The aim of this paper was to determine the clinical significance of the MHC class I chain-related molecule A(MICA) and NKG2D receptor on NK cells in pancreatic cancer. We compared MICA expression in malignant (n = 103), inflammatory (n = 28), and normal (n = 17) pancreatic tissues using immunohistochemistry and assessed serum levels of soluble MICA (sMICA) and NKG2D expression on NK cells in patients with pancreatic cancer (n = 103), in patients with chronic pancreatitis (n = 28), and in healthy volunteers (n = 43). Expression of MICA was detected in 89.3% of pancreatic cancer tissues, whereas fewer were expressed in inflammatory and normal pancreatic tissues. The levels of sMICA were frequently elevated in patients with advanced pancreatic cancer. The elevation of sMICA was associated with down-regulated NKG2D expression and impaired activity of NK cells. The successful tumor resection significantly decreased serum levels of sMICA and increased the NKG2D expression; there was an inverse correlation between change in sMICA levels and that in NKG2D expression. MICA expression, preoperative sMICA levels and NKG2D intensity were found to be independent prognostic factors in resected pancreatic cancer. This study supports the clinical significance of release of MICA for the malignant progression of pancreatic cancer. The successful tumor resection for pancreatic cancer may have a beneficial effect on NKG2D-mediated antitumor immunity. Our results also suggest sMICA and NKG2D expression on NK cells may be useful to identify risk patients at time point of diagnosis.

It is reported that both the homozygous and heterozygous states of GBA mutations which are the causes of Gaucher disease (GD) are linked to the risk of PD. However, the GBA variant p.E326K (c.1093G > A, rs2230288), which does not result in GD in homozygous carriers, has triggered debate among experts studying Parkinson's disease (PD). In order to determine if the E326K variant of GBA is associated with the risk of PD, a standard meta-analysis was conducted by searching and screening publications, data extraction, and statistical analysis. Finally, a total of 15 publications, containing 5,908 PD patients and 5,605 controls, were included in this analysis. The pooled OR of the E326K genotype analysis was 1.99 (95% CI: 1.57–2.51). The minor allele frequencies of E326K for PD patients and controls were 1.67% and 1.03%, respectively. The pooled OR for the minor allele A was 1.99 (95% CI: 1.58–2.50). According to the subgroup analysis, we found that the significant differences between PD patients and controls for both genotype and allele of E326K also exist in Asians and Caucasians, respectively. In this study, we found that E326K of GBA is associated with the risk of PD in total populations, Asians, and Caucasians, respectively. Further studies are needed to clarify the role of GBA in the pathogenesis of PD.

The aim of this paper was to identify novel proteins involved in the development of gastric cancer (GC). Isobaric tags for relative and absolute quantification (iTRAQ) analysis was adopted to separate the differentially expressed proteins between normal gastric epithelial cell line GES-1 and GC cell line SGC7901. Western blotting was utilized to validate the increased expression of sorcin in SGC7901; immunohistochemistry was performed to investigate its relationship with clinicopathological features of GC. Twelve differential proteins were identified. Seven proteins were found to be significantly upregulated (≥two-fold), while five proteins were markedly downregulated (≤0.5-fold), in SGC7901 cells. Sorcin was detected by this proteomic approach with a 5.4-fold upregulation in SGC7901. Western blotting and immunohistochemistry confirmed the overexpression of sorcin in GC. Immunohistochemistry showed us that sorcin was overexpressed in 55 samples of GC tissue (55/85, 64.71%) and was related closely to the depth of invasion, TNM stage, and lymph node metastasis of GC (P<0.05). The development of GC is regulated by multiple genes. Sorcin will be a novel molecular biomarker for the diagnosis, treatment, and prognosis of GC.

Gastric cancer (GC) is one of the most common cancers worldwide and results in the second greatest rate of cancer-associated mortality globally. Multidrug resistance (MDR) often develops during the chemotherapy, resulting in the failure of treatment. To investigate the molecular mechanism of MDR, the roles of microRNA (miR)-1 were studied in GC. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression levels of miR-1 and sorcin in SGC7901/ADM and SGC7901/VCR cell lines. The effect of miR-1 on the half maximal inhibitory concentration (IC 50 ), cell apoptosis rates and drug accumulation was uncovered by MTT assay and flow cytometric analysis. Furthermore, dual-luciferase assay and western blotting were used to determine the target of miR-1 in GC. It was demonstrated that miR-1 was highly downregulated in MDR GC cell lines, including SGC7901/ADM and SGC7901/VCR. Overexpression of miR-1 in MDR GC cells decreased IC 50 , but increased the cell apoptosis rates and promoted the drug accumulation in cancer cells. Dual-luciferase activity assay indicated that sorcin was the target of miR-1 in GC. In addition, overexpression of sorcin could partially reverse the effect of miR-1 in MDR GC cells. The role of miR-1 in MDR GC cells makes it a potential therapeutic target for a successful clinical outcome.

Recent studies have proposed that pyruvate dehydrogenase E1 component subunit alpha (PDHA1), a cuproptosis-key gene, is crucial to the glucose metabolism reprogram of tumor cells. However, the functional roles and regulated mechanisms of PDHA1 in multiple cancers are largely unknown. The Cancer Genome Atlas (TCGA), GEPIA2, and cBioPortal databases were utilized to elucidate the function of PDHA1 in 33 tumor types. We found that PDHA1 was aberrantly expressed in most cancer types. Lung adenocarcinoma (LUAD) patients with high PDHA1 levels were significantly correlated with poor prognosis of overall survival (OS) and first progression (FP). Kidney renal clear cell carcinoma (KIRC) patients with low PDHA1 levels displayed poor OS and disease-free survival (DFS). However, for stomach adenocarcinoma (STAD), the downregulated PDHA1 expression predicted a good prognosis in patients. Moreover, we evaluated the mutation diversity of PDHA1 in cancers and their association with prognosis. We also analyzed the protein phosphorylation and DNA methylation of PDHA1 in various tumors. The PDHA1 expression was negatively correlated with tumor-infiltrating immune cells, such as myeloid dendritic cells (DCs), B cells, and T cells in pan-cancers. Mechanically, we used single-cell sequencing to discover that the PDHA1 expression had a close link with several cancer-associated signaling pathways, such as DNA damage, cell invasion, and angiogenesis. At last, we conducted a co-expressed enrichment analysis and showed that aberrantly expressed PDHA1 participated in the regulation of mitochondrial signaling pathways, including oxidative phosphorylation, cellular respiration, and electron transfer activity. In summary, PDHA1 could be a prognostic and immune-associated biomarker in multiple cancers.

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Background: In the new era, medical teaching is faced with the dual tasks of knowledge transmission and value guidance. In this study, we applied CBL combined with humanistic literacy to undergraduate medical students’ internal medicine diagnostics teaching, so as to promote medical students’ better acquisition of knowledge and improvement of literacy.Methods: Fifty-six five-year undergraduate medical students from Xiangya Medical College of Central South University were randomly divided into experimental group and control group, with 28 students in each group. In the experimental group, CBL combined with humanistic literacy teaching mode was adopted, while in the control group, traditional teaching methods were adopted. The two groups were compared to explore the effect of innovative teaching mode in the course of medical diagnostics. Result: The scores of multiple choice questions and comprehensive analysis questions of the experimental group were significantly higher than those of the control group. The teaching satisfaction survey of the two groups of students shows that the students in the experimental group are significantly higher than the control group. In addition, the comprehensive ability questionnaire survey showed that the experimental group of students compared to the control group of students, this group of students believed that the innovative teaching mode of CBL combined with humanistic literacy could significantly improve humanistic literacy, learning motivation, independent thinking, clinical thinking, teamwork, clinical communication and other abilities ( P＜0.05) .Conclusion: Under the background of new medicine, CBL combined with humanistic literacy teaching mode is obviously superior to the traditional teaching mode in improving the professional knowledge level and cultivating the comprehensive quality and ability of undergraduate medical students. This teaching mode can not only improve the teaching quality, but also improve students’ learning ability, exercise their learning enthusiasm, and improve students' happiness in learning.

The polymeric immunoglobulin receptor (PIGR), an exosome-associated glycoprotein, plays an important role in the occurrence and development of different tumors. This study aimed to investigate whether PIGR is essential for colorectal cancer (CRC). Comprehensive bioinformatics analysis and immunohistochemistry (IHC) revealed that expression of PIGR was significantly decreased in CRC patients. Upregulated PIGR displayed favorable prognostic values in CRC patients. Several algorithms, such as TISIDB and TIMER, were used to evaluate the roles of PIGR expression in the regulation of immune response in CRC. Moreover, GSEA enrichment analysis indicated the underlying role of PIGR in the regulation of fatty acid metabolism in CRC. Taken together, our findings might provide a new potential prognostic and immune-associated biomarker for CRC and supply a new destination for PIGR-related immunotherapy in clinical treatment.