April to June. There were reports of brucellosis cases in all age groups nationwide, and the age distribution showed an inverted "V" shape. The peak incidence occurred in the 50 - 54 years old (5.43/100 000), followed by the 60 - 64 years old (4.94/100 000). From 2004 to 2018, the top 3 age groups of incidence rate changed from 40 - 44, 50 - 54 and 35 - 39 years old in 2004 to 50 - 54, 60 - 64 and 55 - 59 years old in 2018. Conclusions:The incidence of brucellosis is on the rise nationwide and in most provinces from 2004 to 2018. The high incidence age is gradually changing to the elderly population.

Sphingomyelin phosphodiesterase 3 (SMPD3) encodes neutral sphingomyelinase 2 (nSMase2), which plays an important role in tumor development as a key enzyme regulating cell growth variation and inducing apoptosis with the important messenger molecule ceramide. On one hand, the common epigenetic alteration of SMPD3 methylation mediates carcinogenesis through the disruption of gene expression by regulating cell proliferation, differentiation, and apoptosis. Meanwhile, SMPD3 also induces apoptosis and cell cycle arrest in tumor cells through its hydrolysis products. On the other hand, SMPD3 is also closely related to pro-cancer processes such as exosome secretion, inflammatory response, and tumor cell proliferation. In this paper, the biological action of SMPD3 in tumor diseases was reviewed to enhance the understanding of the role of SMPD3 in the development of different tumors and provide broader ideas for basic research and clinical diagnosis and treatment of tumor diseases.