[Meta-analysis and trial sequential analysis of Shenshao Capsules in treatment of angina pectoris in coronary heart disease].

The efficacy and safety of Shenshao Capsules in combination with conventional western medicine for the treatment of angina pectoris in coronary heart disease were systematically evaluated. Computer search of seven databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library, was conducted to identify randomized controlled trial(RCT) on Shenshao Capsules for the treatment of angina pectoris in coronary heart disease up to December 2023. According to inclusion and exclusion criteria, articles were screened, and data was extracted. Cochrane bias risk assessment tool 2.0(RoB 2.0) was used to evaluate the quality of the included articles. Meta-analysis was performed by RevMan 5.4 and Stata/SE 15.1 software, and evidence quality was rated by the GRADE system. TSA 0.9.5.10 beta software was used for the trial sequential analysis(TSA). Twelve RCTs, with a total of 1 128 participants(567 in the experimental group and 561 in the control group), were included. Meta-analysis showed that Shenshao Capsules + conventional western medicine significantly improved clinical efficacy(RR=1.20, 95%CI[1.15, 1.26], P<0.000 01) and electrocardiogram efficacy(RR=1.16, 95%CI[1.04, 1.30], P=0.01), reduced the frequency of weekly angina pectoris attacks(MD=-2.85, 95%CI[-5.27,-0.43], P=0.02), daily angina pectoris attacks(MD=-0.30, 95%CI[-0.57,-0.03], P=0.03) and the duration of angina pectoris attacks(RR=-2.28, 95%CI[-3.44,-1.12], P=0.000 1). There was no statistically significant difference in adverse reactions between the two groups(RR=1.33, 95%CI[0.71, 2.51], P=0.37). TSA indicated that the cumulative evidence for clinical efficacy exceeded the traditional boundary but did not exceed the TSA boundary, suggesting a potential false positive result. According to GRADE assessment, except for clinical efficacy, which was rated as low-quality evidence, the remaining outcomes were rated as very low-quality evidence. The results indicate that Shenshao Capsules + conventional western medicine may have certain advantages in improving clinical efficacy and electrocardiographic efficacy, reducing the frequency and duration of angina pectoris attacks. However, due to the limitations of this study, more rigorous and high-quality RCT is needed to validate its efficacy and safety.

[Evidence map of clinical research on Chinese patent medicines for post-acute myocardial infarction heart failure].

An evidence map was established to comprehensively sort out the clinical research in the treatment of post-acute myocardial infarction heart failure(P-AMI-HF) with Chinese patent medicines, so as to reveal the distribution of evidence in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and EMbase were searched for the randomized controlled trial(RCT), systematic reviews/Meta-analysis, and guidelines/consensus in this field. The evidence was analyzed and displayed in the form of a combination of text, charts, bubble charts, and bar charts, and the quality of RCT, systematic reviews/Meta-analysis, and guidelines/consensus were evaluated by RoB 1.0, AMSTAR2, and AGREE Ⅱ, respectively. A total of 163 RCTs, 4 systematic reviews/Meta-analysis, 1 network Meta-analysis, 2 observational studies, and 5 guidelines/consensus were included. In recent years, the total number of publications in this field has shown an upward trend. There were a variety of Chinese patent medicines in the treatment of P-AMI-HF, among which Shenfu Injection received the most attention. The clinical RCT and systematic reviews/Meta-analysis generally had poor quality, and the RCT mostly had a small size, a single center, and a short cycle. The outcome indicators mainly included cardiac function indicators, myocardial injury markers, total response rate, hemodynamic indicators, and safety indicators, while the characteristic efficacy indicators of TCM received insufficient attention. The development processes of some guidelines/consensus lack standardization, which compromised their authority and rationality. Chinese patent medicines have advantages in the treatment of P-AMI-HF, while there are also problems, which remain to be solved by more high-quality evidence. That is, more large-sample and multi-center clinical studies should be carried out in the future, and the formulation process of relevant systematic reviews/Meta-analysis and guideline/consensus should be standardized and the quality of evidence should be improved. In this way, the effectiveness and safety of Chinese patent medicines in the treatment of P-AMI-HF can be explored.

Bloodstream infections in patients undergoing extracorporeal membrane oxygenation.

OBJECTIVE: We aimed to evaluate the incidence, risk factors, and prognosis of bloodstream infections (BSIs) during extracorporeal membrane oxygenation (ECMO) treatment in a Chinese population. METHODS: Patients receiving ECMO treatment from January 2013 to August 2019 were retrospectively studied. The incidence of BSIs was calculated. The clinical characteristics between patients with a BSI (BSI group) and without a BSI (non-BSI group). RESULTS: Among 69 included patients, 19 (27.5%) developed at least one BSI. Gram-negative bacteria (73.7%) were mainly responsible for the BSIs, with Klebsiella pneumoniae (6/19, 31.5%) ranking as the top related pathogen. The BSI group had a greater proportion of methicillin-resistant Staphylococcus aureus (MRSA) prophylactic regimens (52.6% vs. 26.0%, P = 0.036), a higher pre-ECMO Sequential Organ Failure Assessment (SOFA) score (11 vs. 8, P = 0.008), more applications of continuous renal replacement therapy (CRRT) during ECMO (63.1% vs. 36.1%, P = 0.042). Longer ECMO support duration, period of ventilator use before ECMO weaning and hospital stay were observed in the BSI group. The SOFA score (OR: 1.174; 95% CI: 1.039-1.326; P = 0.010) was an independent risk factor for BSIs. CONCLUSION: BSIs during ECMO therapy frequently involve Gram-negative bacteria. Stringent care and monitoring should be provided for patients with high SOFA scores.

Effect of neoadjuvant chemotherapy in patients with gastric cancer: a PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is extensively used in the treatment of patients with gastric cancer (GC), particularly in high risk, advanced gastric cancer. Previous trials testing the efficacy of NAC have reported inconsistent results. METHODS: This study compares the combined use of NAC and surgery with surgery alone for GC by using a meta-analytic approach. We performed an electronic search of PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials (RCTs) on NAC published before Oct 2015. The primary outcome of the studies was data on survival rates for patients with GC. The summary results were pooled using the random-effects model. We included 12 prospective RCTs reporting data on 1538 GC patients. RESULTS: Patients who received NAC were associated with significant improvement of OS (P = 0.001) and PFS (P < 0.001). Furthermore, NAC therapy significantly increased the incidence of 1-year survival rate (SR) (P = 0.020), 3-year SR (P = 0.011), and 4-year SR (P = 0.001). Similarly, NAC therapy was associated with a lower incidence of 1-year (P < 0.001), 2-year (P < 0.001), 3-year (P < 0.001), 4-year (P = 0.001), and 5-year recurrence rate (P = 0.002). Conversely, patients who received NAC also experienced a significantly increased risk of lymphocytopenia (P = 0.003), and hemoglobinopathy (P = 0.021). CONCLUSIONS: The findings of this study suggested that NAC is associated with significant improvement in the outcomes of survival and disease progression for GC patients while also increasing some toxicity.

The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is regarded as an important and promising target in the treatment of HER2-positive breast cancers. However, the correlation of clinicopathological characteristics and prognostic significance of HER2 overexpression in gastric cancer patients remains unclear. Our aim was to clarify this issue. METHODS: Embase, PubMed, and the Cochrane Library were searched for relevant articles published up to May 2016. Outcomes of interest contained sex, age, tumor size, tumor site, tumor node metastasis (TNM) stage, distant metastasis, lymph node metastasis, Lauren's classification, differentiation grade, lymphovascular invasion, neural invasion, and multivariate analysis data for overall survival. RESULTS: A total of 41 studies of 17,494 gastric cancer patients were identified with HER2 test. HER2 positive rate was 19.07% (95% CI = 9.16, 28.98). There existed statistical significance between HER2 overexpression and patients' prognosis (RR = 1.47, 95% CI = 1.09, 1.98). Male patients (OR = 1.48, 95% CI = 1.34, 1.65), proximal tumors (OR = 1.25, 95% CI = 1.07, 1.47), intestinal-type tumors (OR = 3.37, 95% CI = 2.54, 4.47), advanced stage cancers (OR = 1.35, 95% CI = 1.10, 1.66), lymph node metastasis (OR = 1.26, 95% CI = 1.14, 1.41), well-differentiated cancers (OR = 1.79, 95% CI = 1.15, 2.76), and distant metastasis (OR = 1.91, 95% CI = 1.08, 3.38) were correlated with higher HER2 expression rates. However, no statistical differences existed in age, tumor size, lymphovascular invasion, or neural invasion. Subgroup analysis revealed that HER2 expression rates reported in articles from Asian (19.52%) countries were quantitatively higher than those from European (16.91%) areas. Results were consistent with those reports that define HER2 status according to trastuzumab for gastric cancer (ToGA) criteria. CONCLUSION: This study showed that HER2 overexpression was associated with poor prognosis in gastric cancer patients. HER2 positive rates may be associated with sex, tumor site, TNM staging system, distant metastasis, lymph node metastasis, Lauren's classification, and differentiation grade in gastric cancer patients. The HER2 expression rate in Asians may be higher than that in Europeans. This study offers a convenient way for doctors to select patients for relevant HER2 detection and following treatment.

Macroscopic Serosal Classification as a Prognostic Index in Radically Resected Stage pT3-pT4b Gastric Cancer.

BACKGROUND: Macroscopic serosal classification (MSC) is an important clinicopathologic index of gastric cancer (GC). To investigate the prognostic significance of MSC status in patients with radically resected stage pT3-pT4b GC, we examined the relationship between MSC type and pT stage. METHODS: Clinicopathologic and survival data of 1613 patients with stage pT3-pT4b GC were studied retrospectively, in the aftermath of radical surgery. RESULTS: MSC types, including reactive, nodular, tendonoid, and color-diffused type, correlated significantly with overall survival (OS) in this cohort, but prognosis was similar for all stages of color-diffused type GC. We proposed a revised pT stage in which color-diffused type cancers at pT3 or pT4a stage were reclassified into pT4b stage. In two-step multivariate analysis, revised pT stage (stage pT4b for all color-diffused types) proved more suitable for determining prognosis, surpassing both Union for International Cancer Control/American Joint Committee on Cancer pT stage and MSC type as an independent prognostic index. CONCLUSIONS: MSC type is a significant and independent prognostic index of OS in patients with radically resected stage pT3-pT4b GC. For prognostic purposes, tumors of color-diffused type at pT3 or pT4a stage should be considered stage pT4b disease.

Borrmann type IV gastric cancer should be classified as pT4b disease.

BACKGROUND: The impact of macroscopic pathologic features of primary tumor that could be obtained preoperatively on pT classification has not been reported so far. The aim of this study was to investigate the feasibility of incorporation of Borrmann type IV gastric cancer into the pT classification. MATERIALS AND METHODS: Clinicopathologic and prognostic data of 1622 patients with advanced gastric cancer who underwent radical surgery were retrospectively studied. RESULTS: Of 1622 patients, 135 (8.32%) patients were classified as having Borrmann type IV gastric cancer. We first confirmed that Borrmann type IV gastric cancer was one of the independent prognostic factors for patients with advanced gastric cancer who underwent radical surgery. Interestingly, we found that overall survival of patients with Borrmann type IV gastric cancer could be clearly distinguished by pN classification and pathological TNM stage but not by pT classification. Importantly, further analysis demonstrated that the prognosis of Borrmann type IV gastric cancers was homogeneous with that of pT4b cancers but poorer than pT2, pT3, pT4a cancers. Therefore, we proposed a novel pT classification in which pT4b disease was defined as cancers that were Borrmann type IV or those that had invaded adjacent structures. Two-step multivariate analysis demonstrated that the novel pT classification was more suitable for prognostic assessment than the original classification. CONCLUSIONS: Classifying Borrmann type IV gastric cancer as pT4b disease improves pT classification prediction of prognosis in patients with advanced gastric cancer after radical surgery.

Lung cancer cells induce senescence and apoptosis of pleural mesothelial cells via transforming growth factor-beta1.

Pleural dissemination is commonly associated with metastatic advanced lung cancer. The injury of pleural mesothelial cells (PMCs) by soluble factors, such as transforming growth factor-beta1 (TGF-ß1), is a major driver of lung cancer pleural dissemination (LCPD). In this study, we examine the effects of TGF-ß1 on PMC injury and the ability of TGF-ß1 inhibition to alleviate this effect both in vitro and in vivo. PMCs were co-cultured with the high TGF-ß1-expressing lung cancer cell line A549 and with various TGF-ß1 signaling inhibitors. Expression of cleaved-caspase 3, cleaved-caspase 9, p21, and p16 were evaluated by Western blot and immunofluorescent confocal imaging. Apoptosis was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltrazoliumbromide assay and AnnexinV-propidium iodide (PI) staining. PMC senescence was assessed by staining for senescence-associated ß-galactosidase (SA-ß-Gal). The ability of lung cancer cells (LCCs) to adhere to injured PMCs was investigated using an LCC-PMC adhesion assay. In our mouse model, PMC injury status was monitored by hematoxylin-eosin (H&E) and Masson's trichrome staining. LCCs expressing high levels of TGF-ß1 induce apoptosis and senescence of PMCs in a co-culture system. Injured PMCs adhere to LCCs, which may further promote LCPD. Importantly, PMC monolayer injury could be reversed with TGF-ß1 inhibitors. This was consistent with our in vivo data showing that the TGF-ß1 inhibitor SB-431542 attenuated PMC barrier injury induced by A549 culture medium in our mouse model. Our study highlights the importance of TGF-ß1 signaling in LCPD and establishes this signaling pathway as a potential therapeutic target in the disease.

Low junctional adhesion molecule A expression correlates with poor prognosis in gastric cancer.

BACKGROUND: The aberrant expression of junctional adhesion molecule A (JAM-A), which has a close correlation with the development, progression, metastasis, and prognosis of cancer, has been frequently reported. However, neither JAM-A expression nor its correlation with clinicopathologic variables and patient survival has been defined in gastric cancers. Moreover, little is known about the role of JAM-A in gastric cancer progression. We carried out the present study to investigate the prognostic value of JAM-A expression in gastric cancer patients. Furthermore, the biological roles of JAM-A in gastric cancer progression were also investigated. METHODS: We determined JAM-A expression in 167 primary gastric cancer tissues and 94 matched adjacent non-tumor tissues by immunohistochemistry. Transwell migration assays and matrigel invasion assays were used to explore the role of JAM-A in gastric cancer cells migration and invasion. CCK-8 assays were used to examine the effect of JAM-A on the proliferation of gastric cancer cells. RESULTS: JAM-A was downregulated in gastric cancer tissues. Low JAM-A expression was significantly associated with tumor size, lymphatic vessel invasion, lymph node metastasis, and TNM stage. Low JAM-A expression was also significantly associated with poor disease-specific survival in gastric cancer patients. Multivariate analysis demonstrated low JAM-A expression as an independent factor predicting poor survival. In addition, JAM-A had the effect on inhibition of gastric cancer cells migration and invasion. However, JAM-A had no significant effects on proliferation of gastric cancer cells. CONCLUSIONS: Low JAM-A expression correlates with poor clinical outcome and promotes cell migration and invasion in gastric cancer.

Identification critical host factors for Japanese encephalitis virus replication via CRISPR screening of human sgRNA library.

Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.

Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

The prognostic impact of occult lymph node metastasis in node-negative gastric cancer: a systematic review and meta-analysis.

PURPOSE: To conduct a meta-analysis to clarify whether occult lymph node metastasis (OLNM), which is identified by molecular detection techniques but is not detected by routine histological examination within regional lymph nodes, represents a prognostic factor for patients with node-negative gastric cancer. METHODS: PubMed, Embase, and the Cochrane Library were searched from their inception to November 2012. The published studies that investigated the association between OLNM and the prognosis of patients with node-negative gastric cancer were included. We extracted hazard ratios (HRs) and associated standard errors from the identified studies and performed random-effects model meta-analyses on overall survival and disease-specific survival. Subgroup analyses were also conducted. RESULTS: A total of 14 eligible studies that included 1,478 patients were identified. Meta-analyses revealed that OLNM was associated with poor overall survival [HR 2.72; 95% confidence interval (CI) 1.61-4.60], and disease-specific survival (HR 2.91; 95% CI 1.25-6.79). Subgroup analyses suggested that OLNM was associated with poor survival in early gastric cancer (HR 3.57; 95% CI 1.23-10.33). However, subgroup analyses of studies that exclusively enrolled patients with D2 lymph node dissection demonstrated that OLNM did not have an influence on the prognosis (HR 1.97; 95% CI 0.82-4.70). CONCLUSIONS: OLNM correlates with poor prognosis for patients with node-negative gastric cancer, and D2 lymph node dissection could eliminate this correlation. For OLNM-positive patients with node-negative gastric cancer, D2 lymph node dissection is necessary.

Diastereodivergent cis- and trans-fused [4 + 2] annulations of cyclic 1,3-dienes and 1-azadienes via ligand-controlled palladium catalysis.

Despite the blossoming of reports of diastereodivergent synthesis over the past years, switchable control of the stereochemistry of the bridgehead atoms of the fused frameworks has been significantly underdeveloped. Here we disclose the ability of Pd0-π-Lewis base catalysis to finely reverse the concerted inverse-electron-demand aza-Diels-Alder cycloaddition reaction between cyclic 1,3-dienes and aurone-derived 1-azadienes. In contrast, the in situ-formed HOMO-energy-increased Pd0-η2-complexes of cyclic 1,3-dienes underwent a cascade vinylogous Michael addition/allylic amination process with 1-azadienes. Moreover, judicious selection of chiral ligands allowed for switchable diastereodivergent [4 + 2] annulations to be accomplished, resulting in the construction of both cis- and trans-fused tetrahydropyridine architectures in high yields with moderate to excellent stereoselectivity levels. A variety of acyclic 1,3-dienes and 1-heterodienes were also applied, and furnished a structural diversity of enantioenriched frameworks.

Role of micronutrients in Alzheimer's disease: Review of available evidence.

Alzheimer's disease (AD) is one of the most common age-related neurodegenerative disorders that have been studied for more than 100 years. Although an increased level of amyloid precursor protein is considered a key contributor to the development of AD, the exact pathogenic mechanism remains known. Multiple factors are related to AD, such as genetic factors, aging, lifestyle, and nutrients. Both epidemiological and clinical evidence has shown that the levels of micronutrients, such as copper, zinc, and iron, are closely related to the development of AD. In this review, we summarize the roles of eight micronutrients, including copper, zinc, iron, selenium, silicon, manganese, arsenic, and vitamin D in AD based on recently published studies.

Shexiang Tongxin Dropping Pill () Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3ß Phosphorylation.

OBJECTIVE: To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STDP) following sodium laurate-induced coronary microembolization (CME) in rats. METHODS: Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg·kg-1·d-1), and high-dose STDP pretreatment group (40 mg·kg-1·d-1). The rats were intragastric administrated with STDP 2 weeks before operation. Moreover, the histopathological alterations were observed using optical microscopy and transmission electron microscopy. Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay. Mitochondrial functions including the mitochondrial permeability transition pore (mPTP) mtDNA copy number were determined and proteins of AKT/GSK3ß were analyzed by Western blot. RESULTS: The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3ß-Ser9 phosphorylation (P<0.05 or P<0.01). CONCLUSION: STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3ß phosphorylation.

Increased Expression of LIPC Is Associated with Aggressive Phenotype of Borrmann Type 4 Gastric Cancer.

PURPOSE: To investigate lipase C hepatic type (LIPC) expression in Borrmann type 4 gastric cancer and its correlation with clinical outcome. The biological roles of LIPC in Borrmann type 4 gastric cancer progression were also investigated. METHODS: We determined LIPC expression in 324 primary gastric cancer tissues and 178 matched adjacent non-tumor tissues by immunohistochemistry. We explored the role of LIPC in Borrmann type 4 gastric cancer cell (OCUM-1) migration, invasion, proliferation, cell cycle, and expression of epithelial-mesenchymal transition-related genes by knocking down LIPC expression. RESULTS: LIPC expression was upregulated in Borrmann type 4 gastric cancer tissues compared with other types of gastric cancer and adjacent non-tumor tissues. High LIPC expression correlated with lymph node metastasis, advanced TNM stage, and poor overall survival in Borrmann type 4 gastric cancer patients. Multivariate analysis demonstrated that high LIPC expression was an independent prognostic factor in patients with Borrmann type 4 gastric cancer. By reducing LIPC expression, OCUM-1 cell invasion and migration were suppressed and Snail and MMP2 expression was downregulated, while E-cadherin expression was upregulated. CONCLUSIONS: High LIPC expression correlates with poor clinical outcome and plays an important role in regulating cell migration and invasion in Borrmann type 4 gastric cancer.

Genome variation in colorectal cancer patient with liver metastasis measured by whole-exome sequencing.

BACKGROUND: Liver metastasis of colorectal cancer (CRC) is an important cause of death from CRC, but its molecular mechanism is still unclear. In recent years, whole-exome sequencing has played an increasingly important role in the study of the occurrence and development of diseases, especially malignant tumors. Its high throughput and low cost advantages enable researchers to explore the pathogenic genes of diseases, and screen potential molecular markers and therapeutic targets from the level of genomics. METHODS: This study collected the primary tumor tissues, matched paracancerous, normal tissues, and liver metastases of 4 CRC patients admitted to the Department of General Surgery of the First Affiliated Hospital of Soochow University, and performed high-depth whole-exome sequencing, with the sequencing depth of each sample reaching 123× on average, then filtered the sequencing data, compared them, and analyzed the bioinformatics data. RESULTS: we found 8,565 single nucleotide variants (SNV) and 429 insertions/deletions (InDel) in the primary and hepatic lesion tissues, and the genes with the highest mutation frequency were titin (TTN), obscurin (OBSCN), and homeodomain-interacting protein kinase 2 (HIPK2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the mutant genes was conducted, and it was found that the mutant genes were mainly concentrated in the cells, cell parts, and cellular process of GO. The results of KEGG pathway analysis showed that mutations were mainly distributed in circadian entrainment, insulin secretion, and glutamatergic synapse. Further, we identified 723 SNV and Indel genes with high frequency mutations including TTN, OBSCN, and hydrocephalus-inducing protein homolog (HYDIN) across all tissues of liver metastases. The GO analysis showed that the mutated genes in liver metastatic tissues were mainly concentrated in cell, cell part, and cellular process. The KEGG pathway analysis showed that high frequency mutation genes were focused on gastric acid secretion, bile secretion, and melanogenesis. CONCLUSIONS: This study found some candidate genes related to the occurrence of CRC and liver metastasis through whole-exome sequencing of relevant tissues in CRC patients with liver metastasis, which is expected to provide new markers and therapeutic targets for such patients.

Mineralocorticoid receptor, CYP11B2 mRNA expression, and atrial matrix remodelling in patients with atrial fibrillation.

OBJECTIVE: Atrial fibrillation is associated with the activation of the renin-angiotensin-aldosterone system in the atria. It is not clear whether the expression of mineralocorticoid receptor (MR) and aldosterone synthase CYPII B2 in patients with atrial fibrillation is altered. This study aimed to investigate the mRNA expression of MR and CYPIIB2 and to reveal the correlation between CYPIIB2 mRNA and matrix remodelling in patients with atrial fibrillation. METHODS: Twenty-five patients with rheumatic heart valve disease, 12 in sinus rhythm and 13 in atrial fibrillation (> or = 6 months), underwent a valve replacement operation and right and left atrial lateral wall tissue samples were obtained. The MR and CYPI IB2 expressions were analysed at the mRNA level and collagen volume fraction was determined by Van Gieson's staining. Results - Collagen volume fraction was found to be increased significantly in atrial fibrillation groups compared with sinus rhythm groups (P < 0.001). Both the mRNA of MR and CYPIIB2 were significantly increased in the fibrillation group compared with the group in sinus rhythm (P < 0.01). Collagen volume fraction significantly and positively correlated with left atrial dimension (r = 0.845, P < 0.001).There was a positive correlation between CYPI I B2 mRNA and collagen volume fraction (r = 0.757, P < 0.001). CONCLUSION: Increased expression of MR and CYPIIB2 in the atria is one of the molecular mechanisms for the development of atrial interstitial fibrosis in patients with atrial fibrillation.

Prevalence of depressive symptoms in patients with Heart Failure in China: a meta-analysis of comparative studies and epidemiological surveys.

BACKGROUND: Although depressive symptoms is a frequent psychiatric comorbidity in people with Heart Failure (HF) in China, its prevalence was not estimated. This is a meta-analysis of studies examining depressive symptoms in HF patients in China. METHODS: The following databases including PubMed, the Cochrace Library, Embase, China National Knowledge Infrastructure (CNKI), WanFang and VIP were independently and systematically searched from inception until March 31, 2019. Statistical analyses were performed using the Stata 13.0 software. The pooled prevalence of depressive symptoms was performed using a random-effects model. In addition, subgroup analysis was conducted based on the New York Heart Association (NYHA) functional class, the assessment tools of depression and gender. RESULTS: Altogether 53 studies (10649 participants) met the inclusion criteria for the analysis. The point prevalence of depressive symptoms in HF was 43%. In subgroup analyses, the prevalence of depressive symptoms was higher in females than in males (46% vs 34%, respectively), and the prevalence of depressive symptoms positively correlated with New York Heart Association functional classes (II 28%, III 46%, IV 52%) . Rates of depression were highest when measured using BDI scale (62%), and lowest when measured using the CES-D (31%). CONCLUSIONS: This meta-analysis confirmed that the prevalence of depressive symptoms was common in HF patients in China and it is related to the severity of heart failure, gender and the diversity of assessment tools. Appropriate strategies for prevention and treatment of depressive symptoms in this population need greater attention.

Low SOX12 Expression Is Correlated With Poor Prognosis in Patients With Gastric Cancer.

BACKGROUND: SRY-related HMG box-12, which is associated with the prognosis of cancer, has been frequently described. However, both SRY-related HMG box-12 expression and its relationship with clinicopathological variables and patient survival have not been defined in gastric cancer. The aim of our study was to examine the prognostic value of SRY-related HMG box-12 expression in patients with gastric cancer. METHODS: In this study, we determined SRY-related HMG box-12 expression in 79 primary gastric cancer tissues and 79 matched adjacent nontumor tissues by immunohistochemistry and then calculated the survival rate using the Kaplan-Meier method. Cox proportional hazard regression model was used to analyze predictors of gastric cancer. Western blot and quantitative real-time polymerase chain reaction were used to investigate the difference in SRY-related HMG box-12 expression between normal gastric epithelial cells and gastric cancer cells at the protein level and RNA level, respectively. RESULTS: SRY-related HMG box-12 was downregulated in gastric cancer tissues. Low SRY-related HMG box-12 expression was significantly associated not only with lymph node metastasis (P = .027) and TNM stage (P = .021) but also with disease-specific survival in patients with gastric cancer. Multivariate analysis demonstrated TNM stage was an independent factor predicting poor survival (P = .034). CONCLUSIONS: Low SRY-related HMG box-12 expression is associated with poor clinical outcomes in gastric cancer.