A comparative study of the chloroplast genomes of five Lepidium species with high medicinal value.

Plantgenomics is a rapidly developing field in medicinal plant research. This study analysed the relevant information of chloroplasts genome sequences of five medicinal plants from the genus Lepidium . We sequenced the complete chloroplast (cp) genomes of Lepidium apetalum Willd. and Lepidium perfoliatum Linnaeus., and assessed their genetic profiles against the reported profiles of Lepidium sativum Linnaeus., Lepidium meyenii Walp., and Lepidium virginicum Linn. We found that L. apetalum and L. perfoliatum possessed 130 distinct genes that included 85 protein-coding, 37 transfer RNA (tRNA), and eight ribosomal RNA (rRNA) genes. Our repeat analyses revealed that L. apetalum harboured 20 direct repeats, 16 palindrome repeats, 30 tandem repeats, and 87 simple sequence repeats, whereas, L. perfoliatum had 15 direct repeats, 20 palindrome repeats, four reverse repeats, 21 tandem repeats, and 98 simple sequence repeats. Using syntenic analysis, we also revealed a high degree of sequence similarity within the coding regions of Lepidium medicinal plant cp genomes, and a high degree of divergence among the intergenic spacers. Pairwise alignment and single-nucleotide polymorphism (SNP) examinations further revealed certain Lepidium -specific gene fragments. Codon usage analysis showed that codon 14 was the most frequently used codon in the Lepidium coding sequences. Further, correlation investigations suggest that L. apetalum and L. perfoliatum originate from similar genetic backgrounds. Analysis of codon usage bias of Lepidium cp genome was strongly influenced by mutation and natural selection. We showed that L. apetalum and L. perfoliatum will likely enhance breeding, species recognition, phylogenetic evolution, and cp genetic engineering of the Lepidium medicinal plants.

Anesthesia and perioperative management for giant adrenal Ewing's sarcoma with inferior vena cava and right atrium tumor thrombus: A case report.

BACKGROUND: Ewing's sarcoma of the adrenal gland with inferior vena cava (IVC) and right atrium thrombus is extremely rare. Here, we report a case of giant adrenal Ewing's sarcoma with IVC and right atrium tumor thrombus and summarize the anesthesia and perioperative management. CASE SUMMARY: A young female was admitted to the Department of Urology with intermittent pain under the right costal arch for four months. Enhanced abdominal computed tomography revealed a large retroperitoneal mass (22 cm in diameter), which may have originated from the right adrenal gland and was closely related to the liver. Transthoracic echocardiography showed a strong echogenic filling measuring 70 mm extended from the IVC into the right atrium and ventricle. After preoperative preparation with cardiopulmonary bypass, sufficient blood products, transesophageal echocardiography and multiple monitoring, tumor and thrombus resection by IVC exploration and right atriotomy were successfully performed by a multidisciplinary team. Intraoperative hemodynamic stability was the major concern of anesthesiologists and the status of tumor thrombus and pulmonary embolism were monitored continuously. During transfer of the patient to the intensive care unit (ICU), cardiac arrest occurred without external stimulus. Cardiopulmonary resuscitation was performed immediately and cardiac function was restored after 1 min. In the ICU, extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) were provided to maintain cardiac, liver and kidney function. Histopathologic examination confirmed the diagnosis of Ewing's sarcoma. After postoperative treatments and rehabilitation, the patient was discharged from the urology ward. CONCLUSION: An adrenal Ewing's sarcoma with IVC and right atrium thrombus is extremely rare, and its anesthesia and perioperative management have not been reported. Thus, this report provides significant insights in the perioperative management of patients with adrenal Ewing's sarcoma and IVC tumor thrombus. Intraoperative circulation fluctuations and sudden cardiovascular events are the major challenges during surgery. In addition, postoperative treatments including ECMO and CRRT provide essential support in critically ill patients. Moreover, this case report also highlights the importance of multidisciplinary cooperation during treatment of the disease.

Genome-Scale Methylation Analysis of Circulating Cell-Free DNA in Gastric Cancer Patients.

BACKGROUND: Aberrant DNA hypermethylation of CpG islands (CGIs) occurs frequently and is genome-wide in human gastric cancer (GC). A DNA methylation approach in plasma cell-free DNA (cfDNA) is attractive for the noninvasive detection of GC. Here, we performed genome-scale cfDNA methylation analysis in patients with GC. METHODS: We used MCTA-Seq, a genome-scale DNA methylation analysis method, on the plasma samples of patients with GC (n = 89) and control participants (n = 82), as well as 28 pairs of GC and adjacent noncancerous tissues. The capacity of the method for detecting GC and discriminating GC from colorectal cancer (CRC) and hepatocellular carcinoma (HCC) was assessed. RESULTS: We identified 153 cfDNA methylation biomarkers, including DOCK10, CABIN1, and KCNQ5, for detecting GC in blood. A panel of these biomarkers gave a sensitivity of 44%, 59%, 78%, and 100% for stage I, II, III, and IV tumors, respectively, at a specificity of 92%. CpG island methylation phenotype (CIMP) tumors and NON-CIMP tumors could be distinguished and detected effectively. We also identified several hundreds of cfDNA biomarkers differentially methylated between GC, CRC, and HCC, and showed that MCTA-Seq can discriminate early-stage GC, CRC, and HCC in blood by using a high specificity (approximately 100%) algorithm. CONCLUSIONS: Our comprehensive analyses provided valuable data on cfDNA methylation biomarkers of GC and showed the promise of cfDNA methylation for the blood-based noninvasive detection of GC.

Effects of continuous cropping Jiashi muskmelon on rhizosphere microbial community.

Introduction: The continuous cropping of crops can result in the deterioration of the soil environment and cause a decline in plant health and yield, which complicates agricultural production. However, the effects of continuous melon cropping on rhizospheric microbial communities remain poorly understood. Methods: In this study, high-throughput absolute quantification 16S rRNA gene amplicon sequencing was employed to analyze the bacterial community structure of greenhouse rhizosphere soil from Jiashi muskmelon replanted for 0, 1, 2, and 3 years (CK, 1a, 2a, and 3a, respectively). Results: The results showed that long- term continuous cropping caused significant changes in soil physicochemical properties. The bacterial absolute abundances increased, but the bacterial community richness and diversity were significantly lost (p < 0.05). The composition of bacterial community was more similar after 2 and 3 years of continuous cropping. The longer the continuous cropping years were, the greater the shift in the bacterial diversity and abundance. Analysis of potential functional components revealed that different bacterial groups were enriched in different continuous cropping years. The significant reduction of the taxa associated with nitrate reduction may be responsible for the loss of soil nitrogen in continuous cropping soil. Discussion: In summary, continuous cropping had a significant impact on the bacterial community structure of Jiashi muskmelon rhizospheric soil, and these results will provide a reference for soil management and scientific fertilization of melon and other crops under a continuous cropping regime.

Isolation and Characterization of Cold-Adapted PGPB and Their Effect on Plant Growth Promotion.

Cold-adapted plant growth-promoting bacteria (PGPB) with multiple functions are an important resource for microbial fertilizers with low-temperature application. In this study, culturable cold-adapted PGPB strains with nitrogen fixation and phosphorus solubilization abilities were isolated. They were screened from root and rhizosphere of four dominant grass species in nondegraded alpine grasslands of the Qilian Mountains, China. Their other growth-promoting characteristics, including secretion of indole-3-acetic acid (IAA), production of siderophores and ACC deaminase, and antifungal activity, were further studied by qualitative and quantitative methods. In addition, whether the PGPB strains could still exert plant growth-promoting activity at 4°C was verified. The results showed that 67 isolates could maintain one or more growth-promoting traits at 4°C, and these isolates were defined as cold-adapted PGPB. They were divided into 8 genera by 16S rRNA gene sequencing and phylogenetic analysis, of which Pseudomonas (64.2%) and Serratia (13.4%) were the common dominant genera, and a few specific genera varied among the plant species. A test-tube culture showed that inoculation of Elymus nutans seedlings with cold-adapted PGPB possessing different functional characteristics had a significant growth-promoting effect under controlled low-temperature conditions, including the development of the roots and aboveground parts. Pearson correlation analysis revealed that different growth-promoting characteristics made different contributions to the development of the roots and aboveground parts. These cold-adapted PGPB can be used as excellent strain resources suitable for the near-natural restoration of degraded alpine grasslands or agriculture stock production in cold areas.

CTCs detection from intraoperative salvaged blood in RCC-IVC thrombus patients by negative enrichment and iFISH identification: a preliminary study.

BACKGROUND: Intra-operative cell salvage (IOCS) and leukocyte-depleted filter (LDF) are widely used and effective in saving blood. However, the safety issue concerning reinfusion of IOCS-LDF processed blood to renal cell carcinoma (RCC) patients with inferior vena cava (IVC) thrombus were inconclusive for fear of increased risk of cancer metastases. This study intends to analyze the circulating tumor cell (CTC) eliminating effect of IOCS-LDF in 5 RCC-IVC thrombus patients. METHODS: A novel strategy integrating negative enrichment by immunomagnetic beads and immunostaining-fluorescence in situ hybridization with probes identifying aneuploid of 8 and/or 7 were used to detect CTCs from salvages blood. Blood samples were collected from 4 stages in each patient. RESULTS: Of the 5 RCC patients, the number of CTCs decreased (from 3, 4, 10, 7, 3, respectively, to all zero) after IOCS-LDF treatment. The triploid of chromosome 7 and/or chromosome 8 were most common karyotype for RCC patients with IVC thrombus. Tetraploid of chromosome 8 occurred in only one sample and no polypoid (number of chromosome > 4) were found. CONCLUSION: IOCS-LDF might be a promising way of reducing of allogeneic product transfusion based on current preliminary outcome. More convincing conclusions are to be drawn with enlarged sample size and long-term follow-up for patients prognosis.

Bacterial Diversity and Community Structure in the Rhizosphere of Four Halophytes.

The study of the rhizosphere microbial community in salinized soils aids in the elucidation of new and important microbial functional groups, which is of great importance in vegetation restoration and ecological reconstruction of salinized soil. The rhizosphere soil bacterial diversity and community structures of four halophytes, including Kalidium foliatum, Lycium ruthenicum, Karelinia caspia and Phragmites australis, typically distributed in the saline-alkaline land of Southern Xinjiang, China, were studied using an Illumina paired-end sequence platform. The study aims to reveal the alpha diversity, species composition, abundance and the differences of rhizosphere bacteria among the four halophytes, explore their correlation with environmental factors. The results showed that the highest bacterial species diversity was associated with P. communis, followed by K. foliatum, K. caspia, and L. ruthenicum. The species richness was the lowest for L. ruthenicum, while the others showed no significant difference. Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes were the most dominant phyla. And Bacillus and Halomonas were the most common dominant genera. The bacterial communities associated with K. foliatum and K. caspia were similar, while that of L. ruthenicum was significantly different from other halophytes. Soil total nitrogen and total phosphorus, soil organic matter, soil water content, electronic conductivity and pH were identified as the key factors affecting bacterial abundance associated with the assayed halophytes. These results indicate that the four halophytes evaluated in the present study have a similar rhizosphere bacterial community structure due to their being in the same region. However, the bacterial abundance is different among the plant species, and soil properties are the important factors driving the structures of bacterial communities.

The complete chloroplast genome sequence of Lepidium perfoliatum L.

This study was based on the collection of the complete genome of Lepidium perfoliatum chloroplast (cp). The full cp genome is 154,264 bp long, containing 130 genes, in which 8 genes are specified for ribosomal RNA (rRNA), while 85 and 37 genes for protein-coding and transfer RNA (tRNA) respectively. Phylogenetic analyss revealed the closed cluster of Lepidium perfoliatum with other Lepidium species such as Lepidium apetalum, Lepidium sativum, Lepidium meyenii and Lepidium virginicum, which helps for the evaluation of how Lepidium perfoliatum is phylogenetically related to other species.

Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine.

The intestine plays an important role in nutrient digestion and absorption, microbe defense, and hormone secretion. Although major cell types have been identified in the mouse intestinal epithelium, cell type-specific markers and functional assignments are largely unavailable for human intestine. Here, our single-cell RNA-seq analyses of 14,537 epithelial cells from human ileum, colon, and rectum reveal different nutrient absorption preferences in the small and large intestine, suggest the existence of Paneth-like cells in the large intestine, and identify potential new marker genes for human transient-amplifying cells and goblet cells. We have validated some of these insights by quantitative PCR, immunofluorescence, and functional analyses. Furthermore, we show both common and differential features of the cellular landscapes between the human and mouse ilea. Therefore, our data provide the basis for detailed characterization of human intestine cell constitution and functions, which would be helpful for a better understanding of human intestine disorders, such as inflammatory bowel disease and intestinal tumorigenesis.

Detection of Colorectal Cancer in Circulating Cell-Free DNA by Methylated CpG Tandem Amplification and Sequencing.

BACKGROUND: Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-wide DNA hypermethylation analysis technique using circulating cell-free DNA (cfDNA) is attractive for the noninvasive early detection of CRC and discrimination between CRC and other cancer types. METHODS: We applied the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, with a fully methylated molecules algorithm, to plasma samples from patients with CRC (n = 147) and controls (n = 136), as well as cancer and adjacent noncancerous tissue samples (n = 66). We also comparatively analyzed plasma samples from patients with hepatocellular carcinoma (HCC; n = 36). RESULTS: Dozens of DNA hypermethylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5, CHST11, APBB1IP, and TJP2) genes were identified for effectively detecting CRC in cfDNA. A panel of 80 markers discriminated early-stage CRC patients and controls with a clinical sensitivity of 74% and clinical specificity of 90%. Patients with early-stage CRC and HCC could be discriminated at clinical sensitivities of approximately 70% by another panel of 128 markers. CONCLUSIONS: MCTA-Seq is a promising method for the noninvasive detection of CRC.

Disruption of Phaffia rhodozyma cells and preparation of microencapsulated astaxanthin with high water solubility.

A novel process was developed for encapsulation of astaxanthin from Phaffia rhodozyma. The yeast cells were disrupted by glass beads and the high shearing force partially emulsified the astaxanthin in aqueous phase. The enzymolysis method was then adopted to prepare the yeast extract for a full use of the cells. The gelatin and porous starch were used to microencapsulate the emulsified astaxanthin. Under optimized conditions, the recovery of amino nitrogen and solid reached 3.68 ± 0.32% and 49.22 ± 2.34%, respectively. The microencapsulation conditions were optimized through orthogonal experiment and the encapsulation efficiency, loading astaxanthin, and amino-nitrogen reached 88.56%, 1.55 mg/g, and 1.35 ± 0.14%, respectively. The water solubility of microcapsules reached 81.5 ± 0.35%. Color and storage stability analysis showed that microencapsulation of astaxanthin possessed higher thermal stability. The results demonstrated that the established process was effective and practical.

Single-cell multiomics sequencing and analyses of human colorectal cancer.

Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multiomics sequencing together with multiregional sampling of the primary tumor and lymphatic and distant metastases, we developed insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 patients whose DNA we sequenced. The cancer cells' DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue and those of repetitive element long interspersed nuclear element 1. Our work demonstrates the feasibility of reconstructing genetic lineages and tracing their epigenomic and transcriptomic dynamics with single-cell multiomics sequencing.

A growth factor-free culture system underscores the coordination between Wnt and BMP signaling in Lgr5+ intestinal stem cell maintenance.

Lgr5+ intestinal stem cells (ISCs) drive the fast renewal of intestinal epithelium. Several signaling pathways have been shown to regulate ISC fates. However, it is unclear what are the essential signals to sustain the ISC self-renewal. Here we show that coordination between Wnt and BMP signaling activity is necessary and sufficient to maintain Lgr5+ ISCs self-renewal. The key function of R-spondin1 is to achieve a high activity of Wnt signaling in the organoid culture. Using the GSK3 inhibitor CHIR-99021 and the BMP type I receptor inhibitor LDN-193189, we can maintain Lgr5+ ISCs without growth factors in vitro. Our results define the basic signaling pathways sustaining Lgr5+ ISCs and set up a convenient and economical culture system for their in vitro expansion. This work also set up an example for growth factor-free culture of other adult stem cells.

Investigation on hydrogen production from paper sludge without inoculation and its enhancement by Clostridium thermocellum.

The feasibility and performance of hydrogen production from paper sludge without inoculation was investigated under thermophilic conditions. The maximum hydrogen production reached 64.32 mM with 7.4% PS. The dynamic changes in bacterial community structures during hydrogen production were investigated by analyzing 16S rDNA gene sequences using high throughput sequencing technology. The results showed that microbial community was dominated by order Clostridiales and Thermoanaerobacterales. Genus Thermoanaerobacterium and Ruminiclostridium played a leading role in the fermentation process, which was responsible for the hydrolysis of PS and hydrogen production. Effect of inoculation with Clostridium thermocellum on hydrogen production from PS was also studied. The results showed that C. thermocellum supplement significantly increased hydrogen yield and holocellulose degradation rate by 96.80% and 32.95%, respectively. In addition, inoculation of C. thermocellum enhanced VFA generation and shortened the lag phase of hydrogen production. The present study lays the foundation on the valorization of waste lignocellulose.

TGF-ß signaling regulates DACT1 expression in intestinal epithelial cells.

DACT1, was first identified as a Dishevelled-associated antagonist of Wnt signaling pathway. It has been reported that DACT1 functions in embryonic development and tumorigenesis. However, the regulation of DACT1 still remains unclear. We found Wnt signaling has no effect on DACT1, but TGF-ß increases expression of DACT1 in intestinal epithelial cells. In addition, the minimal promoter is located in the region of -500bp to +1bp and the region between -3000bp to +1bp enhanced promoter activity. Site-directed mutation analysis was performed and indicated that potential regulatory elements was near -335bp. Our study provided the basic information for the exploration of DACT1 regulation and expression. Moreover, TGF-ß inhibits Wnt signaling to enhance the function of DACT1 inhibiting Wnt signaling.

TGFß induced factor homeobox 1 promotes colorectal cancer development through activating Wnt/ß-catenin signaling.

Colorectal cancer (CRC) is one of the most common cancers, but the mechanisms underlying its initiation and progression are largely unknown. TGIF1 (TGFB induced factor homeobox 1) is a transcriptional corepressor that belongs to the three-amino acid loop extension (TALE) superclass of atypical homeodomains. It has been reported that TGIF1 is highly expressed in mammary cancer and non-small cell lung cancer and can enhance tumor progression. However, the role of TGIF1 in colorectal cancer remains unknown. Here, we report that TGIF1 is significantly upregulated in colorectal cancers, and its high expression predicts poor prognosis. Overexpression of TGIF1 markedly promotes the proliferation of colorectal cancer cells both in vivo and in vitro. In addition, TGIF1 activates Wnt/ß-catenin signaling, and the homeodomain is indispensable for Wnt activation and ß-catenin interaction. Taken together, our results suggest that TGIF1 is a novel colorectal tumor promoter and indicate that TGIF1 enhances colorectal cancer tumorigenesis through activating Wnt signaling.

Comparison between different approaches applied in laparoscopic right hemi-colectomy: A systematic review and network meta-analysis.

AIM: Several different operative approaches have been applied nowadays in laparoscopic right hemi-colectomy. This study aims to evaluate the potential benefits of different approaches by conducting a network meta-analysis (NMA). METHOD: A comprehensive literature research of the PubMed, Embase, Medline, the Cochrane Central Library, Wan Fang and China National Knowledge Infrastructure (CNKI) databases was performed. Original articles comparing two of three different approaches including medial to lateral (MtL) approach, lateral to medial (LtM) approach and cranial to caudal (CtC) approach of laparoscopic right colon resection for patients with both neoplastic and benign diseases were included. RESULTS: 3 RCTs and 3 NRCTs with a total of 571 patients were included in this NMA. The result revealed that LtM approach needs shorter postoperative flatus recovery time than both MtL approach with a WMD of 1.40 (95% CI: 0.13 to 2.67, P < 0.05) and CtC approach (WMD = -1.25, 95% CI: -1.90 to -0.61, P < 0.05). The length of hospital stay of LtM approach is shorter than that of MtL approach (WMD = 0.29, 95% CI: 0.08 to 0.50, P < 0.05). CtC approach can achieve less postoperative complications (OR = 3.37, 95% CI: 1.06 to 10.70, P < 0.05) compared with MtL approach. CONCLUSION: All three approaches are safe and acceptable in laparoscopic right hemi-colectomy since the pooled evidence revealed that most aspects of different approaches are comparable in general. The postoperative flatus recovery time and hospitalization time of LtM approach is shorter compared with MtL approach. And CtC approach may have slight superiority in postoperative complications compared with MtL approach.

Risk Factors Associated With Nonclosure of Defunctioning Stomas After Sphincter-Preserving Low Anterior Resection of Rectal Cancer: A Meta-Analysis.

BACKGROUND: Some patients receiving defunctioning stomas will never undergo stoma reversal, but it is difficult to preoperatively predict which patients will be affected. OBJECTIVE: The aim of this meta-analysis was to identify the risk factors associated with nonclosure of temporary stomas after sphincter-preserving low anterior resection for rectal cancer. DATA SOURCES: We performed a comprehensive search of the PubMed, Embase, and Cochrane Central Library databases for all of the studies analyzing risk factors for nonclosure of defunctioning stomas. STUDY SELECTION: We only included articles published in English in this meta-analysis. The inclusion criteria were as follows: 1) original article with extractable data, 2) studies including only defunctioning stomas created after low anterior resection for rectal cancer, 3) studies with nonclosure rather than delayed closure as the main end point, and 4) studies analyzing risk factors for nonclosure. INTERVENTION: Defunctioning stomas were created after low anterior resection for rectal cancer. MAIN OUTCOME MEASURES: Stoma nonclosure was the only end point, and it included nonclosure and permanent stoma creation after primary stoma closure. The Newcastle-Ottawa Scale was used to assess methodologic quality of the studies, and risk ratios and 95% CIs were used to assess risk factors. RESULTS: Ten studies with 8568 patients were included. The nonclosure rate was 19% (95% CI, 13%-24%; p < 0.001; I= 96.2%). Three demographic factors were significantly associated with nonclosure: older age (risk ratio= 1.50 (95% CI, 1.12-2.02); p = 0.007; I= 39.3%), ASA score >2 (risk ratio = 1.66 (95% CI, 1.51-1.83); p < 0.001; I= 0%), and comorbidities (risk ratio = 1.58 (95% CI, 1.29-1.95); p < 0.001; I= 52.6%). Surgical complications (risk ratio = 1.89 (95% CI, 1.48-2.41); p < 0.001; I= 29.7%), postoperative anastomotic leakage (risk ratio = 3.39 (95% CI, 2.41-4.75); p < 0.001; I= 53.0%), stage IV tumor (risk ratio = 2.96 (95% CI, 1.73-5.09); p < 0.001; I= 88.1%), and local recurrence (risk ratio = 2.84 (95% CI, 2.11-3.83); p < 0.001; I= 6.8%) were strong clinical risk factors for nonclosure. Open surgery (risk ratio = 1.47 (95% CI, 1.01-2.15); p = 0.044; I= 63.6%) showed a borderline significant association with nonclosure. LIMITATIONS: Data on some risk factors could not be pooled because of the low number of studies. There was conspicuous heterogeneity between the included studies, so the pooled data were not absolutely free of exaggeration or influence. CONCLUSIONS: Older age, ASA score >2, comorbidities, open surgery, surgical complications, anastomotic leakage, stage IV tumor, and local recurrence are risk factors for nonclosure of defunctioning stomas after low anterior resection in patients with rectal cancer, whereas tumor height, radiotherapy, and chemotherapy are not. Patients with these risk factors should be informed preoperatively of the possibility of nonreversal, and joint decision-making is preferred.

High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma.

AIMS: Recent studies showed that muscarinic acetylcholine receptor 3 (M3), as a muscarinic acetylcholine receptor family member that plays an important role in normal physiological function, is engaged in cancer progression. However, the role of M3 in pancreatic ductal adenocarcinoma (PDAC) is not known. The aim of this study is to investigate the expression and prognostic value of M3 in patients with PDAC. MATERIALS AND METHODS: The localization and expression of M3 in PDAC were examined by immunohistochemistry. VAChT was employed to detect parasympathetic nerve fibers in the corresponding M3 PDAC tissues. The correlation between M3 expression and patients' survival was assessed by Kaplan-Meier analysis. RESULTS: M3 was discovered predominantly localized in the cell cytoplasm and expressed in all specimens of PDAC patients. Significant correlation was noted between increased M3 intensity and high grade of PDAC (P<0.01), more lymph node metastasis (P<0.01) as well as shorter patient overall survival (P<0.01). Morphologically, cells with high M3 expression were more frequently located at the invasive tumor front/tumor budding cells, metastatic lymph nodes and parasympathetic nerve fibers. CONCLUSION: High expression of M3 is a prognostic marker for PDAC.

Heart rate variability in the prediction of survival in patients with cancer: A systematic review and meta-analysis.

PURPOSE: Although the predictive value of vagal nerve activity, indexed by heart rate variability (HRV), has been confirmed in a variety of diseases, its value in the prediction of survival in cancer patients still remains controversial. The aim of this meta-analysis was to evaluate the predictive value of HRV in cancer patients in an evidence based manner. METHODS: A systematic review and meta-analysis was conducted through a comprehensive search of the PubMed, EMBASE and the Cochrane Central Library databases for all studies regarding HRV, vagal nerve activity and cancer. Pooled data of overall survival was analyzed. RESULTS: Six studies with 1286 patients were included in our meta analysis. Analysis of the pooled data revealed that overall survival was significantly longer in the higher HRV group than in the lower HRV group (HR 0.70, 95% CI [0.60, 0.82]; P<0.001, I2=27%). CONCLUSION: The current evidence indicates a predictive value of HRV in the survival of patients with cancer and higher vagal nerve activity might predict longer survival, but the results should be applied with caution considering the heterogeneity between included studies.