Objective To explore the risk factors of frozen shoulder,and to provide the basis for the prevention of frozen shoulder.Methods A total of 114 patients with frozen shoulder who were hospitalized in the First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to August 2022 were included in case group,and 114 physical examination patients with no history of frozen shoulder were included in control group.The clinical data of two groups were collected and the risk factors of frozen shoulder were analyzed by multivariate Logistic regression.Results There were statistically significant differences in cervical radiculopathy,type 2 diabetes mellitus,hepatitis,chronic non-atrophic gastritis,lumbar disc herniation,osteoporosis and thyroid sarcoidosis between two groups(P<0.05).Multivariate Logistic analysis showed that cervical radiculopathy(OR=6.114,95%CI:1.458-25.642)and type 2 diabetes mellitus(OR=24.069,95%CI:4.023-144.007)were independent risk factors for the onset of frozen shoulder.Conclusion Patients with type 2 diabetes mellitus and cervical radiculopathy have a higher risk of frozen shoulder,and should pay attention to early prevention.

Objective To investigate the clinical outcomes of cranioplasty with polyether ether ketone(PEEK)or titanium after large craniectomy in patients.Methods Clinical data of 150 patients undergoing skull repair due to large frontotemporal skull defect in our hospital from April 2018 to June 2022 were retrospectively analyzed,and they were divided into titanium mesh group and PEEK group according to different repair materials.The conditions of surgical site infection,bleeding,subcutaneous effusion,seizure,implant rupture or exposure in the two groups were compared.Results In the PEEK group,96.3％of patients needed to implant the repair material under the temporal muscle,which was significantly higher than that in the titanium mesh group(78.1％)(P＜0.05).There were no significant differences in postoperative complications including infection,bleeding,seizure,implant rupture or leakage between the two groups(P＞0.05).However,the incidence of postoperative subcutaneous effusion in PEEK group was higher than that in titanium mesh group(14.8％VS4.2％,P＜0.05),and the difference was statistically significant.Conclusion Both titanium and PEEK can be used in cranioplasty for patients with large frontotemporal cranial defects.Subcutaneous effusion is common in patients underwent cranioplasty with PEEK postoperatively,which needs to be paid more attention.

Objective To investigate the predictive value of neutrophil-to-lymphocyte ratio(NLR)and other factors for hemorrhagic transformation(HT)after intravenous thrombolysis in acute ischemic stroke(AIS).Methods A retrospective study was conducted on 260 AIS patients who received intravenous thrombolysis with alteplase in Department of Neurology of Hexian People's Hospital from August 2020 to June 2024.According to HT occurred or not after thrombolysis,they were divided into HT group(n=42)and non-HT group(n=218).The clinical baseline data were compared between the two groups.Multivariate logistic regression analysis was used to iden-tify the risk factors of HT,and ROC curve was drawn to analyze the predictive value of NLR and other risk factors for HT in AIS patients after intravenous thrombolysis.Results Among the 260 AIS patients,42 cases(16.2％)had HT.The proportion of atrial fibrillation and cardioembolism type(TOAST subtype CE),white blood cell count,neutrophils count,NLR,and baseline NHISS score were significantly higher,and the lymphocyte count was obviously lower in the HT group than the non-HT group(all P＜0.05).Multivariate logistic regression analysis showed that atrial fibrillation(OR=3.361,95％CI:1.015-15.381),NHISS score ≥15(OR=7.785,95％CI:1.348-21.312),TOAST classification CE(OR=4.104,95％CI:1.156-17.256),and NLR(OR=3.165,95％CI:1.231-5.265)were independent risk factors for HT(all P＜0.05).ROC curve analysis showed that the AUC value of NLR combined with above other factors was 0.841(95％CI:0.763-0.967,P＜0.01).In Hosmer-Lemeshow goodness of fit test on the model(P=0.354),the best critical value was 0.701,the sensitivity was 86.3％,and the specificity was 84.3％.Conclu-sion NLR combined with TOAST etiological classification and other factors have a certain pre-dictive value for the occurrence of HT after intravenous thrombolysis.

OBJECTIVE: To investigate the potential mechanisms that mediate the inhibitory effect of porcine recombinant NKlysin (prNK-lysin) against liver cancer cell metastasis. METHODS: HPLC-tandem mass spectrometry was used to identify the differentially expressed proteins in prNK-lysin-treated hepatocellular carcinoma SMMOL/LC-7721 cells in comparison with the control and PBS-treated cells. GO functional annotation and KEGG pathway analysis of the differentially expressed proteins were performed using GO and KEGG databases. RT-qPCR was used to determine the mRNA expression levels of polypeptide-N-acetylgalactosaminotransferase 13 (GALNT13), transmembrane protein 51 (TMEM51) and FKBP prolyl isomerase 3 (FKBP3) in the cells, and the protein expression of FKBP3 was verified using Western blotting. RESULTS: Proteomic analysis identified 1989 differentially expressed proteins in prNK-lysin-treated cells compared with the control cells, and 2753 compared with PBS-treated cells. Fifteen proteins were differentially expressed between PBS-treated and the control cells, and 1909 were differentially expressed in prNK- lysin group compared with both PBS and control groups. These differentially expressed proteins were involved mainly in the viral process, translational initiation and RNA binding and were enriched mainly in ribosome, protein process in endoplasmic reticulum, and RNA transport pathways. RT-qPCR showed that compared with the control group, prNK-lysin treatment significantly increased the mRNA expressions of GALNT13 (P < 0.05) and TMEM51 (P < 0.01) and lowered FKBP3 mRNA expression (P < 0.05). Western blotting also showed a significantly decreased expression of FKBP3 protein in prNK-lysin-treated cells (P < 0.001). CONCLUSION Treatment with prNK-lysin causes significant changes in protein expression profile of SMMOL/LC-7721 cells and inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 protein and affecting the cellular oxidative phosphorylation and glycolysis pathways.
Animals ; Swine ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Oxidative Phosphorylation ; Proteomics ; Glycolysis ; RNA, Messenger

Objective:To investigate the early clinical outcomes of a minimally invasive anterolateral approach (Orthopadische chirurgie munchen, OCM) versus a conventional (posterolateral approach, PLA) hemiarthroplasty in the treatment of senior femoral neck fractures.Methods:A retrospective analysis was performed on 90 elderly patients with femoral neck fractures who received anterolateral and posterolateral approaches for hemiarthroplasty in the Second Affiliated Hospital of Soochow University from December 2019 to June 2021 and were followed up. In the OCM group, there were 45 cases, including 18 males and 27 females, aged 83.33±5.29 years (range, 76-96 years); In the PLA group, there were 45 cases, including 13 males and 32 females, aged 81.87±5.00 years (range, 75-94 years). Postoperative, surgical indices, perioperative bleeding, and soft tissue injury were assessed; pain was assessed using the visual analogue scale (VAS), and hip function was evaluated using the Harris score and the University of California at Los Angeles (UCLA) score.Results:The incision length, postoperative hospital stay, hemoglobin reduction, and occult blood loss were lower in the OCM group than in the PLA group ( P<0.05), but there was no significant difference in intraoperative bleeding and postoperative transfusion rate ( P>0.05). Serum creatine kinase and C-reactive protein levels (232.98±83.70 IU/L and 81.67±48.85 mg/L) were lower in the OCM group than in the PLA group (296.93±124.58 IU/L and 104.79±36.75 mg/L) 1 day after surgery, and the differences were statistically significant ( t=2.86, P=0.005; t=2.54, P=0.013). Postoperative pain was significantly improved in all patients, and VAS scores were lower in the OCM group than in the PLA group at 12 h, 24 h, and 48 h postoperatively ( P<0.05). The time to get out of bed after surgery was 20.73±4.99 h in the OCM group compared with 41.69±13.58 h in the PLA group, with a statistically significant difference ( t=9.71, P<0.001). Harris scores (63.31±6.21 and 75.76±4.91) and UCLA scores (1.84±0.42 and 3.69±0.76) were higher in the OCM group on the day of discharge and at 1 month postoperatively than in the PLA group (52.69±10.01 and 71.33±3.66); (1.62±0.54 and 3.16±0.80) points, all with statistically significant differences ( P<0.05). However, the differences in Harris score and UCLA score between the two groups at 6 months postoperatively were not statistically significant ( P>0.05). There were two cases of intermuscular vein thrombosis in the OCM group, with a complication rate of 4% (2/45), and one case of dislocation in the PLA group, with a complication rate of 2% (1/45), there was no significant difference between the two groups ( P=1.000). Conclusion:The minimally invasive anterolateral approach is a more ideal procedure for elderly patients with femoral neck fractures undergoing hemiarthroplasty. It has the advantages of a short incision, small soft tissue damage, low occult blood loss, early removal from bed, a short postoperative hospital stay, an improvement in pain, and a good early recovery of hip function.

FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^-/- gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

Objective : To investigate the factors affecting concurrent sarcopenia among patients with cardiovascular diseases, so as to provide insights into early identification and prevention of cardiovascular diseases complicated with sarcopenia. Methods: A total of 250 inpatients with cardiovascular diseases in the Sixth Division Hospital of Xinjiang Production and Construction Corps were recruited and divided into the sarcopenia and non-sarcopenia groups according to the diagnostic criteria of sarcopenia. Subjects' basic characteristics, body mass index, blood biochemical indicators and human body composition parameters were collected using questionnaire surveys, and factors affecting concurrent sarcopenia among patients with cardiovascular diseases using a multivariable logistic regression model. Results: Among the 250 patients with cardiovascular diseases, there were 149 males (59.60%) and 101 females (40.40%). The overall prevalence of sarcopenia was 8.40% among the study subjects. The mean age and body mass index were (75.19±9.74) and (20.77±2.19) kg/m2 in the sarcopenia group and (65.24±11.50) years and (25.85±2.87) kg/m2 in the non-sarcopenia group. Multivariable logistic regression analysis identified age (OR=1.115, 95%CI: 1.030-1.207) and body mass index (OR=0.582, 95%CI: 0.445-0.761) were as factors affecting concurrent sarcopenia among patients with cardiovascular diseases. Conclusion Advanced age and low body mass index may increase the risk of concurrent sarcopenia among patients with cardiovascular diseases.

Carnosic acid (CA) is a natural phenolic diterpene compound found in rosemary (Rosmarinus officinalis) characterized as an ortho-dihydroquinone - type molecule. Multiple lines of studies have shown that CA has potent neuroprotective effects in vitro and in vivo in Parkinson's disease (PD). The aim of the present review is to summarize the pharmacological neuroprotective actions of CA, and provide a comprehensive review of the molecular mechanism by which CA exert neuroprotective effect in PD. The current review highlights CA is a therapeutic potential for PD.

Interleukin-2 (IL-2) is one of the most important regulators in immune system, as it plays an essential part both in immune activation and suppression. However, as the first immunotherapy drug approved for the treatment of cancer, IL-2 is limited in clinical application by the serious adverse reactions. The long-felt needs in clinical practice, including prolonged half-lives, T cell subset specificity, and toxicity reduction can be achieved by polyethylene glycol (PEG) modification, Fc fusing, or protein mutation of IL-2. NKTR-214, the most advanced IL-2 pathway-targeted agent in clinical development for oncology, shows exciting results in treatment of melanoma in combination with nivolumab. At the same time, many more other modified molecules against cancer and autoimmune diseases are being tested in clinical research, an exciting future lying ahead for IL-2 therapeutics.
Drug Development ; Humans ; Immunotherapy/methods* ; Interleukin-2/therapeutic use* ; Melanoma/drug therapy* ; Nivolumab/therapeutic use* ; Polyethylene Glycols

Objective: To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes. Materials and Methods: Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses. Results: Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness. Conclusion The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.