Comprehensive multi-omics analysis and experimental verification reveal PFDN5 is a novel prognostic and therapeutic biomarker for gastric cancer.

Prefoldin Subunit 5 (PFDN5) plays a critical role as a member of the prefoldins (PFDNs) in maintaining a finely tuned equilibrium between protein production and degradation. However, there has been no comprehensive analysis specifically focused on PFDN5 thus far. Here, a comprehensive multi-omics (transcriptomics, genomics, and proteomics) analysis, systematic molecular biology experiments (in vitro and in vivo), transcriptome sequencing and PCR Array were performed for identifying the value of PFDN5 in pan-cancer, especially in Gastric Cancer (GC). We found PFDN5 had the potential to serve as a prognostic and therapeutic biomarker in GC. And PFDN5 could promote the proliferation of GC cells, primarily by affecting the cell cycle, cell death and immune process etc. These findings provide novel insights into the molecular mechanisms and precise treatments of in GC.

The gut microbiota-constipation connection: Insights from a two sample bidirectional Mendelian randomization study.

OBJECTIVE: The dysbiosis of the gut microbiota has been implicated in various maladies. Research has identified an association between the dysbiosis of the gut microbiota and the risk of constipation, prompting this study to elucidate the potential causal relationship between gut microbiota imbalance with constipation through a two sample bidirectional Mendelian randomization (MR) study, shedding light on the genetic mechanisms underlying the connection between gut microbiota and constipation. METHODS: The forward MR analysis aimed to scrutinize whether alterations in the composition and abundance of gut microbiota impact the risk of constipation, while the reverse MR analysis explored whether the genetic predisposition to constipation influences the abundance of gut microbiota. Genomic correlation data for the gut microbiota were sourced from the comprehensive statistics of the MiBioGen consortium. Genomic correlation data for constipation were obtained from the IEU database, encoded as the dataset ebi-a-GCST90018829. The correlation was assessed using various analytical techniques, including inverse variance weighting (IVW), Mendelian randomization-Egger regression (MR-Egger), and weighted median and mode methodologies. To ensure the robustness of the results, a meticulous sensitivity analysis was conducted, incorporating Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and a Leave-one-out analysis. RESULTS: In the forward Mendelian randomization analyses, a negative correlation was discerned between the abundance of Coprococcus in the gut microbiota and the occurrence of constipation (IVW: OR = 0.74, 95 % CI = 0.64-0.86, p = 0.0001), whereas a positive correlation was observed between the abundance of Bacteroidetes in the gut microbiota and constipation (IVW: OR = 1.22, 95 % CI = 1.00-1.50, p = 0.04). In the forward Mendelian randomization analyses, we were unsuccessful in obtaining valid instrumental variables for scrutiny, and we deemed that constipation exerts no influence on the composition of the gut microbiota. CONCLUSION: Genetic predisposition towards increased abundance of Coprococcus and decreased abundance of Bacteroidetes is correlated with a diminished susceptibility to constipation. This investigation showed that alterations in the gut microbiota precipitated the onset of constipation, rather than constipation inducing modifications in the microbial flora.

A nomogram of anastomotic stricture after rectal cancer: a retrospective cohort analysis.

BACKGROUND: Anastomotic stricture significantly impacts patients' quality of life and long-term prognosis. However, current clinical practice lacks accurate tools for predicting anastomotic stricture. This study aimed to develop a nomogram to predict anastomotic stricture in patients with rectal cancer who have undergone anterior resection. METHODS: A total of 1542 eligible patients were recruited for the study. Least absolute shrinkage selection operator (Lasso) analysis was used to preliminarily select predictors. A prediction model was constructed using multivariate logistic regression and presented as a nomogram. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration diagrams, and decision curve analysis (DCA). Internal validation was conducted by assessing the model's performance on a validation cohort. RESULTS: 72 (4.7%) patients were diagnosed with anastomotic stricture. Participants were randomly divided into training (n = 1079) and validation (n = 463) sets. Predictors included in this nomogram were radiotherapy, diverting stoma, anastomotic leakage, and anastomotic distance. The area under the ROC curve (AUC) for the training set was 0.889 [95% confidence interval (CI) 0.840-0.937] and for the validation set, it was 0.930 (95%CI 0.879-0.981). The calibration curve demonstrated a strong correlation between predicted and observed outcomes. DCA results showed that the nomogram had clinical value in predicting anastomotic stricture in patients after anterior resection of rectal cancer. CONCLUSION: We developed a predictive model for anastomotic stricture following anterior resection of rectal cancer. This nomogram could assist clinicians in predicting the risk of anastomotic stricture, thus improving patients' quality of life and long-term prognosis.

Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

BACKGROUND: The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78 years). METHODS: This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. RESULTS: Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. CONCLUSIONS: LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

Establishment of a risk prediction model for bowel necrosis in patients with incarcerated inguinal hernia.

INTRODUCTION: Incarceration occurred in approximately 5% to 15% of inguinal hernia patients, with around 15% of incarcerated cases progressing to intestinal necrosis, necessitating bowel resection surgery. Patients with intestinal necrosis had significantly higher mortality and complication rates compared to those without necrosis.The primary objective of this study was to design and validate a diagnostic model capable of predicting intestinal necrosis in patients with incarcerated groin hernias. METHODS: We screened the clinical records of patients who underwent emergency surgery for incarcerated inguinal hernia between January 1, 2015, and December 31, 2022. To ensure balanced representation, the enrolled patients were randomly divided into a training set (n = 180) and a validation set (n = 76) using a 2:1 ratio. Logistic regression analysis was conducted using the rms package in R software, incorporating selected features from the LASSO regression model, to construct a predictive model. RESULTS: Based on the results of the LASSO regression analysis, a multivariate logistic regression model was developed to establish the predictive model. The predictors included in the model were Abdominal effusion, Hernia Sac Effusion, and Procalcitonin. The area under the receiver operating characteristic (ROC) curve for the nomogram graph in the training set was 0.977 (95% CI = 0.957-0.992). In the validation set, the AUC for the nomogram graph was 0.970. Calibration curve and decision curve analysis (DCA) verified the accuracy and practicability of the nomogram graph in our study. CONCLUSION: Bowel necrosis in patients with incarcerated inguinal hernia was influenced by multiple factors. The nomogram predictive model constructed in this study could be utilized to predict and differentiate whether incarcerated inguinal hernia patients were at risk of developing bowel necrosis.

Modified Q-type purse-string suture duodenal stump embedding method for laparoscopic gastrectomy for gastric cancer.

OBJECTIVE: This study introduced the modified Q-type purse-string suture duodenal stump embedding method, a convenient way to strengthen the duodenum, and compared it to the conventional one to assess its efficacy and safety. METHODS: This retrospective analysis examined 612 patients who received laparoscopic gastrectomy for gastric Cancer at a single center. The patients were divided into Not Reinforced Group (n = 205) and Reinforced Group (n = 407) according to the surgical approach to the duodenal stump. The reinforced group was further divided into a modified Q-type purse-string suture embedding method group (QM, n = 232) and a conventional suture duodenal stump embedding method group (CM, n = 175) according to the methods of duodenal stump enhancement. Clinicopathological characteristics, operative variables, and short-term complications were documented and analyzed. RESULTS: The incidence of duodenal stump leakage(DSL) in the Not Reinforced Group was higher compared to the Reinforced Group, although the difference was not statistically significant [2.4% (5/205) vs 0.7% (3/407), p = 0.339]. Additionally, the Not Reinforced Group exhibited a higher rate of Reoperation due to DSL compared to the Reinforced Group [2 (1.0%) vs. 0, p = 0.046], with one patient in the Not Reinforced Group experiencing mortality due to DSL [1 (0.5%) vs 0, p = 0.158]. Subgroup analysis within the Reinforced Group revealed that the modified Q-type purse-string suture embedding group (QM) subgroup demonstrated statistically significant advantages over the conventional suture embedding group (CM) subgroup. QM exhibited shorter purse-string closure times (4.11 ± 1.840 vs. 6.05 ± 1.577, p = 0.001), higher purse-string closure success rates (93.1% vs. 77.7%, p = 0.001), and greater satisfaction with purse-string closure [224 (96.6%) vs 157 (89.7%), p = 0.005]. No occurrences of duodenal stump leakage were observed in the QM subgroup, while the CM subgroup experienced two cases [2 (1.1%)], though the difference was not statistically significant. Both groups did not exhibit statistically significant differences in secondary surgery or mortality related to duodenal stump leakage. CONCLUSION: Duodenal Stump Leakage (DSL) is a severe but low-incidence complication. There is no statistically significant relationship between the reinforcement of the duodenal stump and the incidence of DSL. However, laparoscopic reinforcement of the duodenal stump can reduce the severity of fistulas and the probability of Reoperation. The laparoscopic Q-type purse-string suture duodenal stump embedding method is a simple and effective technique that can, to some extent, shorten the operation time and enhance satisfaction with purse-string closure. There is a trend towards reducing the incidence of DSL, thereby improving patient prognosis to a certain extent.

miR397-LACs mediated cadmium stress tolerance in Arabidopsis thaliana.

Cadmium (Cd) is a non-essential heavy metal, assimilated in plant tissue with other nutrients, disturbing the ions' homeostasis in plants. The plant develops different mechanisms to tolerate the hazardous environmental effects of Cd. Recently studies found different miRNAs that are involved in Cd stress. In the current study, miR397 mutant lines were constructed to explore the molecular mechanisms of miR397 underlying Cd tolerance. Compared with the genetically modified line of overexpressed miR397 (artificial miR397, amiR397), the lines of downregulated miR397 (Short Tandem Target Mimic miR397, STTM miR397) showed more substantial Cd tolerance with higher chlorophyll a & b, carotenoid and lignin content. ICP-OES revealed higher cell wall Cd and low total Cd levels in STTM miR397 than in the wild-type and amiR397 plants.Further, the STTM plants produced fewer reactive oxygen species (ROS) and lower activity of antioxidants enzymes (e.g., catalase [CAT], malondialdehyde [MDA]) compared with amiR397 and wild-type plants after stress, indicating that silencing the expression of miR397 can reduce oxidative damage. In addition, the different family transporters' gene expression was much higher in the amiR397 plants than in the wild type and STTM miRNA397. Our results suggest that miR397 plays a role in Cd tolerance in Arabidopsis thaliana. Overexpression of miR397 could decrease Cd tolerance in plants by regulating the expression of LAC 2/4/17, changing the lignin content, which may play an important role in inducing different stress-tolerant mechanisms and protecting the cell from a hazardous condition. This study provides a basis to elucidate the functions of miR397 and the Cd stress tolerance mechanism in Arabidopsis thaliana.

Combined metabolome and transcriptome analysis reveals a critical role of lignin biosynthesis and lignification in stem-like pneumatophore development of the mangrove Avicennia marina.

MAIN CONCLUSION: Transcriptional and metabolic regulation of lignin biosynthesis and lignification plays crucial roles in Avicennia marina pneumatophore development, facilitating its adaptation to coastal habitats. Avicennia marina is a pioneer mangrove species in coastal wetland. To cope with the periodic intertidal flooding and hypoxia environment, this species has developed a complex and extensive root system, with its most unique feature being a pneumatophore with a distinct above- and below-ground morphology and vascular structure. However, the characteristics of pneumatophore lignification remain unknown. Studies comparing the anatomy among above-ground pneumatophore, below-ground pneumatophore, and feeding root have suggested that vascular structure development in the pneumatophore is more like the development of a stem than of a root. Metabolome and transcriptome analysis illustrated that the accumulation of syringyl (S) and guaiacyl (G) units in the pneumatophore plays a critical role in lignification of the stem-like structure. Fourteen differentially accumulated metabolites (DAMs) and 10 differentially expressed genes involved in the lignin biosynthesis pathway were targeted. To identify genes significantly associated with lignification, we analyzed the correlation between 14 genes and 8 metabolites and further built a co-expression network between 10 transcription factors (TFs), including 5 for each of MYB and NAC, and 23 enzyme-coding genes involved in lignin biosynthesis. 4-Coumarate-CoA ligase, shikimate/quinate hydroxycinnamoyl transferase, cinnamyl alcohol dehydrogenase, caffeic acid 3-O-methyltransferase, phenylalanine ammonia-lyase, and peroxidase were identified to be strongly correlated with these TFs. Finally, we examined 9 key candidate genes through quantitative real-time PCR to validate the reliability of transcriptome data. Together, our metabolome and transcriptome findings reveal that lignin biosynthesis and lignification regulate pneumatophore development in the mangrove species A. marina and facilitate its adaptation to coastal habitats.

Prediction model of anastomotic leakage after anterior resection for rectal cancer-based on nomogram and multivariate analysis with 1995 patients.

BACKGROUND: Postoperative anastomotic leakage for rectal cancer shows higher morbidity with grievous concomitant symptoms. Accurate assessment of the incidence of anastomotic leakage, multivariate analysis, and establishment of a scientific prediction model can be useful to dispose of its possible severe clinical consequences. METHODS: This retrospective study collected 1995 consecutive patients who underwent anterior resection of rectal cancer with primary anastomosis at Northern Jiangsu People's Hospital between January 2016 and June 2022. Independent risk factors associated with anastomotic leakage were analyzed by univariate and multivariate logistic regression. The chosen independent risk factors were used to construct a nomogram risk prediction model whose availability was evaluated by using a bootstrapped-concordance index and calibration plots with R software. RESULTS: A total of 1995 patients who underwent anterior resection for rectal cancer were included while 120 patients were diagnosed with anastomotic leakage, an incidence of 6.0%. Univariate analysis and its concomitant multivariate cox regression analysis indicated that independent risk factors associated with anastomotic leakage included male gender (odds ratio (OR) = 2.873), diabetes (OR = 2.480), neoadjuvant therapy (OR = 5.283), tumor's distance from the anus verge < 5 cm (OR = 5.824), tumor size ≥ 5 cm (OR = 4.888), and the blood lose > 50 mL (OR = 9.606).We established a nomogram prediction model with proper applicability (concordance index, 0.83) and the calibration curve to justify its predictive ability that the predicted occurrence probability keeps a high degree of consistency with the actual occurrence probability. Meanwhile, the area under the receiver operating characteristic (ROC) curve was 0.83. CONCLUSIONS: The characteristics of patients and tumor surgery-related conditions can affect the incidence of anastomotic leakage. However, whether the surgical method will affect morbidity is still controversial. Our nomogram can be seen as an effective instrument to predict anastomotic leakage after anterior resection for rectal cancer precisely.

Predicting survival and prognosis in early-onset locally advanced colon cancer: a retrospective observational study.

OBJECTIVE: To predict cancer-specific survival, a refined nomogram model and brand-new risk-stratifying system were established to classify the risk levels of patients with early-onset locally advanced colon cancer (LACC). METHODS: The clinical factors and survival outcomes of LACC cases from the SEER database from 2010 to 2019 were retrieved retrospectively. Early-onset and late-onset colon cancer were grouped according to the age (50 years old) at diagnosis. Differences between groups were compared to identify mutual significant variables. A multivariate Cox regression analysis was further performed and then constructed a nomogram. We compared it with the AJCC-TNM system. The external validation was performed for evaluation. Finally, a risk-stratifying system of patients with early-onset LACC was established. RESULTS: A total of 32,855 LACC patients were enrolled in, 4548 (13.84%) patients were included in the early-onset LACC group, and 28,307 (86.16%) patients were included in the late-onset LACC group. The external validation set included 228 early-onset LACC patients. Early-onset colon cancers had poorer prognosis (T4, N2, TNM stage III, CEA, tumor deposit, and nerve invasion), and a higher proportion received radiotherapy and systemic therapy (P<0.001). In the survival analysis, cancer-specific survival (CSS) was better in patients with early-onset LACC than in those with late-onset LACC (P <0.001). This nomogram constructed based on the results of COX analysis showed better accuracy in CSS prediction of early-onset LACC patients than AJCC-TNM system in the training set and external validation set (0.783 vs 0.728; 0.852 vs 0.773). CONCLUSION: We developed a novel nomogram model to predict CSS in patients with early-onset LACC it provided a reference in prognosis prediction and selection of individualized treatment, helping clinicians in decision-making.

Evaluation of multiple biological indicators for the combined diagnosis of metastases from colorectal cancer-a retrospective study based on 1163 patients.

OBJECTIVE: This study aimed to investigate the efficacy of inflammatory markers (NLR, PLR) combined with tumor markers (CA50, CA199, CEA) in the diagnosis of colorectal cancer metastasis by a single-center retrospective study. METHODS: A total of 1163 CRC patients who received treatments in our hospital from January 2017 to December 2021 were enrolled retrospectively. Patients were grouped according to the absence of metastasis. The separate efficacy of tumor markers, NLR and PLR, was evaluated in the diagnosis of metastasis of colorectal cancer using ROC curve analysis, and their optimal cut-off values for distant metastases from colorectal cancer were determined. The area under the ROC curve (AUC) of the tumor markers combined with NLR and PLR was calculated by binary logistic regression analysis to evaluate the diagnostic efficacy of metastasis of colorectal cancer. In addition, patients were divided into two groups of high and low levels according to the optimal cut-off values, and the effects of NLR, PLR, and tumor markers on distant metastasis of colorectal cancer were evaluated using multiple logistic regression analysis. RESULT: The abnormal rate of CA50, CA199, CEA, NLR, and PLR in two subgroupsIt was statistically significant (P < 0.05). After AUC testifying, the diagnostic efficacy of NLR and PLR was equivalent to that of tumor marker (P > 0.05). In assessment of liver metastasis, peritoneal metastasis, and multiple metastasis, AUC of NLR and PLR with CRC-specific tumor markers showed higher predictive efficacy than AUC without combined NLR nor PLR. The CA50, CA199, CEA, PLR, and NLR were proved independently associated with metastasis using multiple logistic regression analysis (P < 0.05). CONCLUSION: NLR and PLR are noted tumor markers of colorectal cancer, which are characterized by noninvasive, high diagnostic efficacy, easy availability, and low cost. They can be combined with traditional tumor markers to evaluate and diagnose colorectal cancer metastasis by clinicians.

Combined Metabolome and Transcriptome Analysis Elucidates Sugar Accumulation in Wucai (Brassica campestris L.).

Wucai (Brassica campestris L.) is a leafy vegetable that originated in China, its soluble sugars accumulate significantly to improve taste quality during maturation, and it is widely accepted by consumers. In this study, we investigated the soluble sugar content at different developmental stages. Two periods including 34 days after planting (DAP) and 46 DAP, which represent the period prior to and after sugar accumulation, respectively, were selected for metabolomic and transcriptomic profiling. Differentially accumulated metabolites (DAMs) were mainly enriched in the pentose phosphate pathway, galactose metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, and fructose and mannose metabolism. By orthogonal projection to latent structures-discriminant s-plot (OPLS-DA S-plot) and MetaboAnalyst analyses, D-galactose and ß-D-glucose were identified as the major components of sugar accumulation in wucai. Combined with the transcriptome, the pathway of sugar accumulation and the interact network between 26 DEGs and the two sugars were mapped. CWINV4, CEL1, BGLU16, and BraA03g023380.3C had positive correlations with the accumulation of sugar accumulation in wucai. The lower expression of BraA06g003260.3C, BraA08g002960.3C, BraA05g019040.3C, and BraA05g027230.3C promoted sugar accumulation during the ripening of wucai. These findings provide insights into the mechanisms underlying sugar accumulation during commodity maturity, providing a basis for the breeding of sugar-rich wucai cultivars.

Transcriptome analysis and differential gene expression profiling of wucai (Brassica campestris L.) in response to cold stress.

BACKGROUND: Wucai suffers from low temperature during the growth period, resulting in a decline in yield and poor quality. But the molecular mechanisms of cold tolerance in wucai are still unclear. RESULTS: According to the phenotypes and physiological indexes, we screened out the cold-tolerant genotype "W18" (named CT) and cold-sensitive genotype "Sw-1" (named CS) in six wucai genotypes. We performed transcriptomic analysis using seedling leaves after 24 h of cold treatment. A total of 3536 and 3887 differentially expressed genes (DEGs) were identified between the low temperature (LT) and control (NT) comparative transcriptome in CT and CS, respectively, with 1690 DEGs specific to CT. The gene ontology (GO) analysis showed that the response to cadmium ion (GO:0,046,686), response to jasmonic acid (GO:0,009,753), and response to wounding (GO:0,009,611) were enriched in CT (LT vs NT). The DEGs were enriched in starch and sucrose metabolism and glutathione metabolism in both groups, and α-linolenic acid metabolism was enriched only in CT (LT vs NT). DEGs in these processes, including glutathione S-transferases (GSTs), 13S lipoxygenase (LOX), and jasmonate ZIM-domain (JAZ), as well as transcription factors (TFs), such as the ethylene-responsive transcription factor 53 (ERF53), basic helix-loop-helix 92 (bHLH92), WRKY53, and WRKY54.We hypothesize that these genes play important roles in the response to cold stress in this species. CONCLUSIONS: Our data for wucai is consistent with previous studies that suggest starch and sucrose metabolism increased the content of osmotic substances, and the glutathione metabolism pathway enhance the active oxygen scavenging. These two pathways may participated in response to cold stress. In addition, the activation of α-linolenic acid metabolism may promote the synthesis of methyl jasmonate (MeJA), which might also play a role in the cold tolerance of wucai.

Whether stoma support rods have application value in loop enterostomy: a systematic review and meta-analysis.

PURPOSE: The purpose of the systematic review and meta-analysis is to analyze the application value of the stoma support rods in loop enterostomy. METHODS: The studies on the application of stoma rods in loop enterostomy published from January 2000 to January 2020 were searched in the databases of PubMed, Embase, Cochrane library, and Clinical trials. All randomized controlled trials (RCTs) and cohort studies that observed the value of stoma rods were included according to inclusion criteria. The RevMan5.3 software was used for statistical analysis. RESULTS: A total of 1131 patients with loop enterostomy in six studies were included in this study; there were 569 cases in the experimental group and 562 cases in the control group. All six studies analyzed the effect of support rods on the incidence of stoma retraction; the meta-analysis showed that in a total of 32 patients, stoma retraction occurred, with a total incidence of about 2.8% in 1131 patients. The incidence of stoma retraction in the rod group was not significantly lower than that in the non-rod group, and the difference was not statistically significant (OR = 0.65, 95% CI 0.32~1.32, I2 = 0%, P = 0.23), and the studies were homogeneous. The incidences of stoma necrosis (OR = 6.41, 95% CI 2.22~18.55, I2 = 0%, P = 0.0006), peristomal dermatitis (OR = 2.93, 95% CI 2.01~4.27, I2 = 0%, P < 0.00001), and mucocutaneous separation (OR = 2.14, 95% CI 1.03~4.47, I2 = 0%, P = 0.04) were significantly increased in the rod group. CONCLUSIONS: It is not recommended to routinely use stoma support rods in the clinical practice.

Chlorpyrifos exposure induces lipid metabolism disorder at the physiological and transcriptomic levels in larval zebrafish.

Chlorpyrifos (CPF) is a widely used insecticide in pest control, and it can affect aquatic animals by contaminating the water. In this study, larval zebrafish were exposed to CPF at concentrations of 30, 100 and 300 µg/l for 7 days. In the CPF-treated group, lipid droplet accumulation was reduced in larval zebrafish. The levels of triglyceride (TG), total cholesterol (TC), and pyruvate were also decreased after CPF exposure. Cellular apoptosis were significantly increased in the heart tissue after CPF exposure compared with the control. Transcription changes in cardiovascular genes were also observed. Through transcriptome analysis, we found that the transcription of 465 genes changed significantly, with 398 upregulated and 67 downregulated in the CPF-treated group, indicating that CPF exposure altered the transcription of genes. Among these altered genes, a number of genes were closely related to the glucose and lipid metabolism pathways. Furthermore, we also confirmed that the transcription of genes related to fatty acid synthesis, TC synthesis, and lipogenesis were significantly decreased in larval zebrafish after exposure to CPF. These results indicated that CPF exposure induced lipid metabolism disorders associated with cardiovascular toxicity in larval zebrafish.

Short-term propamocarb exposure induces hepatic metabolism disorder associated with gut microbiota dysbiosis in adult male zebrafish.

Propamocarb (PM) is a pesticide that is widely used to protect cucumbers and other plants from downy mildew. Recently, some studies indicated that PM exposure had potential toxic effects in animals. In this study, adult male zebrafish were exposed to 100 and 1000 µg/l PM for 7 days to assess its effects on metabolism and the gut microbiota. We observed a significant decrease in triglyceride (TG) in the livers of zebrafish that were exposed to 1000 µg/l PM for 7 days. At the same time, some genes related to glycolysis and lipid metabolism in the livers of zebrafish, including hexokinase-1 (HK1), pyruvate kinase (PK), acyl-CoA oxidase (Aco), peroxisome proliferator activated receptor alpha (Ppar-α), apolipoprotein A-IV-like (Apo), Acetyl CoA carboxylase-1 (Acc1), diacylglycerol acyltransferase (Dgat), and fatty acid synthase (Fas), were also decreased significantly after PM exposure. Based on GC-MS metabolomics analysis, a total of 48 metabolites changed significantly in the 1000 µg/l PM treatment group in comparison with the control group. These altered metabolites were mainly associated with the glycolysis, amino acid metabolism, and lipid metabolism pathways. Interestingly, we further found that the 1000 µg/l PM treatment group also showed significant elevations in Proteobacteria, Bacteroidetes, and Firmicutes at the phylum level. Sequencing of the 16S rRNA gene in the V3-V4 region also showed a significant change in the abundance and diversity of the gut microbiota in the 1000 µg/l PM treatment group. Our results indicated that exposure to PM for a short time could induce hepatic metabolic disorders and gut microbiota dysbiosis in adult male zebrafish.

Chronic exposure to low doses of Pb induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels of mice.

Lead (Pb), a non-essential heavy metal, is a major global environmental contaminant with serious toxicological consequences. In the present study, the effects on hepatotoxicity of mice with chronic exposure to low doses of Pb were evaluated. While oral exposure to 0.03 or 0.1 mg/L Pb for 15 weeks in male adult mice had no significant effect on body weights, Pb exposure resulted in liver histopathological effects and increase of hepatic activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). In addition, hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) significantly accumulated after treatment. Conversely, glutathione (GSH) decreased significantly in both 0.03 and 0.1 mg/L Pb-treated groups. Moreover, the hepatic activities of superoxide dismutase 1 (SOD) and catalase (CAT) increased significantly following treatment with 0.1 mg/L Pb for 15 weeks, concomitant with increases in transcriptions of hepatic Sod, Cat, and Gpx. Furthermore, transcriptions of hepatic metallothionein (MT), zinc transporter 5 (Znt5) and copper transporter 1 (Ctr1), and subsequent protein levels were also increased in liver of mice when exposed to 0.1 mg/L Pb for 15 weeks. In addition, the transcriptome data showed that Pb has substantial influence on several pathways, including PPAR signaling pathways, AMPK signaling pathways, fatty acid metabolism, and drug metabolism. Our data suggested that chronic Pb exposure could induce hepatotoxicity at the physiological, biochemical, and transcriptomic levels in mice.

Propamocarb exposure decreases the secretion of neurotransmitters and causes behavioral impairments in mice.

Propamocarb (PM) is a type of fungicide, which is widely used in the greenhouse-based production of vegetables and fruits globally. It has been considered to have generally low toxicity. However, the teratogenicity or neurotoxicity for mammals remains unclear. In this study, we aimed to explore its effect on the secretion of neurotransmitters and behavioral impairments. Male adult mice were exposed to 10 and 40 mg/L PM for 2 weeks (acute exposure) or 3 and 10 mg/L PM for 10 weeks (chronic exposure). It was observed that acute or chronic exposure to PM changed the levels of serotonin (5-HT) and dopamine in the serum and colon and the transcription of TPH2 and DRD2 in the colons of mice. In addition, the locomotor test, the open field test, and the Morris water maze analysis also showed that acute exposure to PM caused behavioral impairments to some extent. The results obtained in the present study indicated that PM has the potential to induce neurotoxicity in animals.

miR-192 Is Overexpressed and Promotes Cell Proliferation in Prostate Cancer.

OBJECTIVE: Prostate cancer (PCa) is one of the most prevalent types of cancer among men worldwide. The incidence of PCa is increasing in China. Therefore, there is an urgent need to identify novel diagnostic and prognostic markers for PCa to improve the treatment of the disease. METHODS: The Cancer Genome Atlas (TCGA) and GEO database were used to analyze the expression of miR-192, and the relationship between miR-192 and the clinical features of patients with PCa. Cell cycle and cell proliferation assay were used to detect the functional roles of miR-192 in PCa. Bioinformatic analysis for miR-192-5p was performed using gene ontology and KEGG analysis. RESULTS: By analyzing the dataset of TCGA, we found that miR-192 was overexpressed in PCa samples compared to normal tissues and was upregulated in high-grade PCa compared to low-grade PCa. We also observed that higher miR-192 expression was associated with a shorter biochemical recurrence-free survival time. Our results also demonstrated that miR-192 promoted PCa cell proliferation and cell cycle progression. CONCLUSION: These results suggest that miR-192 may be considered for use as a potential diagnostic and therapeutic target of PCa.

Effects of a foliar spray of selenite or selenate at different growth stages on selenium distribution and quality of blueberries.

BACKGROUND: Foliar spraying of selenium (Se) has increasingly been applied to improve Se concentrations in grain crops, although little information is available about the properties of Se-enriched fruits. In the present study, selenium distribution in blueberry and Se effect on blueberry quality were investigated by foliar spraying selenite or selenate (200 g ha-1 ) on two blueberry cultivars (Bluecrop and Northland) during the young fruit or coloring stage. RESULTS: Selenium concentration in blueberry was mainly affected by cultivar and spray stage relative to the Se source. Northland was 1.3- to 1.5-fold higher than Bluecrop with respect to Se enrichment. Se treatment at the young fruit stage induced a 1.5- to 2.3-fold increase compared to that at the coloring stage with respect to the Se concentration of blueberry. Additionally, selenium was mainly stored in pomace, with an accumulative distribution ratio of 89.3-94.9%. The proportion of organic Se reached up to 77.0% in blueberry. Furthermore, the foliar application of Se significantly increased the anthocyanin concentration and the intact fruit rate of blueberry. CONCLUSION: Se-enriched blueberry can be used as a 'functional food'. Because Se was mainly accumulated in the pomace, the consumption of blueberries as fresh fruit, dried fruit and jam can improve the efficiency of Se supplement. © 2018 Society of Chemical Industry.