Incidence and associated risk factors of congenital hypothyroidism among newborns in Hainan, China: a retrospective study.

OBJECTIVES: This study aims to investigate the incidence and risk factors of congenital hypothyroidism (CH) in newborns in Hainan Province, China, to provide a reference for early and effective prevention strategies. METHODS: Newborns born in Hainan Province from 2017 to 2021 were the subjects of this study. Time-resolved immunofluorescence was used for initial screening and chemiluminescence for confirmatory diagnosis. Based on the diagnosis, newborns were classified into CH and non-CH groups. Statistical analysis was conducted on the initial screening and confirmed CH cases in newborns in Hainan Province, and potential risk factors for CH were explored. RESULTS: From 2017 to 2021, a total of 585,886 newborns were screened, revealing 6,856 initial positive results, 614 positive rescreens, and 420 confirmed CH cases, yielding an incidence rate of 1/1,395 (420/585,886). The annual initial positive screening rate of newborns in Hainan Province showed a rising trend from 2017 to 2021 (p=0.000). No significant differences were found regarding gender (p=0.400) and ethnicity (p=0.836). Multivariate logistic regression analysis indicated that residing in coastal areas, especially those with salt fields (OR=2.151, 95 % CI: 1.364-3.390), was risk factors for the development of CH in newborns. CONCLUSIONS: The incidence of CH in newborns showed a year-on-year increase in Hainan Province from 2017 to 2021. Residing in coastal areas, particularly those with salt fields, was identified as a risk factor for the development of CH.

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

AIMS: Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. METHODS AND RESULTS: We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). CONCLUSION: Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.

Anlotinib combined with pembrolizumab as first-line treatment for advanced pulmonary sarcomatoid carcinoma: a case report and literature review.

Pulmonary sarcomatoid carcinoma (PSC) is an uncommon variant of non-small cell lung cancer (NSCLC), known for its unfavorable prognosis. Previous studies have elucidated that PSC generally exhibits a significant expression of programmed death-ligand 1 (PD-L1), an elevated tumor mutation burden, and marked vascular invasion. These factors imply the possible effectiveness of treatments like immunotherapy and anti-angiogenic therapy. The subject of this case was a 65-year-old male diagnosed with advanced PSC, characterized by high PD-L1 expression and devoid of known driver gene mutations. Owing to the restrictions imposed by the COVID-19 pandemic, the patient initially underwent home-based treatment with anlotinib, which led to symptomatic improvement after a single treatment cycle. Subsequent hospitalization allowed for the administration of anlotinib plus Pembrolizumab, resulting in a partial response. Radiotherapy was necessitated due to local disease progression. But after 15 cycles of treatment with Pembrolizumab, hyperprogression was observed. The patient's overall survival spanned 14 months, with no evident adverse reactions to the medications. Genomic analysis revealed potential associations between treatment efficacy and mutations in the TP53, NF1, and MET genes. This case underscores the effectiveness and safety of a first-line treatment regimen combining pan-target anti-angiogenic therapy (anlotinib) with anti-tumor immunotherapy.

AHSA1 Regulates Hepatocellular Carcinoma Progression via the TGF-ß/Akt-Cyclin D1/CDK6 Pathway.

Background: Activator of heat shock protein 90 (HSP90) ATPase Activity 1 (AHSA1) regulates proliferation, apoptosis, migration, and invasion of osteosarcoma and hepatocellular carcinoma (HCC). However, the novel mechanism of AHSA1 in the tumor biology of hepatocellular carcinoma (HCC) remains unclear. Methods: We analyzed AHSA1 expression in 85 pairs of clinical samples of HCC and the Cancer Genome Atlas database. The role of AHSA1 in HCC was proved by cell proliferation, colony formation, migration, cell cycle analysis in vitro, xenograft models and tumor metastasis assay in vivo, and bioinformatics. Results: High AHSA1 expression was demonstrated in HCC and associated with invasive depth, clinical stage, and poor overall survival of patients. Univariate Cox analysis confirmed that AHSA1 was an independent prognostic factor for patients with HCC. Meanwhile, AHSA1 upregulation promoted cell proliferation, colony formation, and cell migration in vitro and tumor cell proliferation and metastasis of HCC cells in vivo. AHSA1 upregulation increased the cell cycle transition from G1 to S phase by increasing the expression of cyclinD1, cyclinD3, and cyclin-dependent kinase 6(CD). Transforming growth factor beta 1 (TGF-ß1)-induced protein kinase B (Akt) signaling regulated the expression of downstream targets, including cyclinD1. AHSA1 expression was closely correlated with the expression of TGF-ß, Akt, cyclinD1, cyclinD3, and CDK6 using the Gene Expression Profiling Interactive Analysis database. AHSA1 upregulation participated in HCC progression by regulating TGF-ß/Akt-cyclinD1/CDK6 signaling. Conclusion: AHSA1 might serve as a biomarker for predicting the clinical outcome of patients with HCC. It is vital in tumor metastasis and disease progression of HCC and may facilitate the development of clinical intervention strategies against HCC.

EMSY promoted the growth and migration of ovarian cancer cells.

Epithelial ovarian cancer is one of the most common and aggressive diseases among the female reproductive organ malignancies, and the molecular mechanism underlying this disease remains largely unknown. EMSY, a binding partner of BRCA2, has been reported to be amplified in ovarian cancer. However, the expression pattern and biological functions of EMSY in the progression of ovarian cancer are not fully understood. In this study, it was found that the expression of EMSY was significantly elevated in ovarian cancer samples compared to their adjacent normal tissues. Moreover, overexpression of EMSY promoted the growth and migration of ovarian cancer cells, while knocking down the expression of EMSY inhibited the growth, migration, and tumorigenesis of ovarian cancer cells in vitro and in vivo. Mechanistically, EMSY was found to interact with beta-catenin and activate beta-catenin/TCF signaling. Our study demonstrated that EMSY played an oncogenic role in the progression of ovarian cancer cells and EMSY might be a promising target for the treatment.

Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer.

MicroRNA-203 (miR-203), possessing tumor suppressive or promotive activities, has been found to be downregulated or upregulated in different cancer types. The purpose of this study was to investigate whether the increased expression of miR-203 can be used as a noninvasive diagnostic and prognostic biomarker in epithelial ovarian cancer (EOC). Real-time quantitative PCR was performed to detect the expression levels of miR-203 in EOC tissues. The expression levels of miR-203 were significantly higher in EOC tissues compared to adjacent non-cancerous tissues (p < 0.001). High expression of miR-203 was observed in 65.38 % (102/156) of EOC. In addition, high miR-203 expression was found to be closely correlated with advanced FIGO stage (p < 0.001), higher histological grade (p = 0.02), lymph node involvement (p < 0.001), and positive recurrence (p < 0.001). Moreover, high miR-203 expression was correlated with shorter overall survival (p < 0.001) and shorter progression-free survival (p < 0.001) of EOC patients. Furthermore, multivariate analysis showed that the status of miR-203 expression was an independent predictor for both overall survival and progression-free survival in EOC. These findings provide the convincing evidence for the first time that the upregulation of miR-203 may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of EOC patients.