BACKGROUND:Currently,numerous experiments delve into the intricate anatomy and biomechanical behavior of distinct segments of the supraspinatus muscle.However,the impact of shoulder joint stress resulting from damage to various regions of this muscle remains a scarcely explored domain.Understanding the repercussions of supraspinatus muscle injuries across different regions on the stress distribution and magnitude of articular cartilage and the glenoid is crucial for providing some theoretical support for clinical diagnosis and treatment. OBJECTIVE:To ascertain the maximum stress values by simulating different degrees of supraspinatus muscle rupture on the humeral cartilage surface,glenoid lip,and glenoid cartilage joint surface using three-dimensional finite element software. METHODS:Normal and healthy shoulder joint CT or MRI scans were processed through Mimics and Geomagic to extract molds.Subsequently,models were constructed via Solidworks.Varying degrees of supraspinatus muscle damage were simulated for each model to mimic fractures in different regions.Finally,Ansys,mechanical software,was employed for three-dimensional finite element biomechanical analysis,calculating stress values for the humeral cartilage surface,glenoid lip,and glenoid cartilage joint surface. RESULTS AND CONCLUSION:(1)With worsening degrees of supraspinatus muscle injury,the stress on the shoulder joint cartilage surface and glenoid lip escalated.(2)Among various regions,the anterior part of the supraspinatus muscle exhibited paramount significance.(3)While supraspinatus muscle fractures of differing degrees impacted the magnitude of cartilage stress on the glenoid labial surface,the stress distribution remained constant.(4)It is indicated that during the initial stages of horizontal abduction of the shoulder joint,the anterior region assumes a pivotal role,followed by the posterior deep region.Injury to the anterior part of the supraspinatus muscle leads to a significant surge in stress within the shoulder joint's soft tissue,potentially causing damage to the top of the glenoid lip and the anterior part of the glenoid cartilage.

[摘 要] 肿瘤微环境（TME）对肿瘤的生长发展至关重要，靶向TME是肿瘤治疗的新策略。纳米酶的酶样活性能够调节细胞的氧化还原水平，并且在动态TME中具有协同催化活性，其在肿瘤学领域的应用已取得出色的进展。然而，纳米酶的底物选择性差、活性受TME限制、催化机制受多因素调控等阻碍了纳米酶的推广应用。本文系统地总结了纳米酶的类型及氧化还原纳米酶的抗肿瘤作用和TME的特征，重点探讨了靶向TME纳米酶的治疗策略及现状；同时，对基于纳米酶的增强型肿瘤治疗方法进行综述，以期推动靶向TME的肿瘤治疗纳米酶的研发及临床应用转化。

[摘 要] 随着乳腺癌患者生存期的延长，肿瘤耐药性成为治疗过程的严峻挑战之一，临床通常将细胞死亡标志物的增加作为预测乳腺肿瘤患者生存率提高的标准。通过刺激肿瘤细胞死亡途径来提高抗肿瘤药物治疗的效果，使用某些佐剂是一种可行的方法。研究表明，二甲双胍（Met）是治疗Ⅱ型糖尿病的一线药物，同时具有抗肿瘤特性，其能增强细胞死亡机制，尤其是促进肿瘤细胞自噬、凋亡和铁死亡。同时证明，Met对免疫系统的刺激作用在诱导肿瘤细胞死亡方面发挥作用，其诱导不同细胞死亡机制在增敏抗肿瘤药物治疗中起着关键作用。本文论述了Met对乳腺癌肿瘤微环境（TME）的调控作用机制及其在抗肿瘤药物治疗中的增敏作用，对Met在临床前和临床免疫治疗中的研究方向提出建议。

Objective To explore the mechanism of the demethylase fat mass and obesity associatal(FTO)gene on the proliferation of human liver cancer cell line HepG2.Methods HepG2 cells were divided into the control group,FTO group(transfected with FTO over-expression plasmid),si-FTO group(transfected with si-FTO)and si-FTO+si-FoxO1 group(simultaneously transfected with si-FTO and si-FoxO1).The expression of FTO in cells was detected by RT-qPCR.Cell proliferation,invasion and apoptosis were examined using CCK-8 assay,Transwell chamber assay and flow cytometry,respectively.Dot blot assay was performed to measure m6 A methylation,and protein expression of FoxO1 in cells was detected by Western blot.Results Analysis of overall survival in liver cancer patients using The Cancer Genome Atlas(TCGA)showed higher expression of FTO associated with shorter survival(P＜0.05).Compared with normal liver cells HL7702,FTO relative expression was significantly increased in human liver cancer cells HepG2(P＜0.05).The relative expression of FTO in si-FTO group cells was lower than that in the control group,while the relative expression of FTO in FTO group was higher than that in the control group(P＜0.05).The relative expression of FTO in the si-FTO+si-FoxO1 group was higher than that in the si-FTO group(P＜0.05).Compared with the Control group,cell viability,count of invasive cells,relative level of m6 A were significantly decreased,while apoptosis rate and protein expression of FoxO1 were significantly increased in the si-FTO group(P＜0.05).Cell viability,count of invasive cells,and relative expression level of m6 A were sig-nificantly higher,while apoptosis rate and protein expression of FoxO1 were significantly lower in the FTO group compared to the Control group(P＜0.05).Compared with the si-FTO group,cell viability,invasive cells and rela-tive level of m6 A were significantly increased,while apoptosis rate and protein expression of FoxO1 were significant-ly decreased in the si-FTO+si-FoxO1 group(P＜0.05).Conclusion High expression of FTO is associated with poor clinical prognosis.Knockdown of the demethylase FTO gene inhibits proliferation and invasion of liver cancer cells and induces their apoptosis.The mechanism is potentially related to the regulation of FoxO1.

Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

Objective To investigate the clinical and imaging features of adult brain stroke with Wallerian degeneration.Methods The clinical and imaging data of 3 adult patients with post-stroke Wallerian degeneration were retrospectively analyzed,and the literature was reviewed.Results All the three patients had a history of stroke,and the disease recurred several months later.Head MRI examination showed abnormal signals in the pontine,which were consistent with the disfigurement of the pyramidal tract of the primary lesion.Combined with the clinical symptoms of the patients,they were diagnosed as post-stroke Wallerian degeneration.Conclusions Patients with Wallerian degeneration after stroke may show changes in clinical symptoms,and are easily misdiagnosed as cerebral infarction,often with poor prognosis.Clinical awareness of this disease should be improved to avoid misdiagnosis,so as to improve the prognosis of patients and improve the quality of life.

Purpose To investigate the expression and re-lationship of phosphatidic acid phosphatase 2 domain 1A(PPAPDC1A),also known as phospholipid phosphatase 4(PLPP4),in colorectal cancer(CRC)tissues and different colorectal cancer cells.Methods Immunohistochemical EnVi-sion method was applied to detect the expression of PPAPDC1A in 60 CRC tissues and paired paracancerous tissues.Stable over-expression and silencing cell lines of PPAPDC1A were success-fully constructed by gene transfection,and the effects of this gene on different colorectal cancer cell lines were investigated by CCK-8,Transwell,subcutaneous tumor formation in nude mice and tail vein injection in nude mice.Results PPAPDC1A ex-pression was upregulated in CRC tissues compared with paracan-cerous tissues,and the intensity of PPAPDC1A expression was negatively correlated with cell differentiation(P=0.011).PPAPDC1A stable overexpression and interference cell lines were successfully constructed.The results of in vitro and in vivo experiments showed that the growth rate(SW480-PPAPDC1A,RKO-PPAPDC1A groups:0.38±0.03,0.25±0.01),the number of cells crossing the compartment(SW480-PPAPDC1 A,RKO-PPAPDC1A groups:218.33±7.09,96.33±1.52),the number of clone formation(SW480-PPAPDC1 A,RKO-PPAP-DC1A groups:174.33±5.03,245.00±7.00),the in vivo tumor volume(4.16±0.91),and the number of lung metasta-sis in nude mice(5.1±3.84)were significantly higher in the PPAPDC1A stably overexpressing cell lines compared with the Vector group(P＜0.05).However,the growth rate(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:0.14±0.02,0.16±0.05),number of cells crossing the chambers(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:13.33±0.57,18.33±0.51),number of clone formation(SW620-shPPAP-DC1A,LOVO-shPPAPDC1A groups:28.33±1.52,8.67± 0.57),tumor volume(0.56±0.21),and number of lung me-tastasis in nude mice(1.2±1.03)were significantly lower(P＜0.05)in the PPAPDC1 A-silenced cell line compared with the NC group.Conclusion Down-regulation of PPAPDC1A expres-sion inhibits the proliferation,invasion,migration and metastatic ability of CRC cells.

Objective To evaluate the potential clinical value of T2 mapping and mDixon Quant in the diagnosis of early interver-tebral disc degeneration.Methods A total of 79 volunteers who underwent lumbar MRI examination were enrolled.All subjects were examined for 3.0T MR with T2WI,T2 mapping,and mDixon Quant while recording the condition of low back pain.The differ-ences between T2 mapping(map)value and fat fraction(FF)values of the vertebral(V)and nucleus pulposus(NP)within the Pfir-rmann Ⅰ and Pfirrmann Ⅱ intervertebral disc(grade Ⅰ 76,grade Ⅱ 87)were statistically analyzed.Receiver operating characteristic(ROC)curve analyses were performed for meaningful parameters.Results V-FF showed a mild positive correlation with degenera-tive intervertebral disc lesions,and NP-FF and NP-map values showed a mild negative correlation with lesions.There were statistically significant differences between the two groups in V-FF(P＜0.001),NP-FF(P=0.005),and NP-map(P＜0.001).Some measure-ments had statistically significant differences when different intervertebral disc segments were compared.Conclusion V-FF,NP-FF,and NP-map are associated with intervertebral disc degeneration.T2 mapping and mDixon Quant are potentially valuable as diagnostic tools to quantitatively assess early intervertebral disc degeneration and help diagnose.

Objective:To investigate the effects of the taurochenodeoxycholic acid(TCDCA)on cartilage degeneration in tem-poromandibular joint osteoarthritis(TMJ OA).Methods:36 female SD rats aged 6 weeks were randomly divided into 3 groups:con-trol group(CON),unilateral anterior crossbite group(UAC),UAC plus TCDCA injection group(UAC+TCDCA).UAC model was es-tablished in all rats in UAC and UAC+TCDCA groups.Samples were collected at 8 and 12 weeks(control group,UAC group,UAC+TCDCA group)after set up of the experiment(n=6),and TMJ morphological examination was performed.The expression of CYP7A1,BAAT and TGR5 in the tissue and cells was examined by immunohistochimical staining.Results:(1)Compared with the CON group of the same age,the cells in the condylar cartilage were disordered,the cartilage matrix was reduced and thinner in UAC group.Compared with UAC group of the same age,cell arrangement,cell number,cartilage matrix and cartilage thickness were im-proved in UAC+TCDCA group(P＜0.05).(2)Compared with the CON group of the same age,the positive cells for TCDCA-specific receptor TGR5 and the key enzymes CYP7A1 and BAAT were mainly distributed in the anterior hypertrophic layer and hypertrophic layer at each time point.The number of positive cells in the UAC group was significantly reduced compared with the CON group.Conclusion:TCDCA has obvious therapeutic effects on the degeneration in TMJ OA.

Objective:To investigate the clinical characteristics of patients with myocardial infarction with non-obstructive coronary arteries(MINOCA)and the risk factors of major adverse cardiovascular events(MACE)within 1 year of follow-up.Methods:A total of 1 866 patients who met the diagnosis of acute myocardial infarction and underwent coronary angiography in the Department of Cardiovascular Medicine of our hospital from Sep 2018 to Sep 2021 were selected.According to the results of coronary angiography,the patients were divided into MINOCA group and myocardial infarction with obstructive coronary artery disease(MI-CAD)group.The clinical characteristics and the occurrence of MACE in the two groups were compared.According to the occurrence of MACE,patients in MINOCA group were divided into MACE group and non-MACE group.Binary logistic regression analysis was used to explore the risk factors for MACE in MINOCA patients.Results:The age of patients in MINOCA group was lower than that in MI-CAD group,and more patients were female(P＜0.05).The risk factors of cardiovascular diseases in MINOCA group were less than those in MI-CAD group(P＜0.05).Some indexes of laboratory were lower than those in MI-CAD group(P＜0.05).Left ventricular ejection fraction(LVEF)were higher than that in MI-CAD group(P＜0.05).Left ventricular end-diastolic inner diameter(LVEDD)was lower than that in MI-CAD group,and the proportion of patients with abnormal ventricular wall motion and high cardiac function grade was lower than that in MI-CAD group,and the difference was statistically significant(P＜0.05).The 1-year follow-up showed no significant difference in the incidence of MACE between the two groups(P=0.115).Binary logistic regression analysis showed that smoking(OR=13.095,95%CI:1.799-7.398)and low LVEF(OR=0.036,95%CI:0.012-0.679)were independent risk factors for MACE in MIONCA patients.Conclusions:MINOCA patients are more common in women,with lower age and fewer cardiovascular risk factors,but the incidence of MACE is not less than that of MI-CAD patients.Smoking and low LVEF are independent risk factors for MACE in MINOCA patients.