Objective To elucidate the causal relationships between colorectal cancer (CRC) and prevalent psychiatric disorders through a two-sample Mendelian randomization approach. Methods Utilizing publicly available genome-wide association study data, we explored the connections between CRC and various psychiatric disorders, including depression, anxiety, bipolar disorder, and schizophrenia. We applied three statistical analyses: inverse variance weighting, MR-Egger, and median weighting. Sensitivity analyses were conducted to ensure the reliability and validity of the results. Results Inverse variance weighting analysis showed no significant links between CRC and depression (P=0.090), anxiety (P=0.099), or schizophrenia (P=0.899). Conversely, a significant inverse relationship was found with bipolar disorder (P=0.010). Conclusion No causal connection exists between CRC and the psychiatric conditions of depression, anxiety, or schizophrenia. However, CRC may have a causal association with a reduced risk of bipolar disorder, further supporting the existence of the gut-brain axis.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains unclear. Methods We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAP-periodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM specimens.Glioma stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional culture.For the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were studied. Results VM and high pATM expression occurred in 38.5%and 41.8%of tumors,respectively,and were significantly associated with reduced progression-free and overall survival.Patients with VM-positive GBMs exhibited higher pATM levels(rs=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in vitro.ATM inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin B2. Conclusion VM may predict a poor GBM prognosis and is associated with pATM expression.We propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P＜0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P＜0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P＜0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P＜0.05)and the proportion of specific CD8+T cells(P＜0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5％,while all mice in the other groups had died(P＜0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.

Objective:To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score (TBS) (hereinafter referred to as STS) in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection, and to construct a nomogram model.Methods:The clinical data (including the degree of tumor differentiation, vascular cancer thrombus, and lymph node metastasis, etc.) of 258 ICC patients who received radical resection at People′s Hospital of Zhengzhou University (170 cases, training set) and Cancer Hospital of Zhengzhou University (88 cases, validation set) from January 1, 2016 to January 31, 2020 were retrospectively analyzed and graded by SII, TBS and STS. Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC. Kaplan-Meier survival curve and receiver operating characteristic curve (ROC) were drawn to evaluate the predictive efficiency of SII, TBS and STS in the overall survival of patients with ICC after radical resection. The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index (C-index) and calibration curve.Results:Among 170 ICC patients in the training set, there were 106 cases of SII grade 1 and 64 cases of SII grade 2; 137 cases of TBS grade 1 and 33 cases of TBS grade 2; and 98 cases of STS grade 1, 47 cases of STS grade 2, and 25 cases of STS grade 3. Among 88 ICC patients in the validation set, there were 33 cases of SII grade 1 and 55 cases of SII grade 2; 66 cases of TBS grade 1 and 22 cases of TBS grade 2; and 30 case of STS grade 1, 39 cases of TBS grade 2, and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree (highly differentiated vs. moderately differentiated HR=0.157, 95% confidence interval(95% CI) 0.045 to 0.546, highly differentiated vs. poorly differentiated HR=0.452, 95% CI 0.273 to 0.750), STS (grade 3 vs. grade 2 HR=1.966, 95% CI 1.148 to 3.469; grade 3 vs. grade 1 HR=1.405, 95% CI 0.890 to 2.216), vascular cancer thrombus ( HR=2.006, 95% CI 1.313 to 3.066), nerve invasion ( HR=1.865, 95% CI 1.221 to 2.850), and lymph node metastasis ( HR=1.802, 95% CI 1.121 to 2.896) were independent influencing factors of overall survival in ICC patients after radical resection (all P<0.05). The Kaplan-Meier survival curve showed that SII, TBS, and STS were independent influencing factors of overall survival in ICC patients (all P<0.05). The results of ROC analysis showed that the areas under the curve of SII, TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566 (95% CI 0.479 to 0.652), 0.585 (95% CI 0.499 to 0.672), and 0.657 (95% CI 0.522 to 0.692), respectively. Tumor differentiation, vascular tumor thrombus, nerve invassion, lymph node metastasis, and STS were included to constract the nomogram model. The C-indexes of the training set and validation set based on the nomogram model were 0.792 (95% CI 0.699 to 0.825) and 0.776 (95% CI 0.716 to 0.833), respectively. The calibration curves of the survival rate of the training set and the validation set were close to the reference lines, and the nomogram model had better predictive ability in both the training set and the validation set. Conclusions:Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section. Compared with SII and TBS alone, it has better predictive value for the prognosis of patients with ICC.

Objective To analyze the correlation between T lymphocyte subsets,neutrophil/lymphocyte ratio(NLR),procalcitonin(PCT)and the severity of sepsis.Methods A prospective research method was adopted.A total of 78 sepsis patients admitted to the department of intensive care medicine of Zibo Central Hospital from January 2021 to December 2022 were selected as the research subjects.Patients were divided into a septic shock group(37 cases)and a sepsis group(41 cases)based on the severity of their condition,with 40 healthy examinees from our hospital as the healthy control group.Using flow cytometry to measure the levels of CD4+ T lymphocytes count(CD4+ T)and CD8+ T lymphocytes count(CD8+ T)in three groups of subjects,calculate the CD4+ T/CD8+ T lymphocyte ratio(CD4+ T/CD8+ T)and NLR.The levels of PCT and interleukin-6(IL-6)were measured using electrochemiluminescence immunoassay,and the levels of C-reactive protein(CRP)were measured using immunoassay turbidimetry.Acute physiology and chronic health evaluationⅡ(APACHEⅡ)score within 24 hours was recorded for the two groups of patients,and the differences in lymphocyte subsets and various inflammatory indicators were compared between the groups.Pearson correlation analysis was used to analyze the correlation between various indicators and APACHEⅡscore.Results The CD4+ T,CD8+ T,and CD4+T/CD8+T levels in the septic shock and sepsis groups were significantly lower than those in the healthy control group[CD4+ T(×106/L):168.27±76.68,266.08±131.57 vs.789.60±173.78,CD8+ T(×106/L):156.50±68.37,205.81±75.60 vs.636.42±90.59,CD4+ T/CD8+ T:1.09±0.39,1.27±0.34 vs.1.44±0.38,all P<0.01],NLR,PCT,CRP and IL-6 were significantly higher than those in the healthy control group[NLR:25.85±11.62,15.94±8.72 vs.2.68±1.31,PCT(μg/L):21.82±15.28,9.09±4.96 vs.0.13±0.10,CRP(mg/L):158.65±62.33,106.97±51.49 vs.6.48±2.08,IL-6(ng/L):1 344.64±899.21,245.31±176.99 vs.3.25±1.83,all P<0.01].The APACHEⅡscore in the septic shock group was significantly higher than that in the sepsis group(32.00±1.00 vs.22.01±1.09,P<0.05).Correlation analysis showed that the levels of CD4+ T,CD8+ T,CD4+ T/CD8+ T in two groups of sepsis patients were negatively correlated with the APACHEⅡscore(r values were-0.571,-0.506,and-0.555,respectively,all P<0.01),while the levels of NLR,PCT,CRP,and IL-6 were positively correlated with the APACHEⅡscore(r values were 0.711,0.709,0.777,and 0.707,respectively,all P<0.01).Conclusions As the levels of T lymphocyte subsets decrease,inflammatory indicators like NLR and PCT rise,indicating a more severe sepsis condition.Therefore,T lymphocyte subsets and levels of various inflammatory indicators can serve as markers for evaluating the severity of sepsis.

Objective:To construct and validate a machine learning model for preoperative prediction of perineural invasion (PNI) status in intrahepatic cholangiocarcinoma (ICC).Methods:Clincial data of 329 patients, including 245 admitted to Zhengzhou University People's Hospital from January 2018 to June 2023 and 84 admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to January 2020 were retrospectively analyzed. Patients were divided into a training set ( n=231) and a validation set ( n=98). Clinicopathological data including age, gender, hepatitis B virus (HBV) infection status were collected. Predictive variables were determined using least absolute shrinkage and selection operator (LASSO) regression analysis. Six machine learning algorithms including random forest (RF), logistic regression, and linear kernel-based support vector machine were selected to construct the preoperative prediction model for PNI in ICC. Performance metrics of the model were calculated using a confusion matrix, and the final model was selected. The model performance was evaluated in the validation set. Calibration curves were plotted to evaluate the final model, and a Pareto chart was used to visualize the importance of predictive variables. Results:LASSO regression identified nine predictive variables included in the prediction model, including carbohydrate antigen 19-9 (CA19-9), HBV infection status, alkaline phosphatase, alanine aminotransferase, prothrombin time, total bilirubin, albumin, neutrophil times gamma-glutamyl transferase to lymphocyte ratio, and tumor burden score. Among the trained six models, the area under the curve (AUC) of the RF model was 0.909, with a sensitivity of 0.842 and an accuracy of 0.870. Compared with the AUC of the RF model, the AUCs of the other 5 models were lower (all P<0.05). The AUC of the RF model for predicting PNI in ICC in validation set was 0.736. Calibration curves showed good fit of the RF model's prediction of PNI in ICC in both training and validation sets. The Pareto chart showed that CA19-9 was the most important predictive variable in the model, followed by HBV infection status. Conclusion:The machine learning model based on the RF algorithm has a high accuracy in preoperative prediction of PNI status in ICC.

Objective To construct an evidence-based practice model for nurses in preventing deep vein thrombosis(DVT)and provide a scientific and targeted theoretical basis for nurses to carry out evidence-based nursing practice in DVT prevention.Methods Based on the previous evidence-based nursing practice project on DVT prevention after hip and knee arthroplasty,the research team used theoretical analysis and brainstorming to develop a draft of the work model.Expert meetings were organized to validate the content of the draft using the Delphi method,leading to the finalization of the evidence-based practice model for nurses in preventing DVT.Results The Knowledge-to-Action(KTA)framework was selected as the basic framework for constructing the evidence-based nursing practice model for preventing DVT.Theoretical Domain Framework,Theory of Planned Behavior,and Social Cognitive Theory were chosen to explore the influencing factors of nurses'behavior change in preventing DVT through evidence-based practice.The authority coefficient of the participating experts was 0.904,indicating high reliability.The final model consisted of 6 key components:knowledge generation,problem identification,localization and adaptation,knowledge application,sustained knowledge use,and conceptual framework for behavior change through evidence-based practice.Conclusion Based on theoretical analysis and clinical practice,this study developed an evidence-based practice model for nurses in preventing DVT using the expert meeting.The research methodology was scientific,and the content was reliable,providing a theoretical basis for nurses to engage in evidence-based nursing practice for DVT prevention.

Objective:To explore the cognition and intention of patients with lower limb deep vein thrombosis (DVT) to participate in patient-reported outcomes (PROs), so as to provide references for the promotion, application, and practice of PROs in lower limb DVT patients in China.Methods:This study adopted the phenomenological qualitative research method. From February to June 2023, 13 lower limb DVT patients admitted to Peking Union Medical College Hospital were selected for semi-structured in-depth interviews. Colaizzi 7-step analysis method was used for analyzing and summarizing data.Results:Thirteen patients with lower limb DVT highly recognized their own value in participating in PROs, namely health benefits, prevention of DVT complications, and reduction of disease uncertainty. Lower limb DVT patients expected to receive support from healthcare professionals, families, and portable and simplified reporting formats to promote their participation in PROs. From the patient 's own perspective, they perceived that insufficient attention to DVT caused by lack of awareness of the hazards of DVT and limited understanding of PROs made it difficult for them to participate in PROs. Conclusions:Lower limb DVT patients have a high intention to participate in PROs. The application and promotion of PROs in lower limb DVT patients in China require joint support from various sectors of society, among which strengthening effective health education for patients and their families and providing multi-channel reporting forms are the key to promoting of PROs.

Objective:To construct a tool to evaluate the knowledge, attitude, and practice of nurses in the prevention of thrombosis related to peripherally inserted central catheter (PICC) .Methods:From December 2022 to April 2023, based on the theory of knowledge, attitude, and practice, a preliminary draft of the PICC-related Thrombosis Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses was formed through systematic literature review, two rounds of Delphi expert consultations, and pre-survey. In May 2023, convenience sampling was used to select 573 nurses from Chinese Academy of Medical Sciences & Peking Union Medical College Hospital as the research subject for a survey to conduct item analysis, validity testing, and reliability testing on the questionnaire.Results:The final version of the PICC-related Thrombosis Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses included 20 knowledge items, 10 attitude items, and 10 practice items. In the content validity of the questionnaire, the average content validity index was 0.984, the overall consensus content validity index was 0.850, and the item level content validity index was 0.857 to 1.000. Exploratory factor analysis extracted three common factors with eigenvalues>1.000, with a cumulative variance contribution rate of 64.540% and factor loadings of 0.450 to 0.908 for each item. The total Cronbach's α coefficient of the questionnaire was 0.895, the half reliability coefficient was 0.947, and the retest reliability coefficient was 0.966.Conclusions:The PICC-related Thrombosis Prevention Knowledge, Attitude, and Practice Questionnaire for Nurses has good reliability and validity, and can be used to evaluate PICC-related thrombosis prevention knowledge, attitude, and practice among nurses.