Comprehensive analysis of INTS family related to expression, prognosis, diagnosis and immune features in hepatocellular carcinoma.

Purpose: The integrator subunit (INTS) family, a group exclusive to metazoans, participates in various biologic processes. However, their roles in hepatocellular carcinoma (HCC) remain largely unexplored. Methods: Public databases were utilized to investigate the transcriptional and protein expression, and clinical relevance of the INTS family in HCC. Meanwhile, the effects of INTS13 knockdown and overexpression on cell proliferation and apoptosis were studied using HCC cell lines. Results: The mRNA expression of most INTSs were higher in tumor than normal tissues. Higher expression of INTS1/2/3/4/7/8/9/11/12/13 were correlated with poorer overall survival (OS) in Kaplan-Meier Survival Analysis. Multivariate analysis revealed higher level of INTS13 was an independent prognostic factor for shorter OS. Furthermore, genetic alteration of INTS3/6/7/8/9/10 were found in HCC patients and was associated with shorter disease-free survival and progression-free survival. INTS1/2/3/5/7/11/13/14 were associated with activation of tumor-induced immune response and immune infiltration in HCC. Knockdown of INTS13 inhibited cell proliferation and induced apoptosis in HCC cell lines, while overexpression of INTS13 had the opposite effect. Conclusion: Our results indicate that INTS13 is an independent prognostic biomarker in HCC. Furthermore, INTS13 enhances cell proliferation and decreases cell apoptosis in HCC cell lines leading to a poorer OS in HCC patients.

Effect of electroacupuncture stimulation of "Sibai"(ST2) and "Quanliao"(SI18) on excitatory neurons of sensorimotor cortex in mice. / 电针"四白"和"颧髎"æ¿€æ´»å°é¼ èº¯ä½“æ„Ÿè§‰è¿åŠ¨çš®å±‚çš„å ´å¥‹æ€§ç¥žç»å ƒ.

OBJECTIVES: To observe the activation state and neuronal types of somatosensory cortex and the primary motor cortex induced by electroacupuncture (EA) stimulation of "Sibai" (ST2) and "Quanliao" (SI18) acupoints in mice. METHODS: Male C57BL/6J mice were randomly divided into blank control and EA groups, with 6 mice in each group. Rats of the EA group received EA stimulation (2 Hz, 0.6 mA) at ST2 and SI18 for 30 minutes. Samples were collected after EA intervention, and immunofluorescence staining was performed to quantify the expression of the c-Fos gene (proportion of c-Fos positive cells) in the somatosensory cortex and primary motor cortex. The co-labelled cells of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and gamma-aminobutyric acid (GABA) in the somatosensory cortex and primary motor cortex were observed and counted by using microscope after immunofluorescence staining. Another 10 mice were used to detect the calcium activity of excitatory neurons in the somatosensory cortex and primary motor cortex by fiber photometry. RESULTS: In comparison with the blank control group, the number of c-Fos positive cells, and the proportion of c-Fos and CaMKⅡ co-labelled cells in both the somatosensory cortex and primary motor cortex were significantly increased after EA stimulation (P<0.05). No significant changes were found in the proportion of c-Fos and GABA co-labeled cells in both the somatosensory cortex and primary motor cortex after EA. Results of fiber optic calcium imaging technology showed that the spontaneous calcium activity of excitatory neurons in both somatosensory cortex and primary motor cortex were obviously increased during EA compared with that before EA (P<0.01), and strikingly reduced after cessation of EA compared with that during EA (P<0.05). CONCLUSIONS: Under physiological conditions, EA of ST2 and SI18 can effectively activate excitatory neurons in the somatosensory cortex and primary motor cortex.

Village doctors' dilemma in China: A systematic evaluation of job burnout and turnover intention.

Background: Village doctors (VDs) in China undertook arduous primary healthcare missions. However, they received little attention in comparison to doctors in urban public secondary and tertiary hospitals. There is an urgent need to explore the overall situation of turnover intention and job burnout among VDs to evaluate and adjust current health manpower policy. Methods: In this study, seven databases like PubMed, EMBASE, Web of Science (WOS), WanFang, China Science and Technology Journal Database (VIP), Chinese BioMedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) were systematically searched, relevant experts were consulted, and empirical research on job burnout and turnover intention among VDs in international publications was evaluated. Therefore, we evaluated the prevalence of job burnout among VDs in general, across all dimensions and different severity levels, as well as the scores of each category. For turnover intention, we assessed the prevalence of different groups and their overall situation and also identified significant contributors. Results: In this study, we integrated 20 research evidences on job burnout and turnover intention among 23,284 VDs from almost all provinces in China, and the prevalence of turnover intention among VDs in China was as high as 44.1% [95% confidence interval (CI): 34.1-54.2], which was two to four times that of primary health workers in high-income countries, but not much different from some developing countries. Simultaneously, VDs with the highest risk of turnover intention were men [odds ratio (OR): 1.22 (1.05-1.43)], those with a monthly income below USD 163.4 [OR: 0.88 (0.78-0.98)], those with a high educational level [OR: 0.88 (0.78-0.98)], and those <40 years old [OR: 1.27 (1.16-1.40)]. Similarly, the detection rate of job burnout toward them was 59.8% (95% CI: 38.7-79.1) with the MBI-GS score being 44.44 (95% CI: 37.02-51.86) in a total of 90, while the detection rate of job burnout in moderate and above almost reached 20%. The most significant contributor that affects job burnout was low personal accomplishment (LPA), and the detection rate for moderate and higher severity was 65.2% (95% CI: 58.7-71.7). Conclusion: Attention should be paid to the high turnover intention and severe job burnout of primary health workers in rural areas of developing countries, and targeted measures should be taken to improve the situation. Health policymakers should increase financial subsidies for VDs, set a reasonable workload, improve various health policies such as pension insurance for VDs, and encourage "targeted training" for medical students to enrich and expand their team. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021289139.