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 causal relationship among 731 types of immune cells and breast cancer.Methods Genome-wide association data for immune cells and breast cancer were used.Mendelian randomization analysis was performed using the inverse variance weighting(IVW)and weighted median(WM)methods,and sensitivity analysis was conducted to assess heterogeneity and pleiotropy.Results A total of 19 immune cell phenotypes were identified to potentially have a causal association with breast cancer,using IVW as the main analysis method(P>0.05)and correcting P values using the false discovery rate method at a significance level of 0.05,excluding reverse causality.Of these,eight and 11 immune phenotypes may increase and decrease the risk of breast cancer,respectively.Conclusion This study explored the causal relationship between immune cells and breast cancer.Results show that certain immune cell phenotypes could serve as predictive markers for the early diagnosis of breast cancer and the development of new immun-otherapeutic strategies.

BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.

BACKGROUND:The incidence of medial collateral ligament injuries in the knee joint is easy to lead to secondary meniscus and cartilage damage,and long-term chronic damage can lead to the occurrence of osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by medial collateral ligament rupture. OBJECTIVE:To investigate the effect of different degrees of medial collateral ligament injury on the biomechanics of meniscus and cartilage of knee joint. METHODS:The CT and MRI examinations of the knee joint of a healthy volunteer were performed to obtain the image data.The scanning data were imported into Mimics,Geomagic,and Solidworks software in turn.After registration and fusion,a 3D model of normal knee joint was established.On this basis,models of medial collateral ligament injury in different degrees of knee joint were simulated,which were divided into four groups,including:(1)medial collateral ligament was intact;(2)deep medial collateral ligament fracture;(3)superficial medial collateral ligament fracture;(4)complete rupture of medial collateral ligament.Finally,Ansys software was introduced to apply three modes of loads to the knee joint:(1)10 N·m valvaration torque was applied to the top of the femur.(2)A 4 N·m internal torque was applied to the top of the femur.(3)A 4 N·m external torque was applied to the top of the femur.The effects of four groups of models on knee biomechanics under different loads were analyzed. RESULTS AND CONCLUSION:(1)In the extension position of the knee joint,when a 10 N·m valgus torque was applied to the knee joint,the overall stress of the posterolateral meniscus increased with different degrees of medial collateral ligament injuries,while the stress of the articular cartilage did not change significantly.The peak stress of the posterolateral meniscus increased significantly with superficial medial collateral ligament rupture.(2)In the knee extension position,when a 4 N·m internal rotation torque was applied to the knee joint,the overall stress of the medial and lateral meniscus increased after different degrees of medial collateral ligament injury.When superficial medial collateral ligament rupture occurred,the peak stress of the meniscus shifted from the anterior horn of the medial meniscus to the anterior horn of the lateral meniscus.(3)In the knee extension position,applying a 4 N·m external rotation torque to the knee joint,the peak stress of the posterolateral meniscus increased more significantly than that of the medial meniscus,and the stress of the articular cartilage changed less.(4)These results show that the risk of meniscus injury secondary to superficial medial collateral ligament rupture is much higher than that of deep medial collateral ligament rupture when the knee is in extension,and the lateral meniscus is more vulnerable to injury than the medial meniscus.Both superficial medial collateral ligament and deep medial collateral ligament play an important role in the rotational stability of the knee joint.

Objective To investigate the dyadic coping experience of patients undergoing cancer surgery and their spouses.Methods Sixteen cancer patients who were initially diagnosed with cancer and underwent cancer surgery in a general hospital in Henan province as well as and their spouses were selected as the study subjects by objective sampling method.All the patients and their spouses were included in the postoperative follow-up for dyadic coping experiences though a 3 months interview.The acquired data were summarised and analysed by Colaizzi's phenomenological method to identify relevant themes.Results A total of eight themes were identified,including three themes over the phase of confirmed diagnosis,strong stress response,coping with stress alone and consistent attitude towards seeking medical treatment;two themes over the perioperative phase,lack of coping ability and change in relationship;and three themes over the phase of home recovery,lack of disease information,poor communication skills and post-trauma growth of both patient and spouse.Conclusions The dyadic coping experience of patients who undergo cancer surgery and their spouses varies with the stages across the treatment.Therefore,medical staff should offer targeted nursing care according to the dyadic coping experience at different stages,hence to improve the physical and mental health of the cancer patients and their spouses.

Although a great deal of research has been done on sepsis in children，its pathogenesis remains controversial and unresolved，one of which is immune dysfunction.Immunosuppression is the core part of immune dysfunction，and it is related to the disease progression，treatment options，and prognosis changes in patients with sepsis.Since T lymphocytes play a crucial role in immune function，they have been regarded as an important indicator for judging changes in immune function in clinical practice.This review explained the mechanism of immunosuppression caused by some T lymphocyte subsets and its clinical application value in the evaluation，prognosis and immune intervention of sepsis.

Objective To investigate the levels of soluble tyrosine kinase-1(sFlt-1)and chemokine C-C ligand 3(CCL3)in serum of patients with coronary heart disease(CHD)and their correlation with the severity of the disease.Methods A total of 230 elderly CHD patients admitted to the De-partment of Cardiovascular Medicine of Xinxiang Central Hospital from November 2020 to No-vember 2022 were collected as the study subjects(CHD group),and according to their Gensini score,they were divided into mild(n=89),moderate(n=95),and severe(n=46)CHD sub-groups.Another 230 healthy individuals who taking physical examination during the same period served as the control group.ELISA was applied to measure serum levels of sFlt-1 and CCL3.ROC curve was plotted to analyze the diagnostic values of serum sFlt-1 and CCL3 levels for CHD.Pear-son correlation analysis was employed to analyze the relationship between serum sFlt-1 and CCL3 levels and the CHD severity.Results The serum levels of sFlt-1 and CCL3 were obviously higher in the CHD group than the control group(121.71±29.80 ng/L vs 98.70±17.57 ng/L,18.22± 5.41 ng/L vs 13.68±3.89 ng/L,P＜0.01).ROC curve analysis showed that the AUC value of the two indicators combined together was significantly greater than that of them alone in diagnosis of CHD(0.886 vs 0.791,0.775,P＜0.01).The serum levels of sFlt-1 and CCL3 were increased along with the severity of the disease and Gensini score when the levels and the score were compared among the mild,moderate and severe subgroups(P＜0.05).Pearson correlation analysis indicated that the serum levels of sFlt-1 and CCL3 were positively correlated with the Gensini score(r=0.420,r=0.479,P＜0.01).Conclusion The levels of serum sFlt-1 and CCL3 are obviously ele-vated in CHD patients,and closely associated with the severity of coronary lesions.

Objective To investigate the application value of prognostic nutritional index and urea/creatinine ratio in nutritional status assessment for patients with esophageal cancer undergoing radiotherapy and chemotherapy.Methods A total of 138 patients with esophageal cancer who received radiotherapy and chemotherapy were screened.NRS 2002 nutritional screening was used as the standard.Prognostic nutritional index(PNI)and urea/cre-atinine ratio(UCR)were used to evaluate the malnutrition of patients with esophageal cancer.ROC curve was used to evaluate and compare the diagnostic efficacy of different nutritional screening tools.Results The biochemical and hematological indexes of patients with esophageal cancer showed certain characteristics,in which the levels of urea,creatinine,UCR,ALB,PALB,TP,TC,TG,HDL and LDL all fluctuated within the normal range.In terms of nutritional risk screening,the NRS 2002 score identified nutritional risk in 57.97%of patients,while the PNI and UCR predicted nutritional risk in 31.16%and 40.58%of patients,respectively.Consistency test showed that the Kappa value of PNI and NRS 2002 scores was 0.460(P<0.05),and the Kappa value of UCR and NRS 2002 scores was 0.522(P<0.05),indicating that there was a certain correlation between them and NRS 2002 scores in nutri-tional risk screening.Correlation analysis showed that NRS 2002 score was significantly correlated with UCR,ALB,PALB,PBL,Cr,HDL and TP(P<0.05),while PNI was significantly correlated with ALB,PALB,PBL,Cr,HDL,TP and UREA(P<0.05).There were significant correlations between UCR and PALB,UREA and Cr(P<0.05).Logistic univariate regression analysis further confirmed these correlations and revealed that malnutrition was negatively correlated with albumin,prealbumin,total protein,lymphocytes,creatinine and BMI,and positively correlated with urea.However,multivariate regression analysis did not find any statistical difference between these related factors and the two objective evaluation measures.The results of diagnostic efficacy evaluation showed that the area under ROC curve of PNI and UCR evaluation to predict esophageal cancer malnutrition was 0.779 and 0.736,respectively,with statistical significance(P<0.001).Among them,UCR showed higher sensitivity and PNI showed higher specificity,but there was no significant difference in diagnostic value between them.Conclusion PNI and UCR as nutritional assessment tools have certain application value in the nutritional risk screening of patients with esophageal cancer,but their consistency with NRS 2002 score needs to be improved.When assessing the nutritional status of patients,a combination of various indicators and methods should be used to achieve more accurate diagnostic results.