BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

[摘 要] 目的：开发新型溶瘤呼肠孤病毒（Reo）递送系统，以克服中和抗体对Reo的中和作用并提升其肿瘤靶向性。方法：通过切向流过滤联合超高速离心法制备自然杀伤细胞外泌体（NKexo），叶酸（FA）修饰后采用挤压法包载Reo，构建FA-NKexo-Reo递送系统；通过透射电镜（TEM）、纳米粒径分析、蛋白质印迹（WB）法、核磁共振氢谱及流式细胞术等技术表征其理化性质；采用CCK-8、流式细胞术、Transwell实验及激光共聚焦显微镜评估FA-NKexo-Reo递送系统体外细胞毒性及细胞摄取能力；通过人卵巢癌裸鼠皮下移植瘤模型评价FA-NKexo-Reo的肿瘤靶向性、疗效及安全性。结果：FA-NKexo-Reo粒径为（94.0 ± 28.5）nm，Zeta电位为（-21.26 ± 1.57）mV，包封率达（49.7 ± 15.6）%；在中和抗体的存在下，FA-NKexo-Reo对卵巢癌细胞SKOV3和A2780仍可表现出显著的细胞毒性（P < 0.01）；荷瘤鼠活体成像显示FA-NKexo-Reo肿瘤靶向性显著优于NKexo组，肿瘤抑制率提升60%（P < 0.001）。结论：成功制备FA-NKexo-Reo递送系统，在中和抗体的存在下，FA-NKexo-Reo可保护并靶向递送Reo到高表达叶酸受体的卵巢癌细胞，从而增强Reo的抗肿瘤作用。

Objective To investigate the value of 3.0 T MRI in-phase/opposed-phase (IP-OP) imaging features in the quantitative assessment of hepatic steatosis after liver transplantation. Methods Clinical data of 115 patients who underwent liver transplantation and completed MRI IP-OP examination and liver biopsy within 3 months were retrospectively collected. According to the gold standard of pathological results, patients were divided into the steatosis group (n=18) and the non-steatosis group (n=97). The relative signal intensity of hepatic parenchyma was measured on MRI IP-OP sequences, and the hepatic fat fraction (HFF) was calculated. Differences in clinical data and imaging features between the two groups were compared, and the efficacy of HFF in the diagnosis of graft hepatic steatosis was evaluated using the receiver operating characteristic (ROC) curve. Results Among the 115 recipients, 18 cases were diagnosed with hepatic steatosis by liver biopsy, including 13 cases of mild steatosis, 3 cases of moderate steatosis and 2 cases of severe steatosis. Compared with the non-steatosis group, the steatosis group had a lower proportion of hepatitis B virus (HBV)-related hepatocellular carcinoma, higher proportions of HBV-related liver failure and alcoholic liver cirrhosis, and higher platelet levels (all P<0.05). There were statistically significant differences in hepatic imaging features between the two groups (all P<0.05). The ROC curve showed that the area under the curve (AUC) of the quantitative value calculated by IP-OP in the diagnosis of graft hepatic steatosis was 0.925 (95% confidence interval 0.870-0.980). Conclusions 3.0 T MRI IP-OP sequence may accurately and non-invasively quantitatively assess the severity of hepatic steatosis after liver transplantation, which is of great value for the early detection of graft hepatic steatosis and the guidance of clinical intervention.

Objective To observe the value of multi-detector CT(MDCT)for evaluating changes of aortic root parameters caused by aortic stenosis(AS).Methods MDCT data of 20 cases with severe AS were retrospectively analyzed.The changes of the long diameter,short diameter,mean diameter,area,circumference,as well as diameter derived from area(DA)and diameter derived from circumference(DC)of aortic annulus(AA),left ventricular outflow tract(LVOT)and sinotubular junction(STJ)during early systole,late systole,early diastole and late diastole were measured and calculated,respectively.Results In early systole,the short diameter,mean diameter,area,circumference,DA and DC of A A were all significantly larger than that those in late systole,early diastole and late diastole(all P＜0.05).No significant difference of the long diameter of AA was found among different phases(all P＞0.05).Meanwhile,the short diameter,mean diameter,area,circumference,DA and DC of LVOT in early systole were all significantly larger than those in late systole,early diastole and late diastole(all P＜0.05).The long diameter of LVOT in early systole was larger than in late systole(P＜0.05),but not significantly different compared with that in early and late diastole(both P＞0.05).No significant difference of the above parameters of STJ was found among different phases(all P＞0.05).At early systole,DA and the mean diameter of AA were both significantly smaller than those of DC(both P＜0.05).Conclusion AA parameters obtained with MDCT in patients with severe AS were valuable for selecting prosthetic valves during transcatheter aortic valve replacement.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.