[A study of mismatched negative in normal hearing patients of different ages].

Objective:To study the characteristics of Mismatch negativity（MMN） in normal hearing patients of different ages, and to compare the MMN of normal hearing subjects at different ages to explore the differences in MMN between different ages. Methods:MMN test was performed on both ears using the classic Oddball mode. A frequency of 1 000 Hz（standard stimuli） and 2 000 Hz（deviant stimuli） was used to evoked the MMN. According to different age groups: the juvenile group（7-17 years old）, the youth group（18-44 years old）, the middle-aged group（45-59 years old）, and the elderly group（60-75 years old）, with 25 cases in each group. The MMN characteristics of normal hearing subjects in different age groups were analyzed statistically and the differences between groups were compared. All subjects underwent pure tone threshold test, tympanic reactance test and ABR test before MMN test. Results:MMN waveform could be elicited from both ears of 100 subjects. Among them, the average latency of the juvenile group was（159.70±20.34） ms while the average amplitude was（4.34±2.26） µV, For the youth group, the average latency was（166.01±28.67） ms and the average amplitude was（3.70±2.28） µV. Then in the middle-aged group, the average latency was（175.16±37.24） ms, meanwhile, the average amplitude was（2.69±0.84） µV. Finally, the elderly group has an average latency of（178.03±14.37） ms and an average amplitude of（2.11±0.70） µV. Therefore, there was no statistical difference in latency and amplitude between all groups（P>0.05）, and there was no statistical difference in latency and amplitude between left and right ears among all subjects as a whole（P>0.05）. However, when the left and right ears of all groups were compared, it was found that the latency between the left and right ears of the Juvenile group had statistical significance（P<0.05）, and the amplitude difference was not statistically significant（P>0.05）, while the latency and amplitude differences between the left and right ears of other groups had no statistical significance（P>0.05）. There were also no significant differences in latency and amplitude between men and women（P>0.05）. Conclusion:There was no statistically significant difference in the latency and amplitude of mismatched negative among normal hearing subjects of different ages, and no statistically significant difference in the MMN latency and amplitude between the left and right ears of subjects and between men and women. Therefore, the study inferred that the auditory cerebral cortex of subjects aged 7-75 years old maintained a stable state for a long time after maturity, and the latency and amplitude of mismatched negative waves were relatively stable. It is not affected by age, gender and ear side, and can stably reflect the auditory cortex function of the subjects. It has broad application prospects in clinical practice, and provides a reliable detection means for future research on the changes of the auditory cerebral cortex of patients, which is worthy of our further research and clinical promotion.

Multi-Biomarkers Panel in Identifying Benign and Malignant Lung Diseases and Pathological Types of Lung Cancer.

With the discovery of many tumor markers, there are new strategies for the early diagnosis and treatment of lung cancer and the prediction of prognosis. We examined the multi-protein markers panel (4MP, consisting of Pro-SFTPB, CA125, Cyfra21-1, and CEA) diagnosis performance in differentiating benign and malignant lung diseases and identifying pathological types of lung cancer. Meantime, the complementary performance of three conventional tumor markers (NSE, SCC, and Pro-GRP) for 4MP was assessed. A total of 294 patients with lung cancer or benign lung disease are contained in this study. The AUCs of 4MP and 7MP (NSE, SCC, Pro-GRP, and 4MP) in distinguishing benign lung disease and lung cancer were 0.808 and 0.832, respectively. In distinguishing SQCLC and SCLC, the AUCs were 0.716 and 0.985, respectively. In distinguishing LADC and SCLC, the AUCs were 0.849 and 0.998, respectively. This study demonstrated that 4MP can distinguish lung cancer from benign disease. Traditional biomarkers NSE, SCC, and Pro-GRP can significantly improve the performance of 4MP in the differentiation of LADC, SQCLC, and SCLC, which is expected to contribute to the accurate diagnosis and personalized treatment of patients.

Hepatic arterial infusion chemotherapy and trastuzumab in gastric cancer with liver metastases: a case report.

Background: Gastric cancer is a common cancer worldwide and is responsible for over one million new cases in 2020 and an estimated 769,000 deaths, ranking fifth for incidence and fourth for mortality globally. Incidence rates are highest in Eastern Asia and Eastern Europe. Gastric cancer is highly heterogeneous and progresses rapidly. The prognosis of gastric cancer with liver metastases is poor, and clinical treatment remains challenging. Human epidermal growth factor receptor 2 (HER2) positivity is correlated to a bad prognosis for gastric cancer. Trastuzumab combined with systemic chemotherapy is the preferred treatment for HER2-positive advanced gastric cancer. However, intravenous chemotherapy has severe systemic toxicity, which reduces the local drug concentration and tumor uptake rate, and the effect is unsatisfactory. Case summary: We reported a 66-year-old patient with HER2-positive advanced gastric cancer with jaundice due to multiple liver metastases, after 6 cycles of trastuzumab combined with hepatic arterial infusion chemotherapy (HAIC), the tumor retracted significantly, the jaundice subsided, and the patient recovered well. The patient achieved disease control with an intensive regimen followed by less toxic maintenance therapy. Trastuzumab combined with capecitabine maintenance therapy followed up for more than 16 months. Conclusion: HAIC plus trastuzumab may be a tolerable treatment option for patients with severe liver metastases from HER2-positive gastric cancer to achieve local control and prolong survival.

Disruption of LTBP4 Induced Activated TGFß1, Immunosuppression Signal and Promoted Pulmonary Metastasis in Hepatocellular Carcinoma.

INTRODUCTION: The current prognosis of hepatocellular carcinoma (HCC) is unsatisfactory due to high rates of recurrence and metastasis, which has led to research focused on the discovery of metastasis genes. METHODS: In this study, we combined in silico analysis and in vitro transwell experiments to identify a metastasis gene. Then, we used an in vivo experiment to validate the metastasis. Furthermore, a series of experiments such as FACS, Western blot, and ELISA were applied to explore the function of the metastasis gene. RESULTS: LTBP4 (latent transforming growth factor beta binding protein 4) was confirmed as a metastasis gene, whose expression levels are correlated with the overall survival rate of HCC patients. We further showed that the knockout of LTBP4 in an HCC cell line increased cell proliferation, activated the cell cycle, and induced metastasis events. Moreover, we proved that LTBP4-KO could increase the percentage of active TGFß1 secreted by HCC cell lines, as well as the recruitment of MDSCs (myeloid-derived suppressor cells) by active TGFß1 (transforming growth factor beta 1), which further inhibited CD8+ T cell proliferation and activated the immune suppression signal. CONCLUSION: Our results demonstrate that the LTBP4-TGFß1-MDSCs axis is a critical pathway for the immune suppression signals of HCC primary tumors.

An immune-related gene pairs signature predicts overall survival in serous ovarian carcinoma.

BACKGROUND: Ovarian cancer has the highest death rate of all fatal gynecological cancers. Increasing evidence has depicted the correlation between serous ovarian carcinoma prognosis and immune signature. Therefore, the aim of this study is to develop a robust prognostic immune-related gene pairs (IRGPs) signature for estimating overall survival (OS) of HGSOC. METHODS: Gene expression profiling and clinical information of serous ovarian carcinoma patients were derived from three public data sets, divided into training and validation cohorts. Immune genes significantly associated with prognosis were selected. RESULTS: Among 1,534 immune genes, a 20 IRGPs signature was built which was significantly associated with OS in the training cohort (P=1.44×10-14; hazard ratio [HR] =3.05 [2.26, 4.10]). In the validation datasets, the IRGPs signature significantly divided patients into high- vs low- risk groups considering their prognosis (P=4.30×10-3; HR =1.48 [1.13, 1.95]) and was prognostic in multivariate analysis. Functional analysis showed that several biological processes, including EMT and TGF-ß related pathways, enriched in the high-risk group. Macrophages M2 was significantly higher in the high-risk group compared with the low-risk group. CONCLUSION: We successfully constructed a robust IRGPs signature with prognostic values for serous ovarian carcinoma, providing new insights into post-operational treatment strategies.

Evaluation of a semi-quantitative ELISA for IgA antibody against Epstein-Barr virus capsid antigen in the serological diagnosis of nasopharyngeal carcinoma.

OBJECTIVES: This study was designed to establish an ELISA method, as well as the cut-off value, for IgA against Epstein-Barr virus (EBV) viral capsid antigen (VCA), as a screening assay for nasopharyngeal carcinoma (NPC) in southern China. In addition, the correlation between relative optical density (rOD) values from ELISA and titers from the immunoenzymatic assay (IEA) was also evaluated. METHODS: Two hundred and fifty-eight NPC cases, 33 non-NPC head and neck cancer patients, and 1156 healthy controls were recruited for this study. VCA-IgA and early antigen (EA)-IgA were measured by ELISA kits and IEA in parallel. RESULTS: The total precision of the VCA-IgA ELISA achieved a level of <13.0% coefficient of variation. An rOD value of 1.60 for the VCA-IgA ELISA was determined as the cut-off point for southern China, and the sensitivity and specificity for NPC diagnosis when using this cut-off value were 93.0% and 92.4%, respectively. The area under the receiver operating characteristic curve (ROC-AUC) value was 0.969. The correlation coefficient between titers and rOD values was 0.957. rOD values were correlated with NPC overall stage and lymph node involvement. CONCLUSIONS: The cut-off level established in our study could be used to facilitate more accurate diagnosis of NPC in southern China. The rOD value might be an index for NPC prognosis, since it shows a good correlation with the titer from IEA.

A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23.

Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.