Incidence and predictors of chronic pain after inguinal hernia surgery: a systematic review and meta-analysis.

PURPOSE: The mesh is currently the preferred treatment option for hernia repair surgery. Chronic postoperative inguinal pain (CPIP), lasting more than 3 months after surgery, is a complication that significantly impacts patients' quality of life. Currently, there is a lack of evidence-based information describing the incidence and independent predictive factors of chronic pain, posing a serious challenge in clinical practice for devising personalized prevention strategies. Hence, we conducted this systematic review and meta-analysis to investigate the incidence and predictive factors, aiming to provide a reference for developing plans to prevent chronic pain. METHODS: We conducted a systematic search of PubMed, Cochrane, Embase, and Web of Science, with the retrieval cutoff date set at December 17, 2022. The included studies underwent assessment using the NOS scale, and subgroup analysis for the incidence was carried out based on different regions. RESULTS: Ultimately, 18 studies were included, involving 29,466 patients. Meta-analysis showed that the pooled incidence of chronic pain was 17.01% (95%CI 12.78% ~ 21.71%). The incidence was 18.65% (95%CI 13.59% ~ 24.29%) in Europe, 14.70% (95%CI 7.87% ~ 23.17%) in Asia, and 6.04%(95%CI 4.62 ~ 7.64) in North America. Furthermore, We also found that the risk factors for CPIP are younger age [OR = 2.261 (95%CI 1.126 ~ 4.549)], presence of other postoperative complications [OR = 1.849 (95%CI 1.034 ~ 3.305)], hernial sac defect < 3 cm [OR = 1.370 (95%CI 1.012 ~ 1.853)], being female [OR = 1.885 (95%CI 1.024 ~ 3.472)], postoperative pain [OR = 1.553 (95%CI 1.276 ~ 1.889)], preoperative pain [OR = 2.321 (95%CI 1.354 ~ 3.979)], and having a history of ipsilateral inguinal hernia repair [OR = 2.706 (95% CI 1.445 ~ 5.069)]. CONCLUSIONS: The incidence of persistent pain following hernia repair surgery is high in current clinical practice, a concern that should not be overlooked. Stratified assessment tools need to be established for patients experiencing early chronic pain, and personalized follow-up strategies and preventive interventions should be developed for those with potentially high risks. These measures aim to enhance the quality of life for patients after hernia repair.

[A Dual-Aware deep learning framework for identification of glioma isocitrate dehydrogenase genotype using magnetic resonance amide proton transfer modalities].

OBJECTIVE: To propose a Dual-Aware deep learning framework for genotyping of isocitrate dehydrogenase (IDH) in gliomas based on magnetic resonance amide proton transfer (APT) modality data as a means to assist non-invasive diagnosis of gliomas. METHODS: We collected multimodal magnetic resonance imaging (MRI) imaging data of the brain from 118 cases of gliomas, including 68 wild-type and 50 mutant type cases. The delineation of the ROI of brain glioma was completed in all the cases. APT modality imaging does not require contrast agents, and its signal intensity on tumors is positively correlated with tumor malignancy, and the signal intensity on wild-type IDH is higher than that on mutant IDH. For APT modalities, tumor imaging and derived areas are morphologically variable and lack prominent edge contour characteristics compared with other modalities. Based on these characteristics, we propose the Dual-Aware framework, which introduces the Multi-Aware framework to mine multi-scale features, and the Edge Aware module mines the edge features for automatic genotype identification. RESULTS: The introduction of two types of Aware mechanisms effectively improved the identification rate of the model for glioma IDH genotyping. The accuracy and AUC for each modality data were enhanced, and the best performance was achieved on the APT modality with a prediction accuracy of 83.1% and an AUC of 0.822, suggesting its advantages and effectiveness for identifying glioma IDH genotypes. CONCLUSION: The proposed deep learning algorithm model constructed based on the image characteristics of the APT modality is effective for glioma IDH genotyping and identification task and may potentially replace the commonly used T1CE modality to avoid contrast agent injection and achieve non- invasive IDH genotyping.

[Study of R2* value to evaluate regulation of liver regeneration by hepatic warm ischemia-reperfusion injury after partial hepatectomy in rabbits].

Objective: To investigate the effect of R2* value on the evaluation of different degrees of hepatic warm ischemia-reperfusion injury (WIRI) and liver regeneration after partial hepatectomy in rabbits. Methods: Thirty healthy adult male New Zealand White rabbits were randomly divided into five groups. Hepatic caudal lobectomy was performed in both the control and the warm ischemia time-dependent variation group. After reperfusion, routine MRI and BOLD MRI scans were performed for each group at 6 h, 3 d, 7 d, 14 d and 30 d, respectively, and then R2* value and liver regeneration rate (LRR) were measured and calculated. After 30 days of scanning, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6) and proliferating cell nuclear antigen (PCNA) were detected in frozen rabbit liver tissues, and the pathological sections were collected. Repeated measures analysis of variance was used to evaluate the changes of R2* value, LRR and its influencing factors at different follow-up time and warm ischemia time in each group. Pearson's or Spearman's correlation analysis was used to evaluate the correlation of R2* value with LRR and various biochemical indexes. Results: The interaction between different follow-up time and warm ischemia time (F = 24.600, P < 0.001) and the single effect of the both on the R2* value had statistically significant difference (P < 0.05). The interaction of different follow-up time and different warm ischemia time had no effect on LRR, and the difference was not statistically significant (F = 0.925, P = 0.528), but the difference in the main effect of the both on LRR was statistically significant (P < 0.05). At the same follow-up time, except for the 40-min ischemia group, the R2* values ​​were significantly positively correlated with LRR (3, 7, 14, 30 days after operation, r = 0.510, 0.681, 0.612, 0.541 respectively, P < 0.05). At the same warm ischemia time, the R2* value were significantly negatively correlated with LRR (3, 7, 14, 30 and 40 days after operation, r = - 0.800, -0.852, -0.893, -0.648, -0.853, respectively, P < 0.05). There was no correlation between R2 * value and biochemical indexes at 30 days after operation (P > 0.05). Conclusion: The R2* value may be used for noninvasive and quantitative evaluation of microstructural changes of WIRI and affect liver regeneration after partial hepatectomy in rabbits. A certain degree of WIRI (≤30 min) after partial hepatectomy can promote liver regeneration in rabbits. Furthermore, as the warm ischemia time prolongs, the promoting effect becomes more pronounced, and if the warm ischemic time exceeds 30 minutes, the promoting effect is significantly reduced.

Histological subtypes of solid-dominant invasive lung adenocarcinoma: differentiation using dual-energy spectral CT.

AIM: To investigate the value of dual-energy spectral computed tomography (DESCT) for evaluating the histological subtypes of solid-dominant invasive lung adenocarcinoma (SILADC). MATERIALS AND METHODS: Sixty-seven patients with SILADC were enrolled. All patients underwent DESCT and were divided into Group I (those with a lepidic/acinar/papillary predominant pattern) and Group II (those with a solid/micropapillary predominant pattern) based on their correlation with prognosis. Patient clinicopathological characteristics, DESCT morphological features, and quantitative parameters of the tumours were compared between both groups. Multiparametric analysis was performed using binary logistic regression with DESCT findings. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of single-parameter and multiparametric analysis. RESULTS: Patient gender, lymph nodes status, pathological TNM stage, and histological differentiation significantly differed between the two groups (all p<0.05). Moreover, significant differences were observed between both groups in DESCT morphological features including tumour size, necrosis, calcification, air bronchogram, and vascular convergence sign, and quantitative parameters including K40-65 keV, effective atomic number, and water concentration on unenhanced CT and iodine concentration in the arterial and venous phases (all p<0.05). Multiparametric analysis showed that tumour size, air bronchogram, K40-65 keV and effective atomic number on unenhanced CT were the most effective variations for predicting the histological subtypes of SILADC and obtained an area under the ROC curve (AUC) of 0.906. CONCLUSIONS: DESCT was useful for differentiating histological subtypes with different prognosis of SILADC.

[Clinical research on the expression of three vascular regulatory factors in different morphological regions of Marjolin ulcer and their relationship with angiogenesis].

Objective: To investigate the expressions of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), and epidermal growth factor receptor (EGFR) in different morphological regions of Marjolin ulcer and their clinical relationship with angiogenesis. Methods: From January 2012 to December 2017, the patients admitted to our hospital who met the inclusion criteria were selected, including 92 patients with Marjolin ulcer [56 males and 36 females, aged (55±15) years], 100 patients with chronic non-cancerous skin ulcer [59 males and 41 females, aged (51±16) years], and 100 patients performed with other skin-related surgery [58 males and 42 females, aged (52±15) years], and they were enrolled into Marjolin ulcer group (MU), chronic non-cancerous ulcer group (CNU), and other skin surgery group (OSS) respectively. The etiology, pathogenic site, ulcer diameter, and course of patients in group MU were retrospectively analyzed. Ulcer tissue specimens from patients of group MU and group CNU and specimens of normal skin tissue attached to the tissue resected during operation from patients of group OSS were collected. The expressions of VEGF, HIF-1α, EGFR, and CD34 in the above-mentioned tissue and the surrounding normal skin, ulcer, epitheliomatous hyperplasia, and canceration areas in Marjolin ulcer tissue were detected by immunohistochemical method, and the positive expression rate and protein expression level were calculated. Data were processed with Pearson chi-square test, Mann-Whitney U test, Bonferroni method, and Bonferroni correction, and Spearman correlation analysis was used to analyze the relationship among the total protein expression levels. Results: In group MU, burns accounted for 91.3% (84/92) of the causes of patients, 44.6% (41/92) of the patients had tumors in the lower extremities, 62.0% (57/92) of the patients had skin ulcer diameter of 2.1-5.0 cm, and 75.0% (69/92) of the patients had a course of disease of more than 20 years. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group CNU were 41.0% (41/100), 77.0% (77/100), and 83.0% (83/100), respectively, significantly higher than those of normal skin tissue of patients in group OSS [12.0% (12/100), 45.0% (45/100), and 67.0% (67/100), χ(2)=21.589, 21.522, 6.827, P<0.01]. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group MU were 91.3% (84/92), 100.0% (92/92), and 100.0% (92/92), respectively, which were significantly higher than those in corresponding tissue of patients in group CNU and group OSS (χ(2)=53.372, 24.772, 17.159; 120.543, 72.777, 36.661, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of VEGF in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ(2)=87.120, 42.368, 89.624, P<0.01); the positive expression rates of VEGF in canceration and ulcer areas were significantly higher than the rate in epitheliomatous hyperplasia area (χ(2)=22.586, 16.060, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ(2)=21.679, 27.600, 27.600, P<0.01), but the positive expression rates of HIF-1α in four morphological areas were similar (χ(2)=3.008, P>0.05). In ulcer tissue of patients in group MU, the protein expression levels of VEGF and CD34 in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.765, -6.819; -6.765, -6.640; -6.765, -6.819, P<0.01), the protein expression levels of VEGF and CD34 in epitheliomatous hyperplasia area were significantly lower than those in ulcer area (Z=-4.484, -5.266, P<0.01), and the protein expression levels of VEGF and CD34 in canceration area were significantly higher than those in ulcer area (Z=-6.427, -6.723, P<0.01) and epitheliomatous hyperplasia area (Z=-6.427, -6.462, P<0.01). In ulcer tissue of patients in group MU, the protein expression levels of HIF-1α and EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.819, -6.393; -6.819, -6.393; -6.819, -6.393, P<0.01), the protein expression levels of HIF-1α and EGFR in ulcer area were significantly lower than those in epitheliomatous hyperplasia and canceration areas (Z=-6.118, -5.638; -6.640, -6.393, P<0.01), and the protein expression levels of HIF-1α and EGFR in canceration area were significantly higher than those in epitheliomatous hyperplasia area (Z=-6.558, -6.819, P<0.01). In ulcer tissue of patients in group MU, the total protein expression levels of VEGF, HIF-1α, and EGFR were significantly positively correlated with the total protein expression level of CD34 (r=0.772, 0.415, 0.502, P<0.01) respectively; the total protein expression level of EGFR was significantly positively correlated with that of HIF-1α (r=0.839, P<0.01), both of which were significantly positively correlated with the total protein expression level of VEGF (r=0.531, 0.440, P<0.01) respectively. Conclusions: The expressions of VEGF, HIF-1α, and EGFR are the highest in Marjolin ulcer canceration area, and EGFR may promote angiogenesis through HIF-1α or directly increasing the expression of VEGF.

The expression and significance of lncRNA HOST2 and microRNA let-7b in HPV-positive cervical cancer tissues and cell lines.

OBJECTIVE: This study attempted to investigate the expression and significance of lncRNA HOST2 (human ovarian cancer-specific transcript 2) and microRNA let-7b in human papillomavirus (HPV)-positive cervical cancer (CC) tissues and cell lines. PATIENTS AND METHODS: The expression of levels of HOST2 and let-7b were detected by qRT-PCR in HPV-positive CC tissues and cell lines. The HPV-positive CaSki and HeLa cells were divided into the Blank, NC, pcDNA3.0-HOST2, siHOST2, let-7b mimic, and pcDNA3.0-HOST2+let-7b mimic groups. Dual-luciferase reporter gene assay was employed to verify the targeting relationship between HOST2 and let-7b, MTT and flow cytometry to determinate cell proliferation and apoptosis, and wound-healing and transwell assays to evaluate cell migration and invasion capabilities. RESULTS: HOST2 was up-regulated but let-7b was down-regulated in HPV-positive CC tissues and cells. Dual-luciferase reporter gene assay confirmed the targeting relationship between HOST2 and let-7b. Over-expressed HOST2 reduced let-7b expression, promoted proliferation migration and invasion and inhibited the apoptosis of CaSki and HeLa cells; however, silencing HOST2 or overexpressing let-7b enhanced the expression of let-7b, inhibited proliferation migration and invasion, and promoted the apoptosis of CaSki and HeLa cells, and let-7b mimic could reverse the promoting effect of HOST2 on the growth of CC cells. CONCLUSIONS: HOST2 was upregulated in HPV-positive CC tissues and cells, which could promote the proliferation, migration and invasion, but inhibit the apoptosis of HPV-positive CC cells via inhibition of let-7b.

Utility of arterial spin labelling MRI for discriminating atypical high-grade glioma from primary central nervous system lymphoma.

AIM: To evaluate the ability of arterial spin labelling (ASL) magnetic resonance imaging (MRI) in differentiating primary central nervous system lymphoma (PCNSL) from atypical high-grade glioma (HGG), as well as exploring the underlying pathological mechanisms. METHODS AND MATERIALS: Twenty-three patients with PCNSL and 17 patients with atypical HGG who underwent ASL-MRI were identified retrospectively. Absolute cerebral blood flow (aCBF) and normalised cerebral blood flow (nCBF) values were obtained, and were compared between PCNSL and atypical HGG using the Mann-Whitney U-test. The performance in discriminating between PCNSL and atypical HGG was evaluated using receiver-operating characteristics analysis and area-under-the-curve (AUC) values for aCBF and nCBF. The correlation between microvessel density (MVD) and aCBF was determined by Spearman's correlation analysis. RESULTS: Atypical HGG demonstrated significantly higher aCBF, nCBF, and MVD values than PCNSL (p<0.05). The diagnostic accuracy of discriminating PCNSL from atypical HGG showed AUC=0.877 (95% confidence interval [CI] 0.735-0.959) for aCBF, and AUC=0.836 (95% confidence interval [CI] 0.685-0.934) for nCBF. There was a moderate positive correlation between aCBF values of region of interest (ROI >30 mm2) in the enhanced area and MVD values (rho=0.579, p=0.0001), and a strong positive correlation between aCBF values MVD based on "point-to-point biopsy" (rho=0.83, p=0.0029). Interobserver agreements for aCBF and nCBF were excellent (ICC >0.75). CONCLUSIONS: ASL perfusion MRI is a useful imaging technique for the discrimination between atypical HGG and PCNSL, which may be determined by the difference of MVD between them.

Long non-coding RNA HOST2 enhances proliferation and metastasis in gastric cancer.

This study investigates the influence of long noncoding RNA HOST2 on the biological functions of gastric cancer cells; including proliferation, migration and invasion. Differentially expressed lncRNAs in gastric cancer (GC) were screened by microarray analysis, and HOST2 expression in GC tissues and cell lines was determined by quantitative real-time PCR (qRT-PCR). GC cell proliferation, migration and invasion were detected by CCK-8, wound healing and transwell assays. Western blot investigated expression of epithelial-mesenchymal transition (EMT) related proteins, and association was established between over-expressed HOST2 and the number of patients with lymph node and distant metastasis. HOST2 expression was also positively related to GC cell invasion ability, and although its expression in the p-shHOST2 group was remarkably decreased, it was significantly higher than in the Mock and NC groups. Compared to the Mock and NC groups, the p-shHOST2 group presented significant decreases in proliferation and wound healing rates, and the reverse result was noted in the p-HOST2 group. In addition, the number of p-shHOST2 group invasive cells was remarkably less than in the Mock and NC group, and the opposite result was achieved in the p-HOST2 group. Moreover, p-HOST2 had more significant EMT, but this was suppressed in the p-shHOST2 group. Finally, HOST2 silencing suppressed GC cell proliferation, migration and invasion; and it could therefore be considered as a novel biomarker and therapeutic target in gastric cancer.

Increased expression of long noncoding RNA HMMR-AS1 in epithelial ovarian cancer: an independent prognostic factor.

OBJECTIVE: Evidence has indicated that long noncoding RNA (lncRNAs) may have significant roles in cancer. In this study, we aimed to investigate the expression pattern and prognostic value of a noncoding RNA named as HMMR antisense RNA 1 (HMMR-AS1) in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Differences in the expression of HMMR-AS1 between EOC and matched normal tissues were analyzed using RT-PCR. The correlation between HMMR-AS1 levels and the clinicopathological factors of the EOC patients was analyzed by x2-test. Kaplan-Meier analysis and Cox proportional hazards regression models were explored to reveal the correlations of HMMR-AS1 expression with survival of patients. RESULTS: HMMR-AS1 was significantly upregulated in human EOC tissues compared with adjacent normal tissues (p < 0.01). Clinicopathologic analysis revealed that high expression of HMMR-AS1 was associated with advanced FIGO stage (p = 0.013) and positive lymphatic metastasis (p = 0.010). Moreover, patients with higher HMMR-AS1 expression displayed shorter overall survival time (p = 0.0075) and progression-free survival time (p = 0.0013) than those with lower HMMR-AS1 expression. More importantly, multivariate analysis suggested that high expression of HMMR-AS1 was an independent prognostic indicator for EOC patients. CONCLUSIONS: Our data suggested that HMMR-AS1 may be considered a novel prognostic factor in EOC and a specific diagnostic indicator for patients with EOC.

Melatonin promotes osteoblast differentiation of bone marrow mesenchymal stem cells in aged rats.

OBJECTIVE: The current study was to explore the effect of melatonin on osteoporosis and relevant mechanisms. MATERIALS AND METHODS: We performed micro-CT to detect bone microstructure and ELISA to detect the contents of osteocalcin (OCN) and bone alkaline phosphatase (BAP) in serum. Double fluorescence labeling of calcein and tetracycline and toluidine blue staining were used to determine morphological indexes of bone tissues. Alizarin red staining and Oil Red O staining were performed to recognize bone cells and adipocytes. RT-PCR was performed to determine the expression of osteoblast differentiation related genes. RESULTS: In the current study, data from micro-CT indicated that melatonin significantly increased the bone mass density (BMD), bone volume/tissue volume (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th), and decreased the Structure Model Index (SMI) and trabecular Separation/Spacing (Tb.Sp) in elderly rats. Melatonin reduced calcium and phosphorus losses in urine and increased BAP and OCN levels in serum in elderly rats and increased bone formation rate (BFR) and bone mineralization rate (MAR) in elderly rats. Melatonin increased the number of osteoblasts in bone marrow and reduced the number of adipocytes in elderly rats. Melatonin also promoted the expression of osteogenic differentiation genes and suppressed the expression of adipogenic differentiation genes. CONCLUSIONS: WE suggest that melatonin could alleviate osteoporosis in aged rats' models probably by promoting osteoblast differentiation.

[Clinical value of the early use of ulinastatin in patients with moderately severe or severe acute pancreatitis].

Objective: To observe the clinical efficacy and the effects on serum inflammatory factors of early use of ulinastatin in patients with moderately severe or severe acute pancreatitis (MSAP/SAP). Methods: This prospective, randomized, controlled trial was conducted in the First Affiliated Hospital of Soochow University from September 2013 to May 2016. A total of 42 cases were enrolled and assigned into either observation group or conventional treatment group (n=21 each). The conventional treatment group received somatostatin, while the observation group received somatostatin combined with ulinastatin. After treatment, clinical characteristics, serum indicators, clinical complications and serum level of inflammatory factors were analyzed. Results: Intra-abdominal pressure and relief time of abdominal pain were significantly decreased in observation group [ (10.4±2.1) cmH(2)O; (2.5±1.2) d ] compared with the conventional treatment group [ (11.7±2.2) cmH(2)O; (3.33± 1.2) d ], P<0.05. White blood cells (WBC) were lower in observation group than those in conventional treatment group [ (11.2±1.8) ×10(9)/L vs (12.5±2.3) ×10(9)/L; P<0.05 ]. After treatment serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α(TNF-α) in observation group [ (30.5±3.3), (34.7± 6.5), (22.6±4.0) µg/L] were significantly lower than those in conventional treatment group [ (39.6±4.0), (40.9±3.4), (33.1±6.6) µg/L], P<0.05. There were no differences between the two groups in modified CT severity index (MCTSI), recovery time of defecation, ICU length of stay, serum amylase, C-reactive protein (CRP) and incidence rates of clinical complications. Conclusions: The early use of ulinastatin in the patients with MSAP/SAP can down-regulated the levels of TNF-α, IL-6 and IL-8, reduce the inflammatory response, decrease intra-abdominal pressure and shorten abdominal pain time. It was beneficial and worthy of wider popularization.

mTORC2 controls Th9 polarization and allergic airway inflammation.

BACKGROUND: T helper type 9 (Th9) cells, a subpopulation of CD4+ T cells, play a critical role in the pathogenesis of allergic airway inflammation. However, it remains unknown whether mTORC2 regulates Th9 differentiation or function during allergic inflammation. METHODS: T-cell-specific Rictor-deficient mice, a mouse model of allergic airway inflammation induced by ovalbumin (OVA) sensitization and a mouse model of adoptive transfer of induced Th9 cells, were used to address the roles of mTORC2 in the pathogenesis of allergic airway inflammation. The in vitro Th9 induction, multiple colors flow cytometry, real-time PCR, and Western blots were used to investigate the molecular effects of mTORC2 in Th9 induction. RESULTS: The differentiation of naïve CD4+ T cells into Th9 cells was significantly diminished in the absence of Rictor, the core component of mTORC2. Using a mouse model of allergic airway inflammation induced by OVA sensitization, T-cell-specific Rictor-deficient mice show much less severe allergic airway inflammation characterized by decreased pathological alterations and fibrosis of the lungs, which was accompanied with reduced Th9 differentiation and infiltration. Importantly, the isolated Rictor-deficient Th9 cells mediate less severe allergic pathogenesis upon adoptive transfer. Rictor deficiency impairs Th9 cell differentiation by reducing IRF4 expression rather than affecting Foxo1/Foxo3a transcriptional activity, which is likely due to decreased Akt and/or STAT6 activation. CONCLUSIONS: These findings uncover a novel role of mTORC2 in Th9 cell differentiation and may have important implications for therapeutic intervention of allergic diseases.

Anti-Aging Effect of Riboflavin Via Endogenous Antioxidant in Fruit fly Drosophila Melanogaster.

OBJECTIVES: This study investigated the effect of riboflavin on aging in Drosophila melanogaster (fruit fly). DESIGN: Experimental study. SETTING: Naval Medical Research Institute. PARTICIPANTS: Fruit fly Drosophila melanogaster. INTERVENTION: After lifelong supplement of riboflavin, the lifespan and the reproduction of fruit flies were observed. Hydrogen peroxide (H2O2) was used to mimic oxidative stress damage to fruit flies and the survival time was recorded. MEASUREMENTS: The activity of copper-zinc-containing superoxide dismutase (SOD1), manganese containing SOD (SOD2) and catalase (CAT) and lipofuscin (LF) content were determined. RESULTS: Riboflavin significantly prolonged the lifespan (Log rank χ2=16.677, P<0.001) and increased the reproductive capacity (P<0.01 for day 15; P<0.05 for day 30) of fruit flies by lifelong supplement. The survival time of fruit flies damaged by H2O2 was significantly prolonged (Log rank χ2=15.886, P<0.001), the activity of SOD1 (P<0.01) and CAT (P<0.01) was enhanced, and the accumulation of LF (P<0.01) was inhibited by riboflavin supplement. CONCLUSION: Riboflavin prolonged the lifespan and increased the reproduction of fruit flies through anti-oxidative stress pathway involving enhancing the activity of SOD1 and CAT and inhibiting LF accumulation. Riboflavin deserves more attention for slowing human aging.

[Analysis on clinical characters of pharyngeal paraesthesia in patients with different degrees of anxiety].

Objective:To investigate the therapeutic effect and potential reason for anxiety in pharyngeal paraesthesia in patients with different degrees of anxiety based on their characteristics.Method:All patients were divided into three groups according to self-rating anxiety scale(SAS)，including group 1（mild anxiety），group 2（moderate anxiety）and group 3（severe anxiety）.The characteristics,risk factors and prognosis in each group were compared and analyzed．Meanwhile，State-Trait Anxiety Inventory(STAI)was used to analyze anxiety state of all patients and healthy participates(Group 4)．SPSS13.0 statistical software was used for data analysis. Result:The proportions of female patients(54.05%) who had anxiety symptom were higher than those of male patients(45.95%).The proportions of moderate anxiety in female patients were higher(P<0.01),but those of mild anxiety were lower(P<0.01) compared with male patients. There was no gender difference about the proportions of severe anxiety. The patients aged 40-59 years had the highest proportions of anxiety(60.14%)and a higher proportions of moderate and severe anxiety compared with the patients aged 18~39 years and over 60 years old(P<0.05).However, there was no significant difference in proportions of different degrees of anxiety between the patients aged 18-39 years and over 60 years old(P>0.05).The proportions of mild anxiety in patients with 5-10 years duration and those of moderate anxiety in patients with the course of less than 5 years were all the highest.However, no difference was found in proportions of severe anxiety among different courses(P>0.05).The proportions of moderate anxiety(except mild and severe anxiety) in patients with no fixed occupation and no senior middle school education were higher than those in patients with fixed occupation and senior middle school education or above(P<0.05).But there were no relationships between the degrees of anxiety and other general conditions of patients,including marital status and live condition. Among different degrees of anxiety,the proportions of patients who feared cancer were all the highest, followed by stress and mental stimulation factors.The proportions of patients who feared cancer and felt stress were higher in severe anxiety than those in mild and moderate anxiety.But there was no significant difference between any two groups in other related factors,including mental stimulation factors, obsessive-compulsive disorder(OCD) and family history of psychosis.Male and female patients with different degrees of anxiety compared with healthy controls respectively,had significant difference in state anxiety(SAI) scores(P<0.05),but showed no significant difference in trait anxiety(T-AI) scores(P>0.05). Both recovery rates and total effective rates of mild and moderate anxiety were higher than those of severe anxiety(P<0.01).However,there was no difference between mild and moderate anxiety whether in recovery rates or in total effective rates (P>0.05). Conclusion:Pharyngeal paraesthesia in patients with different degrees of anxiety has different clinical features and prognosis .The main cause of anxiety appears to be a long duration of treatment. No obvious anxiety potential was found in patients compared with normal people.

[Influence of anti anxiety and anti depression treatment on sudden hearing loss].

Objective:To study the influence of anti-anxiety and antidepression treatment on patients diagnosed as sudden hearing loss with anxiety and depression symptoms.Method:A prospective and controlled study was carried out. A total number of 248 patients with anxiety and depression symptoms were randomly divided into experimental group or control group by Stochastic tables law. A number of 126 patients in experimental group accepted anti anxiety and anti depression treatment, while 122 patients in control group did not accepted anti anxiety and anti depression treatment. The hearing and tinnitus effects were evaluated.SPSS 13.0 statistical software was used for data processing.Result:According to the results of pure-tone threshold audiometry, in the 126 cases of experimental group, 48 were cured (38.1%), 25 were markedly improved (19.8%), 23 were effective (18.3%), and 30 were invalid (23.8%).The total effective rate was 76.2% (96/126). In the 122 cases of control group, 34 were cured (27.9%),17 were markedly improved (13.9%),18 were effective (14.8%),and 53 were invalid (43.4%).The total effective rate was 56.6%(69/122).The two groups had no significant difference in recovery rates but it showed significant difference in total effective rates. Moreover, the total effective rate of the flat type of sudden hearing loss in experimental group was superior to that in control group, however there was no significant difference in total effective rates of other three types between two groups. The patients who had concomitant symptom of tinnitus in experimental group and control group accounted for 85.7% (108/126) and 84.4%(103/122), respectively. However, no significant difference was found in proportions of patients with tinnitus between the two groups. According to the tinnitus results, in the 108 cases of experimental group, 32 were cured (29.6%),19 were markedly improved (17.6%), 36 were effective (33.3%), and 21 were invalid (19.4%). The total effective rate was 80.6%(87/108). In the 103 cases of control group, 19 were cured (18.4%), 15 were markedly improved (14.6%),22 were effective(21.4%),and 47 were invalid (45.6%).The total effective rate was 54.4% (56/103).The two groups had no significant difference in recovery rates but it showed significant difference in total effective rates. There was no significant difference in total effective rate of the low-middle frequency sudden hearing loss between two groups, but the total effective rates of other three types in experimental group were all higher than those in control group.Conclusion:The total effective rates of hearing and tinnitus can be improved after combination treatment with anti-anxiety and anti-depression in sudden hearing loss patients with anxiety and depression symptoms. Moreover, different types of the hearing curves of sudden deafness have different improvement degrees.

PRMT5 enhances generation of induced pluripotent stem cells from dairy goat embryonic fibroblasts via down-regulation of p53.

OBJECTIVES: Protein arginine methyltransferase 5 (PRMT5), is thought to play a role in epigenetic reprogramming of mouse germ cells. However, up to now there has been little information concerning its expression profile and effects on generation of induced pluripotent stem cells (iPSCs) from somatic cells, in livestock. Here, we have explored PRMT5 expression profiles in dairy goats and its consequences to derivation of iPSCs from dairy goat embryonic fibroblasts (GEFs). MATERIALS AND METHODS: We investigated effects of PRMT5 on iPS-like cells production in vitro. alkaline phosphatase (AP) staining, QRT-PCR and western blotting analysis of expression of related markers were used to evaluate efficiency of generation of iPSCs derived from GEFs. RESULTS: These showed PRMT5 to be a conservative gene widely expressed in various tissues and different-aged testes. PRMT5 overexpression in combination with OCT3/4, SOX2, KLF4 and C-MYC (POSKM) significantly increased number of AP positive iPS-like colony-derived GEFs compared to OSKM alone, in our dairy goats. Moreover, our results demonstrated that PRMT5 overexpression stimulated GEF proliferation and down-regulated p53, p21 (a target gene of p53) and the apoptotic marker caspase 3, to enhance somatic cell reprogramming. CONCLUSION: This study provides an efficient model for future studies on mechanisms underlying goat somatic cell reprogramming and differentiation.

piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma.

Aberrant DNA hypermethylation contributes to myelomagenesis by silencing tumor-suppressor genes. Recently, a few reports have suggested that a novel class of small non-coding RNAs, called Piwi-interacting RNAs (piRNAs), may be involved in the epigenetic regulation of cancer. In this study, for the first time we provided evidence that the expression of piRNA-823 was upregulated in multiple myeloma (MM) patients and cell lines, and positively correlated with clinical stage. Silencing piRNA-823 in MM cells induced deregulation of cell cycle regulators and apoptosis-related proteins expression, accompanied by inhibition of tumorigenicity in vitro and in vivo. Moreover, piRNA-823 was directly relevant to de novo DNA methyltransferases, DNMT3A and 3B, in primary CD138(+) MM cells. The inhibited expression of piRNA-823 in MM cells resulted in marked reduction of DNMT3A and 3B at both mRNA and protein levels, which in turn led to decrease in global DNA methylation and reexpression of methylation-silenced tumor suppressor, p16(INK4A). In addition, piRNA-823 abrogation in MM cells induced reduction of vascular endothelial growth factor secretion, with consequent decreased proangiogenic activity. Altogether, these data support an oncogenic role of piRNA-823 in the biology of MM, providing a rational for the development of piRNA-targeted therapeutic strategies in MM.

Detection of interleukin-33 in serum and carcinoma tissue from patients with hepatocellular carcinoma and its clinical implications.

OBJECTIVE: To study the clinical significance of intercellular interleukin (IL)-33 in hepatocellular carcinoma (HCC). METHODS: Using immunohistochemistry, this prospective study compared IL-33 protein levels in samples of HCC tissue and normal tissue adjacent to the tumour in 60 patients with HCC, and in normal liver tissue from six healthy controls. Interferon (IFN)-α, IFN-γ and IL-33 serum levels were also analysed by enzyme-linked immunosorbent assay in HCC 30 patients and 10 healthy controls. The level of IL-33 immunohistochemical staining was compared with the rate of lymph node metastasis in HCC patients. RESULTS: IL-33 was strongly positive in the cytoplasm of hepatocytes. The median percentage of IL-33-positive tissue was higher in HCC than in normal liver tissue samples (adjacent to the tumour or from controls). Serum IFN-α, IFN-γ and IL-33 levels were higher in pre- and postoperative samples from HCC patients than in control samples, and in patients with metastasis compared with those without metastasis. CONCLUSIONS: Increased IL-33 protein levels were observed in serum and liver tissue from HCC patients; IL-33 may be a useful biological marker for monitoring HCC growth and metastasis.

miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer.

BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) is an oncogene known to promote tumour metastasis, especially in colorectal cancer (CRC). Here, we demonstrate that the miR-21, miR-17 and miR-19a expressions induced by PRL-3 are involved in the proliferation and metastasis of colon cancer. METHODS: Microarray analysis and quantitative reverse-transcription polymerase chain reactions (qRT-PCR) were used to investigate the changes in miRNA expression due to the overexpression of PRL-3. Transwell chamber invasion assays, CCK-8 proliferation assays and RNA interference assays were used to explore the effects of PRL-3 on miR-21, miR-17 and miR-19a expression in colon cancer cells. Immunohistochemistry and qRT-PCR were performed in colon cancer tissues to evaluate the expression of PRL-3, signal transducer and activator of transcription 3 (STAT3), miR-21, miR-17 and miR-19a. RESULTS: Our study demonstrated that the overexpression of PRL-3 in colon cancer cells induced the expression of miR-21, miR-17 and miR-19a by activating STAT3. Subsequently, these microRNAs contributed to the increased proliferation and invasiveness of the colon cancer cells. Positive correlations between PRL-3 and these microRNAs were also observed in matched primary colon cancer tissues and metastatic lesions. CONCLUSION: miR-21, miR-17 and miR-19a induced by PRL-3 contribute to the proliferation and invasion of colon cancer.

Two types of burst firing in gonadotrophin-releasing hormone neurones.

Gonadotrophin-releasing hormone (GnRH) neurones fire spontaneous bursts of action potentials, although little is understood about the underlying mechanisms. In the present study, we report evidence for two types of bursting/oscillation driven by different mechanisms. Properties of these different types are clarified using mathematical modelling and a recently developed active-phase/silent-phase correlation technique. The first type of GnRH neurone (1-2%) exhibits slow (∼0.05 Hz) spontaneous oscillations in membrane potential. Action potential bursts are often observed during oscillation depolarisation, although some oscillations were entirely subthreshold. Oscillations persist after blockade of fast sodium channels with tetrodotoxin (TTX) and blocking receptors for ionotropic fast synaptic transmission, indicating that they are intrinsically generated. In the second type of GnRH neurone, bursts were irregular and TTX caused a stable membrane potential. The two types of bursting cells exhibited distinct active-phase/silent-phase correlation patterns, which is suggestive of distinct mechanisms underlying the rhythms. Further studies of type 1 oscillating cells revealed that the oscillation period was not affected by current or voltage steps, although amplitude was sometimes damped. Oestradiol, an important feedback regulator of GnRH neuronal activity, acutely and markedly altered oscillations, specifically depolarising the oscillation nadir and initiating or increasing firing. Blocking calcium-activated potassium channels, which are rapidly reduced by oestradiol, had a similar effect on oscillations. Kisspeptin, a potent activator of GnRH neurones, translated the oscillation to more depolarised potentials, without altering period or amplitude. These data show that there are at least two distinct types of GnRH neurone bursting patterns with different underlying mechanisms.