Association of mitochondrial homeostasis and dynamic balance with malignant biological behaviors of gastrointestinal cancer.

Mitochondria determine the physiological status of most eukaryotes. Mitochondrial dynamics plays an important role in maintaining mitochondrial homeostasis, and the disorder in mitochondrial dynamics could affect cellular energy metabolism leading to tumorigenesis. In recent years, disrupted mitochondrial dynamics has been found to influence the biological behaviors of gastrointestinal cancer with the potential to be a novel target for its individualized therapy. This review systematically introduced the role of mitochondrial dynamics in maintaining mitochondrial homeostasis, and further elaborated the effects of disrupted mitochondrial dynamics on the cellular biological behaviors of gastrointestinal cancer as well as its association with cancer progression. We aim to provide clues for elucidating the etiology and pathogenesis of gastrointestinal cancer from the perspective of mitochondrial homeostasis and disorder.

RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma.

BACKGROUND: Recently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNAs may regulate the progression of a variety of tumors, and tsRNAs is expected to become a new diagnostic biomarker of cancer. However, the expression of tsRNAs is obscure and should be elucidated in CCA. METHODS: High-throughput RNA sequencing technology (RNA-seq) was utilized to determine the overall expression profiles of tsRNAs in three pairs CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The target genes of dysregulated tsRNAs were predicted and the biological effects and potential signaling pathways of these target genes were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 11 differentially expressed tRFs with 12 pairs CCA and adjacent normal tissues. RESULTS: High-throughput RNA-seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated, such as tRF-21-YLKZKWE5D，tRF-16-9NF5W8B，tRF-27-78YLKZKWE52，tRF-19-RLXN48KP，tRF-33-IK9NJ4S2I7L7DV，tRF-19-F8DHXYIV, and 294 tsRNAs were downregulated (tRF-20-739P8WQ0, tRF-34-JJ6RRNLIK898HR, tRF-17-VL8RPY5, tRF-23-YP9LON4VDP, tRF-39-EH623K76IR3DR2I2, tRF-17-18YKISM, tRF-19-Q1Q89PJZ, etc.) in CCA compared with adjacent normal tissues (|log2 [fold change] | ≥ 1 and p value <0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, and tRF-39-0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, cAMP signaling pathway and in growth hormone synthesis, secretion and action, etc. qRT-PCR result showed that tRF-34-JJ6RRNLIK898HR/tRF-38-0668K87SERM492V/tRF-39-0668K87SERM492E2 was downregulated (p = 0.021), and tRF-20-LE2WMK81 was upregulated in CCA (p = 0.033). CONCLUSION: Differentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the tumor progression and have potential to be diagnostic biomarkers and therapeutic targets of CCA.

Pepsinogen C expression-related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer.

The expression of pepsinogen C (PGC) is considered an ideal negative biomarker of gastric cancer, but its pathological mechanisms remain unclear. This study aims to analyze competing endogenous RNA (ceRNA) networks related to PGC expression at a post-transcriptional level and build an experimental basis for studying the role of PGC in the progression of gastric cancer. RNA sequencing technology was used to detect the differential expression (DE) profiles of PGC-related long non-coding (lnc)RNAs, circular (circ)RNAs, and mRNAs. Ggcorrplot R package and online database were used to construct DElncRNAs/DEcircRNAs co-mediated PGC expression-related ceRNA networks. In vivo and in vitro validations were performed using quantitative reverse transcription-PCR (qRT-PCR). RNA sequencing found 637 DEmRNAs, 698 DElncRNAs, and 38 DEcircRNAs. The PPI network of PGC expression-related mRNAs consisted of 503 nodes and 1179 edges. CFH, PPARG, and MUC6 directly interacted with PGC. Enrichment analysis suggested that DEmRNAs were mainly enriched in cancer-related pathways. Eleven DElncRNAs, 13 circRNAs, and 35 miRNA-mRNA pairs were used to construct ceRNA networks co-mediated by DElncRNAs and DEcircRNAs that were PGC expression-related. The network directly related to PGC was as follows: SNHG16/hsa_circ_0008197-hsa-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p-PGC. qRT-PCR validation results showed that PGC, PPARG, SNHG16, and hsa_circ_0008197 were differentially expressed in gastric cancer cells and tissues: PGC positively correlated with PPARG (r = 0.276, P = 0.009), SNHG16 (r = 0.35, P = 0.002), and hsa_circ_0008197 (r = 0.346, P = 0.005). PGC-related DElncRNAs and DEcircRNAs co-mediated complicated ceRNA networks to regulate PGC expression, thus affecting the occurrence and development of gastric cancer at a post-transcriptional level. Of these, the network directly associated with PGC expression was a SNHG16/hsa_circ_0008197-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p - PGC axis. This study may form a foundation for the subsequent exploration of the possible regulatory mechanisms of PGC in gastric cancer.

Clinical Outcomes of Myocardial Bridging versus No Myocardial Bridging in Patients with Apical Hypertrophic Cardiomyopathy.

OBJECTIVE: To determine the prevalence and clinical effects of myocardial bridging (MB) in patients with apical hypertrophic cardiomyopathy (AHCM). METHODS: Angiograms from 212 AHCM patients were reviewed to identify MB. The patients were classified into 2 groups: AHCM with and AHCM without MB. We reviewed patient records on cardiovascular (CV) risk factors, symptoms, CV events, and CV mortality. RESULTS: In all, 60 patients with MB and 100 without MB were included. Rates of angina (61.7 vs. 40%; p = 0.008), mimicking non-ST-segment elevation myocardial infarction (15 vs. 3%, p = 0.013), and Canadian Cardiovascular Society class III/IV angina (18.3 vs. 4%; p = 0.003) were higher in patients with MB than in those without. Mean follow-up periods (65.5 ± 50.5 vs. 64.4 ± 43.6 months, p = 0.378) and CV mortality (3.3 vs. 1%; p = 0.652) were similar in the 2 groups. Kaplan-Meier estimates demonstrated that CV event-free survival rates were lower in patients with MB than in those without (71.7 vs. 88%; p = 0.022). MB, late gadolinium enhancement, and female sex were independent risk factors for CV events in a multivariate Cox regression analysis adjusted for other risk factors. CONCLUSION: More serious symptoms and a higher risk of CV events were observed in AHCM patients with MB than in those without MB. CV mortality was similar in these 2 groups.

Clinical characteristics and risk factors of intracranial hemorrhage after spinal surgery.

BACKGROUND: Intracranial hemorrhage after spinal surgery is a rare and devastating complication. AIM: To investigate the economic burden, clinical characteristics, risk factors, and mechanisms of intracranial hemorrhage after spinal surgery. METHODS: A retrospective cohort study was conducted from January 1, 2015, to December 31, 2022. Patients aged ≥ 18 years, who had undergone spinal surgery were included. Intracranial hemorrhage patients were selected after spinal surgery during hospitalization. Based on the type of spinal surgery, patients with intracranial hemorrhage were randomly matched in a 1:5 ratio with control patients without intracranial hemorrhage. The patients' pre-, intra-, and post-operative data and clinical manifestations were recorded. RESULTS: A total of 24472 patients underwent spinal surgery. Six patients (3 males and 3 females, average age 71.3 years) developed intracranial hemorrhage after posterior spinal fusion procedures, with an incidence of 0.025% (6/24472). The prevailing type of intracranial hemorrhage was cerebellar hemorrhage. Two patients had a poor clinical outcome. Based on the type of surgery, 30 control patients were randomly matched in 1:5 ratio. The intracranial hemorrhage group showed significant differences compared with the control group with regard to age (71.33 ± 7.45 years vs 58.39 ± 8.07 years, P = 0.001), previous history of cerebrovascular disease (50% vs 6.7%, P = 0.024), spinal dura mater injury (50% vs 3.3%, P = 0.010), hospital expenses (RMB 242119.1 ± 87610.0 vs RMB 96290.7 ± 32029.9, P = 0.009), and discharge activity daily living score (40.00 ± 25.88 vs 75.40 ± 18.29, P = 0.019). CONCLUSION: The incidence of intracranial hemorrhage after spinal surgery was extremely low, with poor clinical outcomes. Patient age, previous stroke history, and dura mater damage were possible risk factors. It is suggested that spinal dura mater injury should be avoided during surgery in high-risk patients.

Efficacy and safety of aranidipine enteric-coated tablets compared with amlodipine in Chinese patients with mild to moderate essential hypertension: a multicenter, randomized, double-blind, parallel-controlled clinical trial.

This is a multicenter, randomized, double-blind, parallel-controlled study, conducted in Chinese patients with mild to moderate essential hypertension. After a 2-week washout period, 236 eligible patients were randomly to receive aranidipine 5-10 mg/d (n = 118) or amlodipine 5-10 mg/d (n = 118) for 10 weeks. The blood pressure and heart rate were evaluated in outpatient clinics, and ambulatory blood pressure monitoring was performed in 24 patients in each group. The blood pressure was significantly decreased in both groups. Compared with amlodipine, the patients who received aranidipine had less response in blood pressure (P < 0.01). The trough/peak ratios of diastolic blood pressure in aranidipine and amlodipine groups were 0.57 ± 0.20 and 0.68 ± 0.19, respectively (P = 0.119). Adverse events occurred at 11.86% and 7.63% in the aranidipine and amlodipine groups, respectively (P = 0.348). Headache was observed at an incidence of >3.0% in both groups, and the serum glucose and lipid profile had no significant change in the amlodipine group. In conclusion, once-daily administration of aranidipine (5-10 mg) effectively controlled blood pressure, and the short-term treatment might result in it being less effective than amlodipine. It had a stable action over 24-hour period, and the mechanism of that is not yet clear. Aranidipine had a good safety similar to that of amlodipine.

Non-coding RNA and hepatitis B virus-related hepatocellular carcinoma: A bibliometric analysis and systematic review.

Objectives: A bibliometric analysis for non-coding RNA and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) was performed to describe international research status and visualize the research scope and emerging trends over the last two decades on this topic. Materials and methods: Research data of non-coding RNA and HBV-related HCC were retrieved and extracted from the Web of Science Core Collection (WoSCC) database from 1 January 2003 to 13 June 2022 and then analyzed by means of bibliometric methods. A total of 1,036 articles published in this field were assessed for specific characteristics, including the year of publication, journal, author, institution, country/region, references, and keywords. VOSviewer was employed to perform co-authorship, co-occurrence, and co-citation analyses accompanied by constructing a visual network. Results: Overall, 1,036 reports on non-coding RNA and HBV-related HCC from 2003 to 2022 were retrieved from WoSCC. The publication has gradually increased during the last two decades with 324 journals involved. Most research records (748 publications and 23,184 citations) were concentrated in China. A co-occurrence cluster analysis for the top 100 keywords was performed and four clusters were generated: (1) non-coding RNA as a molecular marker for the diagnosis and prognosis of HBV-related HCC; (2) dysregulation of non-coding RNA by hepatitis B virus X protein (HBx); (3) non-coding RNA affecting the biological behaviors of HBV-related HCC; and (4) epidemiological study for the effects of non-coding RNA on the risk of HBV-related HCC. Conclusion: The publications and citations involved in non-coding RNA and HBV-related HCC have increased over the last two decades associated with many countries, institutions, and authors. Our study revealed current development trends, global cooperation models, basic knowledge, research hotspots, and emerging frontiers in this field.

Predicting Prognosis of Hepatocellular Carcinoma Patients Based on the Expression Signatures of Mitophagy Genes.

Background: The unbalance of mitophagy was closely related to hepatocellular carcinoma (HCC) progression. At present, it has not been uncovered about the influence of mitophagy genes on HCC prognosis and their potential pathogenesis. Materials and Methods: The expression and clinical information of HCC in TCGA cohort were used to identify mitophagy differentially expressed genes (MDEGs) with prognostic value. The prognostic model of mitophagy genes was built and externally validated by LASSO regression in TCGA cohort and ICGC cohort, respectively. The function of the prognostic signature and its association with immune cell infiltration were explored. The profile of MDEGs was validated with 39 pairs HCC and paracarcinoma tissues by quantitative reverse transcription-PCR (qRT-PCR). Results: A total of 18 mitophagy genes that were upregulated and contributed to poor prognosis in HCC were identified. These genes could interact with each other. The correlation analysis showed that there was positively correlation among mitophagy genes. According to optimal λ value, 8 mitophagy gene signatures were involved in prognostic model. Based on median risk scores, HCC patients were divided into high-risk group and low-risk group. Compared with the low-risk group, the high-risk group has worse overall survival in TCGA cohort and ICGC cohort. The univariate and multivariate Cox regression analysis suggested that risk score was an independent prognostic factor of HCC patients. Time-dependent ROC curve was used to identify and validate good predicting performance of the prognostic model. Enrichment analysis showed that risk differentially expressed genes were enriched in various metabolism and cell division processes. The immune cell infiltration score and immune function were significantly different in two groups. qRT-PCR validation result showed that QSTM1, CSNK2B, PGAM5, and ATG5 were upregulated. Conclusion: Mitophagy genes could influence HCC progression through regulating the metabolism and immune functions and could be used to predict prognosis and considered as potential prognostic biomarker and precise therapeutic target of HCC.

Comprehensive Analysis and Validation of Solute Carrier Family 25 (SLC25) and Its Correlation with Immune Infiltration in Pan-Cancer.

As the largest gene family functioning in protein transport among human solute carriers, the SLC25 family (mitochondrial carrier family) can participate in development of cancer. However, a comprehensive exploration for the exactly roles of SLC family remains lacking. In the present study, a total of 15 functional SLC25 family genes were retrieved from all current publications. And multidimensional analyses were systematically performed based on the transcriptome and genome data of SLC25 family from a variety of online databases for their expression, immune cell infiltration, and cancer prognosis. Validation by qPCR and immunohistochemistry were further conducted for the expression of partial SLC25 family members in some tumor tissue. We found that the SLC25 family had strong correlation with immune cells, such as macrophages M2, CD8+ T cell, CD4+ T cell memory activated, and memory resting. Among them, SLC25A6 was most correlated with Macrophage M1 in uveal melanoma (r = -0.68, P = 1.9e - 0.5). Expression of mRNA level showed that SLC25A4 was downregulated in stomach adenocarcinoma and colon adenocarcinoma. SLC25A7 was highly expressed in stomach adenocarcinoma and colon adenocarcinoma. SLC25A23 was decreased in colon adenocarcinoma. qPCR and immunohistochemistry validation results were consistent with our bioinformatics prediction. SLC25A8 was associated with the prognosis of cancer. All these findings suggested that the SLC25 family might affects the immune microenvironment of the cancer and then had the potential to be predictive biomarkers for early diagnosis and prognosis as well as novel targets for individualized treatment of cancer.

[Clinical features and prognosis of 188 Chinese patients with apical hypertrophic cardiomyopathy].

OBJECTIVE: To analyze the clinical characteristics and prognosis of Chinese patients with apical hypertrophic cardiomyopathy (AHCM). METHODS: A total of 188 patients with AHCM diagnosed at Fuwai Hospital were included in this retrospective study. Clinical characteristics, mortality and cardiovascular morbidity were analyzed. A multiple logistic regression was performed to adjust for potential confounding factors. RESULTS: Males predominated with a number of 139 (73.9%) in this cohort. Patient's age ranged from 15 to 81 (51.9 ± 12.6) years. There were 120 patients (63.8%) with "pure" type and 68 patients (36.2%) with "mixed" type of AHCM, 171 patients were followed up for (5.0 ± 3.0) years, cardiovascular mortality was 1.2%, 28 patients (16.4%) experienced one or more cardiovascular events. CONCLUSION: The prevalence of AHCM is high in Chinese HCM patients, pure type AHCM is more common, and AHCM patients have a benign clinical course.

[Comparison of benazepril monotherapy to amlodipine plus benazepril in the treatment of patients with mild and moderate hypertension: a multicentre, randomized, double-blind, parallel-controlled study].

OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring. METHODS: In a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP < 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients (the combination therapy group n = 38, monotherapy therapy group n = 36) completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis. RESULTS: The randomized, double-blind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment (a SeDBP < 90 mm Hg or a decrease of 10 mm Hg or more from baseline) were (11.7 ± 6.8) mm Hg, 65.7% and 88.5% in the combination therapy group, respectively, and were (7.7 ± 6.9) mm Hg, 35.5% and 65.5% in the monotherapy group, respectively. There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs (P < 0.001). The fixed combination significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P < 0.001). CONCLUSIONS: The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.

Mitochondria-related core genes and TF-miRNA-hub mrDEGs network in breast cancer.

BACKGROUND: Mitochondria-nuclear cross-talk and mitochondrial retrograde regulation are involved in the genesis and development of breast cancer (BC). Therefore, mitochondria can be regarded as a promising target for BC therapeutic strategies. The present study aimed to construct regulatory network and seek the potential biomarkers of BC diagnosis and prognosis as well as the molecular therapeutic targets from the perspective of mitochondrial dysfunction. METHODS: The microarray data of mitochondria-related encoding genes in BC cell lines were downloaded from GEO including GSE128610 and GSE72319. GSE128610 was treated as test set and validation sets consisted of GSE72319 and TCGA tissue samples, intending to identify mitochondria-related differentially expressed genes (mrDEGs). We performed enrichment analysis, PPI network, hub mrDEGs and overall survival analysis and constructed transcription factor (TF)-miRNA-hub mrDEGs network. RESULTS: A total of 23 up-regulated and 71 down-regulated mrDEGs were identified and validated in BC cell lines and tissues. Enrichment analyses indicated that mrDEGs were associated with several cancer-related biological processes. Moreover, 9 hub mrDEGs were identified and validated in BC cell lines and tissues. Finally, 5 hub coregulated mrDEGs, 21 miRNAs and 117 TFs were used to construct TF-miRNA-hub mrDEGs network. MYC associated zinc finger protein (MAZ), heparin binding growth factor (HDGF) and Sp2 transcription factor (SP2) regulated 3 hub mrDEGs. Hsa-mir-21-5p, hsa-mir-1-3p, hsa-mir-218-5p, hsa-mir-26a-5p and hsa-mir-335-5p regulated 2 hub mrDEGs. Overall survival analysis suggested that the up-regulation of fibronectin 1 (FN1), as well as the down-regulation of discoidin domain receptor tyrosine kinase 2 (DDR2) correlated with unfavorable prognosis in BC. CONCLUSION: TF-miRNA-hub mrDEGs had instruction significance for the exploration of BC etiology. The hub mrDEGs such as FN1 and DDR2 were likely to regulate mitochondrial function and be novel biomarkers for BC diagnosis and prognosis as well as the therapeutic targets.

Single nucleotide polymorphisms of whole genes and atrophic gastritis susceptibility:a systematic review and meta-analysis.

BACKGROUND: Atrophic gastritis (AG) is one of the important precancerous lesions of gastric cancer. Single nucleotide polymorphisms (SNPs) are closely related to AG susceptibility. However, the research conclusions on the predictive potential of SNPs are inconsistent. The study aims to retrospect the association between SNPs of whole genes and AG risk by meta-analysis. MATERIALS AND METHODS: Up to April 29, 2020, a systematic literature search for the relationship of SNPs with AG susceptibility was performed utilizing PubMed, Web of Science and Chinese National Knowledge Infrastructure. The overall and stratified meta-analyses on extracted data were conducted by Stata11.2. RESULTS: 33 case-control studies were enrolled containing 9951 AG patients and 17,252 healthy controls, and 17 SNPs in 12 different genes were systematically reviewed. The results indicated that 12 genes could be categorized based on their functions, including immune response, cell proliferation and apoptosis, and DNA damage repair. For the SNPs in immune response-related genes, the C allele of TLR1 rs4833095 T/C increased AG risk to 1.21-fold and the recessive model of TLR4 rs11536878 in the TLR gene family decreased AG susceptibility to 0.48-fold. The variant alleles of IL-10 rs1800871 (OR = 1.21) and IL-8 rs4073 (OR = 1.22) in the IL gene family were positively associated with AG risk. PSCA rs2294008 enhanced AG risk in all genetic models. SNPs associated with AG susceptibility were mainly focused on immune response-related genes. CONCLUSION: These SNPs related to immune response could influence on AG risk and have potential to be AG predictive biomarkers. It is worth noting that the number of studies for each SNPs were insufficient due to the limited published researches and updated meta-analysis needs to be performed based on extensive relevant studies for more reliable results.

Comprehensive Pan-Cancer Analysis of Heat Shock Protein 110, 90, 70, and 60 Families.

Background: Here we carried out a panoramic analysis of the expression and prognosis of HSP110, HSP90, HSP70, and HSP60 families in 33 types of cancer, with the aim of deepening the systematic understanding of heat shock proteins (HSPs) in cancer. Materials and Methods: Next-generation sequencing data of multiple tumors were downloaded from TCGA, CCLE and Oncomine databases. RStudio 3.6.1 was used to analyze HSP110, HSP90, HSP70 and HSP60 families based on their expression in 33 types of cancer. The validations in vivo (stomach adenocarcinoma and colon adenocarcinoma tissues) were performed by qRT-PCR. Results: HSPs were differentially expressed in different cancers. The results revealed mainly positive correlations among the expressions of HSPs in different cancers. Expressions of HSP family members were generally associated with poor prognosis in respiratory, digestive, urinary and reproductive system tumors and associated with good prognosis in cholangiocarcinoma, pheochromocytoma and paraganglioma. TCGA mutation analysis showed that HSP gene mutation rate in cancers was 0-23%. CCLE mutation analysis indicated that HSP gene mutation rate in 828 cell lines from 15 tumors was 0-17%. CNV analysis revealed that HSPs have different degrees of gene amplifications and deletions in cancers. Gene mutations of 15 HSPs influenced their protein expressions in different cancers. Copy number amplifications and deletions of 22 HSPs also impacted protein expression levels in pan-cancer. HSP gene mutation was generally a poor prognosis factor in cancers, except for uterine corpus endometrial carcinoma. CNVs in 14 HSPs showed varying influences on survival status in different cancers. HSPs may be involved in the activation and inhibition of multiple cancer-related pathways. HSP expressions were closely correlated with 22 immune cell infiltrations in different cancers. The qRT-PCR validation results in vivo showed that HSPA2 was down-regulated in stomach adenocarcinoma and colon adenocarcinoma; HSPA7 and HSPA1A also were down-regulated in colon adenocarcinoma. HSPA2-HSPA7 (r = 0.031, p = 0.009) and HSPA1A-HSPA7 (r = 0.516, p < 0.001) were positive correlation in colon adenocarcinoma. Conclusion: These analysis and validation results show that HSP families play an important role in the occurrence and development of various tumors and are potential tumor diagnostic and prognostic biomarkers as well as anti-cancer therapeutic targets.

The role of Transfer RNA-Derived Small RNAs (tsRNAs) in Digestive System Tumors.

Transfer RNA-derived small RNA(tsRNA) is a type of non-coding tRNA undergoing cleavage by specific nucleases such as Dicer. TsRNAs comprise of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Based on the splicing site within the tRNA, tRFs can be classified into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. TiRNAs can be classified into 5'-tiRNA and 3'-tiRNA. Both tRFs and tiRNAs have important roles in carcinogenesis, especially cancer of digestive system. TRFs and tiRNAs can promote cell proliferation and cell cycle progression by regulating the expression of oncogenes, combining with RNA binding proteins such as Y-box binding protein 1 (YBX1) to prevent transcription. Despite many reviews on the basic biological function of tRFs and tiRNAs, few have described their correlation with tumors especially gastrointestinal tumor. This review focused on the relationship of tRFs and tiRNAs with the biological behavior, clinicopathological characteristics, diagnosis, treatment and prognosis of digestive system tumors, and would provide novel insights for the early detection and treatment of digestive system tumors.

Dysfunctional putamen modulation during bimanual finger-to-thumb movement in patients with Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder affecting middle-aged and elderly people. PD can be viewed as "circuit disorder," indicating that large scale cortico-subcortical pathways were involved in its pathophysiology. The brain network in an experimental context is emerging as an important biomarker in disease diagnosis and prognosis prediction. This context-dependent network for PD and the underling functional mechanism remains unclear. In this paper, the brain network profiles in 11 PD patients without dementia were studied and compared with 12 healthy controls. The functional magnetic resonance imaging (fMRI) data were acquired when the subjects were performing a pseudorandomized unimanual or bimanual finger-to-thumb movement task. The activation was detected and the network profiles were analyzed by psychophysiological interaction (PPI) toolbox. For the controls and PD patients, the motor areas including the primary motor and premotor areas, supplementary motor area, the cerebellum and parts of the frontal, temporal and parietal gyrus were activated. The right putamen exhibited significant control > PD activation and weaker activity during the bimanual movement relative to the unimanual movement in the control group. The decreased putamen modulation on some nucleus in basal ganglia, such as putamen, thalamus and caudate, and some cortical areas, such as cingulate, parietal, angular, frontal, temporal and occipital gyrus was detected in the bimanual movement condition relative to the unimanual movement condition. Between-group PPI difference was detected in cingulate gyrus, angular gyrus and precuneus (control > PD) and inferior frontal gyrus (PD > control). The deficient putamen activation and its enhanced connectivity with the frontal gyrus could be a correlate of impaired basal ganglia inhibition and frontal gyrus compensation to maintain the task performance during the motor programs of PD patients.

Clinical characteristics and prognosis of 60 patients with midventricular obstructive hypertrophic cardiomyopathy.

BACKGROUND: Midventricular obstructive hypertrophic cardiomyopathy (MVOHCM) is a rare form of hypertrophic cardiomyopathy. Knowledge regarding the diagnosis, morbidity and cardiovascular mortality is limited. In this study, we aimed to describe the long-term outcomes of patients with MVOHCM followed in a tertiary referral centre.Methods A retrospective study of 60 patients with MVOHCM diagnosed at FuWai Hospital was performed. Clinical features, mortality and cardiovascular morbidity were analysed. RESULTS: The 60 patients with MVOHCM represented 2.9% of all the hypertrophic cardiomyopathy cases (n = 2068). At diagnosis, the mean age was 40.2 ±â€Š15.0 years. During 7.1 ±â€Š6.3 years of follow-up after diagnosis, the cardiovascular mortality was 15.0%. The probability of survival at 10 years was 77.0 ±â€Š8.0%. The following two predictors of cardiovascular mortality were identified: severe ventricular septal hypertrophy at least 30  mm (hazard ratio, 3.19; P = 0.031) and unexplained syncope (hazard ratio, 4.59; P = 0.002) at baseline. Thirty patients (50.0%) had one or more morbid events, and the most frequent was nonsustained ventricular tachycardia. Apical aneurysm formation was identified in 20% of patients, and the patients with apical aneurysms were more inclined to experience nonsustained ventricular tachycardia than patients without apical aneurysm (58.3 vs. 16.7%; P = 0.003). Peak pressure gradient at least 70  mm Hg (hazard ratio, 3.00; P = 0.01) at baseline was identified as the only predictor of apical aneurysm. CONCLUSION: In Chinese patients, MVOHCM is associated with an unfavourable prognosis of cardiovascular mortality. One-half of these patients experience major cardiovascular events, and 20% develop an apical aneurysm, which significantly increases arrhythmia events. These data warrant measures to ensure the early recognition of MVOHCM followed by appropriate therapeutic interventions.

[Motor cortex by real-time imaging process functional MRI during finger movements].

OBJECTIVE: To explore the techniques of RTIP-fMRI scanning and the correspondence between structure and functional changes of motor cortex during self-paced finger movements by RTIP-fMRI in normal volunteers. METHODS: The 15 healthy volunteers were studied by RTIP-fMRI, and the activation tasks consisted of self-paced finger movements performed with the right and the left hands. Image postprocessing was done on the workstation by "correlation coefficient" algorithm analysis method, IAC and SPM software. RESULTS: There was a good correspondence between the anatomical landmarks of the somatotopical organization of primary motor areas in the 15 volunteers; during the finger tasks, the functional changes occurred in the contralateral primary motor-somatosensory cortex (M1/S1), the supplementary motor area (SMA), and the ipsilateral primary motor cortex. CONCLUSION: RTIP, a promising new technique, can localize the motor cortex accurately. It is superior to any other fMRI techniques, and may be used widely in the function research of the brain.

A pro-atherogenic HDL profile in coronary heart disease patients: an iTRAQ labelling-based proteomic approach.

OBJECTIVES: This study aims to compare the protein composition of high-density lipoprotein (HDL) particles in coronary heart disease (CHD) patients and controls by proteomic methods. BACKGROUND: HDL has been reported to exert pro-atherogenic properties in CHD patients. Accumulating evidence indicates that HDL composition, rather than the HDL-C level, determines its functions. The changes in HDL composition involved in the conversion of anti-atherogenic to pro-atherogenic properties in CHD patients are currently unknown. METHODS AND RESULTS: iTRAQ combined with nanoLC-MS/MS was performed to obtain a differential expression profile of the HDL pooled samples of the male age-matched CHD patients and controls (n = 10/group). Of the 196 proteins identified in the examined HDL, 12 were differentially expressed between the CHD patients and the controls, including five up-regulated proteins and seven down-regulated proteins. Using GO analysis, we determined that the up-regulated proteins were mostly involved in inflammatory reactions, displaying a potential pro-atherogenic profile. In contrast, the down-regulated proteins were mostly involved in lipid metabolism processes, displaying anti-atherogenic properties. To confirm the proteomic results, serum amyloid A (SAA) and apoC-I were selected and quantified by ELISA, in the same population as the proteomic analysis, as well as another independent population (n = 120/group). Consistent with the proteomic results, the amount of SAA was significantly increased, and apoC-I was significantly decreased in the HDL particles of CHD patients compared with those of controls (P<0.05). CONCLUSIONS: Our study shows that the HDL proteome changes to a pro-atherogenic profile in CHD patients, which might compromise the protective effects of HDL. Proteomic analysis of HDL composition may provide more relevant information regarding their functional properties than steady-state HDL-C levels.