BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

Plasminogen activator is a kind of enzyme that plays a key role in the process of physiological hemostasis and thrombolysis. Its main function is to convert plasminogen into active plasmin, thereby initiating the dissolution of fibrin and maintaining blood mobility. This article discusses the safety of plasminogen activator in the intraocular application, elaborates on the types, structure, physiological function and mechanism of action of plasminogen activator in the eye. The analysis addresses the ocular tissue damage and systemic adverse reactions that may be caused by the application of plasminogen activator in the eye, and the risks and countermeasures combined with relevant research examples, aiming to provide reference for the safe application of plasminogen activator in clinical practice.

Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

ObjectiveTo explore the mechanism by which Qiangjing tablets （QJT） alleviate the spermatogenic function damage caused by varicocele （VC） based on the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway-mediated oxidative stress. MethodsTen Sprague-Dawley （SD） rats were randomly assigned into a control group and a model group. Pathological examination confirmed the stability of the model. Thirty-six SD rats were randomized into control， model， low-dose （0.23 g·kg^-1） QJT， medium-dose （0.46 g·kg^-1） QJT， high-dose （0.92 g·kg^-1） QJT， and mazhilin （61.7 mg·kg^-1） groups， with 6 rats in each group. A rat model of experimental left varicocele （ELV） was established by partially ligating the left renal vein to simulate the human nutcracker syndrome. The rats were administrated with corresponding agents once a day for 28 consecutive days. The in vitro testicular culture model of rats was established through the Transwell chamber method and intervened with QJT-containing sera （2.3， 4.6， and 9.2 g·kg^-1）. Microscopic observation was carried out for the morphology of the left kidney. A micrometer was used to measure the diameter of the left spermatic vein （LSV）. The body weights of rats were recorded weekly， and the epididymis and testis weights were measured. The pathological changes of the testicular tissue was observed via hematoxylin-eosin （HE） staining. The levels of testosterone （T） in the cell culture supernatant and reactive oxygen species （ROS） in the rat testicular tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Flow cytometry was employed to determine the ROS content. Immunohistochemical staining was conducted to analyze Keap1， Nrf2， 3β-hydroxysteroid dehydrogenase （3β-Hsd）， GATA-binding protein-4 （Gata-4）， and proto-oncogene receptor tyrosine kinase （C-kit）. The ultrastructure of the tissue was observed by transmission electron microscopy （TEM）. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining. The expression of Keap1， Nrf2， glutathione S-transferase α2 （Gsta2）， glutathione S-transferase μ1 （Gstm1）， heme oxygenase-1 （HO-1）， quinone oxidoreductase 1 （Nqo1）， and thioredoxin reductase 1 （Txnrd1） was quantified by Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot. ResultsCompared with the control group， the ROS content and the percentage of apoptotic cells in the model group were significantly increased （P<0.01）， the T concentration was significantly decreased （P<0.01）， the mRNA and protein expressions of Keap1 were significantly increased （P<0.01）， and the mRNA and protein expressions of Nrf2， Gsta2， Gstm1， HO-1， Nqo1 and Txnrd1 were significantly decreased （P<0.05）. Compared with the model group， the ROS content and the percentage of apoptotic cells in each dose group of the Qiangjing Tablets were significantly reduced （P<0.05）， and the mRNA and protein expressions of Keap1 were significantly decreased （P<0.05）， while the mRNA and protein expressions of Nrf2， Gsta2， Gstm1， HO-1， Nqo1 and Txnrd1 were significantly increased （P<0.05）. ConclusionQJT improves sperm motility in the rat model of VC by modulating the Keap1/Nrf2 signaling pathway and reducing oxidative stress injury.

Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.

The rapid development of the pharmaceutical research and development (R&D) has brought new challenges to occupational health management, including the high uncertainty in the R&D process, emerging hazards, and compliance complexities associated with novel business models. Traditional management approaches exhibit limitations in effectively addressing the occupational health risks associated with these challenges. Based on the perspective of agile governance, this paper proposed an optimized pathway characterized by dynamic response, adaptive flexibility, and multi-stakeholder collaboration. It further offered countermeasures and recommendations from three aspects: concept renewal, mechanism innovation, and tool empowerment, aiming to provide reference for the effective management and control of occupational health risks in the innovation and development of the pharmaceutical R&D industry.

Objective To analyze the changing trends of the burden of non-alcoholic fatty liver disease(NAFLD)in China from 1990 to 2021 and provide a basis for formulating prevention and treatment strategies.Methods The standardized incidence rate,prevalence,mortality,and disability-adjusted life year(DALY)rate of NAFLD in China from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021.The average annual percentage change of rate data was calculated by Joinpoint 4.2 and the age,period,and birth cohort effects of the prevalence and DALY rate were analyzed by the age-period-cohort model.Results Compared to 1990,the incidence rate and prevalence of NAFLD have been on the rise,while the mortality and DALY rate have been declining.The age effect curves of prevalence and DALY rate showed an upward trend followed by a downward trend for both males and females.With the period from 1992 to 1996 as the reference group,the period effect curve of prevalence showed a downward trend followed by an upward trend,being the lowest in the period from 2002 to 2006(RR=0.93).The period effect curve of DALY rate showed a downward trend from 1992 to 2011 and then tended to flatten out.With the period from 1972 to 1981 as the reference group,the birth cohort effect curve of prevalence showed a steady upward trend in the general population and both male and female populations.The birth cohort effect curve of DALY rate showed an overall upward trend followed by a downward trend,with the peak occurring in the birth cohort group between 1922 and 1931.The DALY rate of NAFLD caused by smoking and high fasting blood glucose has shown a downward trend since 2014,and fasting blood glucose gradually became the dominant factor as age increased.Conclusions From 1990 to 2021,NAFLD in China has shown a rising prevalence but a significantly declining DALY rate.This suggests that current prevention and control strategies are effective,and further efforts should be made to raise residents' health awareness in controlling the occurrence and development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/epidemiology* ; China/epidemiology* ; Prevalence ; Female ; Male ; Incidence ; Disability-Adjusted Life Years ; Middle Aged ; Adult

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.