A machine learning-based predictive model for biliary stricture attributable to malignant tumors: a dual-center retrospective study.

Background: Biliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes. Methodology: Through a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People's Hospital affiliated with Jiangsu University and the Second People's Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model's accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model's predictions. Results: RF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor. Conclusion: The model's effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.

Effect modification by aging on the associations of nicotine exposure with cognitive impairment among Chinese elderly.

Active and passive exposure to tobacco smoke may increase risk of cognitive decline. However, effects of enhanced the aging process on the association of urinary nicotine metabolites with cognitive impairment remain unclear. In this study, 6657 Chinese older adults completed the physical examinations and cognitive tests. We measured urinary nicotine metabolite levels, mitochondrial DNA copy number (mtDNA-CN), and relative telomere length (RTL) and analyzed effects of urinary nicotine metabolites and their interaction with mtDNA-CN or RTL on cognitive impairment by generalized linear models and qg-computation, respectively. Each 1-unit increase in urinary 3-OHCot, 3-OHCotGluc, CotGluc, or NicGluc levels corresponded to a 1.05-, 1.09-, 1.04-, and 0.90-fold increased risk of cognitive impairment. Each 1-quantile increment in the mixture level of 8 nicotine metabolites corresponded to an increment of 1.40- and 1.34-fold risk of cognitive impairment in individuals with longer RTL or low mtDNA-CN. Urinary 3-OHCotGluc and RTL or mtDNA-CN exhibited an additive effect on cognitive impairment in addition to the mixture of 8 nicotine metabolites and mtDNA-CN. The findings suggested that aging process may increase the risk of tobacco-related cognitive impairment.

The advanced lung cancer inflammation index predicts chemotherapy response and infection risk in multiple myeloma patients receiving induction chemotherapy.

Objective: This study aims to determine the clinical significance of the advanced lung cancer inflammation index (ALI) in predicting prognosis, chemotherapy response, and infection risk in newly diagnosed multiple myeloma (MM) patients receiving induction therapy. Methods: A retrospective analysis of the clinical characteristics and laboratory data of 111 newly diagnosed MM patients from the Haematology Department of the Third Xiangya Hospital of Central South University from January 2014 to March 2020 was performed. We first determined the relationship between ALI and overall survival (OS), as well as clinical and laboratory parameters. Second, predictive factors for chemotherapy response were analysed by univariate and multivariate regression analyses. Third, univariate regression analysis of risk factors was performed using infection as the evaluable outcome. Results: Of the 111 evaluable patients, the low ALI group (<32.7) exhibited significantly poorer survival than the high ALI group (51 months versus 77 months). Multivariable analysis showed that advanced age, chemotherapy response and serum calcium level were independent prognostic factors for OS. Better chemotherapy efficacy in the high ALI group (89.3%) than in the low ALI group (42.2%) (p < 0.001) was noted. Multivariate analysis suggested that only ALI [HR: 0.110, 95% CI (0.035-0.350), p = 0.000] is an independent predictive factor in evaluating the efficiency of induction chemotherapy. Forty patients (36.04%) presented with infection after induction chemotherapy. Univariate analysis suggested that low ALI and abnormal renal function increase risk of infection in newly diagnosed MM patients. Conclusion: Our study confirmed that ALI is not only a prognostic biomarker for newly diagnosed patients, but also predicts chemotherapy efficacy in newly diagnosed MM patients receiving induction therapy.

Non-linear dose-response relation between urinary levels of nicotine and its metabolites and cognitive impairment among an elderly population in China.

BACKGROUND: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. METHODS: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. RESULTS: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment. CONCLUSIONS: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

Comparing mortality between positive and negative blood culture results: an inverse probability of treatment weighting analysis of a multicenter cohort.

BACKGROUND: The association between blood culture status and mortality among sepsis patients remains controversial hence we conducted a tri-center retrospective cohort study to compare the early and late mortality of culture-negative versus culture-positive sepsis using the inverse probability of treatment weighting (IPTW) method. METHODS: Adult patients with suspected sepsis who completed the blood culture and procalcitonin tests in the emergency department or hospital floor were eligible for inclusion. Early mortality was defined as 30-day mortality, and late mortality was defined as 30- to 90-day mortality. IPTW was calculated from propensity score and was employed to create two equal-sized hypothetical cohorts with similar covariates for outcome comparison. RESULTS: A total of 1405 patients met the inclusion criteria, of which 216 (15.4%) yielded positive culture results and 46 (21.3%) died before hospital discharge. The propensity score model showed that diabetes mellitus, urinary tract infection, and hepatobiliary infection were independently associated with positive blood culture results. There was no significant difference in early mortality between patients with positive or negative blood culture results. However, culture-positive patients had increased late mortality as compared with culture-negative patients in the full cohort (IPTW-OR, 1.95, 95%CI: 1.14-3.32) and in patients with severe sepsis or septic shock (IPTW-OR, 1.92, 95%CI: 1.10-3.33). After excluding Staphylococcal bacteremia patients, late mortality difference became nonsignificant (IPTW-OR, 1.78, 95%CI: 0.87-3.62). CONCLUSIONS: Culture-positive sepsis patients had comparable early mortality but worse late mortality than culture-negative sepsis patients in this cohort. Persistent Staphylococcal bacteremia may have contributed to the increased late mortality.

Submental Island Flap Combined With Reconstruction Titanium Plate: A New Way to Treat Mandibular Osteoradionecrosis.

Objective. The purpose of this study was to investigate the effect of reconstruction for bone defects in patients with mandibular osteoradionecrosis using submental flap combined with reconstructive titanium plate. Methods. A total of 23 patients with mandibular osteoradionecrosis were included. All patients underwent surgical resection and immediate reconstruction with submental flap combined with reconstructive titanium plate. The postoperative effects and flap success rate were evaluated with a 6- to 18-month follow-up. Results. Twenty-two flaps were successful; 1 flap suffered from partial necrosis in the distal end, but the patient was treated with hyperbaric oxygen therapy and iodoform gauze dressing, and no plate exposure was found after operation in the follow-up period. Conclusion. The use of submental flap combined with reconstructive titanium plate for treating the patients with osteoradionecrosis is a feasible, cost-effective, simple, and safe procedure.

The prognostic value of CD2, CD4, and HLA-DR expression and FLT3-ITD mutation in adult acute promyelocytic leukemia.

In order to explore the prognostic value of CD2, CD4, and human leucocyte antigen-DR (HLA-DR) expression and Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in leukemia cells in the bone marrow of patients with acute promyelocytic leukemia (APL), we retrospectively collected and analyzed the immunophenotype, molecular features and clinical characteristics of 219 newly diagnosed adult patients with APL in Henan Provincial People's Hospital from January 2010 to December 2019. It turned out that the relapse rates of patients with CD2, CD4, or HLA-DR expression and the early mortality rates of patients with CD2 expression, HLA-DR expression, or FLT3-ITD mutation were higher than those of their counterparts. Moreover, reduced overall survival was found for patients who showed CD2 expression, HLA-DR expression or FLT3-ITD mutation. Therefore, CD2 expression, HLA-DR expression and FLT3-ITD mutation were adverse prognostic factors in adults with APL.

LncRNA ANRIL promotes cell proliferation, migration and invasion during acute myeloid leukemia pathogenesis via negatively regulating miR-34a.

OBJECTIVE: LncRNA ANRIL (antisense non-coding RNA in the INK4 locus) was highly expressed in acute myeloid leukemia (AML) patients to promote AML pathogenesis. In this study, we aimed to investigate the roles and molecular events of ANRIL associated with AML progression. METHODS: Expression patterns of ANRIL and miR-34a in the bone marrow (BM) samples and cell lines were determined using qRT-PCR. Cell proliferation, apoptosis, migration and invasion of cells with ANRIL knockdown or miR-34a overexpression were assessed by CCK-8, EdU staining, flow cytometry and Transwell assays, respectively. The dual-luciferase reporter assay was employed to validate the relationship between miR-34a and Histone deacetylase 1 (HDAC1). The binding of E2 F1 (E2 F transcription factor 1) with gene promoter was analyzed by ChIP. Furthermore, the tumorigenicity of AML was determined by xenograft transplantation in nude mice. RESULTS: ANRIL was up-regulated both in the BM samples from AML patients and cell lines (HL-60 and THP-1), of which expression was negatively correlated with miR-34a expression. ANRIL knockdown inhibited cell proliferation, migration and invasion but promoted apoptosis of AML cells, while overexpression of miR-34a exerted opposite effects. miR-34a was verified as a downstream gene targeted by ANRIL. Moreover, HDAC1 was a direct target of miR-34a, and HDAC1 overexpression impaired the recruitment of E2 F1 to ASPP2 (apoptosis stimulating proteins of p53) gene promoter. ANRIL knockdown significantly inhibited the tumorigenesis of AML. CONCLUSION: ANRIL promotes AML development through HDAC1-mediated epigenetic suppression of ASPP2 via negatively regulating miR-34a, which might serve as a therapeutic target for AML treatment.

MyoD-induced circular RNA CDR1as promotes myogenic differentiation of skeletal muscle satellite cells.

Many protein coding and non-coding genes interplay in governing skeletal muscle formation. Nevertheless, comparing with the linear transcripts, functions of covalently closed circular RNAs (circRNAs), the new frontier of regulatory non-coding RNA (ncRNAs) molecules, remain largely unknown. Here, we identify CDR1as (antisense to the cerebellar degeneration-related protein 1 transcript, also termed as ciRS-7), a well-known cancer and neuron circRNA, plays a significant role in virtually controlling muscle differentiation. CDR1as is highly expressed in muscles of the mid-embryonic goat foetus, and activated at the initiation of myogenic differentiation in vitro. MyoD (myogenic differentiation protein 1), a driven transcription factor for myogenesis, promotes CDR1as by binding on its 5' flank region (-646 to -634 bp, neighbouring the predicted transcription start site at -580 bp). Overexpression or knockdown of CDR1as dramatically induces or impedes muscle differentiation program, respectively. By competitively binding to miR-7 (microRNA 7), CDR1as relieves the downregulation of IGF1R (insulin like growth factor 1 receptor) caused by miR-7 and consequently activates muscle differentiation. These results unveil that CDR1as plays critical roles in myogenic differentiation, which extends the versatile functions of CDR1as in mammal development and disease.

Combining procalcitonin with the qSOFA and sepsis mortality prediction.

To investigate whether procalcitonin (PCT) can improve the performance of quick sequential organ failure assessment (SOFA) score in predicting sepsis mortality, we conducted a retrospective multicenter cohort study with independent validation in a prospectively collected cohort in 3 tertiary medical centers. Patients with presumed sepsis were included. Serum PCT levels were measured at admission. Quick SOFA score and systemic inflammatory response syndrome (SIRS) criteria were calculated for each patient. PCT levels were assigned into 0, 1, and 2 points for a serum level of <0.25, 0.25 to 2, and >2 ng/mL, and added to the quick sepsis-related organ failure assessment (qSOFA) score. The incremental value of PCT to qSOFA was then evaluated by logistic regression, receiver-operating characteristic (ROC) curve, and reclassification analysis.In all, 1318 patients with presumed severe infection were enrolled with a 30-day mortality of 13.5%. Serum level of PCT showed a high correlation with qSOFA score and 30-day inhospital mortality. The area under the ROC curve was 0.56 for SIRS criteria, 0.67 for qSOFA score, and 0.73 for qSOFA_PCT in predicting 30-day mortality. The risk prediction improvement was reflected by a net reclassification improvement of 35% (17%-52%). Incorporation of PCT into the qSOFA model could raise the sensitivity to 86.5% (95% confidence interval 80.6%-91.2%). In the validation cohort, qSOFA_PCT greatly improved the sensitivity to 90.9%.A simple modification of qSOFA score by adding the ordinal scale of PCT value to qSOFA could greatly improve the suboptimal sensitivity problem of qSOFA and may serve as a quick screening tool for early identification of sepsis.