The construction of a prognostic model by apoptosis-related genes to predict survival, immune landscape, and medication in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly aggressive and invasive malignant tumor of the bile duct, with a poor prognosis and a high mortality rate. Currently, there is a lack of effective targeted treatment methods and reliable biomarkers for prognosis. METHODS: We downloaded RNA-seq and clinical data of CCA from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as training and test sets. The apoptosis-related genes were obtained from the Molecular Signatures Database (MsigDB) database. We used univariate/multivariate Cox regression and Lasso regression analyses to construct a riskscore prognostic model. Based on the median riskscore, we clustered the patients into high-risk (HR) and low-risk (LR) groups. We carried out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) in HR and LR groups. The single sample gene set enrichment analysis (ssGSEA) was employed to analyze the immune infiltration of the HR and LR groups. The CellMiner database was utilized to predict drugs and perform molecular docking on drugs and target proteins. RESULTS: We identified 8 genes with prognostic significance to construct a prognostic model. Results of GO and KEGG demonstrated that DEGs were mainly enriched in biological functions such as fatty acid metabolic processes and pathways such as the cAMP signaling pathway. Results of ssGSEA uncovered that immune cells such as DCs and Macrophages in the HR group, as well as immune functions such as Check-point and Parainflammation, were considerably higher than those in the LR group. Drug sensitivity prediction and results of molecular docking revealed that Rigosertib targeted the prognostic genes MAP3K1. HYPOTHEMYCIN and AMG900 effectively targeted JUN. CONCLUSION: Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients.

Prediction of early-phase cytomegalovirus pneumonia in post-stem cell transplantation using a deep learning model.

BACKGROUND: Diagnostic challenges exist for CMV pneumonia in post-hematopoietic stem cell transplantation (post-HSCT) patients, despite early-phase radiographic changes. OBJECTIVE: The study aims to employ a deep learning model distinguishing CMV pneumonia from COVID-19 pneumonia, community-acquired pneumonia, and normal lungs post-HSCT. METHODS: Initially, 6 neural network models were pre-trained with COVID-19 pneumonia, community-acquired pneumonia, and normal lung CT images from Kaggle's COVID multiclass dataset (Dataset A), then Dataset A was combined with the CMV pneumonia images from our center, forming Dataset B. We use a few-shot transfer learning strategy to fine-tune the pre-trained models and evaluate model performance in Dataset B. RESULTS: 34 cases of CMV pneumonia were found between January 2018 and December 2022 post-HSCT. Dataset A contained 1681 images of each subgroup from Kaggle. Combined with Dataset A, Dataset B was initially formed by 98 images of CMV pneumonia and normal lung. The optimal model (Xception) achieved an accuracy of 0.9034. Precision, recall, and F1-score all reached 0.9091, with an AUC of 0.9668 in the test set of Dataset B. CONCLUSIONS: This framework demonstrates the deep learning model's ability to distinguish rare pneumonia types utilizing a small volume of CT images, facilitating early detection of CMV pneumonia post-HSCT.

Study on the influence of syphilis on the outcome of frozen-thawed embryo transfer in infertility patients.

Objective: In this study, the effect of in vitro Fertilization-Embryo Transfer (IVF-ET) on the clinical outcome of patients with syphilis infertility during resuscitation cycle. Methods: A retrospective single-center method was adopted. This study included 4430 pairs of infertile patients who underwent syphilis detection. The influence of the syphilis freeze-thaw embryos transplantation outcome was studied in the patients with infertility by comparing the general clinical characteristics of patients (age, years of infertility, body mass index (BMI), basal follicle stimulating hormone (FSH), serum basal estradiol (Estradiol, E2), transplanted intimal thickness, the number of embryos transferred) and the clinical pregnancy (biochemical pregnancy rate, clinical pregnancy rate, implantation rate, live birth rate and abortion rate). Results: Firstly, in the clinical outcome of one frozen-thawed embryos transfer, the live birth rate of the woman's syphilis-infected group was lower than that of the uninfected group (71.3 % vs. 50.0 %), while the abortion rate was higher than that of the uninfected group (7.8 % vs. 26.7 %), and there was a statistical difference (P < 0.05), and there was no statistical difference in other indicators between other groups (P > 0.05). Secondly, in the clinical outcome of two frozen-thawed embryos transfers, the biochemical pregnancy rate (61.3 % vs. 28.6 %) and clinical pregnancy rate (42.9 % vs. 14.3 %) of the group which was infected with syphilis alone were lower than those of the uninfected group (P < 0.05), and other indicators among the other groups showed no statistical difference (P > 0.05). Thirdly, in the clinical outcomes of frozen-thawed embryos transfer three times or more, there was no significant difference in the clinical indicators between the syphilis infertility patients and the non-infected infertility patients (P > 0.05). Conclusion: When the syphilis infertility patients and the non-infected infertile patients underwent IVF-ET treatment for the first time, the live birth rate and abortion rate of the syphilis group were significantly different (P < 0.05). In the outcome of two transplants, the biochemical pregnancy rate and clinical Pregnancy rates were significantly reduced so patients with syphilis infertility who undergo IVF-ET should be informed about the risk of adverse clinical outcomes.

A Novel Tablet-Based Approach for Hearing Screening of the Pediatric Population, 516-Patient Study.

OBJECTIVE: Assess a tablet hearing game as a screening instrument for pediatric hearing loss. METHODS: All children age 3 to 13 presenting to the ENT clinic of a tertiary hospital clinic over a 3-month period were eligible for study. Five hundred sixteen were entered by completing the tablet screen with calibrated tablet/headphones. All had full standard audiometry or otoacoustic emission testing to assess hearing status. Tablet game data was analyzed to find the best correlation to the air conduction audiogram. The appropriate pass threshold of the tablet game was established and the statistical accuracy of the tablet game versus the air conduction audio was assessed. RESULTS: The overall rate of hearing loss was 29.7% (153 subjects). Conductive hearing loss predominated and was present in 128 children. The tablet game pure tone average from 500- 4000 Hz correlated best with the air conduction audiogram, and was most predictive of hearing loss. Setting the pass level at 20 dB for the tablet screen prioritized detection of hearing loss, yielding a sensitivity of 91% and corresponding specificity of 73.5% for ages 4 and older. Specificity progressively improved with increasing age and was over 90% for all ages 7 and older. CONCLUSION: Tablet game audiometry as a screening tool performs well in a controlled setting. Based on these results, it can be considered as a reliable screening method for school-age children and to monitor resolution of otitis media. LEVEL OF EVIDENCE: 4, case series Laryngoscope, 130:2245-2251, 2020.

Radiologic Complete Response In Lung Adenocarcinoma With Symptomatic Brain Metastasis After Systematic Therapy: A Case Study.

Patients diagnosed as lung adenocarcinoma with brain metastasis usually result in poor prognosis with limited survival time. Palliative systematic therapy has emerged as the primary choice for non-small cell lung cancer patients with brain metastasis harboring wild-type drive genes. However, the objective response rate and long-term survival for patients treated with this therapy remained unsatisfied. Herein, we present a case with lung adenocarcinoma accompanied with symptomatic brain metastasis who achieved radiologic complete response after receiving combined therapy including stereotactic body radiation therapy, anti-angiogenesis, and chemotherapy. He has achieved a duration of disease-free survival of thirty-six months, and is still in extension.

Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study.

BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. OBJECTIVE: We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). METHODS: Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. RESULTS: We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. CONCLUSIONS: We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02804100.

Diagnostic and Clinical Significance of Serum Levels of D-Lactate and Diamine Oxidase in Patients with Crohn's Disease.

BACKGROUND: Crohn's disease (CD) is a chronic intestinal inflammatory disease. An ideal laboratory marker that can predict the prognosis in terms of relapse of the disease is clinically desirable. METHODS: A total of 59 CD patients were enrolled in this study. Enzyme-Linked Immunosorbent Assay (ELISA) was used to quantitatively detect the content of D-lactate (D-LA) and the diamine oxidase (DAO) levels in sera obtained from patients and 28 healthy controls. The correlation between these two biomarkers and disease activity scores was assessed. In addition, the ROC curve was used to evaluate the diagnostic accuracy of these two biomarkers. RESULTS: The levels of D-LA in the serum of CD patients in the active stage and remission stage were 16.08 ± 4.8 mg/L and 11.16 ± 3.17 mg/L, respectively, and the difference was statistically significant (t = 4.67, P < 0.001). DAO levels were significantly higher in patients with the active stage compared to controls. The levels of D-LA and DAO in CD patients were positively correlated with the disease activity (r = 0.68 and 0.53, respectively, P < 0.05). The area under the ROC curve (AUC) when CD activity was diagnosed with D-LA and DAO alone was 0.815 and 0.748, respectively. The diagnostic efficacy of the two biomarkers was not significantly different from that of the erythrocyte sedimentation (ESR) and hypersensitive C-reactive protein (CRP) (P > 0.05). However, the area under the curve was 0.861 (0.746, 0.937) when the diagnosis was performed using a combination of D-LA, DAO, CRP, and ESR, which was significantly higher than when CRP or ESR were tested alone (P < 0.05). CONCLUSIONS: D-LA and DAO have a good prognostic value for CD activity. Rational combined use of biomarkers can significantly improve the diagnostic efficiency.

Relationship research between auditory neuropathy spectrum disorder and exchange transfusion in neonates with severe hyperbilirubinemia.

OBJECTIVE: To explore the effects of exchange transfusion on auditory neuropathy spectrum disorder (ANSD) in neonates with severe hyperbilirubinemia (SH). METHODS: The clinical data of 2216 SH neonates who met the standard of exchange transfusion and 732 non severe-hyperbilirubinemia (NSH) neonates in the same period who did not require exchange transfusion in the neonatology department of Childrens' Hospital of Chongqing Medical University between January 2010 and December 2015 were retrospectively analyzed. In addition, the SH neonates were further divided into the exchange transfusion group and photography group. Hearing screening was conducted on all neonates using transiently evoked otoacoustic emission (TEOAE) and auto auditory brainstem response (AABR), and neonates who failed the above screening were performed diagnostic hearing test. And then neonates diagnosed with hearing disorder were followed up for 2-5 years. RESULTS: The pass rates of hearing screening were 80.58%, 79.71% and 87.84% in the phototherapy group, exchange transfusion group and NSH group respectively, with a significant difference(P < 0.05). Hearing loss was diagnosed in 10.15%, 12.39% and 8.54% of neonates in the phototherapy group, exchange transfusion group and NSH group. After follow-up, ultimate incidence rates of ANSD were 11.96%, 11.57% and 2.4% respectively in the 3 groups, with a significant difference (P < 0.05). CONCLUSIONS: SH is one of risk factors for ANSD. SH neonates have a lower incidence of ANSD in the exchange transfusion group than in the phototherapy group. Neonates who meet the standards of exchange transfusion adopt this therapy in early stage, which can quickly decrease bilirubin level and ultimately reduce incidence of ANSD.

Meta-analysis for the efficacy of S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

AIM: We performed a meta-analysis to evaluate the efficacy and safety for S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer. PATIENTS & METHODS: Eligible randomized clinical trials (RCTs) were included, of which data were extracted by inclusion criteria and exclusion one. Odds ratio and hazard ratio (HR) of outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects (AEs) were explored for the final analysis. RESULTS: Twenty-one RCTs including 3263 patients were fit into the analysis. Pooled HR for PFS was 1.01 (95% CI: 0.92-1.10; p = 0.88), the pooled HR for OS was 0.95 (95% CI: 0.85-1.06; p = 0.33) and the pooled odds ratio for ORR was 0.74 (95% CI: 0.61-0.90; p = 0.003). S-1-based regimens showed milder AEs in high-grade nausea/vomit, anorexia, leukopenia, neutropenia and febrile neutropenia (all p < 0.05). CONCLUSION: The present study has revealed that S-1-based regimens are accompanied by the similar efficacy and slighter AEs compared with standard regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.