AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Objective:To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock,and to clarify its mechanism.Methods:A total of 54 healthy adult SD rats were randomly divided into normal group,blast injury complicated with hemorrhagic shock(model)group,and the fluid resuscitation(treatment)group,and there were 18 rats in each group.Among them,10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes.The average survival time(ST),24 h and 72 h survival rates of the rats in various groups were observed;the blood pressure(BP),heart rate(HR),and respiratory rate(RR)of the rats in various groups were observed;the levels of serum creatinine(Scr),blood urea nitrogen(BUN),lactate(LAC),glucose(GLU),iron ions,glutathione(GSH),and malondialdehyde(MDA)and the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)in serum of the rats in various groups were detected;Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and heme oxygenase 1(HO-1)proteins in superior mesenteric artery tissue of the rats in various groups;the pathomorphology of the superior mesenteric artery of the rats in various groups was observed.Results:All the rats in normal group survived for 72 h,while the longest ST of the rats in model group did not exceed 9 h.Compared with model group,the ST and 24 h survival rate(SR)of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the BP,HR,and RR of the rats in model group were significantly decreased(P＜0.01).Compared with model group,the BP,HR,and RR of the rats in treatment group were significantly increased after fluid resuscitation(P＜0.05).Compared with normal group,the activities of AST and ALT,and the levels of Scr and BUN in serum of the rats in model group were significantly increased(P＜0.01).Compared with model group,the serum levels of LAC and GLU of the rats in treatment group were significantly decreased(P＜0.01).Compared with normal group,the concentration of iron ion,GSH level,MDA level,LDH activity in serum of the rats in model group were significantly increased(P＜0.05);compared with model group,the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased(P＜0.01).Compared with normal group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased(P＜0.05);compared with model group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased(P＜0.01);compared with model group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased(P＜0.01).The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered,the swelling was significant and the thickness was increased;the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated.The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact,and there was no swelling in the subendothelial matrix;the vascular endothelial cell membrane of the rats in model group was damaged,there were cytoplasmic dissolution and fragmentation,and the swelling of the subendothelial matrix was significant;the swelling of the vascular endothelial cells in treatment group was alleviated.Conclusion:Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock,and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis.

Objective:To develop an Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses and test its reliability and validity.Methods:Based on the theory of knowledge, attitude, and practice, a preliminary scale draft was formed through a literature review, three rounds of Delphi expert consultation, and a pre-survey. Using convenience sampling, 311 hemodialysis nurses were selected for a survey from December 2022 to February 2023 for item analysis, exploratory factor analysis and reliability testing. Another survey was conducted on 260 hemodialysis nurses from February to June 2023 for confirmatory factor analysis, convergent validity, and discriminant validity testing.Results:The Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses included three subscales and five dimensions, with a total of 33 items. The content validity index at the item level was 0.867 to 1.000, and the content validity index at the scale level was 0.992. After exploratory factor analysis, two, one, and two common factors were extracted from the knowledge, attitude, and practice subscales, with cumulative variance contribution rates of 70.114%, 75.192%, and 67.467%, respectively.Confirmatory:factor analysis showed that the model fitted well. The Cronbach's α coefficients of the three subscales were 0.929 to 0.943, the half reliability coefficients were 0.861 to 0.903, and the retest reliability coefficients were 0.824 to 0.874. Conclusions The Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses has good reliability and validity and can be used to evaluate the physical examination ability of hemodialysis nurses for arteriovenous fistula.

Objective:To evaluate and compare the clinical value of unadjusted fracture risk assessment tool(FRAX) and adjusted FRAX in predicting the risk of hip fracture in patients with type 2 diabetes(T2DM).Methods:In this 10-year retrospective cohort study, 1 730 patients with T2DM were collected from August 2009 to July 2013. The 10-year risk of hip fracture was calculated using the China FRAX model. Hip fracture events during the follow-up period were collected through electronic medical records and telephone interviews. The value of FRAX and adjusted FRAX in predicting the risk of hip fracture in T2DM patients was evaluated from two aspects of discrimination and calibration. Cox regression model was used to investigate the relationship between diabetes related factors and hip fracture.Results:A total of 39 participants(2.3%) experienced hip fracture during a median follow-up of 10 years. The area under the curve of unadjusted FRAX was 0.760, but the calibration ability was poor [calibration χ2: 75.78, P<0.001; calibration ratio(observation/prediction): 3.97(95% CI 2.76~5.17)]. There was no significant improvement in calibration ability of adjusted FRAX. After adjustment for unadjusted or adjusted hip fracture probability calculated by FRAX(FRAX-HF), duration, estimated glomerular filtration rate, insulin use, cerebrovascular diseases, and diabetic peripheral neuropathy were significantly associated with an increased risk of hip fracture( P<0.05). Conclusion:The FRAX tool significantly underestimated the risk of hip fracture in T2DM patients, and there was still significantly underestimation after adjustment due to the failure to eliminate the influence of diabetes-related factors such as disease duration and peripheral neuropathy.

Objective:To introduce the discovery and nomenclature of the intercondylar foramen of femur (IFF) and foramen of tibial intercondylar eminence (FTIE) and research the close relationship between the high recurrence rate of aggressive tumors around the knee joint and the foramina around the knee joint.Methods:①Radiographic observation and measurement: 3D reconstruction of CT scan of 200 patients in our hospital were used to obverse the common feature、position and measure of Inter-condylar foramen of femur and Foramen of tibial intercondylar eminence. ②Anatomical and histological observation: To proof the existence of IFF and FTIE through the anatomy of 15 cases of car accidents or tumor amputations and 60 cases of autopsy. Then the specific location, the surrounding structure, the proximal coverage, the contents, the apical construction, the wall and the bottom tissues of the IFF and FTIE were studied and analyzed. ③Histological and pathological observation of tumor anatomy: Through the study of the distal femur and tibia malignant tumor tissues(including primary bone tumors and metastatic tumors), we observed the relationship between the foraminal structures and the tumor, judged the situation of concealed transmission and two-way spread through the foramina, and analyzed the relationship between tumor recurrence and foraminal structures. ④The synovial membrane of foramina, especially in cases where the synovium was suspected to be involved by the lesions judged by the radiography was analyzed to observe whether the synovium was infiltrated by the tumor.Results:IFF and FTIE were the inherent physical structure of the human. Their physiological function was the vascular foramina that lead the branches of arteria media genus into the Intercondylar fossa of femur and tibial intercondylar eminence. Their opening was separated with the joint cavity by the synovial tissues, so IFF and FTIE were isolated with joint cavity by the synovial tissues、meniscus and cruciate ligaments. After invading the IFF and FTIE, the aggressive tumors did not break into the joint cavity immediately, but conceal in the foramina and invade the synovium with specific biological behavior with the sequence: reactive edema, hyperplasia, degeneration, calcification, hyaline degeneration (infiltration in some cases), synovial rupture, and then tumor invasion of the articular cavity. Usually, tumors or recurrence has been observed before synovial rupture. We also observed the tendency of tumors to spread along the arteria media genus to the popliteal vessels, peripheral soft tissues and lymphatic vessels with typical radiographic performance like popliteal lymphadenectasis. Color nodules and tumors in other parts could also invade or metastasize into bone through these foramina.Conclusions:IFF and FTIE are foramina nutricium of arteria media genus. They are the inherent physical structure of the human. The foramina play an important role in the spread, concealment and recurrence of peripheralkneeaggressive tumor.

Objective: To describe the prevalence of problematic mobile phone use and anxiety in college students, and explore the mediating effect of sleep quality on the relationship between problematic mobile phone use and anxiety, and to provide reference for physical and mental health promotion of college students. Methods: One medical college and a comprephensive college were selected in Hefei city of Anhui Province and Shangrao City of Jiangxi Province, respectively, and a cross-sectional survey was conducted. A total of 1 135 valid questionnaires were collected. The self-rating questionnaires regarding basic information of college students, use the Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use(SQAPMPU) and the Self-Rating Questionnaire for Depression-Anxiety-Stress for Adolescent Problematic Mobile Phone Use(DASS-21) was used to evaluate problematic mobile phone use and anxiety, respectively. The Pittsburgh Sleep Quality Index(PSQI) was used to evaluate sleep quality. Conclusion: The detection rates of college students with problematic mobile phone use and poor sleep quality were 24.6% and 13.3%, respectively. The detection rates of college students anxiety grouped by severity were 5.1%, 23.9%. Multiple Logistic regression analysis showed a positive linear correlation between problematic mobile phone use and anxiety[OR values(95%CI) were 1.86(1.01-3.44), 4.34(3.14-5.99), P<0.01]. The results of process showed that sleep quality played a moderating role between problematic mobile phone use and anxiety(R2=0.37, F=220.52, P<0.01). Interaction term s β=0.09(P<0.05). Conclusion The prevalence of problematic mobile phone use is high in college students, and problematic mobile phone use is positively related to anxiety. Good sleep quality can alleviate the relationship between mobile phone dependence and anxiety of college students.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Chimeric antigen receptor modified T cell(CAR-T)immunotherapy has achieved remarkable success in the treatment of hematological malignancies,especially for relapsed/refractory acute B lymphocytic leukemia(B-ALL)leukemia patients,most of whom could obtain complete remissions or partial remissions.However,clinical studies also found a as high as 50%total recurrence rate of these patients,in which more than 20% patients relapsed with tumor cells not expressing the primary CAR-T-targeted CD molecules.Increased relapses with negative targeted-molecules or even lost primary abnormal tumor gene, suggesting that immune escape and even clonal evolution events increased rapidly under the high -precision CAR-T immunotherapy pressure.Monitoring of minimal residual disease(MRD)is important to assess the efficacy and find recurrence trends early in a timely manner to guide further clinical intervention.The new features of disease recurrence after CAR-T treatment have put forward higher requirements for traditional and emerging MRD detection methods so as to ensure their effectiveness in the CAR-T treatment era.

Objective To investigate the effect of using pterional approach combined with partial orbital roof and zygomatic process resection (modified orbitopterional approach)for the management of ruptured anterior communicating artery aneurysms. Methods From October 2013 to October 2016,36 consecutive patients with ruptured anterior communicating artery aneurysm admitted to the Department of Neurosurgery,Binzhou Medical University Hospital were enrolled retrospectively. They were all confirmed by DSA or CT angiography. The orbitopterional approach was used,only part of the orbital roof was removed and the structures of lateral orbital wall and the wings of sphenoid bone were not removed. The clinical manifestations,imaging data,surgical methods,and surgical results of ruptured anterior communicating artery aneurysms were summarized. Results All 36 patients with anterior communicating artery aneurysm in this group were treated with the modified orbitopterional approach. There was no obvious brain retraction injury on CT scan after procedure. At the time of discharge,the Glasgow outcome scale score was 5 in 25 cases, 4 in 8 cases,and 3 in 3 cases. No patients died. The patients were followed up for 3 to 24 months;no rebleeding and recurrence were observed. No complications occurred,such as enophthalmos,damage to the eyeballs, and cranial nerve injury. Conclusion The modified orbitopterional approach increased the operation space,avoided the distraction of brain tissue,significantly shortened the operation distance,and increased the deep observation angle through the removal of part of the orbital roof and the zygomatic process. It is suitable for the treatment of anterior communicating artery aneurysms,especially the rear direction,upper direction and high positioned aneurysms. There was no bone loss in the procedure,no need for orbital roof reconstruction. The gyri rectus was retained anatomically,and it may be helpful to protect the postoperative cognitive function of the patients.

Objective: To study the expression of CD123 in bone marrow (BM) blasts of acute myeloid leukemia (AML) patients to explore the relationship between CD123 expression and therapeutic response and prognosis. Methods: This study retrospectively analyzed expression and distribution of CD123 in BM blasts in 137 cases of newly diagnosed AML (excluded M₃) , CD123 detected by flow cytometry≥20% was defined as positive, including 84 CD123⁺ AML and 53 CD123^- AML, efficacy and prognosis were compared between the two groups. Results: ① Among 137 patients, 84 were in group CD123⁺ (61.3%) , and 53 in group CD123^- (38.7%) . All 137 patients were classified into risk groups based on cytogenetic and molecular biology abnormalities. No significant differences were seen between the three risk groups with regard to their CD123 levels (χ²=0.861, P=0.650) . Compared with CD123^- group, the CD123⁺ group had higher WBC[47.7 (1.0-264.0) vs 22.4 (0.7-211.0) , z=-2.592, P=0.010]. ② The rates of first complete remission (CR1) and recurrence of CD123⁺ group were 54.8% (46/84) and 50.8% (32/63) , respectively; and CD123^- group were 73.6% (39/53) and 41.7% (20/48) , respectively. There was significant difference of CR1 between the two groups (χ²=5.121, P=0.027) , whereas no significant difference of the recurrence rate (χ²=0.911, P=0.340) . ③ The median dutations of OS between CD123⁺ group and CD123^- group were 20.0 (95%CI 13.1-26.9) months vs 44.0 (95%CI 23.6-47.3) months, respectively (χ²=5.874, P=0.015) ; The median durations of DFS were 7.8 (95%CI 1.4-14.1) months vs 18.6 (95%CI 0-39.7) months, respectively, no differences were observed between the two groups (χ²=2.939, P=0.086) . ④ CD123 retained an adverse prognosis value on DFS and OS within the intermediate group and patients ≤ 50 years older. Conclusions CD123 widely expressed in AML patients, which was an independent risk factor for CR1 and OS, which implicating its important role in evaluating the induction chemotherapy response and prognosis of AML.