Comparison of seven CD19 CAR designs in engineering NK cells for enhancing anti-tumour activity.

Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is emerging as a promising cancer treatment, with notable safety and source diversity benefits over CAR-T cells. This study focused on optimizing CAR constructs for NK cells to maximize their therapeutic potential. We designed seven CD19 CAR constructs and expressed them in NK cells using a retroviral system, assessing their tumour-killing efficacy and persistence. Results showed all constructs enhanced tumour-killing and prolonged survival in tumour-bearing mice. In particular, CAR1 (CD8 TMD-CD3ζ SD)-NK cells showed superior efficacy in treating tumour-bearing animals and exhibited enhanced persistence when combined with OX40 co-stimulatory domain. Of note, CAR1-NK cells were most effective at lower effector-to-target ratios, while CAR4 (CD8 TMD-OX40 CD- FcεRIγ SD) compromised NK cell expansion ability. Superior survival rates were noted in mice treated with CAR1-, CAR2 (CD8 TMD- FcεRIγ SD)-, CAR3 (CD8 TMD-OX40 CD- CD3ζ SD)- and CAR4-NK cells over those treated with CAR5 (CD28 TMD- FcεRIγ SD)-, CAR6 (CD8 TMD-4-1BB CD-CD3ζ 1-ITAM SD)- and CAR7 (CD8 TMD-OX40 CD-CD3ζ 1-ITAM SD)-NK cells, with CAR5-NK cells showing the weakest anti-tumour activity. Increased expression of exhaustion markers, especially in CAR7-NK cells, suggests that combining CAR-NK cells with immune checkpoint inhibitors might improve anti-tumour outcomes. These findings provide crucial insights for developing CAR-NK cell products for clinical applications.

Risk factors and prognosis of postoperative acute myocardial infarction in elderly hip fracture patients combined with coronary heart disease.

INTRODUCTION: This article mainly studies the risk factors for postoperative acute myocardial infarction (AMI) in elderly hip fracture patients combined with coronary heart disease (CHD), constructs a prediction model, and evaluates the prognosis of all the patients. METHODS: This article retrospectively collected elderly patients with hip fracture and CHD who underwent hip fracture surgery at the Third Hospital of Hebei Medical University from January 2019 to December 2021. Demographic data, laboratory indicators, and imaging examination results were collected from the medical case system. The risk factors of postoperative AMI were determined by univariate and multivariate logistic regression, and a nomogram prediction model was established. The ROC curve, calibration curve and DCA decision curve were plotted by R language software. The patients in the training set were followed up for 2 years to evaluate their survival situation. RESULTS: 1094 eligible patients were divided into a training set (n = 824 from January 1, 2019 to September 31, 2021) and a validation set (n = 270 from October 1, 2021 to December 31, 2022). In the training set, women accounted for 58.6%; The average age of the patients was 79.45 years old; The main type of fracture was intertrochanteric fracture. There were 64.7% patients taken B receptor blockers; A total of 166 (20.1%) patients underwent percutaneous coronary intervention (PCI); Hypertension accounted for 55.5%; 520 (63.1%) patients had a preoperative waiting time greater than 3 days; The average hemoglobin value upon admission was 101.36 g/L; The average intraoperative bleeding volume was 212.42 ml; The average surgical time was 2.5 ± 0.3 h; Reginal anesthesia accounted for 29.7%; 63 (68.5%) AMI patients had no obvious clinical symptoms; 68 (73.9%) AMI patients did not show ST-segment elevation in ECG; The risk factors of postoperative AMI were age, hemoglobin at admission, diabetes, chronic kidney disease, intraoperative bleeding, and reginal anesthesia. The AUC of the nomogram prediction model was 0.729. The AUC in the validation set was 0.783. Survival analysis showed a significant statistical difference in 2-year mortality between patients with AMI and without AMI, among all the patients with AMI, patients with ECG ST-segment elevation has higher mortality than patients without ECG ST-segment elevation. CONCLUSION: Our research results found that the incidence of postoperative AMI in elderly patients with hip fractures and CHD was 11.1%. Age, diabetes, hemoglobin at admission, regional anesthesia, chronic kidney disease, and intraoperative bleeding are risk factors. The AUC of the nomogram in training set is 0.729. The 2-year mortality rate of the patients with AMI is higher than that of patients without AMI.

Infertility risk assessment with ultrasound in congenital adrenal hyperplasia male patients.

Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and infertility. Early hormonal intervention is preventive, but excessive glucocorticoid poses risks. Developing reliable methods for early TART diagnosis and monitoring is crucial. The present study aims to formulate a scoring system to identify high-risk infertility through analysis of TART ultrasound features. Grayscale and power Doppler ultrasound were employed in this retrospective study to evaluate testicular lesions in male CAH patients. Lesion assessment encompassed parameters such as range, echogenicity, and blood flow, and these were subsequently correlated with semen parameters. Results of 49 semen analyzes from 35 patients demonstrated a notable inverse correlation between lesion scores and both sperm concentration (rs = - 0.83, P < 0.001) and progressive motility (rs = - 0.56, P < 0.001). The ROC curve areas for evaluating oligospermia and asthenozoospermia were calculated as 0.94 and 0.72, respectively. Establishing a lesion score threshold of 6 revealed a sensitivity of 75.00% and specificity of 93.94% for oligospermia and a sensitivity of 53.85% and specificity of 100.00% for asthenozoospermia. These findings underscore the potential utility of incorporating ultrasound into routine CAH patient management, facilitating timely interventions to preserve male fertility.

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression.

Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.

Characteristics of Postoperative Heart Failure in Older Hip Fractures Patients Combined with Coronary Heart Disease and Construction of a Prediction Model of Nomogram, a Retrospective Cohort Study.

Introduction: Older patients combined with coronary heart disease (CHD) develop acute heart failure (AHF) after hip fracture surgery is common, and this study aimed to investigate the risk factors of postoperative AHF in older hip fracture patients and to construct a nomogram prediction model. Methods: We retrospectively collected older hip fracture patients with CHD who underwent hip fracture surgery at the Third Hospital of Hebei Medical University from January 2017 to December 2021. We divided them into a training set and a validation set. We collected the demographic data, laboratory indicators and imaging examination results. We identified risk factors for postoperative AHF and used R language software to establish a nomogram prediction model, plot ROC curves, calibration curves and DCA decision curves. Results: We retrospectively collected 1288 older hip fractures patients with CHD. After excluding 214 patients who did not meet the criteria, 1074 patients were included in our research and we divided them into the training set and the validation set. In the training set, a total of 346 (42.8%) patients developing postoperative AHF. Through univariate and multivariate logistic regression analysis, we identified the risk factors for postoperative AHF and constructed a nomogram prediction model. The AUC of the prediction model is 0.778. The correction curve shows that the model has good consistency. The decision curve analysis shows that the model has good clinical practicality. Conclusion: There were 42.8% older patients combined with CHD develop postoperative AHF. Among them, fracture type, age, anemia at admission, combined with COPD, ASA ≥ 3, and preoperative waiting time >3 days are risk factors for postoperative AHF. We constructed a nomogram prediction model that can effectively predict the risk of postoperative AHF in older hip fracture patients combined with CHD.

Predictive characteristics and model development for acute heart failure preceding hip fracture surgery in elderly hypertensive patients: a retrospective machine learning approach.

BACKGROUND: Hip fractures are a serious health concern among the elderly, particularly in patients with hypertension, where the incidence of acute heart failure preoperatively is high, significantly affecting surgical outcomes and prognosis. This study aims to assess the risk of preoperative acute heart failure in elderly patients with hypertension and hip fractures by constructing a predictive model using machine learning on potential risk factors. METHODS: A retrospective study design was employed, collecting preoperative data from January 2018 to December 2019 of elderly hypertensive patients with hip fractures at the Third Hospital of Hebei Medical University. Using SPSS 24.0 and R software, predictive models were established through LASSO regression and multivariable logistic regression analysis. The models' predictive performance was evaluated using metrics such as the concordance index (C-index), receiver operating characteristic curve (ROC curve), and decision curve analysis (DCA), providing insights into the nomogram's predictive accuracy and clinical utility. RESULTS: Out of 1038 patients screened, factors such as gender, age, history of stroke, arrhythmias, anemia, and complications were identified as independent risk factors for preoperative acute heart failure in the study population. Notable predictors included Sex (OR 0.463, 95% CI 0.299-0.7184, P = 0.001), Age (OR 1.737, 95% CI 1.213-2.488, P = 0.003), Stroke (OR 1.627, 95% CI 1.137-2.327, P = 0.008), Arrhythmia (OR 2.727, 95% CI 1.490-4.990, P = 0.001), Complications (OR 2.733, 95% CI 1.850-4.036, P < 0.001), and Anemia (OR 3.258, 95% CI 2.180-4.867, P < 0.001). The prediction model of acute heart failure was Logit(P) = -2.091-0.770 × Sex + 0.552 × Age + 0.487 × Stroke + 1.003 × Arrhythmia + 1.005 × Complications + 1.181 × Anemia, and the prediction model nomogram was established. The model's AUC was 0.785 (95% CI, 0.754-0.815), Decision curve analysis (DCA) further validated the nomogram's excellent performance, identifying an optimal cutoff value probability range of 3% to 58% for predicting preoperative acute heart failure in elderly patients with hypertension and hip fractures. CONCLUSION: The predictive model developed in this study is highly accurate and serves as a powerful tool for the clinical assessment of the risk of preoperative acute heart failure in elderly hypertensive patients with hip fractures, aiding in the optimization of preoperative risk assessment and patient management.

Risk factors and prognosis of perioperative acute heart failure in elderly patients with hip fracture: case-control studies and cohort study.

BACKGROUND: Elderly patients with hip fracture who develop perioperative acute heart failure (AHF) have a poor prognosis. The aim of the present study is to investigate the potential risks of AHF in elderly hip-fracture patients in the postoperative period and to evaluate the prognostic significance of AHF. METHODS: A retrospective analysis was conducted on hip fracture patients at the Third Hospital of Hebei Medical University, who were continuously in hospital from September 2018 to August 2020. To identify independent risk factors for AHF in elderly patients with hip fracture, univariate and multivariate Logistic regression analysis was employed. The Kaplan-Meier survival curve illustrated the relationship between all-cause mortality in the AHF and non-AHF groups. An assessment of the correlation between baseline factors and all-cause mortality was conducted by means of univariable and multivariable Cox proportional hazards analysis. RESULTS: We eventually recruited 492 patients,318 of whom were in the AHF group. Statistical significance was found between the two groups for age group, concomitant coronary heart disease, COPD, haemoglobin level below 100 g/L on admission, albumin level below 40 g/L on admission, and increased intraoperative blood loss. Age over 75, concomitant coronary artery disease, hemoglobin level below 100 g/L and albumin level below 40 g/L on admission were independent risk factors for AHF in older hip fracture patients. The AHF group exhibited a higher incidence of perioperative complications, such as anemia, cardiovascular issues, and stress hyperglycemia, as well as all-cause mortality. Based on our COX regression analysis, we have identified that the main risk factors for all-cause mortality in AHF patients are concomitant coronary heart disease, absence of pulmonary infection, absence of diabetes, absence of cancer, and absence of urinary tract infection. CONCLUSION: Enhancing hip fracture prevention for AHF is particularly important. It is crucial to make informed decisions to avoid poor prognoses. Patients whose age over 75 years old, concomitant coronary heart disease, hemoglobin < 100 g/L and album< 40 g/L on admission are more likely to develop perioperative AHF. To avert complications and potential fatalities, patients with AHF must receive appropriate care during the perioperative period.

Clinical characteristics of elderly hip fracture patients with chronic cerebrovascular disease and construction of a clinical predictive model for perioperative pneumonia.

INTRODUCTION: The recovery of cerebrovascular disease (CVD) will increase the incidence of perioperative pneumonia (POP). However, there is limited research on POP in elderly patients with hip fractures complicated by CVD. Therefore, our research focuses on the following two issues: (1) What are the clinical features of elderly patients with hip fractures combined with CVD? (2) What are the predictive factors for the occurrence of POP in such patients? HYPOTHESIS: Male, femoral neck fracture and hypoalbuminemia can be predictive factors for the development of POP after hip fracture in CVD patients. MATERIAL AND METHODS: This is a nested case-control study that included patients aged 65 to 105 years with CVD who had a hip fracture between January 2021 and January 2023. According to the occurrence of POP, they were divided into case group and control group. Collecting data includes demographic information, clinical data, and surgical information. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analyses were used to select variables. The constructed predictive model was transformed into a nomogram. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA). RESULTS: We ultimately included 714 patients, 69.3% female, with a median age of 80 years. Asymptomatic cerebral infarction (ACI) is the most common CVD (55.7%). More patients developed intertrochanteric fractures than femoral neck fractures (57.1 vs. 42.9%). In total, 606 patients (84.9%) underwent surgery. The most common perioperative complications were anemia (76.9%) and hypoalbuminemia (71.8%). POP (20.0%) was more common preoperatively (89.5%). Factors such as fracture type, surgical wait time, implant used for surgery, and anesthesia type did not differ between the presence or absence of postoperative pneumonia. 143 patients with POP served as the case group. Five hundred and seventy one patients did not develop POP and served as the control group. The predictors of POP were male (OR 1.699,95%CI 1.150-2.511, p<0.05), femoral neck fracture (OR 2.182,95%CI 1.491-3.192, p<0.05), and hypoalbuminemia (OR 3.062, 95%CI 1.833-5.116, p<0.05). This model has good discrimination, calibration, and clinical practicality. DISCUSSION: In this study, we constructed a clinical prediction model for the occurrence of POP in CVD combined with hip fracture in the elderly, with risk factors including gender, fracture type and perioperative hypoproteinemia. Therefore, we can take effective preventive measures against the occurrence of POP in patients with these factors in our clinical work. LEVEL OF PROOF: IV; nested case-control study.

Integrative analysis of LAG3 immune signature and identification of a LAG3-related genes prognostic signature in kidney renal clear cell carcinoma.

Immune checkpoint blockade (ICB) therapy has resulted in improved overall survival in kidney renal clear cell carcinoma (KIRC), but most treated patients fail to show durable clinical responses. Lymphocyte activation gene-3 (LAG3) is a novel inhibitory immune checkpoint, but its expression pattern, prognostic value, and immunological role in KIRC remain unknown. In this study, we utilized TCGA_KIRC RNA-sequencing data to analyze the relationship between LAG3 expression and clinical features. The single-cell sequencing data and tissue immunofluorescence are employed to investigate the subcellular localization of LAG3 in KIRC. Kaplan-Meier plotter, TIMER, and TISIDB were used to assess the association between LAG3 expression and prognosis, as well as its correlation with immune-related components. We constructed the LAG3 interaction network by using STRING, GeneMANIA, BioGRID, and HitPredict databases. We found that LAG3 is upregulated and correlates with poor prognostic phenotype in KIRC. LAG3 is predominantly expressed on exhausted CD8+ T cells and shows strong co-expression with PDCD1 in KIRC. Moreover, our findings indicated that LAG3 not only inhibits T cell activation but also potentially regulates cell adhesion in KIRC. In conclusion, our study implies that LAG3 can serve as a potential prognostic biomarker for KIRC. Furthermore, blocking both LAG3 and PDCD1 may alleviate resistance to anti-PDCD1 therapy, providing novel insights for immunotherapy decision-making in KIRC patients.

Embodied Conversational Agents for Chronic Diseases: Scoping Review.

BACKGROUND: Embodied conversational agents (ECAs) are computer-generated animated humanlike characters that interact with users through verbal and nonverbal behavioral cues. They are increasingly used in a range of fields, including health care. OBJECTIVE: This scoping review aims to identify the current practice in the development and evaluation of ECAs for chronic diseases. METHODS: We applied a methodological framework in this review. A total of 6 databases (ie, PubMed, Embase, CINAHL, ACM Digital Library, IEEE Xplore Digital Library, and Web of Science) were searched using a combination of terms related to ECAs and health in October 2023. Two independent reviewers selected the studies and extracted the data. This review followed the PRISMA-ScR (Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. RESULTS: The literature search found 6332 papers, of which 36 (0.57%) met the inclusion criteria. Among the 36 studies, 27 (75%) originated from the United States, and 28 (78%) were published from 2020 onward. The reported ECAs covered a wide range of chronic diseases, with a focus on cancers, atrial fibrillation, and type 2 diabetes, primarily to promote screening and self-management. Most ECAs were depicted as middle-aged women based on screenshots and communicated with users through voice and nonverbal behavior. The most frequently reported evaluation outcomes were acceptability and effectiveness. CONCLUSIONS: This scoping review provides valuable insights for technology developers and health care professionals regarding the development and implementation of ECAs. It emphasizes the importance of technological advances in the embodiment, personalized strategy, and communication modality and requires in-depth knowledge of user preferences regarding appearance, animation, and intervention content. Future studies should incorporate measures of cost, efficiency, and productivity to provide a comprehensive evaluation of the benefits of using ECAs in health care.

The Use of Gamification in the Self-Management of Patients With Chronic Diseases: Scoping Review.

BACKGROUND: Chronic disease self-management is a public health issue of worldwide concern, and gamification is an emerging strategy to improve patients' participation in chronic disease self-management. Some studies have summarized designs for the gamification of chronic disease self-management from the perspective of eHealth technology, but they have not mentioned differences in design methods, functions, and evaluation methods of gamified designs for self-management in different chronic diseases. OBJECTIVE: This scoping review aims to synthesize the characteristics of realization forms, functions, and evaluation methods in chronic disease self-management gamification to improve self-management among the chronic disease population. METHODS: We applied a methodological framework for scoping reviews and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist. As of January 7, 2023, we systematically searched 9 databases for relevant studies from January 2012 to December 2022. Related data were extracted based on the research questions. We calculated the frequencies, charted the quantitative data, and coded the extracted material for qualitative content analysis. RESULTS: We retrieved 16,221 records, of which 70 (0.43%) met the eligibility criteria. In the included research, the target populations for gamified designs for self-management of chronic diseases included patients with stroke, cancer, diabetes, chronic obstructive pulmonary disease, coronary heart disease, obesity, and hypertension. Almost all studies mentioned technical support for gamification (68/70, 97%), mainly in the form of active video games (58/70, 83%); however, less than half of the studies mentioned the theoretical basis for gamification (31/70, 44%). There were 37 concepts or theories relevant to gamification design, most of which were in the field of psychology or were cross-disciplinary (n=33, 89%). Gamification for the self-management of chronic diseases has been widely recognized, including for promoting physical exercise and rehabilitation training (48/99, 48%), increasing initiative for symptom management (18/99, 18%), providing psychological support (14/99, 14%), improving cognitive function (12/99, 12%), and improving medication adherence (7/99, 7%). A total of 39 studies mentioned the gamification effect; however, we did not find a unified evaluation standard. CONCLUSIONS: This scoping review focuses on gamification designs for chronic disease self-management and summarizes the realization forms and functions of gamification in self-management for different patient populations. With practice in a gamified internet-based environment, patients can not only master the knowledge and skills of self-management in fascinating scenarios but also benefit from gaming experience and make better health-related decisions in real life. It is worth noting that a comprehensive evaluation of the users as well as a personalized and targeted intervention should be developed before gamification.

Incidence and risk factors of admission deep venous thrombosis in nonagenarians and centenarians with intertrochanteric fracture: a retrospective study.

PURPOSE: The objective of this study was to identify the risk factors for admission deep venous thrombosis (aDVT) and proximal aDVT in nonagenarians and centenarians with intertrochanteric fracture (IF). METHODS: We collected statistics on nonagenarians and centenarians with IF admitting from January 2010 to October 2022. Patients with aDVT were considered as the aDVT group and those without aDVT as the non-aDVT group. Additionally, we also conducted a subgroup analysis based on the location of aDVT to investigate the predictors of proximal aDVT. The demographics, comorbidities and admission laboratory examinations of patients were computed by univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: In our study, the rate of aDVT (109 of 318) was 34.3%, and 5.7% (18 of 318) of patients had proximal aDVT. Logistic regression analysis showed that female patients and a high level of D-dimer were risk factors for aDVT. Similarly, hypoproteinemia and a high level of D-dimer were found to be risk factors for proximal aDVT. ROC curve analysis indicated the cut-off values of D-dimer to predict the aDVT and proximal aDVT were 1.28 mg/L and 1.485 mg/L, respectively. CONCLUSIONS: Our findings investigated the risk factors of aDVT and proximal aDVT in nonagenarians and centenarians with IF and identified the cut-off values of D-dimer, helping us assess the risk of aDVT and proximal aDVT to manage early targeted interventions.

Characteristics of preoperative atrial fibrillation in geriatric patients with hip fracture and construction of a clinical prediction model: a retrospective cohort study.

INTRODUCTION: Atrial fibrillation is the most common atrial arrhythmia in the perioperative period and is associated with prolonged hospital stay, increased costs, and increased mortality. However, there are few data on the predictors and incidence of preoperative atrial fibrillation in hip fracture patients. Our aim was to identify predictors of preoperative atrial fibrillation and to propose a valid clinical prediction model. METHODS: Predictor variables included demographic and clinical variables. LASSO regression analyzes were performed to identify predictors of preoperative atrial fibrillation, and models were constructed and presented as nomograms. Area under the curve, calibration curve, and decision curve analysis (DCA) were used to examine the discriminative power, calibration, and clinical efficacy of the predictive models. Bootstrapping was used for validation. RESULTS: A total of 1415 elderly patients with hip fractures were analyzed. Overall, 7.1% of patients had preoperative atrial fibrillation, and they were at significant risk for thromboembolic events. Patients with preoperative AF had a significantly longer delay in surgery than those without preoperative atrial fibrillation (p < 0.05). Predictors for preoperative atrial fibrillation were hypertension (OR 1.784, 95% CI 1.136-2.802, p < 0.05), C-reactive protein at admission (OR 1.329, 95% CI 1.048-1.662, p < 0.05), systemic inflammatory response index at admission (OR 2.137, 95% CI, 1.678-2.721 p < 0.05), Age-Adjusted Charlson Comorbidity Index (OR 1.542, 95% CI 1.326-1.794, p < 0.05), low potassium(OR 2.538, 95% CI 1.623-3.968, p < 0.05), anemia(OR 1.542, 95% CI 1.326-1.794, p < 0.05). Good discrimination and calibration effect of the model was showed. Interval validation could still achieve the C-index value of 0.799. DCA demonstrated this nomogram has good clinical utility. CONCLUSION: This model has a good predictive effect on preoperative atrial fibrillation in elderly patients with hip fractures, which can help to better plan clinical evaluation.

The m6A demethylase ALKBH5-mediated upregulation of DDIT4-AS1 maintains pancreatic cancer stemness and suppresses chemosensitivity by activating the mTOR pathway.

BACKGROUND: Chemoresistance is a major factor contributing to the poor prognosis of patients with pancreatic cancer, and cancer stemness is one of the most crucial factors associated with chemoresistance and a very promising direction for cancer treatment. However, the exact molecular mechanisms of cancer stemness have not been completely elucidated. METHODS: m6A-RNA immunoprecipitation and sequencing were used to screen m6A-related mRNAs and lncRNAs. qRT-PCR and FISH were utilized to analyse DDIT4-AS1 expression. Spheroid formation, colony formation, Western blot and flow cytometry assays were performed to analyse the cancer stemness and chemosensitivity of PDAC cells. Xenograft experiments were conducted to analyse the tumour formation ratio and growth in vivo. RNA sequencing, Western blot and bioinformatics analyses were used to identify the downstream pathway of DDIT4-AS1. IP, RIP and RNA pulldown assays were performed to test the interaction between DDIT4-AS1, DDIT4 and UPF1. Patient-derived xenograft (PDX) mouse models were generated to evaluate chemosensitivities to GEM. RESULTS: DDIT4-AS1 was identified as one of the downstream targets of ALKBH5, and recruitment of HuR onto m6A-modified sites is essential for DDIT4-AS1 stabilization. DDIT4-AS1 was upregulated in PDAC and positively correlated with a poor prognosis. DDIT4-AS1 silencing inhibited stemness and enhanced chemosensitivity to GEM (Gemcitabine). Mechanistically, DDIT4-AS1 promoted the phosphorylation of UPF1 by preventing the binding of SMG5 and PP2A to UPF1, which decreased the stability of the DDIT4 mRNA and activated the mTOR pathway. Furthermore, suppression of DDIT4-AS1 in a PDX-derived model enhanced the antitumour effects of GEM on PDAC. CONCLUSIONS: The ALKBH5-mediated m6A modification led to DDIT4-AS1 overexpression in PDAC, and DDIT-AS1 increased cancer stemness and suppressed chemosensitivity to GEM by destabilizing DDIT4 and activating the mTOR pathway. Approaches targeting DDIT4-AS1 and its pathway may be an effective strategy for the treatment of chemoresistance in PDAC.

Clinical Effect of Bone Filling Mesh Container Vertebroplasty in Osteoporotic Compression Fracture.

Objective: To investigate the clinical application of bone filling mesh container vertebroplasty in osteoporotic vertebral compression fractures (OVCFs). Methods: Patients with OVCF from October 2018 to April 2020 were selected. Patients in the control and study groups underwent percutaneous kyphoplasty (PKP) and bone filling mesh container vertebroplasty, respectively. The Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA), visual analog scale (VAS) scores before and after surgery, and the incidence of complications were compared between the two groups. Results: The operation time and fluoroscopy time of the study group were significantly lower than those of the control group (P < 0.05). There was no significant difference in the injection volume of bone cement between the study group and the control group (P > 0.05). There was no significant difference in Cobb angle between the two groups. Three months after the operation, the height of the anterior edge increased and the Cobb angle decreased in the two groups (P < 0.05), but there was no significant difference in the height of the anterior edge and the Cobb angle between the two groups (P > 0.05). The JOA scores increased, while the ODI and VAS scores decreased in both groups after surgery (P < 0.05). There was no significant difference in the total effective rate between the study group (96.15%) and the control group (92.31%) (P > 0.05). The incidence of complications in the study group (3.85%) was significantly lower than that in the control group (15.38%) (P < 0.05). Conclusions: For the treatment of OVCFs, bone filling mesh container vertebroplasty is comparable to PKP in terms of functional recovery, but it can safely reduce operative time, fluoroscopy time, and complication rates.

Characteristics and complications of fracture in older adults with chronic kidney disease: a cross-sectional study.

BACKGROUND: The aim of this study was to analyze the clinical characteristics of older fracture patients with chronic kidney disease (CKD) and to determine the risk factors of perioperative cardiovascular complications. METHODS: We retrospectively reviewed clinical data of older fracture patients with CKD admitted to the Third Hospital of Hebei Medical University from January 2016 to October 2021. The data we collected included baseline characteristics and complications. We finally determined the risk factors of perioperative cardiovascular complications by using logistic regression. RESULTS: We ended up enrolling 224 patients, and there were 91 (40.6%) males and 133 (59.4%) females, with a median age of 79 years. 80-84 years old was the age group with high incidence of fracture. The majority of fracture occurred indoors (130 cases, 58.0%) and morning (98 cases, 43.8%). Hip fracture was most common (183 cases, 81.7%), of which femoral neck fracture (101 cases, 45.0%) was the most prevalent. The most common comorbid condition was hypertension (171 cases, 76.3%), and anemia was the most common complication (148 cases, 66.1%). Age ≥ 80 years (OR = 2.023, 95% CI 1.110-3.688), previously combined with cardiovascular calcification (OR = 1.901, 95% CI 1.047-3.451) and admission hemoglobin level < 100 g/L (OR = 3.191, 95% CI 1.744-5.838) were independent risk factors of perioperative cardiovascular disease (CVD). CONCLUSION: It was especially necessary to enhance fracture prevention for CKD. Patients whose age older than 80, hemoglobin less than 100 g/L on admission and have previous cardiovascular calcification are more likely to develop perioperative CVD. Such patients require reasonable decisions during the perioperative period to avoid the occurrence of CVD.

Epiplakin1 promotes the progression of esophageal squamous cell carcinoma by activating the PI3K-AKT signaling pathway.

BACKGROUND: Epiplakin1 (EPPK1) has been associated with disease progression and unfavorable prognosis of many cancers, but its functional involvement in esophageal squamous cell carcinoma (ESCC) remains to be uncovered. METHODS: The Quantitative Real-time PCR (qPCR) assay was employed to determine the expression of EPPK1 in ESCC tissues and cells. CCK-8 assay, colony forming assay, wound healing assay, and transwell invasion assay were utilized to evaluate the effects of EPPK1 on cell proliferation, migration, and invasion capacity in ESCC cells using small interfering ribonucleic acids. Flow cytometry was performed to estimate the cell apoptotic rate caused by silencing of EPPK1. The proteins related to epithelial-to-mesenchymal transition (EMT), apoptosis, and activation of the phosphatidylinositol 3-kinase/serine threonine protein kinase 1 (PI3K/AKT) signaling pathway were measured by western blot. RESULTS: The expression of EPPK1 was dramatically increased in ESCC tissues and cells compared to that in relative controls. Additionally, silencing of EPPK1 suppressed ESCC cell growth, colony formation, migration, invasion, and EMT, while promoting ESCC cell apoptosis. Furthermore, EPPK1 induced ESCC cell progression via mediating the PI3K/AKT signaling pathway. CONCLUSION: EPPK1 promotes ESCC progression by modulating the PI3K/AKT signaling pathway and could serve as a potential target for ESCC treatment.

The application of patient-centered care bundle significantly reduces incidence of perioperative respiratory complications in hip fracture patients aged 80 and over.

This study was designed as a pilot test to analyze the effect of patient-centered care (PCC) bundle intervention on perioperative respiratory complications and other outcomes in hip fracture patients aged ≥80. Between Jan 2018 and Dec 2019, 198 patients comprised the routine care group and 187 comprised the PCC bundle group. After propensity score matching, 151 remained in each group. Incidence of perioperative respiratory complications in the PCC bundle group was significantly lower than in the routine care group (all P < 0.05). Furthermore, significant reductions were observed in surgery delay, length of stay, incidence of arrhythmia, hypoproteinemia, and electrolyte disturbance (all P < 0.05) in the PCC bundle group. Age-Adjusted Charlson Comorbidity Index score was related, but only weakly, to length of stay and the number of perioperative complications. These results suggested that the PCC bundle might be a more suitable care modality for patients ≥80 with hip fracture.

Is There a "Weekend Effect" in Intertrochanteric Fracture Surgery?

INTRODUCTION: Numerous studies reported poorer outcomes for patients who were admitted at weekends or off-hour, which relates to the underlying concept called the "weekend effect." We aimed to assess the effect of adverse outcomes in older patients with intertrochanteric fracture surgery. METHODS: A retrospective cohort study of patients aged ≥65 years with intertrochanteric fracture surgery. Data were collected from computerized medical records and all patients had a long-term follow-up. The association between weekend effect with adverse outcomes and factors for all-cause mortality was studied by 3-group comparison, Spearman and partial correlation analysis, univariate analysis, and multivariate Cox proportional-hazard model. RESULTS: Our results showed no evidence supporting the existence of a weekend effect on adverse outcomes, including mortality rates (p = 0.950, log-rank), length of hospital stay, total hospital costs, rate and volume of transfusion, visual analog scale score, Harris Hip Score, and specific complications (all p > 0.05), except for an average of 0.5 days longer surgical delay found in patients admitted on Fridays relative to other days (p = 0.013). Instead, only age group (with a 10-year interval, HR 1.43, 1.28-1.59 95% CI, p < 0.001) and surgical delay (HR 1.05, 1.02-1.07 95% CI, p < 0.001) were identified as significantly associated with all-cause mortality. CONCLUSIONS: Older patients with intertrochanteric fracture surgery have similar mortality and adverse outcomes rates when admitted on weekends or holidays compared with weekdays. Our findings suggest that collaborative multidisciplinary team care seems both effective and efficient in the management of older patients with intertrochanteric fractures on any day of the week.