Perioperative intravenous infusion of dexmedetomidine for alleviating postpartum depression after cesarean section: A meta-analysis and systematic review.

The efficacy of perioperative dexmedetomidine (DEX) infusion as a precaution against postpartum depression (PPD) in women undergoing cesarean section has not been substantiated systematically. A literature search for RCTs on DEX against PPD was retrieved in the following databases from inception to January 3, 2024: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, CBM, VIP, etc. A total of 13 RCTs with 1711 participants were included. Meta-analysis was performed by RevMan5.3 and Stata16 using a random-effects model. EPDS scores were significantly decreased in the DEX group within one week or over one week postpartum compared to the control group (SMD = -1.25, 95 %CI: -1.73 to -0.77; SMD = -1.08, 95 %CI: -1.43 to -0.73). The prevalence of PPD was significantly inferior to the control at both time points (RR = 0.36, 95 %CI: 0.24 to 0.54; RR = 0.39, 95 %CI: 0.26 to 0.57). Univariate meta-regression suggested that age influenced the heterogeneity of the EPDS scores (P = 0.039), and DEX infusion dose was a potential moderator (P = 0.074). The subgroup analysis results of PPD scores at both time points were consistent, showing that: ① Mothers younger than 30 years old had better sensitivity to DEX for treating PPD. ② The anti-PPD efficacy of continuous infusion of DEX by PCIA was superior to both single infusion and combined infusion. ③ DEX showed a better anti-PPD effect when the total infusion dose was ≤ 2 µg/kg. Moreover, DEX improved analgesia and sleep quality, provided appropriate sedation, and reduced the incidence of nausea, vomiting, and chills. The current evidence confirmed the prophylaxis and superiority of DEX for PPD. More high-quality, large-scale RCTs are required for verifying the reliability and formulating administration methods.

Effect of Dexmedetomidine on Postpartum Depression in Women With Prenatal Depression: A Randomized Clinical Trial.

Importance: Postpartum depression (PPD) is emerging as a major public health problem worldwide. Although the particular period and context in which PPD occurs provides an opportunity for preventive interventions, there is still a lack of pharmacologic prevention strategies for PPD. Objective: To assess the efficacy and safety of dexmedetomidine for prevention of PPD among women with prenatal depression undergoing cesarean delivery. Design, Setting, and Participants: This randomized clinical trial enrolled 338 women who screened positive for prenatal depression at 2 hospitals in Hunan, China from March 28, 2022, to April 16, 2023. Women with an Edinburgh Postnatal Depression Scale score of more than 9 who were 18 years of age or older and were scheduled for elective cesarean delivery were eligible. Interventions: Eligible participants were randomly assigned in a 1:1 ratio to either the dexmedetomidine group or the control group via centrally computer-generated group randomization. Dexmedetomidine, 0.5 µg/kg and 0.9% saline were intravenously infused for 10 minutes after delivery in the dexmedetomidine and control groups, respectively. After infusion, sufentanil or dexmedetomidine plus sufentanil was administered via patient-controlled intravenous analgesia for 48 hours in the control group and dexmedetomidine group, respectively. Main Outcomes and Measures: The primary outcome was positive PPD screening results at 7 and 42 days post partum, defined as a postpartum Edinburgh Postnatal Depression Scale score of more than 9. Analysis was on an intention-to-treat basis. Results: All 338 participants were female, with a mean (SD) age of 31.5 (4.1) years. Positive PPD screening incidence at 7 and 42 days post partum in the dexmedetomidine group vs the control group was significantly decreased (day 7, 21 of 167 [12.6%] vs 53 of 165 [32.1%]; risk ratio, 0.39 [95% CI, 0.25-0.62]; P < .001; day 42, 19 of 167 [11.4%] vs 50 of 165 [30.3%]; risk ratio, 0.38 [95% CI, 0.23-0.61]; P < .001). The dexmedetomidine group showed no significant difference in adverse events vs the control group (46 of 169 [27.2%] vs 33 of 169 [19.5%]; P = .10), but the incidence of hypotension increased (31 of 169 [18.3%] vs 16 of 169 [9.5%]; risk ratio, 2.15 [95% CI, 1.13-4.10]; P = .02). Conclusions and Relevance: Dexmedetomidine administration in the early postpartum period significantly reduced the incidence of a positive PPD screening and maintained a favorable safety profile. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200057213.

Predicting efficacy of sub-anesthetic ketamine/esketamine i.v. dose during course of cesarean section for PPD prevention, utilizing traditional logistic regression and machine learning models.

OBJECTIVE: Increasing researches supported that intravenous ketamine/esketamine during the perioperative period of cesarean section could prevent postpartum depression(PPD). With the effective rate ranging from 87.2 % to 95.5 % in PPD, ketamine/esketamine's responsiveness was individualized. To optimize ketamine dose/form based on puerpera prenatal characteristics, reducing adverse events and improving the total efficacy rate, prediction models were developed to predict ketamine/esketamine's efficacy. METHOD: Based on two randomized controlled trials, 12 prenatal features of 507 women administered the ketamine/esketamine intervention were collected. Traditional logistics regression, SVM, random forest, KNN and XGBoost prediction models were established with prenatal features and dosage regimen as predictors. RESULTS: According to the logistic regression model (ain = 0.10, aout = 0.15, area under the receiver operating characteristic curve, AUC = 0.728), prenatal Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10, thoughts of self-injury and bad mood during pregnancy were associated with poorer ketamine efficacy in PPD prevention, whilst a high dose of esketamine (0.25 mg/kg loading dose+2 mg/kg PCIA) was the most effective dosage regimen and esketamine was more recommended rather than ketamine in PPD. The AUCvalidation set of KNN and XGBoost model were 0.815 and 0.651, respectively. CONCLUSION: Logistic regression and machine learning algorithm, especially the KNN model, could predict the effectiveness of ketamine/esketamine iv. during the course of cesarean section for PPD prevention. An individualized preventative strategy could be developed after entering puerpera clinical features into the model, possessing great clinical practice value in reducing PPD incidence.

A novel prognostic signature contributes to precision treatment in colon adenocarcinoma with KRAS mutation.

BACKGROUND: Approximately 40% of colon cancer harbor Kirsten rat sarcoma viral oncogene ( KRAS ) mutations, but the prognostic value of KRAS mutations in colon cancer is still controversial. METHODS: We enrolled 412 colon adenocarcinoma (COAD) patients with KRAS mutations, 644 COAD patients with KRAS wild-type and 357 COAD patients lacking information on KRAS status from five independent cohorts. A random forest model was developed to estimate the KRAS status. The prognostic signature was established using least absolute shrinkage and selection operator-Cox regression and evaluated by Kaplan-Meier survival analysis, multivariate-Cox analysis, receiver operating characteristic curve and nomogram. The expression data of KRAS -mutant COAD cell lines from the Cancer Cell Line Encyclopedia database and the corresponding drug sensitivity data from the Genomics of Drug Sensitivity in Cancer database were used for potential target and agent exploration. RESULTS: We established a 36-gene prognostic signature classifying the KRAS -mutant COAD as high and low risk. High risk patients had inferior prognoses compared to those with low risk, while the signature failed to distinguish the prognosis of COAD with KRAS wild-type. The risk score was the independent prognostic factor for KRAS -mutant COAD and we further fabricated the nomograms with good predictive efficiency. Moreover, we suggested FMNL1 as a potential drug target and three drugs as potential therapeutic agents for KRAS -mutant COAD with high risk. CONCLUSION: We established a precise 36-gene prognostic signature with great performance in prognosis prediction of KRAS -mutant COAD providing a new strategy for personalized prognosis management and precision treatment for KRAS -mutant COAD.

Correlations between GRIN2B and GRIN3A gene polymorphisms and postpartum depressive symptoms in Chinese parturients undergoing cesarean section: A prospective cohort study.

OBJECTIVE: To investigate the association of postpartum depressive symptoms (PDS) and self-harm ideation with n-methyl-d-aspartate (NMDA) receptor GRIN2B and GRIN3A gene polymorphisms and other risk factors in women undergoing cesarean section. METHODS: A total of 362 parturients undergoing cesarean section under lumbar anesthesia were selected and their postpartum depression level was assessed by the Edinburgh Postpartum Depression Scale (EPDS) at 42 days postpartum, with an EPDS score of 9/10 as the cut-off value. Three GRIN2B SNP loci (rs1805476, rs3026174, rs4522263) and five GRIN3A SNP loci (rs1983812, rs2050639, rs2050641, rs3739722, rs10989563) were selected for genotype detection. The role of each SNP, linkage disequilibrium and haplotypes in the development of postpartum depression was analyzed. Logistic regression analysis was performed for related risk factors. RESULTS: PDS incidence was 16.85%, and self-harm ideation incidence was 13.54%. Univariate analysis showed that GRIN2B rs1805476, rs3026174 and rs4522263 gene polymorphisms were associated with PDS (p < 0.05), with GRIN2B rs4522263 gene also associated with maternal self-harm ideation. GRIN3A rs1983812, rs2050639, rest rs2050641, rs3739722 and rs10989563 alleles were not associated with PDS. Logistic regression analysis indicated that high pregnancy stress, as well as rs1805476 and rs4522263 alleles were PDS risk factors following cesarean delivery. GRIN2B (TTG p = 0.002) and GRIN3A (TGTTC p = 0.002) haplotypes were associated with the lower PDS incidence and higher PDS incidence respectively. CONCLUSION: GRIN2B rs1805476 GG genotype, rs4522263 CC genotype and high stress during pregnancy were risk factors for PDS, whilst a significantly higher incidence of self-harm ideation was evident in parturients carrying GRIN2B rs4522263 CC genotype.

An optimization for postpartum depression risk assessment and preventive intervention strategy based machine learning approaches.

BACKGROUND: Postpartum depression (PPD) is one of the most common psychiatric disorders for women after delivery. The establishment of an effective PPD prediction model helps to distinguish high-risk groups, and verifying whether such high-risk groups can benefit from drug intervention is very important for clinical guidance. METHODS: We collected data of parturients that underwent a cesarean delivery. The Control group was divided into a training cohort and a testing cohort. Six different ML models were constructed and we compared their prediction performance in the testing cohort. For model interpretation, we introduced SHapley Additive exPlanations (SHAP). Then, training cohort, ketamine group and dexmedetomidine (DEX) group were classified as high or low risk for PPD by the model. A 1:1 propensity score matching (PSM) was performed to compare the incidence of PPD between two groups in different risk cohorts. RESULTS: Extreme gradient enhancement (XGB) had the best recognition effect, with an area under the receiver operating characteristic curve (AUROC) of 0.789 (95 % CI 0.742-0.836) in the training cohort and 0.744 (95 % CI 0.655-0.823) in the testing cohort, respectively. A threshold of 21.5 % PPD risk probability was determined. After PSM, the results showed that the incidence of PPD in the two intervention groups was significantly different from the control group in the high-risk cohort (P < 0.001) but not in the low-risk cohort (P > 0.001). CONCLUSION: Our study demonstrated that the XGB algorithm provided a more accurate in prediction of PPD risk, and it was beneficial to receive early intervention for the high-risk groups distinguished by the model.

RAB27A promotes the proliferation and invasion of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancer types worldwide. Despite significant advances in prevention and diagnosis, CRC is still one of the leading causes of cancer-related mortality globally. RAB27A, the member of RAB27 family of small GTPases, is the critical protein for intracellular secretion and has been reported to promote tumor progression. However, it is controversial for the role of RAB27A in CRC progression, so we explored the exact function of RAB27A in CRC development in this study. Based on the stable colon cancer cell lines of RAB27A knockdown and ectopic expression, we found that RAB27A knockdown inhibited proliferation and clone formation of SW480 colon cancer cells, whereas ectopic expression of RAB27A in RKO colon cancer cells facilitated cell proliferation and clone formation, indicating that RAB27A is critical for colon cancer cell growth. In addition, our data demonstrated that the migration and invasion of colon cancer cells were suppressed by RAB27A knockdown, but promoted by RAB27A ectopic expression. Therefore, RAB27A is identified as an onco-protein in mediating CRC development, which may be a valuable prognostic indicator and potential therapeutic target for CRC.

Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma.

Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC. Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC). Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%). Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.

Postoperative high-density lipoprotein cholesterol level: an independent prognostic factor for gastric cancer.

Objective: The relationship between serum lipids and prognosis of gastric cancer has not been confirmed. Our purpose in the study was to investigate the associations between preoperative and postoperative serum lipids level and prognosis in patients with gastric cancer. Methods: A retrospective study was performed on 431 patients who received radical (R0) gastrectomy from 2011 to 2013. Preoperative and postoperative serum lipids level were recorded. Clinical-pathological characteristics, oncologic outcomes, disease-free survival (DFS) and overall survival (OS) were collected. The prognostic significance was determined by Kaplan-Meier analysis and Cox proportional hazards regression model. Results: There was no significant difference in DFS and OS according to preoperative serum lipids level. Regarding postoperative serum lipids level, compared to normal high-density lipoprotein cholesterol (HDL-C), low postoperative HDL-C level indicated a shorter OS (hazard ratio: 1.76, 99% confidence interval: 1.31-2.38; P=0.000) and a shorter DFS (hazard ratio: 2.06, 99% confidence interval: 1.55-2.73; P=0.000). However, other postoperative serum lipid molecules were not associated with DFS and OS. Conclusion: Postoperative HDL-C might be an independent prognostic factor of gastric cancer.

A single intravenous administration of a sub-anesthetic ketamine dose during the perioperative period of cesarean section for preventing postpartum depression: A meta-analysis.

The feasibility of intravenous ketamine administration during the perioperative period of cesarean section to prevent postpartum depression (PPD) has not been determined by meta-analysis. To evaluate the efficacy, safety and dose of prophylactic ketamine in offsetting PPD, we retrieved the following databases in English or Chinese from inception to December 2020: Pubmed, Embase, Web of Science, The Cochrane Library, CNKI, VIP and Wanfang. A total of 10 studies (9 RCTs and 1 retrospective study) were included with 2087 cases. Meta-analysis showed that in ketamine group, the score and the prevalence of PPD within 1 week postpartum were significantly reduced, whereas PPD score after 4 weeks postpartum showed no superiority. There was no significant difference in terms of total adverse events rate, although vomiting occurred more frequently in the ketamine group. In addition, we found that ketamine efficacy emerged at 0.5 mg/kg. By meta-regression, we observed that: (1) Age and BMI are negatively associated with mood response to ketamine. (2) An analgesic pump containing ketamine for continuous 48 h postpartum administration was more efficacious than an intravenous injection of ketamine during cesarean section. Current evidence shows ketamine could be efficacious and safe in the prophylactic management of PPD in women having a cesarean section.

Homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to nivolumab in a patient with lung adenocarcinoma: a case report.

Immune checkpoint inhibitors (ICIs) have greatly improved the treatment of advanced non-small-cell lung cancer, including lung adenocarcinoma (LUAD). Patients treated with ICIs can have long-term clinical outcomes; however, acquired resistance to ICI therapy has been frequently observed. To date, little is known about the underlying mechanisms. In this study, we report the case of a male smoker with metastatic LUAD who initially received multi-line radiotherapy and chemotherapy and achieved stable disease (SD) for almost 10 years. The patient was treated with nivolumab for about 15 months. However, the disease later progressed rapidly. A genetic profile of the patient revealed the homozygous deletion of the human leukocyte antigen (HLA)-B gene, which may have conferred the acquired resistance. Our study is the first to describe the homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to programmed cell death protein 1 (PD-1) blockade in a patient with LUAD. This evidence suggests that tumor cells can selectively lose HLA-A, B, and C to survive under strong immune pressure. This discovery enriches and develops our understanding of the mechanism of drug resistance in ICI therapy in LUAD. However, further investigations are urgently needed to be conducted to determine how this resistance can be overcome.

Next-generation sequencing diagnosis of severe pneumonia from fulminant psittacosis with multiple organ failure: a case report and literature review.

This study includes a retrospective analysis of the diagnosis and treatment of a case of severe pneumonia from fulminant psittacosis with multiple organ failure. Next-generation sequencing (NGS) of the pathogen was conducted. The purpose of this study was to summarize the clinical, laboratory, and imaging characteristics of the case and to improve understanding of the value of NGS in the diagnosis of severe community-acquired pneumonia (CAP). Fulminant psittacosis can be manifested as severe pneumonia with rapid progression, acute respiratory distress syndrome, sepsis, and multiple organ failure. Imaging shows unilateral lung consolidation, which is difficult to differentiate from CAP caused by common pathogens. The NGS technology can early detect rare pathogens, thus reducing unnecessary use of antibiotics and shortening the course of the disease.

Double-Stranded DNA in Exosomes of Malignant Pleural Effusions as a Novel DNA Source for EGFR Mutation Detection in Lung Adenocarcinoma.

Background: Exosomes are cell-derived vesicles and bear a specific set of nucleic acids including DNA (exoDNA). Thus, this study is to explore whether exoDNA in malignant pleural effusions (MPEs) could be a novel DNA source for mutation detection of epidermal growth factor receptor (EGFR). Methods: In this study, 52 lung adenocarcinoma patients were enrolled, and EGFR mutation status was detected with tumor tissues as well as cell blocks and exosomes in MPEs. The sensitivity, specificity and consistency of EGFR detection using exosomes were evaluated, compared with gene detection using tumor tissues and cell blocks. And the clinical response of patients who were detected as EGFR mutation in exosomes and treated with EGFR tyrosine kinase inhibitor (EGFR-TKI) was explored. Results: Gene detection using exosomes showed sensitivity of 100%, specificity of 96.55% and coincidence rate of 98.08% (Kappa = 0.961, P < 0.001), compared with detection using tumor tissues and cell blocks. After EGFR-TKI treatment, patients detected as EGFR mutation by exosomes showed efficacy rate of 83% and disease control rate of 100%. And patients who were detected as wild type in tumor tissues or cell blocks but EGFR mutation in exosomes turned up as PR or SD. Conclusions: These results demonstrated that exoDNA in MPEs could be used as a DNA source for EGFR detection in lung adenocarcinoma.

Advances in nanotechnology and asthma.

According to the World Health Organization, Asthma is the fastest-growing disease in the world alongside HIV/AIDS, and its socioeconomic burden exceeds the sum of HIV/AIDS and tuberculosis. Its high disability and mortality rates have become serious social and public health concerns. Asthma is a heterogeneous disease in which genetic polymorphisms interact with the environmental factors. While no specific treatment has been available for asthma due to its complex pathogenesis, the advances in nanotechnology have brought new hope for the early diagnosis, treatment, and prevention of asthma. Nanotechnology can achieve targeted delivery of drugs or genes, reduce toxic effects, and improve drug bioavailability. The nano-modifications of drugs and the development of new nano-drugs have become new research directions. Studies have demonstrated the safety and effectiveness of nanocarriers. However, many challenges still need to be overcome before nanotherapy can be applied in clinical practice. In this article we review the new research highlights in this area, with an attempt to explore the great potential and feasibility of nanotechnology in treating asthma.

A novel FAPα-based Z-Gly-Pro epirubicin prodrug for improving tumor-targeting chemotherapy.

Fibroblast activation protein-α (FAPα) is a serine protease of the post-prolyl peptidase family that is specifically expressed in the majority of human epithelial tumors, but not in normal tissues. In this study, we demonstrated the anti-tumor activity of a novel targeting drug formed by conjugating epirubicin (EPI) with an FAPα-specific dipeptide (Z-Gly-Pro) and named it Z-GP-EPI. Consistent with this tumor-targeting delivery strategy, the results illustrated that Z-GP-EPI could release EPI efficiently after incubating with FAPα and could exhibit similar antitumor effects as EPI in vitro in FAPα over-expressed tumor cells (4T1/FAPα+). Furthermore, the evaluation of antitumor activity of Z-GP-EPI in vivo was implemented in a 4T1/FAPα+ tumor-bearing mice xenograft model. Our results illustrated that Z-GP-EPI had similar antitumor effects in 4T1/FAPα+ tumor-bearing mice and showed no visible cardiotoxicity side effects compared with free EPI. Thus, our study indicated that this FAPα-activated prodrug targeting strategy may provide a new mechanism for the targeted delivery of antitumor agents and improve their safety levels.

Molecular dysexpression in gastric cancer revealed by integrated analysis of transcriptome data.

Gastric cancer (GC) is often diagnosed in the advanced stages and is associated with a poor prognosis. Obtaining an in depth understanding of the molecular mechanisms of GC has lagged behind compared with other cancers. This study aimed to identify candidate biomarkers for GC. An integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between GC and normal tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed to identify the functions of the DEGs. Furthermore, a protein-protein interaction (PPI) network of the DEGs was constructed. The expression levels of the DEGs were validated in human GC tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A set of 689 DEGs were identified in GC tissues, as compared with normal tissues, including 202 upregulated DEGs and 487 downregulated DEGs. The KEGG pathway analysis suggested that various pathways may play important roles in the pathology of GC, including pathways related to protein digestion and absorption, extracellular matrix-receptor interaction, and the metabolism of xenobiotics by cytochrome P450. The PPI network analysis indicated that the significant hub proteins consisted of SPP1, TOP2A and ARPC1B. RT-qPCR validation indicated that the expression levels of the top 10 most significantly dysexpressed genes were consistent with the illustration of the integrated analysis. The present study yielded a reference list of reliable DEGs, which represents a robust pool of candidates for further evaluation of GC pathogenesis and treatment.

KRAS and BRAF mutations in serum exosomes from patients with colorectal cancer in a Chinese population.

The efficacy of epidermal growth factor receptor- targeted therapy is significantly associated with Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-raf serine/threonine kinase proto-oncogene (BRAF) mutation in patients with colorectal cancer (CRC), for which the standard gene testing is currently performed using tumor tissue DNA. The aim of the present study was to compare the presence of KRAS and BRAF mutations in the serum exosome and primary tumor tissue from patients with CRC. Genomic DNA were extracted from the tumor tissues of 35 patients with histologically-confirmed CRC and exosomal mRNA were obtained from peripheral blood, which were collected from the corresponding patients prior to surgery. Three mutations in the KRAS gene (codons 12, 13 and 61) and a mutation in the BRAF gene (codon 600) were detected using a polymerase chain reaction-based sequencing method and their presence were compared between tumor tissues and the matched serum exosomes. The KRAS mutation rates in tumor tissues and the matched serum exosomes were 57.6 and 42.4%, respectively, which was not significantly different (P=0.063). The detection rate of the BRAF mutation was 24.2 and 18.2% in tumor tissues and the matched serum exosomes, respectively, and there was no significant difference (P=0.500). The patients with CRC that had a KRAS mutation of codon 12 in exon 2 in their tumor tissues and serum exosomes were significantly older compared with those without this mutation (tumor tissue, P=0.002; serum exosome, P=0.022). The sensitivity of KRAS and BRAF mutation detection using exosomal mRNA was 73.7 and 75%, respectively. The specificity of the detected mutations exhibited an efficiency of 100%, and the total consistency rate was 94.9 and 93.9% for KRAS and BRAF mutations, respectively. These results suggested that serum exosomal mRNA may be used as a novel source for the rapid and non-invasive genotyping of patients with CRC.

Effectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis.

Circulating tumor DNA (ctDNA) can be identified in the peripheral blood of patients and harbors the genomic alterations found in tumor tissues, which provides a noninvasive approach for detection of gene mutations. We conducted this meta-analysis to investigate whether ctDNA can be used for monitoring KRAS gene mutations in colorectal cancer (CRC) patients. Medline, Embase, Cochrane Library and Web of Science were searched for the included eligible studies in English, and data were extracted for statistical analysis according to the numbers of true-positive (TP), true-negative (TN), false-positive (FP) and false-negative (FN) cases. Sensitivity, specificity and diagnostic odds ratio (DOR) were calculated, and the area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. After independent searching and reviewing, 21 studies involving 1,812 cancer patients were analyzed. The overall sensitivity, specificity and DOR were 0.67 (95% confidence interval [CI] =0.55-0.78), 0.96 (95% CI =0.93-0.98) and 53.95 (95% CI =26.24-110.92), respectively. The AUROC was 0.95 (95% CI =0.92-0.96), which indicated the high diagnostic accuracy of ctDNA. After stratified analysis, we found the higher diagnostic accuracy in subgroup of patients detected in blood sample of plasma. The ctDNA may be an ideal source for detection of KRAS gene mutations in CRC patients with high specificity and diagnostic value.

A transcriptome profile in hepatocellular carcinomas based on integrated analysis of microarray studies.

BACKGROUND: Despite new treatment options for hepatocellular carcinomas (HCC) recently, 5-year survival remains poor, ranging from 50 to 70%, which may attribute to the lack of early diagnostic biomarkers. Thus, developing new biomarkers for early diagnosis of HCC, is extremely urgent, aiming to decrease HCC-related deaths. METHODS: In the study, we conducted a comprehensive characterization of gene expression data of HCC based on a bioinformatics method. The results were confirmed by real time polymerase chain reaction (RT-PCR) and TCGA database to prove the credibility of this integrated analysis. RESULTS: After integrating analysis of seven HCC gene expression datasets, 1167 differential expressed genes (DEGs) were identified. These genes mainly participated in the process of cell cycle, oocyte meiosis, and oocyte maturation mediated by progesterone. The results of experiments and TCGA database validation in 10 genes was in full accordance with findings in integrated analysis, indicating the high credibility of our integrated analysis of different gene expression datasets. ASPM, CCT3, and NEK2 was showed to be significantly associated with overall survival of HCC patients in TCGA database. CONCLUSION: This method of integrated analysis may be a useful tool to minish the heterogeneity of individual microarray, hopefully outputs more accurate HCC transcriptome profiles based on large sample size, and explores some potential biomarkers and therapy targets for HCC.