Changes in thyroid function levels in female patients with first-episode bipolar disorder.

Objectives: The identification of molecular biomarkers for bipolar disorder is anticipated to greatly improve the diagnosis and treatment of this disease. The objective of this case-control study is to determine whether the blood thyroid hormone levels in bipolar disorder patients are associated with different types of first onset. Methods: From August 1, 2020 to July 31, 2021 a total of 120 female patients diagnosed with bipolar disorder and hospitalized at Qingdao Mental Health Center were recruited as the case group, including 60 patients with depression as their first onset (depression first-episode group, DF) and 60 with mania/hypomania as their first onset (mania/hypomania first-episode group, M/HF). A group of 60 healthy adult females matching general demographic data, such as race and age, were selected as the control group. Blood samples were taken from both groups to measure serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) concentrations. Results: The duration of current onset in the M/HF group was significantly less than that in the DF group (23.1 ± 20.2 vs. 125.2 ± 41.0 days). About 27% of patients in the M/HF group had thyroid abnormalities, in contrast to 60% in the DF group. The blood T3 and T4 levels in both the M/HF group and the DF group, as well as the TF3 levels in the DF group, were significantly lower as compared to control. The M/HF group had significantly higher T3 and FT3 levels than the DF group. The blood T3 levels were inversely correlated with the Young's Mania Scale score and the Hamilton Depression Scale score in both the M/HF and DF groups. Conclusion: Thyroid dysfunction resulting in reduced levels of blood thyroid levels may be involved in the disease progression of bipolar disorder, and correlated with the clinical symptoms in patients with depression or mania as the first episode.

A study on factors influencing Chinese undergraduate EFL learners' self-directed use of mobile English learning resources.

This study aimed to examine the factors that potentially impact the self-directed use of mobile English learning resources (MELR). The participants were 206 Chinese undergraduate EFL learners at Yangzhou University in Mainland China. Applying and modifying the Unified Theory of Acceptance and Use of Technology (UTAUT), this study involved six constructs, including students' performance expectancy, effort expectancy, social influence, facilitating conditions, perceived playfulness, and behavioral intention to use MELR. The structural equation modeling (SEM) technique was adopted to analyze the data collected from the questionnaire. The findings showed that facilitating conditions acted as the most significant predictor of behavioral intention to adopt MELR, followed by effort expectancy, perceived playfulness, and performance expectancy. However, social influence did not have significant effects on students' use of MELR. Pedagogical implications for teachers and students were also presented in the end.

Teaching Platform for Physical Training of Track and Field Events in Colleges and Universities Based on Data Mining Technology.

To a large extent, track and field sports require strong physical fitness of athletes, and athletes' physical fitness determines their competition results. With the improvement of people's living standards, athletes can get better nutritional supplements, but competition in track events has gradually become fierce, and physical fitness is extremely important for athletes. Physical training can improve athletes' endurance, sports coordination, and sensitivity, but coaches should arrange the training intensity reasonably, not exceeding the athlete's tolerance, to avoid problems such as overloading training causing athletes to be injured and sports age shortened. Traditional track and field training methods are no longer suitable for the physical development of modern athletes. This paper mainly studies the college track and field sports training teaching platform based on data mining technology. By using data mining technology, this paper constructs a track and field training platform in colleges and universities. Therefore, this paper designs a teaching platform for physical training in track and field events and puts the teaching platform into training teaching. It uses data mining technology to collect athletes' sports characteristics and analyze athletes. The physical parameters and movement norms of the people develop a personalized training program for them.

Autophagy inhibition induces the repolarisation of tumour-associated macrophages and enhances chemosensitivity of laryngeal cancer cells to cisplatin in mice.

Tumour-associated macrophages (TAMs) are the key components in the tumour microenvironment. TAMs have two major subtypes, M1 and M2. M1 macrophages are tumour inhibitory, while M2 macrophages are tumour promotive. Repolarising TAMs from M2 to M1 is a promising strategy in cancer treatment. M1 and M2 macrophages were generated from murine bone marrow-derived macrophages (BMDMs). We found that chloroquine (CQ), an autophagy inhibitor, was able to repolarise M2 macrophages to the anti-tumour M1 phenotype. The repolarised macrophages demonstrated higher phagocytotic activity towards Hep-2 laryngeal tumour cells and re-sensitised Hep-2 cells to cisplatin (CDDP) treatment in vitro. While CQ did not demonstrate cytotoxicity to Hep-2 cells in vitro, CQ treatment reduced Hep-2 laryngeal tumour growth in vivo and improved CDDP treatment outcomes. It seems that CQ-induced M2-to-M1 macrophage repolarisation played an important role in tumour growth inhibition, and the CQ/CDDP combined therapy might have clinical potential in laryngeal cancer treatment.

Exploratory analysis of introducing next-generation sequencing-based method to treatment-naive lung cancer patients.

BACKGROUND: The utilization of cancer-linked genetic alterations for categorizing patients against optimal treatment is becoming increasingly popular, especially in non-small cell lung cancer (NSCLC). However, disadvantages of the conventional techniques, such as the low throughput and limited detectable alteration types, lead to the demand of large-scale parallel sequencing for different forms of genetic variants. METHODS: We evaluated the potential of performing next-generation sequencing (NGS)-based methods in a cohort of 61 treatment-naive NSCLC patients to profile their driver mutations, using a panel consisting of 8 well-established driver genes of lung cancer. RESULTS: Our data revealed that 80% of patients harbored driver mutations. Moreover, our data revealed a few rare mutations, such as BRAF K601E and EGFR exon 20 insertion, which cannot be detected using commercially available single gene testing kits of conventional methods. We detected one patient with dual driver mutations. Next, correlations between driver mutations and clinical characteristics were interrogated in this cohort. Our results revealed that EGFR alterations were positively correlated with early stage, adenocarcinoma, alveolar and papillary component, TTF1 expression, and negatively correlated with P40 and Ki67 expression. ERBB2 alterations were associated with younger age and micro-invasive feature of tumor. Rearrangements of ALK indicated tumor relapse. CONCLUSIONS: Our study highlights the potential of NGS-based methods in treatment-naive patients, thus paving its way for routine clinical use. Investigation of clinical correlation of driver mutations might be helpful for clinicians in cancer diagnosis and has implications for seeking patients with specific gene alteration in clinical studies.

The microbiota in the intestinal and respiratory tracts of naked mole-rats revealed by high-throughput sequencing.

BACKGROUND: The naked mole-rat (NMR, Heterocephalus glaber) is being bred as a novel laboratory animal due to its unique biological characteristics, including longevity, cancer resistance, hypoxia tolerance, and pain insensitivity. It is expected that differences exist between the microbiota of wild NMRs and that of NMRs in an artificial environment. Overall, the effect of environment on changes in the NMR microbiota remains unknown. In an attempt to understand the microbiota composition of NMRs in captivity, variability in the microbiota of the intestinal and respiratory tracts of two groups of NMRs was assessed under two conditions. RESULTS: The results obtained by high-throughput sequencing revealed significant differences at the phylum, class, order, family and genus levels in the microbiota between the two groups of NMRs examined (first group in conventional environment, second group in barrier environment). For the trachea, 24 phyla and 533 genera and 26 phyla and 733 genera were identified for the first and second groups of animals. Regarding the cecum, 23 phyla and 385 genera and 25 phyla and 110 genera were identified in the microbiota of first and second groups of animals. There were no obvious differences between females and males or young and adult animals. CONCLUSIONS: Our results suggest that the intestinal and respiratory tract NMR microbiota changed during captivity, which may be related to the transition to the breeding environment. Such changes in the microbiota of NMRs may have an effect on the original characteristics, which may be the direction of further research studies.

Role of flexible fiberoptic laryngoscopy in predicting difficult intubation.

BACKGROUND: The ability to precisely predict which intubations will be difficult during administration of anesthesia is an important part of preoperative preparation. This study's goal is to accurately identify patients who will be difficult to intubate using the number of tracheal rings observed preoperatively by fiberoptic laryngoscopy. METHODS: We enrolled 994 adult patients in our study who required general anesthesia and orotracheal intubation for their elective surgeries. All patients received a Mallampati Test, a Wilson Risk-Sum Score, and fiberoptic laryngoscopy before operation. Each patient's age, Body Mass Index (BMI), and neck circumference was recorded preoperatively. Logistic regression analysis was applied to evaluate the association between the recorded risk factors and a potentially difficult intubation. The three preoperative assessments were compared using three parameters: positive predictive value, sensitivity, and specificity. RESULTS: The risk factors which were determined to be predictive for difficult intubation were: BMI, neck circumference, Mallampati Test, Wilson Risk-Sum Score, and fiberoptic laryngoscopy (P<0.05). Fiberoptic laryngoscopy as a predictive factor in the preoperative setting had a higher sensitivity, specificity, and positive predictive value than did the Mallampati Test or the Wilson Risk-Sum Score (P<0.05). CONCLUSIONS: Fiberoptic laryngoscopy is a more accurate and convenient preoperative method to predict difficult intubation.

Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia.

BACKGROUND: Obesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear. METHOD: Two hundred and fifty drug naïve, Chinese Han patients with first-episode schizophrenia were enrolled in the study, and genotyped for four single nucleotide polymorphisms (SNPs rs9939609, rs8050136, rs1421085 and rs9930506) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Body weight and body mass index (BMI) were measured at baseline and six months after risperidone treatment. RESULTS: At baseline, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609; body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p's < 0.05). After 6 months of risperidone treatment, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609 (p's <0.01); body weight and BMI of CC homozygotes were lower than those of A allele carriers in rs8050136 (p's < 0.05); body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p's < 0.05). After controlling for age, gender, age of illness onset, disease duration, weight at baseline and education, weight gain of TT homozygotes at 6 months remained to be lower than those of A allele carriers in rs9939609 (p < 0.01); weight gain of CC homozygotes at 6 months was lower than those of A allele carriers in rs8050136 (p = 0.01). Stepwise multiple regression analysis suggested that, among 4 SNPs, rs9939609 was the strongest predictor of weight gain after 6 months of risperidone treatment (p = 0.001). CONCLUSIONS: The FTO gene polymorphisms, especially rs9939609, seem to be related to weight gain after risperidone treatment in Chinese Han patients with first episode schizophrenia.

SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer.

Lung cancer is one of the leading causes of cancer-related death in developed countries. Despite decades of intensive efforts to comate this malignant disease, the prognosis of lung cancer remains unfavorable and is especially poor in advanced non-small cell lung cancer (NSCLC). Accumulating evidence indicate that one of the main causes of the poor outcome in NSCLC treatment is the innate resistance of NSCLC patients to anticancer drugs. However, the mechanism underling NSCLC development and drug resistance is not fully understood. Here we show that the mitochondrial class III NAD(+)-dependent deacetylase SIRT5 is overexpressed in human NSCLC and high expression of SIRT5 predicts poor survival. SIRT5 knockdown represses lung cancer cell growth and transformation in vitro and in vivo. Furthermore, we find that SIRT5 knockdown makes lung cancer cells more sensitive to drug (cis-diamminedichloroplatinum [CDDP], 5-fluorouracil [5-FU] or bleomycin) treatment in vitro and in vivo. Mechanically, we identify Nrf2, which is a core transcription factor for lung cancer growth and drug resistance, as a target of SIRT5. SIRT5 mRNA level is positively correlated with the expression of Nrf2 in lung cancer tissues and SIRT5 knockdown reduces the expression of Nrf2 and its downstream drug-resistance genes. Taken together, our findings implicate that SIRT5 as a protein responsible for growth and drug resistance in human NSCLC, and SIRT5 may serve as a potential prognostic factor and drug target for intervention.

Altered expression of PTCH and HHIP in gastric cancer through their gene promoter methylation: novel targets for gastric cancer.

Human hedgehog-interacting protein (HHIP) and protein patched homolog (PTCH) are two negative regulators of the hedgehog signal, however, the mechanism of action in gastric cancer is unknown. Methylation of TSG promoters has been considered as a causative mechanism of tumorigenesis. In the present study, we first determined the expression of PTCH and HHIP mRNA and protein in gastric cancer tissues and adjacent normal tissues, and then detected methylation of the two genes to associate their expression and gene promoter methylation in gastric cancer. Expression in gastric cancer tissues and the cancer cells (AGS) were evaluated by reverse transcription-PCR (RT-PCR), qRT-PCR and IHC, while the methylation expression was valued by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). Cell viability and apoptosis were analyzed by MTT assay and flow cytometry following treatment with 5-aza-dc. Results showed that PTCH and HHIP expression was reduced in gastric cancer tissues that were not associated with clinical features. Moreover, methylation of the promoters was reversely correlated with the expression. Following treatment with 5-aza-dc, AGS reduced cell viability and induced apoptosis, which is associated with upregulation of HHIP expression. The data demonstrated that loss of expression of HHIP and PTCH is associated with the methylation of gene promoters. In addition, 5-aza-dc-induced apoptosis correlated with the upregulation of HHIP expression in AGS. The findings demonstrated that the PTCH and HHIP genes may be novel targets for the control of gastric cancer.

[Changes of protein kinase A expressions in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats].

OBJECTIVE: To explore neurobiological mechanisms of the withdrawal-induced aversion. The changes of protein kinase A were measured in central amygdaloid nucleic (CeA) of conditioned place aversion (CPA) model rats. METHODS: (1) All 72 male SD rats were divided into three groups, model group (MN group), and control group (MS group and SN group). MN group was injected with morphine,6.5 days, 10 mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion training, to develop the CPA model. The MS group was administrated equivalent volume of morphine and saline. Also the SN group was injected with equivalent volume of saline and naloxone. (2) During the process of morphine-induced CPA, the expression of protein kinase A was assayed with immunohistochemistry in the CeA. RESULTS: In the MN group, protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA (P < 0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P < 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA expressions were not significantly different both in MS group (P > 0.05)and SN group (P > 0.05). CONCLUSION: (1) Protein kinase A expression, in turn regulating the aversion expression, in the CeA probably is a key pathway contributing to the development of CPA. (2) The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.