piRNA generation is associated with the pioneer round of translation in stem cells.

Much insight has been gained on how stem cells maintain genomic integrity, but less attention has been paid to how they maintain their transcriptome. Here, we report that the PIWI protein SMEDWI-1 plays a role in the filtering of dysfunctional transcripts from the transcriptome of planarian stem cells. SMEDWI-1 accomplishes this through association with the ribosomes during the pioneer round of translation, and processing of poorly translated transcripts into piRNAs. This results in the removal of such transcripts from the cytoplasmic pool and at the same time creates a dynamic pool of small RNAs for post-transcriptional surveillance through the piRNA pathway. Loss of SMEDWI-1 results in elevated levels of several non-coding transcripts, including rRNAs, snRNAs and pseudogene mRNAs, while reducing levels of several coding transcripts. In the absence of SMEDWI-1, stem cell colonies are delayed in their expansion and a higher fraction of descendants exit the stem cell state, indicating that this transcriptomic sanitation mediated by SMEDWI-1 is essential to maintain stem cell health. This study presents a new model for the function of PIWI proteins in stem cell maintenance, that complements their role in transposon repression, and proposes a new biogenesis pathway for piRNAs in stem cells.

Modified Retzius-sparing robot-assisted radical prostatectomy for cases with anterior tumor: a propensity score-matched analysis.

OBJECTIVE: To compare the outcomes between a modified Retzius-sparing robot-assisted radical prostatectomy (mRS-RARP) technique and conventional robot-assisted radical prostatectomy (Con-RARP) technique for cases with anterior prostate cancer (PCa), especially positive surgical margin (PSM) rates and urinary continence (UC). PATIENTS AND METHODS: We retrospectively included 193 mRS-RARP and 473 Con-RARP consecutively performed by a single surgeon for anterior PCa. Perioperative complications, pathology, and continence were compared after propensity score matching using 9 variables. RESULTS: After matching (n = 193 per group), PSM were not significantly different in the two groups (16.1% in mRS-RARP group vs. 15.0% in Con-RARP group, p = 0.779). The UC at catheter removal and at 1-month was significantly higher in the mRS-RARP (24.9% vs. 9.8%, p < 0.001; 29.0% vs. 13.5%, p < 0.001, respectively), but not at 3-, 6-, and 12-month follow-ups (p = 0.261, 0.832, and 0.683, respectively). CONCLUSION: mRS-RARP seems to be an oncologically safe approach for patients with anterior PCa. Compared with the conventional approach, mRS-RARP approach shows benefits in the short-term postoperative UC recovery.

Prediction of false-positive PI-RADS 5 lesions on prostate multiparametric MRI: development and internal validation of a clinical-radiological characteristics based nomogram.

BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.

Membrane separation of antibiotics predicted with the back propagation neural network.

Antibiotics and antibiotic resistance genes (ARGs) have been frequently detected in the aquatic environment and are regarded as emerging pollutants. The prediction models for the removal effect of four target antibiotics by membrane separation technology were constructed based on back propagation neural network (BPNN) through training the input and output. The membrane separation tests of antibiotics showed that the removal effect of microfiltration on azithromycin and ciprofloxacin was better, basically above 80%. For sulfamethoxazole (SMZ) and tetracycline (TC), ultrafiltration and nanofiltration had better removal effects. There was a strong correlation between the concentrations of SMZ and TC in the permeate, and the R2 of the training and validation processes exceeded 0.9. The stronger the correlation between the input layer variables and the prediction target was, the better the prediction performances of the BPNN model than the nonlinear model and the unscented Kalman filter model were. These results showed that the established BPNN prediction model could better simulate the removal of target antibiotics by membrane separation technology. The model could be used to predict and explore the influence of external conditions on membrane separation technology and provide a certain basis for the application of the BPNN model in environmental protection.

Management of biologics in pregnant, lactating patients with inflammatory bowel disease and the impact on neonatal vaccination: A systematic review of clinical practice guidelines and consensus statements.

WHAT IS KNOWN AND OBJECTIVE: The management of biological agents during pregnancy poses challenges as maternal and infant safety must be addressed. This study aims to compare the recommendations of existing guidelines on managing the use of biologics during pregnancy, lactation for patients with inflammatory bowel disease, and the influence on neonatal vaccination. METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database and China Biomedical Database were systematically searched from the inception date to 11 May 2022, to screen all relevant guidelines. Quality assessment was performed using the guideline methodology reporting tool AGREE II. RESULTS AND DISCUSSION: Fourteen guidelines and consensus statements with detailed recommendations were included. All guidance documents cover management comments during pregnancy, and most consider that biologics can be given safely during pregnancy but require suspension at the right time to protect the foetus. However, the roles of vedolizumab and ustekinumab are disputed. Five documents guide lactation and the use of most biologics during lactation is safe, but no guidelines recommend vedolizumab. Six papers provide recommendations for newborns' vaccination, suggesting a delay in infants' live vaccination schedule if their mothers are treated with biologics. WHAT IS NEW AND CONCLUSION: Our study concluded that future guidelines could consider incorporating newer, more robust evidence to update recommendations. The development of future guidelines needs to consider the involvement of multidisciplinary experts, adequately report on the evidence retrieval process, and provide strategies for implementation. Besides, more research is needed to explore the use of biologics during pregnancy and lactation in patients with inflammatory bowel disease.

[PI-RADS score of prostate multi-parametric magnetic resonance imaging predicts pathological features of prostate cancer: An imaging to whole-mount pathology matching study].

OBJECTIVE: To explore the value of the prostate imaging reporting and data system (PI-RADS) score of prostate multi-parametric magnetic resonance imaging (mpMRI) in predicting the pathological features of PCa based on matching images and whole-mount pathology images. METHODS: This retrospective study included 318 cases of PCa treated by radical prostatectomy in our hospital from August 2016 to December 2018, with preoperative mpMRI images and complete whole-mount pathological sections. We obtained PI-RADS scores on the mpMRI lesions corresponding to the cancer lesions, evaluated the Gleason scores, pT stages, pN stages and cribriform structure, and compared them between different groups using Chi-square test or Fisher's exact test. We evaluated the efficiency of the PI-RADS score in distinguishing different pathological features by ROC curve analysis, and obtained the corresponding area under the curve (AUC) and 95% confidence interval (CI). RESULTS: The 318 patients averaged 69 years of age, with a median preoperative PSA level of 11.0 µg/L and a median tumor diameter of 1.8 cm. The PI-RADS score was significantly correlated with the Gleason score, pT stage, pN stage and cribriform structure (all P < 0.01), with AUCs of 0.773 (95% CI: 0.704－0.843) for distinguishing Gleason scores (3+3 vs >3+3), 0.748 (95% CI: 0.694－0.803) for distinguishing pT stages (T2 vs >T2), 0.700 (95% CI: 0.598－0.802) for distinguishing pN stages (N0 vs N1), and 0.831 (95% CI: 0.786－0.876) for distinguishing the cribriform structure (negative vs positive). CONCLUSION: The preoperative PI-RADS score of mpMRI in PCa patients is significantly correlated with postoperative pathological features, and therefore can be used for risk stratification of the malignancy.

Can 68Ga-PSMA-11 PET/CT predict pathological upgrading of prostate cancer from MRI-targeted biopsy to radical prostatectomy?

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) is an ideal tool for staging and restaging of prostate cancer (PCa). This study was designed to investigate the prognostic role of preoperative 68Ga-PSMA-11 PET/CT in predicting pathological upgrading from multiparametric magnetic resonance imaging-targeted biopsy (mpMRI-TB) to final radical prostatectomy (RP) specimens in patients with localized PCa. METHODS: A total of 67 biopsy-confirmed localized PCa patients with mpMRI and 68Ga-PSMA-11 PET/CT prior to RP were included. Clinical and imaging characteristics derived from mpMRI and PET/CT were compared in patients with or without pathological upgrading. Predictors for pathological upgrading were evaluated by using univariate and multivariable analyses. A prediction model was developed based on the identified parameters and validated using internal validation. RESULTS: Pathological upgrading from mpMRI-TB to final RP specimens occurred in 38.8% (26/67) of the patients. Multivariable logistic regression analysis showed SUVmax (OR: 1.223, 95% CI 1.068-1.399, p = 0.003); highest tumor grade at mpMRI-TB, ISUP grade group (ISUP GG) 1 vs. 4 (OR: 0.11, 95% CI 0.000-0.452, p = 0.018) and ISUP GG 2 vs. 4 (OR: 0.16, 95% CI 0.001-0.252, p = 0.003); and multifocality on PET/CT (OR: 9.821, 95% CI 1.438-67.085, p = 0.02) were independent risk factors for pathological upgrading. Our developed prediction model based on the identified parameter showed good calibration at internal validation (mean absolute error = 0.033). CONCLUSION: 68Ga-PSMA-11 PET/CT was found to be an ideal biomarker for the prediction of pathological upgrading from mpMRI-TB to RP, especially for patients with lower tumor grade at mpMRI-TB.

Pulmonary Artery Size Measurements: A Comparison Study Between Electrocardiogram-Gated and Nonelectrocardiogram-Gated Computed Tomography.

OBJECTIVES: The aim of this study was to determine the difference and correlation in pulmonary artery (PA) size when measured from the electrocardiogram (ECG)-gated computed tomography (CT) and non-ECG-gated CT. METHODS: In the retrospective study, 279 patients who underwent both ECG-gated CT and non-ECG-gated CT were enrolled. Maximum and minimum diameters of main pulmonary artery (MPA), right pulmonary artery (RPA), and ascending aorta (AAO) were measured, whereas mean diameters of MPA and RPA were obtained. The same PA size parameters were also measured on non-ECG-gated CT. RESULTS: There was a significant difference in maximum and minimum PA diameters between ECG-gated CT and non-ECG-gated CT, whereas mean PA diameters showed no statistically difference. The PA parameters showed a strong positive correlation between these 2 examinations. CONCLUSIONS: The PA size was different between ECG-gated CT and non-ECG-gated CT, whereas the PA size parameters on non-ECG-gated CT could be used to predict those with ECG-gated CT, which allow for confident prediction of pulmonary hypertension and guide further surgical intervention.

Tumour location determined by preoperative MRI is an independent predictor for positive surgical margin status after Retzius-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To investigate the influence of tumour location zone on positive surgical margin (PSM) status after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). MATERIALS AND METHODS: A total of 203 consecutive patients with prostate cancer (PCa) who underwent RS-RARP at our centre were divided into three cohorts according to the tumour zonal origin described on preoperative magnetic resonance imaging (MRI). Clinical and pathological characteristics were compared among the three groups. The associations of clinicopathological variables with PSM status after RS-RARP were also evaluated. RESULTS: The rates of PSM in patients with transition zone (TZ) and mixed origin tumours were significantly higher than in patients with peripheral zone tumours (P < 0.01). Of the PSMs in patients with TZ and mixed origin cancers, 42.0% and 40.9%, respectively, were located at the anterior part of the gland. On multivariate analysis, presence of a TZ tumour was significantly associated with a higher PSM rate after RS-RARP (P < 0.01). Sub-analysis showed that high-risk patients with TZ tumours had a higher risk of PSM after RS-RARP (P < 0.01). CONCLUSION: Presence of a TZ tumour is an independent risk factor for PSMs after RS-RARP. Preoperative identification of TZ tumours might aid surgical planning for the Retzius-sparing technique, especially in high-risk patients.

Diagnostic performance of 68Ga-PSMA PET/CT for identification of aggressive cribriform morphology in prostate cancer with whole-mount sections.

PURPOSE: To explore the diagnostic performance of 68Ga-PSMA PET/CT for identification of pathological cribriform morphology in prostate cancer (PCa). METHODS: The study retrospectively enrolled 49 PCa patients who had undergone preoperative multiparametric MRI (mpMRI) and 68Ga-PSMA PET/CT, and who had Gleason pattern (GP) 4 and absence of GP 5 on radical prostatectomy specimens. Lesions with GP 4 were outlined and stratified according to their cribriform status. Volumes of interest were drawn on matched mpMRI and PET images, and parameters including average apparent diffusion coefficient (ADCmean), tenth percentile ADC (ADC10%) and maximum standardized uptake value (SUVmax) were derived. The Mann-Whitney U test was used for continuous variables and the chi-squared test for categorical variables. Receiver operating characteristic analysis was used to compare imaging parameters in identifying cribriform morphology. The associations between cribriform-positive PCa and imaging variables were evaluated in a univariate analysis using a logistic regression model. RESULTS: A total of 62 lesions were identified in 49 patients with GP 4. Of these lesions, 37 (59.7%) in 34 patients (69.4%) showed cribriform morphology. ADCmean and ADC10% were similar between cribriform-positive and non-cribriform groups (P > 0.05), while SUVmax was significantly different (median SUVmax 18.3 vs. 9.4 per patient, P = 0.003, 18.2 vs. 7.2 per lesion, P < 0.001), yielding sensitivities and specificities of 76% and 86% in a per-patient analysis, and 77% and 88% in a per-lesion analysis, respectively. Further, PSMA was significantly overexpressed in cribriform-positive PCa (P = 0.003). SUVmax was a significant predictor of cribriform morphology in PCa (odds ratio 8.61, 95% confidence interval 4.96-25.27, per patient; odds ratio 11.93, 95% confidence interval 6.49-33.74, per lesion; both P < 0.001). CONCLUSION: 68Ga-PSMA PET/CT effectively identifies the aggressive cribriform morphology in PCa.

Assessment of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound fusion in Chinese men with prior negative biopsy and elevated prostate-specific antigen.

BACKGROUND: To evaluate the role of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound (mpMRI-TRUS) fusion in Chinese men with repeated biopsy. METHODS: A total of 101 consecutive patients suspicious of prostate cancer (PCa) at the mpMRI scan and with prior negative biopsy and elevated PSA values were prospectively recruited at two urological centers. Suspicious areas on mpMRI were defined and graded using PI-RADS score. Targeted biopsies (TB) were performed for each suspicious lesion and followed a 12-core systematic biopsy (SB). Results of biopsy pathology and whole-gland pathology at prostatectomy were analyzed and compared between TB and SB. The risk for biopsy positivity was assessed by univariate and multivariate logistic regression analysis. RESULTS: Fusion biopsy revealed PCa in 41 of 101 men (40.6%) and 25 (24.8%) were clinically significant. There was exact agreement between TB and SB in 74 (73.3%) men. TB diagnosed 36% more significant cancer than SB (22 vs 13 cases, P = 0.012). When TB were combined with SB, an additional 14 cases (34.1%) of mostly significant PCa (71.4%) were diagnosed (P = 0.036). TB had greater sensitivity and accuracy for significant cancer than SB in 26 men with whole-gland pathology after prostatectomy. PI-RADS score on mpMRI was the most powerful predictor of PCa and significant cancer. CONCLUSIONS: Free-hand transperineal TB guided with MRI-TRUS fusion imaging improves detection of clinical significant PCa in Chinese men with previously negative biopsy. PI-RADS score is a reliable predictor of PCa and significant cancer.

Performance of 18F-FDG PET/MRI and its parameters in staging and neoadjuvant therapy response evaluation in bladder cancer.

18F-FDG PET/MRI shows potential efficacy in the diagnosis of bladder cancer (BLCA). However, the performance of 18F-FDG PET/MRI in staging and neoadjuvant therapy (NAT) response evaluation for BLCA patients remains elusive. Here, we conduct this study to evaluate the performance of 18F-FDG PET/MRI and its derived parameters for tumor staging and NAT response prediction in BLCA. Forty BLCA patients were retrospectively enrolled to evaluate the performance of 18F-FDG PET/MRI in staging and NAT response prediction in BLCA. The feasibility of using 18F-FDG PET/MRI-related parameters for tumor staging and NAT response evaluation was also analyzed. In conclusion, 18F-FDG PET/MRI is found to show good performance in the BLCA staging and NAT response prediction. Moreover, ΔSUVmean is an efficacious candidate parameter for NAT response prediction. This study highlights that 18F-FDG PET/MRI is a promising imaging approach in the clinical diagnosis and treatment for BLCA.

The Value of 68Ga-PSMA PET/MRI for Classifying Patients with PI-RADS 3 Lesions on Multiparametric MRI: A Prospective Single-Center Study.

Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions remain a diagnostic challenge for detecting clinically significant prostate cancer (csPCa). This article evaluates the added value of 68Ga-labeled prostate-specific membrane antigen-11 (68Ga-PSMA) PET/MRI in classifying PI-RADS 3 lesions to avoid unnecessary biopsies. Methods: Sixty biopsy-naïve men with PI-RADS 3 lesions on multiparametric MRI were prospectively enrolled between February 2020 and October 2022. In all, 56 participants underwent 68Ga-PSMA PET/MRI and prostate systematic biopsy. 68Ga-PSMA PET/MRI was independently evaluated and reported by the 5-level PRIMARY score developed within the PRIMARY trial. Receiver-operating-characteristic curve analysis was used to estimate the diagnostic performance. Results: csPCa was detected in 8 of 56 patients (14.3%). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 0% (0/12), 0% (0/13), 6.3% (1/16), 38.5% (5/13), and 100% (2/2), respectively. The estimated area under the curve of the PRIMARY score was 0.91 (95% CI, 0.817-0.999). For a PRIMARY score of 4-5 versus a PRIMARY score of 1-3, the sensitivity, specificity, positive predictive value, and negative predictive value were 87.5%, 83.3%, 46.7%, and 97.5%, respectively. With a PRIMARY score of at least 4 to make a biopsy decision in men with PI-RADS 3 lesions, 40 of 48 patients (83.3%) could avoid unnecessary biopsies, at the expense of missing 1 of 8 (12.5%) csPCa cases. Conclusion: 68Ga-PSMA PET/MRI has great potential to classify patients with PI-RADS 3 lesions and help avoid unnecessary biopsies.

Chromatin analysis of adult pluripotent stem cells reveals a unique stemness maintenance strategy.

Many highly regenerative organisms maintain adult pluripotent stem cells throughout their life, but how the long-term maintenance of pluripotency is accomplished is unclear. To decipher the regulatory logic of adult pluripotent stem cells, we analyzed the chromatin organization of stem cell genes in the planarian Schmidtea mediterranea. We identify a special chromatin state of stem cell genes, which is distinct from that of tissue-specific genes and resembles constitutive genes. Where tissue-specific promoters have detectable transcription factor binding sites, the promoters of stem cell-specific genes instead have sequence features that broadly decrease nucleosome binding affinity. This genic organization makes pluripotency-related gene expression the default state in these cells, which is maintained by the activity of chromatin remodelers ISWI and SNF2 in the stem cells.

The potential mechanism of qinghua quyu jianpi decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic and recurrent inflammation of the gastrointestinal tract. Following the idea of herbal property and compatibility, a traditional Chinese medicine (TCM) formula consists of a number of TCM herbs. Qinghua Quyu Jianpi Decoction (QQJD) has been clinically proven to be effective in treating UC, however, its therapeutic mechanism has not been fully elucidated. AIM OF STUDY: Here, we used network pharmacology analysis and ultra-performance liquid chromatography-tandem mass spectrometry to predict the mechanism of action of QQJD, and then validated our predictions through in vivo and in vitro experiments. MATERIALS AND METHODS: First, based on a number of datasets, relationship network diagrams between QQJD and UC were created. The target network for the QQJD-UC intersection genes was then built, and KEGG analysis was carried out to identify a potential pharmacological mechanism. Finally, the results of the previous prediction were validated in dextran sulfate sodium salt (DSS) induced UC mice and a cellular inflammatory model. RESULTS: Network pharmacology results suggested that QQJD may play a role in repairing intestinal mucosa by activating Wnt pathway. In vivo experiments have shown that QQJD can significantly reduce weight loss, disease activity index (DAI) score, improve colon length, and effectively repair the tissue morphology of UC mice. In addition, we also found that QQJD can activate the Wnt pathway to promote epithelial cell renewal, reduce apoptosis, and repair the mucosal barrier. To further understand how QQJD promotes cell proliferation in DSS-induced Caco-2 cells, we performed a study in vitro experiment. We were surprised to find that QQJD activated the Wnt pathway by inducing nuclear translocation of ß-catenin, accelerating the cell cycle and promoting cell proliferation in vitro. CONCLUSION: Taken together, network pharmacology and experiments showed that QQJD achieves mucosal healing and restores the colonic epithelium barrier by activating Wnt/ß-catenin signaling, regulating cell cycle progression, and promoting the proliferation of epithelial cells.

Adoptive transfer of Fe3O4-SWCNT engineered M1-like macrophages for magnetic resonance imaging and enhanced cancer immunotherapy.

Macrophage-based tumor immunotherapy can effectively kill tumor cells in a direct manner when tumor specific antigens are idle or unknown. However, the presence of M2-like tumor associated macrophages (TAMs) would limit the treatment efficiency. Therefore, reversing the M2-like TAMs phenotype to regulate the immunosuppressive tumor microenvironment (TME) is crucial. Herein, we proposed nano-sized ferroferric oxide/single wall carbon nanotubes composites (Fe3O4-SWCNT) to engineer the macrophages species for powerful cancer therapy. The synthesized Fe3O4-SWCNT revealed good magnetic resonance imaging (MRI) performance, which enabled in vivo tracking of macrophage mediated immunotherapy. In addition, Fe3O4-SWCNT engineered M1-like macrophages (Fe3O4-SWCNT@M1) could maintain M1 phenotype, migrate to tumor cells and release nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α). A series of experimental results showed that Fe3O4-SWCNT@M1 could effectively promote the polarization of endogenous M2-like macrophages to M1-like macrophages, activate tumor immune response and inhibit tumor progression. This work is expected to provide a new vision for macrophage-based tumor immunotherapy.

The Single-Nucleotide Polymorphism of miR-27a rs895819 and the Expression of miR-27a in Helicobacter pylori-Related Diseases and the Correlation with the Traditional Chinese Medicine Syndrome.

Aims: The study aims to explore the effects of the single-nucleotide polymorphism of miR-27a and its expression in Helicobacter pylori (H. pylori)-related diseases and the relationship between gastric pathology and traditional Chinese medicine (TCM). Methods: Subjects were classified into six histopathological groups and five TCM syndrome groups. All specimens underwent H. pylori detection through rapid urease test and methylene blue staining. Histopathological characteristics were observed by hematoxylin-eosin. The expression of miR-27a and its genotype were, respectively, detected by Quantitative Real-Time PCR and direct sequencing. Results: H. pylori promoted the malignant evolution of gastric mucosa and were involved in the formation of TCM syndrome. In H. pylori-positive patients, the frequency of miR-27a CT genotype at the rs895819 locus and its expression in the gastric cancer group were higher than those in other pathological groups. TCM syndrome had a close relationship with histopathological changes, and patients with spleen-qi deficiency syndrome had a higher risk of gastric cancer than other syndromes, regardless of H. pylori infection. Conclusion: The C allele at miR-27a rs895819 locus may be an oncogene in gastric cancer. High levels of miR-27a could play an important role in gastric malignant evolution, especially cancerization. There is a certain connection between TCM syndrome and pathological changes of the gastric mucosa to some extent, where patients with SQD syndrome had a higher risk of GC.

Functional gene polymorphisms and expression alteration of selected microRNAs and the risk of various gastric lesions in Helicobacter pylori-related gastric diseases.

Background: Helicobacter pylori (Hp) persistent infection is an important pathogenic factor for a series of chronic gastric diseases from chronic gastritis to gastric cancer. Genetic and epigenetic abnormalities of microRNAs may play a vital role in the pathological evolution of gastric mucosa in Helicobacter pylori-related gastric diseases (HPGD). This study aimed to investigate the relationship between miR-146a, miR-196a2, miR-149, miR-499 and miR-27a gene single nucleotide polymorphisms (SNPs) and their expressions with pathological changes in gastric mucosa, and to further analyze the interactions between SNPs and Hp. Methods: Subjects in this study included patients diagnosed with HPGD and healthy controls. MiR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs2292832, miR-499 rs3746444 and miR-27a rs895819 were genotyped by direct sequencing. Fluorescence quantitative PCR was used to detect microRNA expressions. Gene-gene and gene-environment interactions were evaluated by multifactor dimensionality reduction (MDR) method. Results: we found that frequency distribution of miR-196a2 rs11614913 CT genotype in gastric precancerous lesion (GPL) group and gastric cancer (GC) group was significantly higher than normal control (NOR) group [adjusted OR = 6.16, 95%CI (1.46-26.03); adjusted OR = 11.83, 95%CI (1.65-84.72), respectively]. CT genotype and C allele of miR-27a rs895819 were associated with increased risk of GC [adjusted OR = 10.14, 95%CI (2.25-45.77); adjusted OR = 3.71, 95%CI(1.46-9.44), respectively]. The MDR analysis results showed that the interaction between miR-196a2 rs11614913 and Hp was associated with the risk of GPL (p = 0.004). Meanwhile, the expression level of miR-196a2 in GC group was significantly higher than NOR, chronic inflammation (CI) and early precancerous lesion (EPL) groups among Hp-positive subjects. And expressions of miR-499 and miR-27a in GC group were both higher than EPL group. Also, miR-27a expression in GC group was higher than CI and gastric atrophy (GA) groups. Conclusion: miR-196a2 rs11614913 and miR-27a rs895819 may affect the genetic susceptibility to GPL or GC. MiR-196a2 rs11614913 and Hp have a synergistic effect in the occurrence and development of GPL. The up-regulation of miR-499, miR-196a2 and miR-27a expression caused by Hp infection may be an important mechanism of gastric carcinogenesis.

PIWI-mediated control of tissue-specific transposons is essential for somatic cell differentiation.

PIWI proteins are known as mediators of transposon silencing in animal germlines but are also found in adult pluripotent stem cells of highly regenerative animals, where they are essential for regeneration. Study of the nuclear PIWI protein SMEDWI-2 in the planarian somatic stem cell system reveals an intricate interplay between transposons and cell differentiation in which a subset of transposons is inevitably activated during cell differentiation, and the PIWI protein is required to regain control. Absence of SMEDWI-2 leads to tissue-specific transposon derepression related to cell-type-specific chromatin remodeling events and in addition causes reduced accessibility of lineage-specific genes and defective cell differentiation, resulting in fatal tissue dysfunction. Finally, we show that additional PIWI proteins provide a stem-cell-specific second layer of protection in planarian neoblasts. These findings reveal a far-reaching role of PIWI proteins and PIWI-interacting RNAs (piRNAs) in stem cell biology and cell differentiation.

Role of gut microbiota in functional constipation.

Functional constipation (FC) is common, yet the etiology is not clear. Accumulating evidence suggests an association between FC and abnormal gut microbiota. The relationship between the gut microbiota and the gut transit is likely bidirectional. This review summarizes the current evidence regarding the impact of gut microbiota on the pathogenesis of FC. By modulating the colonic motility, secretion, and absorption, gut microbiota may contribute to the development of FC through microbial metabolic activities involving bile acids, short-chain fatty acids, 5-hydroxytryptamine, and methane. In support of the key roles of the gut microbiota in FC, treatment with probiotics, prebiotics, synbiotics, and traditional Chinese medicine often result in compositional and functional changes in the gut microbiota. Further studies on the pathogenesis of FC and the therapeutic mechanism of microecological agents will provide a knowledge base for better management of FC.