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Background Cadonilimab (AK104) is a bispecific IgG-single-chain Fv fragment (ScFv) antibody that binds to PD-1 and CTLA-4. Cadonilimab has shown encouraging anti-tumour activity and a favourable safety profile in several tumour types. In second-line treatment, there is no defined standard of care for patients with extensive-stage small-cell lung cancer (ES-SCLC). Cadonilimab is expected to show substantial clinical efficacy. Objective To assess the antitumor activity and safety of cadonilimab monotherapy or combination with conventional therapy in ES-SCLC patients who failed first-line treatment. Methods In this multicenter, open-label, phase II study, ES-SCLC patients who had failed first-line treatment, also aged 18 years to 70 years with histologically or cytologically confirmed ES-SCLC, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0–2 were eligible. Patients will receive cadonilimab 10 mg/kg every three weeks (Q3 W) among 24 months until progressive disease (PD) or adverse events (AE) discovery. The primary endpoint is progression-free survival (PFS). Trial registration NCT05901584.

Objective: This study assessed characteristics and outcomes of younger (18-65) versus older (>65) recipients of simultaneous heart–kidney (SHK) transplantation with varying functional dependence. Methods: This study retrospectively analyzed 1398 patients from the United Network for Organ Sharing database who received SHK between 2010 and 2021. Patients who were 65 years (n = 236), baseline characteristics were similar and well-balanced between the 2 cohorts. Between matched cohorts, older recipients did not have increased posttransplant mortality compared with younger recipients (90-day survival, P = .85; 7-year survival, P = .61). Multivariable Cox regression analysis found that age (hazard ratio [HR], 1.039 [0.975-1.106], P = .2415) and pretransplant functional status with interaction term for age (some assistance, HR, 0.965 [0.902-1.033], P = .3079; total assistance, HR, 0.976 [0.914-1.041], P = .4610) were not significant risk factors for 7-year post-SHK transplantation mortality. Conclusions: Older and more functionally dependent recipients in this study did not have increased post-SHK transplantation mortality. These findings have important implications for organ allocation among elderly patients, as they support the need for thorough assessment of SHK candidates in terms of comorbidities, rather than exclusion solely based on age and functional dependence.

Objective: Neurodevelopmental impairment has been realized as the most common complication in children with congenital heart disease undergoing cardiac surgery during the past 30 years. But little attention has been paid to this problem in China. The potential risk factors for adverse outcomes include demographic, perioperative, and socioeconomic factors, which are vastly different in China compared with the developed countries in previous reports. Methods: Four hundred twenty-six patients (aged 35.9 ± 18.6 months) at about 1- to 3-year follow-up after cardiac surgery were prospectively enrolled from March 2019 to February 2022. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination, and performance skills. Demographic, perioperative, socioeconomic, and feeding type during the first year of life (breastfeeding, mixed, or never breastfeeding) were examined to identify the risk factors for adverse neurodevelopmental outcomes. Results: Mean scores were 90.0 ± 15.5 for development quotient, 92.3 ± 19.4 for locomotor, 89.6 ± 19.2 for personal-social, 85.5 ± 21.7 for language, 90.3 ± 17.2 for eye-hand coordination, and 92 ± 17.1 for performance subscales. For the entire cohort, the impairment in at least 1 subscale was found in 76.1% of the cohort (>1 SD below population mean) with 50.1% being severe (>2 SDs below the mean). The significant risk factors included prolonged hospital stay, peak level of postoperative C-reactive protein, socioeconomic status, and never breastfeeding or mixed feeding. Conclusions: Neurodevelopmental impairment is substantial in terms of incidence and severity in children with congenital heart disease undergoing cardiac surgery in China. Risk factors contributing to the adverse outcomes included prolonged hospital stay, early postoperative inflammatory response, socioeconomic status, and never breastfeeding or mixed feeding. There is an urgent need for standardized follow-up and neurodevelopmental assessment in this special group of children in China.

Aim: Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed malignancy worldwide. Overexpressed of microRNA-21-5p (miR-21-5p) has been reported to be involved in the development of HNSCC. However, the role of miR-21-5p in HNSCC is still not fully elucidated. The purpose of this study was to explore the underlying molecular mechanisms of miR-21-5p in HNSCC. Methods: RT-qPCR was used to determine the differential expression levels of miR-21-5p in tissue samples of HNSCC patients. Meta-analysis was performed based on miRNA expression data collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA), and published articles to evaluate the expression of miR-21-5p in HNSCC. We investigated the biological function of miR-21-5P by gene ontology enrichment and target prediction analysis. Furthermore, RT-qPCR and IHC were conducted to verify the expression of target genes. Finally, Kaplan–Meier survival analysis was performed to assessed the prognostic value of the putative miR-21-5p target genes. Results: MiR-21-5p was significantly overexpressed in HNSCC compared to healthy tissues ( P

Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in the United States, and its incidence is increasing. Ultraviolet radiation is the main environmental risk factor for cSCCs; thus, they tend to arise on sun-exposed skin. Most publications cite the head and neck as the predominant location for cSCCs, but these papers do not account for the differential anatomic predication of cSCCs by sex. No prior studies have examined the differential distribution of cSCCs by sex, particularly invasive cSCCs that have the potential for recurrence and metastasis. Objective: We examined the association between cSCC tumor features, including anatomic site and invasiveness, by key patient features, including age and sex. Methods: Using an institutional cSCC registry, we identified 618 non-Hispanic white patients diagnosed with 2,111 histologically-confirmed cSCCs between 2000–2016. Results: We found differential anatomic distributions of cSCC by patient sex. Men were more likely to have cSCCs arise on the head and neck (51.7%), whereas women were more likely to have cSCCs develop on the lower extremity (41.2%). Stratification by dichotomized age (younger [

In order to overcome the shortage of the current costly DVT diagnosis and reduce the waste of valuable healthcare resources, we proposed a new diagnostic approach based on machine learning pre-test prediction models using EHRs. We examined the sociodemographic and clinical factors in the prediction of DVT with 518 NICU admitted patients, including 189 patients who eventually developed DVT. We used cross-validation on the training data to determine the optimal parameters, and finally, the applied ROC analysis is adopted to evaluate the predictive strength of each model. Two models (GLM and SVM) with the strongest ROC were selected for DVT prediction, based on which, we optimized the current intervention and diagnostic process of DVT and examined the performance of the proposed approach through simulations. The use of machine learning based pre-test prediction models can simplify and improve the intervention and diagnostic process of patients in NICU with suspected DVT, and reduce the valuable healthcare resource occupation/usage and medical costs.

Many long noncoding RNAs reportedly have tumor suppressive roles or are oncogenic in esophageal cancer. We have previously performed a chip-based expression analysis of primary esophageal cancer tissues and found that the expression of LINC00634 in these tissues was higher than that in nontumor tissues. Quantitative real-time–polymerase chain reaction, cell counting kit-8, flow cytometry, caspase3/7 assay, dual-luciferase reporter assay, and restore assay were used to detect the proliferative and apoptotic effects of LINC00634 in esophageal cancer cells. The results showed that the expression of LINC00634 in these tissues was higher than that in nontumor tissues and associated with tumor–node–metastasis (TNM) stage of patients. Knockdown of LINC00634 decreased cell viability and increased cell apoptosis levels in EC9706 and EC1 cells. LINC00634 could target Bcl2L1 through miR-342-3p. In this study, we show that LINC00634 is upregulated in esophageal cancer. We also show that the knockdown of LINC00634 decreased cell viability and increased cell apoptosis levels in EC9706 and EC1 cells through the miR-342-3p/Bcl2L1 axis.

MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs that regulate gene expression, and consequently several important functions including early embryo development, cell cycle, programmed cell death, cell differentiation, and metabolism. While there are no effective treatments available against hepatocellular carcinoma (HCC), some Chinese herbal medicines have been shown to regulate growth, differentiation, invasion, and metastasis of HCC. Many studies have shown that Chinese herbal medicines regulate the expression of miRNAs and this may be associated with their ability to control the development of HCC. In this article, the effects of Chinese herbal medicines on the expression of miRNAs and their functions in the regulation of HCC have been reviewed and discussed. miRNAs such as miRNA-221 and miRNA-222 mediated by Chinese herbal medicines may be good biomarkers and therapeutic targets for HCC.