Case report of a novel mutation in the TNC gene in Chinese patients with nonsyndromic hearing loss.

RATIONALE: Hereditary hearing loss is known to exhibit a significant degree of genetic heterogeneity. Herein, we present a case report of a novel mutation in the tenascin-C (TNC) gene in Chinese patients with nonsyndromic hearing loss (NSHL). PATIENT CONCERNS: This includes a young deaf couple and their 2-year-old baby. DIAGNOSES: Based on the clinical information, hearing test, metagenomic next-generation sequencing (mNGS), Sanger sequencing, protein function and structure analysis, and model prediction, in our case, the study results revealed 2 heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) and the TBC1 domain family member 24 (TBC1D24) gene (c.1570C>T, p.Arg524Trp). These mutations may be responsible for the hearing loss observed in this family. Notably, the heterozygous mutations in the TNC gene (c.2852C>T, p.Thr951Ile) have not been previously reported in the literature. INTERVENTIONS: Avoid taking drugs that can cause deafness, wearing hearing AIDS, and cochlear implants. OUTCOMES: Regular follow-up of family members is ongoing. LESSONS: The genetic diagnosis of NSHL holds significant importance as it helps in making informed treatment decisions, providing prognostic information, and offering genetic counseling for the patient's family.

Ensure the accuracy and consistency of biochemical analyzer test results: Chemometrics for instrument and inter-instrument item comparison in Chinese hospital laboratory.

Biochemical analyzers are vital instruments that utilize the principle of photoelectric colorimetry to quantify a specific chemical composition in body fluids. This analysis provides critical data for the diagnosis, treatment, prognosis, and overall health status of various diseases in clinical practice. However, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Therefore, it is imperative to regularly assess the performance of the analyzer to ensure consistent results for longitudinal studies and to maintain day-to-day data consistency. Additionally, when multiple analyzers are utilized, it is necessary to evaluate the performance of each instrument to ensure accurate results across multiple platforms. In this study, we developed and verified an experimental evaluation scheme for the analytical performance of the instrument, chemometrics for biochemical analyzers, utilizing national reference materials and patient sera as the experimental subjects. We evaluated the performance of the optical system, temperature control system, sample-adding system, and detection system to confirm the feasibility of this scheme. We also compared the analytical performance of different brands of biochemical analyzers for routine biochemical tests, such as liver function, kidney function, ion, blood lipids, blood glucose, and myocardial enzyme spectrum. Using the AU 5400 as a control and the ADVIA 2400 as the comparison system, the relative variation in inter-instrument comparison data was found to be acceptable at the clinical medicine decision level. In conclusion, the performance of a biochemical analyzer can vary significantly between different brands or over time within the same brand. Regular evaluations are necessary to ensure accurate and consistent results across different analyzers. This study provides a feasible scheme for evaluating the analytical performance of biochemical analyzers that can be used to ensure the accuracy and consistency of the results of different brands of automatic chemical analyzers in the laboratory.

MicroRNA­143­3p levels are reduced in the peripheral blood of patients with gestational diabetes mellitus and influences pancreatic ß­cell function and viability.

Pancreatic ß-cell dysfunction has been demonstrated to mediate key roles in the pathogenesis of gestational diabetes mellitus (GDM). Accumulating evidence has supported the functional involvement of microRNAs (miRNAs) in various types of diabetes, including GDM. However, the detailed biological effect of miRNAs in pancreatic ß-cell dysfunction remains poorly understood. In the present study, microarray data of miRNAs in the blood plasma of patients with GDM were retrieved from the Gene Expression Omnibus dataset under the accession number GSE98043. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure the expression levels of miR-143-3p in the blood plasma isolated from 30 female patients with GDM women and 30 healthy female individuals. Subsequently, murine pancreatic ß-cell line, MIN6 cells were treated with high glucose (HG) to construct in vitro cell models of GDM. miR-143-3p in HG-treated MIN6 cells was overexpressed or knocked down using miR-143-3p mimics and miR-143-3p inhibitor. Cell viability, insulin secretion and proinflammatory cytokine production were examined using CCK-8 and ELISA, respectively Cell apoptosis was measured by flow cytometry assay. The protein expression levels of proteins involved in the TAK1/NF-κB pathway were also assessed using western blot. The levels of miR-143-3p were found to be markedly lower in samples from patients with GDM, which were in turn negatively correlated with blood glucose levels. Overexpression of miR-143-3p in MIN6 cells significantly reversed HG-induced cell apoptosis and impairments in cell viability and insulin secretion. In addition, miR-143-3p overexpression attenuated HG-induced proinflammatory cytokine production by MIN6 cells. Subsequently, TGFß-activated kinase 1 (TAK1), an upstream regulator of the NF-κB pathway, was found to be a direct target of miR-143-3p in pancreatic ß cells through luciferase assays and western blot. Overexpression of TAK1 was revealed to abolish the curative effects of miR-143-3p on insulin secretion, cell viability and inflammatory response in HG-treated MIN6 cells. In addition, miR-143-3p could inactivate the NF-κB pathway by inhibiting TAK1 expression. Collectively, these results suggest that miR-143-3p levels are downregulated in the peripheral blood of patients with GDM. Therefore, miR-143-3p overexpression may serve as a method for preventing pancreatic ß cell dysfunction by inhibiting the TAK1/NF-κB pathway.

Investigation of health literacy status and related influencing factors in military health providers of Chinese People's liberation Army, a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate health literacy and analyze its influencing factors in military health providers of the Chinese People's Liberation Army (PLA Army). METHODS: From November to December 2018, cluster sampling was used to select 1512 military health providers from the Army Medical University. Health literacy was measured by using the Chinese Citizen Health Literacy Questionnaire (HLQ) (2015 edition). Influencing factors that may affect health literacy were assessed using the chi-square test and multivariate logistic regression models. RESULTS: The knowledge rate of health literacy was relatively low (21.6%). The knowledge rate of health-related skills (HRS, 18.7%) was the lowest of the three aspects of health literacy, and the knowledge rate of chronic diseases (CD, 19.6%) was the lowest of the six dimensions of health literacy. Participants who were older, were female, were of Han ethnicity, were the only child in their families, came from urban areas, never used tobacco, and had higher household income were likely to have higher health literacy. CONCLUSION: The health literacy levels of military health providers of the PLA Army are relatively low. Further research and health education are necessary to improve health literacy.

Synergistic effects of thalidomide and cisplatin are mediated via the PI3K/AKT and JAK1/STAT3 signaling pathways in cervical cancer.

Thalidomide (THD) has been found to synergize with cisplatin (DDP) in certain types of cancers; however, their combined use in the treatment of cervical cancer has not been reported to date, at least to the best of our knowledge. Thus, the present study aimed to explore the synergistic effects of THD and DDP and determine their regulatory effects on the phosphoinositide 3­kinase (PI3K)/protein kinase B (AKT) and Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) pathways in cervical cancer. For this purpose, 0­160 µM THD and 0­64 µM DDP monotherapy or in combination were used to treat the HeLa and SiHa cervical cancer cell lines. This was followed by the calculation of the combination index (CI) and 160 µM THD and 16 µM DDP were then used to treat the cells. Relative cell viability and apoptosis, as well as the mRNA and protein levels of PI3K, AKT, JAK1 and STAT3 were evaluated. The results revealed that THD and DDP monotherapy suppressed the viability of the HeLa and SiHa cells in a concentration­dependent manner. Moreover, THD and DDP treatment exerted a more prominent suppressive effect on the relative viability of HeLa and SiHa cells compared with DDP monotherapy at several concentration settings; further CI calculation revealed that the optimal synergistic concentrations were 160 µM for THD and 16 µM for DDP. Subsequently, combined treatment with THD and DDP suppressed relative cell viability, whereas it promoted cell apoptosis compared with THD or DPP monotherapy; it also inhibited the PI3K/AKT and JAK1/STAT3 signaling pathways compared with DPP or THD monotherapy in both HeLa and SiHa cells. On the whole, the present study demonstrated that THD synergizes with DDP to exert suppressive effects on cervical cancer cell lines. This synergistic action also inactivated the PI3K/AKT and JAK1/STAT3 pathways. Thus, these findings suggest that the combined use of THD and DPP may have potential for use in the treatment of cervical cancer.

Construction and validation of a prognostic model based on 11 lymph node metastasis-related genes for overall survival in endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the most common malignant tumors in female reproductive system. The incidence of lymph node metastasis (LNM) is only about 10% in clinically suspected early-stage EC patients. Discovering prognostic models and effective biomarkers for early diagnosis is important to reduce the mortality rate. METHODS: A least absolute shrinkage and selection operator (LASSO) regression was conducted to identify the characteristic dimension decrease and distinguish porgnostic LNM related genes signature. Subsequently, a novel prognosis-related nomogram was constructed to predict overall survival (OS). Survival analysis was carried out to explore the individual prognostic significance of the risk model and key gene was validated in vitro. RESULTS: In total, 89 lymph node related genes (LRGs) were identified. Based on the LASSO Cox regression, 11 genes were selected for the development of a risk evaluation model. The Kaplan-Meier curve indicated that patients in the low-risk group had considerably better OS (p = 3.583e-08). The area under the ROC curve (AUC) of this model was 0.718 at 5 years of OS. Then, we developed an OS-associated nomogram that included the risk score and clinicopathological features. The concordance index of the nomogram was 0.769. The survival verification performed in three subgroups from the nomogram demonstrated the validity of the model. The AUC of the nomogram was 0.787 at 5 years OS. Proliferation and metastasis of HMGB3 were explored in EC cell line. External validation with 30 patients in our hospital showed that patients with low-risk scores had a longer OS (p-value = 0.03). Finally, we revealed that the most frequently mutated genes in the low-risk and high-risk groups are PTEN and TP53, respectively. CONCLUSIONS: Our results suggest that LNM plays an important role in the prognosis, and HMGB3 was potential as a biomarker for EC patients.

SIRT2 expression exhibits potential to serve as a biomarker for disease surveillance and prognosis in the management of cervical cancer patients.

This study aimed to compare the sirtuin 2 (SIRT2) expression between tumor tissue and adjacent tissue, and to investigate the association of tumor SIRT2 expression with clinical characteristics and survival profiles in cervical cancer patients.One hundred ninety-one cervical cancer patients were reviewed in this retrospective study. All patients underwent surgical resection and had well-preserved tumor tissue and adjacent tissue, which were obtained for SIRT2 expression detection by immunohistochemistry (IHC). Clinical parameters were obtained. Disease free survival (DFS) and overall survival (OS) were calculated.Both SIRT2 expression by IHC score (P < .001) and the percentage of SIRT2 high expression (defined as IHC score >3) (P < .001) were declined in tumor tissue compared with paired adjacent tissue. In addition, SIRT2 expression in tumor tissue was negatively correlated with tumor size (P = .047), lymph node metastasis (P = .009) and FIGO stage (P = .001). And the DFS (P = .007) as well as OS (P = .008) were better in patients with SIRT2 high expression compared with patents with SIRT2 low expression. Univariate Cox's proportional hazards regression model analyses revealed that high SIRT2 expression in tumor tissue was a predictive factor for more prolonged DFS (P = .009) and OS (P = .011), while multivariate Cox's proportional hazards regression model analysis disclosed that it lacks independent predictive value for DFS (P = .084) or OS (P = .132).SIRT2 expression exhibits potential to serve as a biomarker for disease surveillance and prognosis in the management of cervical cancer patients.

Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-α in Patients with Intrahepatic Cholestasis of Pregnancy.

BACKGROUND/AIMS: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is poorly understood. OBJECTIVE: This study aimed to explore the possible effect of HDAC3 (histone deacetylase) on cytokines IL-18, IL-12 and TNF-α in ICP. METHODS: Serum levels of cytokines IL-18, IL-12 and TNF-α, bile acids and hepatic function parameters were measured. The expression of HDAC3 in the placenta was determined by immunohistochemistry (IHC), western blotting and RT-PCR. RESULTS: IL-18, IL-12 and TNF-α serum levels were significantly higher in the severe ICP group than in the mild ICP group and the control group, and the difference between the mild ICP group and control group was not significant. HDAC3 protein expression was identified in the nucleus of the placental trophoblast by IHC. HDAC3 mRNA and protein expression were significantly lower in the ICP groups (mild ICP and severe ICP groups) than in the control groups, and no significant difference was found between the mild ICP and severe ICP groups. CONCLUSIONS: The low expression of HDAC3 and overexpession of inflammatory cytokines (IL-18, IL-12 and TNF-α) in ICP may be involved in liver cell apoptosis. We suspect that HDAC3 may play an important role in the pathophysiology of ICP.