Nanomedicine and drug delivery strategies for treatment of inflammatory bowel disease

Crohn's disease and ulcerative colitis are two important categories of human inflammatory bowel disease(IBD). Because the precise mechanisms of the inflammation and immune responses in IBD have not been fully elucidated,the treatment of IBD primarily aims to inhibit the pathogenic factors of the inflammatory cascade. Inconsistencies exist regarding the response and side effects of the drugs that are currently used to treat IBD. Recent studies have suggested that the use of nanomedicine might be advantageous for the treatment of intestinal inflammation because nanosized molecules can effectively penetrate epithelial and inflammatory cells. We reviewed nanomedicine treatments,such as the use of small interfering RNAs,antisense oligonucleotides,and anti-inflammatory molecules with delivery systems in experimental colitis models and clinical trials for IBD based on a systematic search. The efficacy and usefulness of the treatments reviewed in this manuscript have been demonstrated in experimental colitis models and clinical trials using various types of nanomedicine. Nanomedicine is expected to become a new therapeutic approach to the treatment of IBD.

Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

Prognosis of metastatic splenic hilum lymph node in patients with gastric cancer after total gastrectomy and splenectomy

AIM:To clarify the significance of combined resection of the spleen to dissect the No.10 lymph node(LN). METHODS:We studied 191 patients who had undergone total gastrectomy with splenectomy,excluding non-curative cases,resection of multiple gastric cancer, and those with remnant stomach cancer.Various clinico-pathological factors were evaluated for any independent contributions to No.10 LN metastasis,usingχ 2 test. Significant factors were extracted for further analysis, carried out using a logistic regression method.Furthermore,lymph node metastasis was evaluated for any independent contribution to No.10 LN metastasis,using the same methods.The cumulative survival rate was calculated using the Kaplan-Meier method.The significance of any difference between the survival curves was determined using the Cox-Mantel test,and any difference was considered significant at the 5%level. RESULTS:From the variables considered to be potentially associated with No.10 LN metastasis,age, depth,invasion of lymph vessel,N factor,the numberof lymph node metastasis,Stage,the number of sites, and location were found to differ significantly between those with metastasis(the Positive Group)and those without(the Negative Group).A logistic regression analysis showed that the localization and Stage were significant parameters for No.10 LN metastasis.There was no case located on the lesser curvature in the Posi-tive Group.The numbers of No.2,No.3,No.4sa,No. 4sb,No.4d,No.7,and No.11 LN metastasis were each found to differ significantly between the Positive Group and the Negative Group.A logistic regression analysis showed that No.4sa,No.4sb,and No.11 LN metastasis were each a significant parameter for No.10 LN metastasis.There was no significant difference in survival curves between the Positive Group and the Negative Group. CONCLUSION:Splenectomy should be performed to dissect No.10 LN for cases which have No.4sa,No. 4sb or No.11 LN metastasis.However,in cases where the tumor is located on the lesser curvature,splenectomy can be omitted.

Characteristics and prognosis of synchronous multiple early gastric cancer

AIM:To assess the clinicopathologic characteristics,risk factors,and prognosis for synchronous multiple early gastric cancer(SMGC).METHODS:A total of 146 patients with SMGC and1194 patients with single gastric cancer who had undergone gastrectomy between 1989 and 2008 were retrospectively analyzed to determine their clinicopathologic characteristics and postoperative survival.Tumors were classified into groups on the basis of location and histology.Smoking habits were evaluated using the Brinkman index.Clinical and pathological factors were compared using either Fisher’s exact test or Pearson’sχ2test.Logistic regression analysis was performed to identify independent risk factors.Survival rate was calculated using the Kaplan-Meier method.RESULTS:SMGCs accounted for 10.9%of gastric cancer cases and occurred predominantly in elderly male patients with a family history of gastric cancer who were both smokers and drinkers.These tumors were typically macroscopically elevated and histologically differentiated.There were no significant differences between SMGC and single gastric cancer patients with respect to tumor location,tumor size,lymph node metastasis,the number of metastatic lymph nodes,venous invasion,or tumor stage(P=0.052,P=0.347,P=0.595,P=0.805,P=0.559,and P=0.408,respectively).Further,there was no significant difference in postoperative survival between the patient groups(P=0.200).Of the 146SMGC patients,a single patient had remnant cancer.CONCLUSION:A careful preoperative endoscopy is necessary for patients who are at high risk of SMGC,and minimally invasive treatment may be indicated in some cases.

Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic manifestations.Thus,HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection.Although the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established.In addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance.In order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc supplements.Little is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported.On the other hand,insulin-sensitizing agents are reported to improve sustained virologic response rates.In this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin resistance.Furthermore,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCVassociated insulin resistance.

Status of colitis-associated cancer in ulcerative colitis

Surgical therapy for ulcerative colitis(UC) depends on the medical therapy administered for the patient's condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer(CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients.

Antibody markers in the diagnosis of inflammatory boweldisease

Inflammatory bowel disease(IBD), including Crohn's disease and ulcerative colitis, is a chronic intestinal inflammation of unknown etiology. The diagnosis of IBD is based on endoscopic, radiologic and histopathologic criteria. Recently, the search for a noninvasive marker that could augment or replace part of this diagnostic process has become a focus of IBD research. In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest. The discovery of novel IBD-specific and sensitive markers is anticipated. Such markers could minimize the use of endoscopic and radiologic examinations and could enable clinicians to implement individualized treatment plans designed to improve the long-term prognosis of patients with IBD.

Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Diagnosis of early gastric cancer using narrow band imaging and acetic acid

AIM: To determine whether the endoscopic findings of depressed-type early gastric cancers(EGCs) could precisely predict the histological type.METHODS: Ninety depressed-type EGCs in 72 patients were macroscopically and histologically identified. We evaluated the microvascular(MV) and mucosal surface(MS) patterns of depressed-type EGCs using magnifying endoscopy(ME) with narrow-band imaging(NBI)(NBI-ME) and ME enhanced by 1.5% acetic acid, respectively. First, depressed-type EGCs were classified according to MV pattern by NBI-ME. Subsequently, EGCs unclassified by MV pattern were classified according to MS pattern by enhanced ME(EME) images obtained from the same angle.RESULTS: We classified the depressed-type EGCs into the following 2 MV patterns using NBI-ME: a fine-network pattern that indicated differentiated adenocarcinoma(25/25, 100%) and a corkscrew pattern that likely indicated undifferentiated adenocarcinoma(18/23, 78.3%). However, 42 of the 90(46.7%) lesions could not be classified into MV patterns by NBI-ME. These unclassified lesions were then evaluated for MS patterns using EME, which classified 33(81.0%) lesions as MS patterns, diagnosed as differentiated adenocarcinoma. As a result, 76 of the 90(84.4%) lesions were matched with histological diagnoses using a combination of NBI-ME and EME.CONCLUSION: A combination of NBI-ME and EME was useful in predicting the histological type of depressedtype EGC.

Clinical characteristics and management of gastric tube cancer with endoscopic submucosal dissection

AIM:To identify the characteristics of gastric tube cancer(GTC) and the complications associated with endoscopic submucosal dissection(ESD) for GTC.METHODS:Between 2007 and 2012,11 individualswith early gastric cancer in the reconstructed gastric tube after esophagectomy who underwent ESD in this hospital were studied.The characteristics of GTC were identified,and the complications of ESD for GTC were analyzed at three phases:preoperative,intraoperative,and postoperative.RESULTS:A total of 11 consecutive patients with 11 GTCs were selected for this study.All cases underwent en bloc resections by ESD.The median procedure time was 142 min.The average GTC diameter was 26.1 mm,and the average size of the resected lesions was 45.5 mm.The histopathological diagnosis in all cases was a differentiated adenocarcinoma.In the preoperative phase,anastomotic strictures(5/11,45%) and food residues(4/11,36.4%) in the gastric tube were the main complications.In the intraoperative phase,bleeding was observed in 5 cases(45%).The postoperative complications observed were delayed bleeding in 2 cases(18.2%) and stenosis in one case(9.1%).The case with stenosis was successfully treated using endoscopic balloon dilatation.CONCLUSION:Minor complications were frequently observed.However,all GTCs underwent en bloc resection with ESD without any serious complications.ESD is considered a useful treatment for GTC.

Prediction of colorectal tumor grade and invasion depth through narrow-band imaging scoring

AIM To determine the usefulness of assigning narrow-band imaging(NBI) scores for predicting tumor grade and invasion depth in colorectal tumors.METHODS A total of 161 colorectal lesions were analyzed from138 patients who underwent endoscopic or surgical resection after conventional colonoscopy and magnifying endoscopy with NBI. The relationships between the surface and vascular patterns of the lesions, as visualized with NBI, and the tumor grade and depth of submucosa(SM) invasion were determined histopathologically.Scores were assigned to distinct features of the surface microstructures of tubular and papillary-type lesions.Using a multivariate analysis, a model was developed for predicting the tumor grade and depth of invasion based on NBI-finding scores.RESULTS NBI findings that correlated with a high tumor grade were associated with the "regular/irregular"(P < 0.0001)surface patterns and the "avascular area" pattern(P =0.0600). The vascular patterns of "disrupted vessels"(P = 0.0714) and "thick vessels"(P = 0.0133) but none of the surface patterns were associated with a depth of invasion of ≥ 1000 μm. In our model, a total NBIfinding score ≥ 1 was indicative of a high tumor grade(sensitivity: 0.97; specificity: 0.24), and a total NBIfinding score ≥ 9(sensitivity: 0.56; specificity: 1.0) was predictive of a SM invasion depth ≥ 1000 μm. Scores less than these cutoff values signified adenomas and a SM invasion depth < 1000 μm, respectively. Associations were also noted between selected NBI findings and tumor tissue architecture and histopathology.CONCLUSION Our multivariate statistical model for predicting tumor grades and invasion depths from NBI-finding scores may help standardize the diagnosis of colorectal lesions and inform therapeutic strategies.

Evaluation of endoscopic biliary stenting for obstructive jaundice caused by hepatocellular carcinoma

AIM:To review the usefulness of endoscopic biliary stenting for obstructive jaundice caused by hepatocellular carcinoma and identify problems that may need to be addressed.METHODS:The study population consisted of 36 patients with obstructive jaundice caused by hepatocellular carcinoma(HCC)who underwent endoscopic biliary stenting(EBS)as the initial drainage procedure at our hospital.The EBS technical success rate and drainage success rate were assessed.Drainage was considered effective when the serum total bilirubin level decreased by 50%or more following the procedure compared to the pre-drainage value.Survival time after the procedure and patient background characteristics were assessed comparatively between the successful drainage group(group A)and the non-successful drainage group(group B).The EBS stent patency duration in the successful drainage group(group A)was also assessed.RESULTS:The technical success rate was 100%for both the initial endoscopic nasobiliary drainage and EBS in all patients.Single stenting was placed in 21 patients and multiple stenting in the remaining 15 patients.The drainage successful rate was 75%and the median interval to successful drainage was 40 d(2-295 d).The median survival time was 150 d in group A and 22 d in group B,with the difference between the two groups being statistically significant(P<0.0001).There were no statistically significant differences between the two groups with respect to patient background characteristics,background liver condition,or tumor factors;on the other hand,the two groups showed statistically significant differences in patients without a history of hepatectomy(P=0.009)and those that received multiple stenting(P=0.036).The median duration of stent patency was 43 d in group A(2-757 d).No early complications related to the EBS technique were encountered.Late complications occurred in 13 patients(36.1%),including stent occlusion in 7,infection in 3,and distal migration in 3.CONCLUSION:EBS is recommended as the initial drainage procedure for obstructive jaundice caused by HCC,as it appears to contribute to prolongation of survival time.

Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity

瞄准：为了检验真细菌类高级轿车的效果，加(E。高级轿车和) 在结肠的上皮的房间线在试管内上，并且到评估 E 的效果。试验性的大肠炎上的高级轿车和。方法：E。高级轿车和被接种厌氧的联盟者和它的代谢物被获得。E 的生长 stimulatory 效果。T84 房间上的高级轿车和代谢物被 IL-6 生产被 SUDH 活动，和反煽动性的效果评估。在象受体 4 一样的使用费(TLR4 ) 的 mRNA 的变化被实时 PCR 评估。大肠炎被用 2.0% 葡聚糖硫酸钠喂 BALB/C 老鼠导致。这些老鼠收到了任何一个 5% lyophilized E。高级轿车和(n = 7 ) 或控制节食(n = 7 ) 。在大肠炎正式就职，临床、组织学的分数，冒号长度，和盲肠的有机酸层次以后的七天是坚定的。结果：E。高级轿车和在 0.25， 1.0， 0.025 和 0.07 mmol/L 生产了丁酸盐，醋酸盐，丙酸盐，和 lactate，分别地在里面中等。在这集中，每酸没有生长在 T84 细胞上刺激活动；然而，当这些酸在上述层次一起被混合时，它比控制显示出显著地高的活动。除了 lactate，这些酸显著地在就 0.1 mmol/L 稀释了 IL-6 生产。在 TNF-alpha 刺激下面，另外，丁酸盐稀释了 TLR4 mRNA 的生产。有 E 的处理。高级轿车和显著地随盲肠的丁酸盐层次的增加稀释了大肠炎的临床、组织学的分数，与控制组相比。结论：E。高级轿车和能改善试验性的结肠的发炎。部分地， E 的代谢物。高级轿车和，丁酸盐，增加粘膜正直和表演经由 TLR4 的粘膜防卫系统的反煽动性的行动调整。

Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular carcinoma.NAFLD is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways.Thus,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)synthesis.In our previous study,the most abundant type of toxic AGEs(TAGE);i.e.,glyceraldehyde-derived AGEs,were found to make a significant contribution to the pathogenesis of DM-induced angiopathy.Furthermore,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells.All of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and NASH.Thus,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH.Here,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.

Clinical significance of tumor-associated macrophage infiltration in supraglottic laryngeal carcinoma

Tumor-associated macrophages(TAMs) can elicit contrasting effects on tumor progression,depending on different tumor microenvironment.This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics,metastasis,and prognosis of supraglottic laryngeal carcinoma.TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody.The density of peritumoral CD68+ TAMs in recurrence cases(9/11) and in dead cases(17/23) were significantly higher than those in non-recurrence cases(33/73) and in survival cases(25/61),with significant differences(P = 0.024 and 0.007,respectively).The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68 + TAMs and the overall survival of patients.The 5year survival rate was significantly lower in the group with a high density of intratumoral CD68+ TAMs than in the group with a low density(39.6% vs.82.5%,P < 0.05).Similarly,the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68+ TAMs than in the group with a low density(50.6% vs.73.1%,P < 0.05).Cox regression analysis revealed that T classification,distant metastasis,and intratumoral or peritumoral CD68 + TAMs were independent factors for disease-free survival,whereas T classification and intratumoral CD68 + TAMs were independent factors for overall survival.The results indicate that TAM infiltration in supraglottic laryngeal carcinoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.

Quality of life after total vs distal gastrectomy with Rouxen-Y reconstruction: Use of the Postgastrectomy Syndrome Assessment Scale-45

AIM To investigate the detrimental impact of loss of reservoir capacity by comparing total gastrectomy(TGRY) and distal gastrectomy with the same Rouxen-Y(DGRY) reconstruction. The study was conducted using an integrated questionnaire, the Postgastrectomy Syndrome Assessment Scale(PGSAS)-45, recently developed by the Japan Postgastrectomy Syndrome Working Party.METHODS The PGSAS-45 comprises 8 items from the Short Form-8, 15 from the Gastrointestinal Symptom Rating Scale, and 22 newly selected items. Uni-and multivariate analysis was performed on 868 questionnaires completed by patients who underwent either TGRY(n = 393) or DGRY(n = 475) for stage I gastric cancer(52 institutions). Multivariate analysis weighed of six explanatory variables, including the type of gastrectomy(TGRY/DGRY), interval after surgery, age, gender, surgical approach(laparoscopic/open), and whether the celiac branch of the vagus nerve was preserved/divided on the quality of life(QOL).RESULTS The patients who underwent TGRY experienced the poorer QOL compared to DGRY in the 15 of 19 main outcome measures of PGSAS-45. Moreover, multiple regression analysis indicated that the type of gastrectomy, TGRY, most strongly and broadly impaired the postoperative QOL among six explanatory variables. CONCLUSION The results of the present study suggested that TGRY had a certain detrimental impact on the postoperative QOL, and the loss of reservoir capacity could be a major cause.

Effect of an extract of Ganoderma lucidum in men with lower urinary tract symptoms： a double-blind, placebo-controlled randomized and dose-ranging study

Aim： To conduct a double-blind, placebo-controlled randomized and dose-ranging study to evaluate the safety and efficacy of the extract of Ganoderma lucidum （G. lucidum） in men with lower urinary tract symptoms （LUTS）. Methods： We enrolled male volunteers （〉 50 years） with an International Prostate Symptom Score （IPSS; questions 1-7） 〉 5 and a prostate-specific antigen （PSA） value 〈 4 ng/mL. Volunteers were randomized into groups of placebo （n = 12）, G. lucidum of 0.6 mg （n = 12）, 6 mg （n = 12） or 60 mg （n = 14）, administered once daily. Efficacy was measured as a change from baseline in IPSS and the peak urine flow rate （Qmax）. Prostate volume and residual urine were estimated by ultrasonography, and blood tests, including PSA levels, were measured at baseline and at the end of the treatment. Results： The overall administration was well tolerated, with no major adverse effects. Statistical significances in the magnitude of changes between the experimental groups were observed at weeks 4 and 8. No changes were observed with respect to Qmax, residual urine, prostate volume or PSA levels. Conclusion： The extract of G. lucidum was well tolerated and an improvement in IPSS was observed. The recommended dose of the extract of G. lucidum is 6 mg in men with LUTS.

Increased vitreal levels of interleukin-10 in diabetic retinopathy:a Meta-analysis

AIM:To conduct a Meta-analysis for the change of interleukin-10(I1-10)concentration in vitreous samples of patients with diabetic retinopathy(DR).METHODS:Systemic search for literature was conducted from the databases of PubMed,Web of Science and Cochrane Library by August 2019.Statistical analyses including standard mean difference(SMD)and its 95%confidence interval(CI)were performed by using RevMan 5.3 software.RESULTS:Totally 194 studies were screened and finally 11 studies were included in the Meta-ana lysis.The concentration of IL-10 in the DR group was higher than in the control group(P=0.003.SMD:0.77.95%CI:0.25-1.28).Significant heterogeneity was found among all studies(P<0.00001,I^2=92%).The subgroup analysis showed that the concentration of IL-10 increased in vitreous samples from patients with DR compared to the non-DR controls(P=0.004.SMD:1.44.95%CI:0.46-2.42).Moreover,the concentration of IL-10 in samples of proliferative diabetic retinopathy(PDR)patients was significantly higher than that of non-proliferative diabetic retinopathy(NPDR)patients(P=0.01.SMD:0.61.95%CI:0.13-1.08).CONCLUSION:The vitreal concentration of IL-10 is significantly increased in patients with DR.Further studies are needed to reveal the mechanisms of IL-10 in DR.

Randomized clinical trial of an ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms

Aim： To evaluate the safety and efficacy of an extract of Ganoderma lucidum that shows the strongest 5α-reductase inhibitory activity among the extracts of 19 edible and medicinal mushrooms by a double-blind, placebo-controlled, randomized and dose-ranging study in men with lower urinary tract symptoms （LUTS）. Methods： In this trial, we randomly assigned 88 men over the age of 49 years who had slight-to-moderate LUTS to 12 weeks of treatment with G. lucidum extract （6 mg once a day） or placebo. The primary outcome measures were changes in the International Prostate Symptom Score （IPSS） and variables of uroflowmetry. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, laboratory values and the reported adverse effects. Results： G. lucidum was effective and significantly superior to placebo for improving total IPSS with 2.1 points decreasing at the end of treatment （mean difference, -1.18 points; 95% confidence interval, -1.74 to -0.62; P 〈 0.0001）. No changes were observed with respect to quality of life scores, peak urinary flow, mean urinary flow, residual urine, prostate volume, serum prostate-specific antigen or testosterone levels. Overall treatment was well tolerated with no severe adverse effects. Conclusion： The extract of G. lucidum was well tolerated and improved IPSS scores. These results encouraged a further, large-scale evaluation of phytotherapy for a long duration using the extract of G. lucidum on men with LUTS.

High-Quality Three-Dimensional Computed Tomography Angiography of Abdominal Viscera with Small Focal Spot, Low Tube Voltage, and Iterative Model Reconstruction Technique

Purpose: To evaluate the quality of three-dimensional (3D) CT angiography images of the abdominal viscera with small focal spot, low tube voltage, and iterative model reconstruction technique (IMR). Materials and Methods: Seven patients with suspected disease of the pancreatobiliary system had undergone CT with high-quality CTA protocol in the present study. There were 5 men and 2 women, ranging in age from 52 to 80 years (mean: 64 years). Results: Depiction of abdominal small artery, small portal vein was possible in all cases. In two cases that we were able to compare, it was superior to standard CTA in small vascular depiction in CTA made clearly in high quality protocol. Conclusions: Although the use of small focal spot, low tube voltage, and IMR can produce higher-quality images of abdominal vessels than standard CTA, this improvement is not significant at elevated radiation doses.