Hyperacute experimental model of rat lung transplantation using a coronary shunt cannula

BACKGROUND Lung transplantation is a well-established treatment of end-stage lung disease.A rodent model is an inexpensive way to collect biological data from a living model after lung transplantation.However,mastering the surgical technique takes time owing to the small organ size.AIM To conduct rat lung transplantation using a shunt cannula(SC)or modified cannula(MC)and assess their efficacy.METHODS Rat lung transplantation was performed in 11 animals in the SC group and 12 in the MC group.We devised a method of rat lung transplantation using a coronary SC for coronary artery bypass surgery as an anastomosis of pulmonary arteri-ovenous vessels and bronchioles.The same surgeon performed all surgical proce-dures in the donor and recipient rats without using a magnifying glass.The success rate of lung transplantation,operating time,and PaO2 values were com-pared after 2-h reperfusion after transplantation.RESULTS Ten and 12 lungs were successfully transplanted in the SC and MC groups,respectively.In the SC group,one animal had cardiac arrest within 1 h after reperfusion owing to bleeding during pulmonary vein anastomosis.The opera-ting time for the removal of the heart-lung block from the donor and preparation of the left lung graft was 26.8±2.3 and 25.7±1.3 min in the SC and MC groups,respectively(P=0.21).The time required for left lung transplantation in the recipients was 37.5±2.8 min and 35.9±1.4 min in the SC and MC groups,respectively(P=0.12).PaO2 values at 2 h after reperfusion were 456.2±25.5 and INTRODUCTION Lung transplantation is a well-established treatment of end-stage lung disease.Many immune and non-immune mech-anisms in lung transplantation are highly complex,and post-transplant complications such as infections and primary and chronic lung allograft dysfunction must be reduced to improve survival.Therefore,there is a need for immunological and pathophysiological analyses using animal lung transplantation models.The rat lung transplantation model was first reported in 1971[1],followed by the Mizuta Cuff model[2]in 1989.Since then,various improvements in surgical techniques,cuffs,and instruments have been reported[3-7].The advantage of using a rodent model is that it permits inexpensive collection of biological data from a living model after lung transplantation.Although trained surgeons can perform the transplantation procedure,mastering the surgical technique takes time due to the small size of the organs.The risks associated with this technique include damage to the vulnerable pulmonary artery(PA)and pulmonary vein(PV)vessel walls during anastomosis,as well as stenosis of the anastomotic site.We developed an anastomotic technique using a coronary shunt cannula(SC)for cardiac coronary artery bypass surgery as an alternative to the previously reported cuff method[2-6].This method enables anastomosis by inserting and ligating a cannula into the lumen of the PA,PV,and bronchus(Br),which is simpler and more reliable than conventional methods.This study aimed to determine problems with rat lung transplantation using the SC,develop an improved cannula,and investigate its utility.RESULTS After creating 11 lung transplantation model animals in the SC group and 12 in the MC group,all animals underwent reperfusion.One animal in the SC group had cardiac arrest 1 h after reperfusion due to hemorrhage caused by vessel wall injury during PV anastomosis.Two hours after reperfusion,we visually confirmed the maintenance of recipient hemody-namics and blood flow in the graft pulmonary cannula in 10 animals in the SC group and 12 in the MC group.The operating time for the removal of the heart-lung block from the donor and graft lung creation was 26.8±2.3 min in the SC group and 25.7±1.3 min in the MC group(P=0.21,Table 1).The duration for left lung transplantation into the recipient was 37.5±2.8 min in the SC group and 35.9±1.4 min(P=0.12,Table 1)in the MC group.Although no significant difference was found between the SC and MC groups,animals in the MC group experienced a slightly shorter operating time,smoother surgical technique,and less stressful procedure for the surgeons compared with those in the SC group.The graft lung coloration(Grade 1/2/3)after reperfusion was 0/2/8(SC group)and 0/2/10(MC group),and all grafts were reported to be successful,except in one animal in the SC group that had cardiac arrest(Table 2).The PaO2 values after 2 h of reperfusion were 456.2±25.5 mmHg in the SC group and 461.2±21.5 mmHg in the MC group(P=0.63,Table 3),showing no significant difference between the groups.

Sex- and Age-Specific Associations of Social Status and Health-Related Behaviors with Health Check Attendance: Findings from the Cross-Sectional Kanazawa Study

Health checks are key features of primary and secondary disease prevention. The aim of this study was to examine the sex- and age-specific association of social status and health-related behaviors with health check attendance in eligible persons. Data were derived from the Kanazawa Study 2011 (n = 12,781), a cross-sectional study which investigated all the residents in model areas of Kanazawa City, Ishikawa Prefecture, Japan. We selected participants aged 23 years or older with National Health Insurance (n = 4920). Attendance at health checks was the outcome. We used social status and health-related behaviors as predictor variables. We analyzed them by sex and applied stratified analyses by age groups for each sex. The bivariate analyses were conducted by means of cross-tabs. We calculated health check attendance rates by each variable. We used Pearson’s χ2-test to examine statistically significant differences. We fitted logistic regression models to estimate adjusted odds ratios (ORs) of attendance in the past one year. We computed ORs in a logistic regression model containing all variables described above. Workingmen and women aged 23 to 39 years and aged 40 to 64 years had significantly increased ORs for health check attendance compared with non-working persons. Men, men aged 23 to 39 years and men aged 65 years or older with more physical activity had significantly increased ORs for health check attendance. Male ex-smokers, female ex- and non-smokers, male ex-smokers aged 65 years or older, and female non-smokers aged 40 to 64 years had significantly increased ORs. The findings suggest that population groups with lower social status or increased risks of adverse health effects are less likely to attend health checks than those with higher social status or decreased risks in particular sex and age groups. It indicates that diverse approaches are required to realize the full benefit of health checks.

Sediment-Loading Processes in a Forested Catchment: Modeling and Observations

In order to investigate sediment-loading processes in a catchment, the daily time series of river discharge and sediment load were applied to a semi-distributed model, the Soil and Water Assessment Tool (SWAT). The time series of discharge and sediment load were obtained by monitoring the river stage and water turbidity of the Oikamanai River, Hokkaido, Japan, in the rainfall season (April-November) of 2011-2014. The catchment is forested (ca 90% area) but underlain by the Neogene sedimentary rocks with currently active faults and forest soils with tephra layers, which tend to frequently produce slope failure such as landslide and bank collapse by rainfall or snowmelt. The water turbidity, T, in ppm was converted into suspended sediment concentration, SSC, in g/L by applying the linear relationship between T and SSC. The acquisition of the time series of discharge, Q (m3/s) and sediment load, L (=Q·SSC in g/s) of the river allowed us to distinguish the fluvial sediment transport, accompanied by slope failure in the upstream, from that under no slope failure. The SWAT was used to simulate soil erosion and identify the region prone to the soil erosion in the Oikamanai River basin. The model’s results showed a satisfactory agreement between daily observed and simulated sediment load as indicated by the high Nash-Sutcliffe efficiency. This evidences that the upper mountainous region of the catchment provides a main sediment source, accompanied by slope failure.

Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination:A case report and review of literature

BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

纳米TiO_2在PET中的分散性及对其性能的影响

用乙二醇(EG)置换水分散TiO_2体系中的H_2O得到TiO_2的EG体系,激光粒度仪测试发现TiO_2在EG中的分散尺寸与在H_2O中相同。以对苯二甲酸二甲酯(DMT)和EG为原料,原位聚合制备了TiO_2/PET复合材料。用扫描电镜(SEM)观察了TiO_2在PET中的分散性,考察了TiO_2含量对TiO_2/PET复合材料力学性能、热稳定性和UV吸收性能的影响,结果发现:TiO_2含量为0.5%～1.0%时材料的拉伸断裂强度和断裂伸长提高,而含量为2.0%～3.0%时材料的断裂强度和断裂伸长下降,结合对拉伸断口形貌的观察,推断TiO_2与基体PET间存在着较强的作用。由于TiO_2极高的表面能,TiO_2/PET复合材料在350～380nm处的UV吸收性能随TiO_2含量的增加而增强,热稳定性变化不大。

肝储脂细胞表达CYP11B2mRNA与实验性肝纤维化的关系研究

目的比较CYP11B2在正常与实验性肝纤维化大鼠肝组织中的表达,评价安体舒通的抗纤维化作用。方法取雄性wistar大鼠160只,随机平均分为4组。模型组:CCLA油0.25mL/100mg皮下注射,每周三次;安舒体通组:CCLA油0.25ml/100mg皮下注射,每周三次;安体舒通20mgkg/d灌胃,1次/曰;马洛替脂组:CCLA油0.25ml/100mg皮下注射。每周三次:马洛替脂50ml/kg/d灌胃,1次/日;对照组:橄榄油0.25/ml/100mg皮下注射,每周次。于2、4、6、8、1O周末在光镜下动态观察组织学改变,图象分析仪测量胶原面积。RT-PCR和原位杂交检测纤维化及正常肝组织CYP11B2mRN的表达。结果 RT-PCR显示CYP11B2mRN在纤维化肝组织中表达上调。原位杂交显示CYP11B2mRNA表达定位于储脂细胞胞浆,在纤维化形成时表达增细。在肝纤维化形成的早中期阶段(6周以前),用安体舒通治疗能使肝纤维化分级和胶原面积减少。结论 CYP11R2mRNA在纤维化肝脏的储脂细胞中表达增强。安体舒通对早中期肝纤维化具有一定的治疗作用。

Pathological classification of intrahepatic cholangiocarcinoma based on a new concept

Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.

Influence of Gaps Between Multiple Floating Bodies on Wave Forces

The present study aims to give general hints about hydrodynamic interactions for water wave diffraction on a super large floating structure composed of a large number of box-shaped modules with many small gaps in between. And meanwhile, it also aims to seek for an effective way to take the gap influence into consideration without numerical difficulties existing in conventional methods. An asymptotic matching technique is exploited by virtue of the smallness of gaps. Formal potential solutions are established for the near field around the gap ends and the far field away from gap ends, respectively, and the unknowns in those solutions are uniquely determined by asymptotic matching. The eigen-function expansion method is used for the outer far field and a series of pulsating sources at each gap end is introduced to simulate the gap influence. Strong hydrodynamic interaction is observed and a new resonant phenomenon, the mechanism of which differs absolutely from any known ones, is revealed in the present study. Sharp peak responses for both vertical and horizontal wave-exciting forces on each block are found around some special resonance frequencies, which depend on the draft of the structure and the gap width. The present results are of practical significance to the design of links (connectors) of modules for super large floating structures. And the importance is also closely related to the hydro-elasticity analysis for super large floating structures, in which local loads may be as important as the integrated loads.

Enhancement patterns of pancreatic adenocarcinoma on conventional dynamic multi-detector row CT:Correlation with angiogenesis and fibrosis

AIM:To evaluate retrospectively the correlation between enhancement patterns on dynamic computed tomography (CT) and angiogenesis and fibrosis in pancreatic adenocarcinoma.METHODS: Twenty-three patients with pancreatic adenocarcinoma underwent dynamic CT and tumor resection. In addition to the absolute and relative enhanced value that was calculated by subtracting the attenuation value on pre-contrast from those on contrast-enhanced CT in each phase, we defined one parameter, "tumor-aorta enhancement ratio", which was calculated by dividing enhancement of pancreatic cancer by enhancement of abdominal aorta in each phase. These enhancement patterns were correlated with the level of vascular endothelial growth factor (VEGF), microvessel density (MVD), and extent of fibrosis.RESULTS: The absolute enhanced value in the arterial phase correlated with the level of VEGF and MVD (P=0.047, P=0.001). The relative enhanced value in arterial phase and tumor-aorta enhancement ratio (arterial) correlated with MVD (P=0.003, P=0.022). Tumor-aorta enhancement ratio (arterial) correlated negatively with the extent of fibrosis (P=0.004). The tumors with greater MVD and higher expression of VEGF tended to show high enhancement in the arterial dominant phase. On the other hand, the tumors with a larger amount of fibrosis showed a negative correlation with the grade of enhancement during the arterial phase.CONCLUSION: Enhancement patterns on dynamic CT correlated with angiogenesis and may be modified by the extent of fibrosis.

Precision surgical approach with lymph-node dissection in early gastric cancer

The gravest prognostic factor in early gastric cancer is lymph-node metastasis,with an incidence of about 10% overall. About two-thirds of early gastric cancer patients can be diagnosed as node-negative prior to treatment based on clinicpathological data. Thus, the tumor can be resected by endoscopic submucosal dissection. In the remaining third, surgical resection is necessary because of the possibility of nodal metastasis. Nevertheless, almost all patients can be cured by gastrectomy with D1+ lymph-node dissection. Laparoscopic or robotic gastrectomy has become widespread in East Asia because perioperative and oncological safety are similar to open surgery. However, after D1+ gastrectomy,functional symptoms may still result. Physicians must strive to minimize postgastrectomy symptoms and optimize long-term quality of life after this operation.Depending on the location and size of the primary lesion, preservation of the pylorus or cardia should be considered. In addition, the extent of lymph-node dissection can be individualized, and significant gastric-volume preservation can be achieved if sentinel node biopsy is used to distinguish node-negative patients.Though the surgical treatment for early gastric cancer may be less radical than in the past, the operative method itself seems to be still in transition.

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience

选择 cyclooxygenase (艇长)-2 禁止者(coxibs ) 作为反煽动性的药之一被开发避免 non-steroidal 的各种各样的副作用反煽动性的药(NSAID ) 。然而， coxibs 也有一个能力禁止各种各样的类型的肿瘤开发 NSAID 的一样的方法。用细胞线和动物模型的许多试验性的研究表明了一个能力阻止 COX-2 禁止者的肿瘤增长。在为息肉 chemoprevention 执行使随机化的研究以后，与家庭腺瘤息肉病( FAP )在病人学习，它证明有 celecoxib 的治疗， coxibs 之一，显著地减少了颜色的数字在 2000 的表面的息肉，美国食物药品管理局(食物及药品管理局)立即为 FAP 病人同意了临床的使用 celecoxib 。然而，某 coxibs 最近被报导包括心脏病和击增加严肃的心血管的事件的风险。在这篇文章，我们在胃肠道的致癌作用考察 COX-2 的一个角色，例如食管，胃和 colorectum，并且也为胃肠道肿瘤的 chemoprevention 分析 coxibs 的前景。

Surgical anatomy of innervation of the gallbladder in humans and Suncus murinus with special reference to morphological understanding of gallstone formation after gastrectomy

瞄准：澄清人的胆囊的神经分布，与在胃切除术以后的胆石形成的词法理解的特殊参考。方法：肝，胆囊和包围结构在乙醇沉浸于茜素红 S 的 10 mg/L 答案在死尸染色周围神经(n = 10 ) 。在区域的神经分布完全在一台双目显微镜下面被把。同样，在 10 Suncus murinus 的一样的区域的神经分布(S。murinus ) 被检验采用整个山免疫组织化学。结果：胆囊的神经分布通过二条线路主要发生了。一个人从前面的肝的丛，神经分布沿着膀胱的动脉和管发生了。总是，这条线路通过了肝十二指肠系带。另外的线路从以后的肝的丛，神经分布沿着膀胱的管 vent 集合发生了。这条线路也通过了肝十二指肠系带欧洲粪金龟子突围。类似的结果在 S 被获得。murinus。结论：从经由膀胱的动脉或管的前面的肝的丛的线路为保存胆囊神经分布是关键的。淋巴节点解剖可以明确地在胃切除术以后在肝十二指肠系带影响胆石的发生。而且，从经由到胆囊的胆总管和膀胱的管的以后的肝的丛的线路不应该被不顾。丛的保藏可以在胃切除术以后稀释胆石形成的发生。

Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma

Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.

Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease

Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis to steatohepatitis,liver cirrhosis,and hepatocellular carcinoma.Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis,a small percentage of individuals will develop progressive liver disease.Notably,both ALD and NAFLD are frequently accompanied by extrahepatic complications,including cardiovascular disease and malignancy.The survival of patients with ALD and NAFLD depends on various disease-associated conditions.This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology,the factors associated with disease susceptibility and progression,and the predictors and characteristics of outcomes.A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases.

Nutrition and exercise in the management of liver cirrhosis

Liver cirrhosis(LC)patients often have protein-energy malnutrition(PEM)and decreased physical activity.These conditions often lead to sarcopenia,which is the loss of skeletal muscle volume and increased muscle weakness.Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients.Nutrition and exercise management can improve PEM and sarcopenia in those patients.Nutrition management includes sufficient dietary intake and improved nutrient metabolism.With the current high prevalence of obesity,the number of obese LC patients has increased,and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients.Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients.Exercise management can increase skeletal muscle volume and strength and improve insulin resistance;however,nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients.The establishment of optimal exercise regimens for LC patients is currently required.In this review,we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients.

Hepatitis B virus X protein induces hepatic stem cell-like features in hepatocellular carcinoma by activating KDM5B

AIM To determine the role of hepatitis B virus X protein(HBx), HBx in regulating hepatic progenitor cell(HPC)-like features in hepatocellular carcinoma(HCC) and the underlying molecular mechanisms.METHODS We used a retrovirus vector to introduce wild type HBx or empty vector into Hep G2 cells. We then used these cells to analyze cell proliferation, senescence, transformation, and stem-like features. Gene expression profiling was carried out on Affymetrix GeneC hip Human U133A2.0 ver.2 arrays according to the manufacturer's protocol. Unsupervised hierarchical clustering analysis and Class Comparison analysis were performed by BRB-Array Tools software Version 4.2.2. A total of 238 hepatitis B virus(HBV)-related HCC patients' array data were used for analyzing clinical features.RESULTS The histone demethylase KDM5 B was significantlyhighly expressed in HBV-related HCC cases(P < 0.01). In HBV proteins, only HBx up-regulated KDM5 B by activating c-myc. Hepatic stem cell(Hp SC) markers(EpC AM, AFP, PROM1, and NANOG) were significantly highly expressed in KDM5B-high HCC cases(P < 0.01). KDM5 B played an important role in maintaining HpS Clike features and was associated with a poor prognosis. Moreover, inhibition of KDM5 B suppressed spheroid formation and cell invasion in vitro.CONCLUSION HBx activates the histone demethylase KDM5 B and induces HPC-like features in HCC. Histone demethylases KDM5 B may be an important therapeutic target against HBV-related HCC cases.

Clinical therapeutic strategies for early stage of diabetic kidney disease

Diabetic kidney disease(DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuousscreening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression.

Pseudolymphoma of the liver associated with primary biliary cirrhosis:A case report and review of literature

We report a case of two pseudolymphomas of the liver in a 63-year-old Japanese woman with primary biliary cirrhosis.One of the lesions was found incidentally during a medical examination,presenting as a 10 mm hypodense nodule that revealed hyperdensity in the early phase and hypodensity in the late phase in computed tomography(CT)after injection of contrast medium.Retrospectively,the 10 mm nodule had first been discovered as a 4 mm nodule during CT 4 years previously.Superparamagnetic iron oxide-enhanced MRI revealed another 4 mm hyperintense nodule in segment 6 in addition to the 10 mm hyperintense nodule in segment 7.CT during arterial portography revealed two hypointense nodules.Findings with other imaging modalities such as ultrasonography,magnetic resonance imaging,and hepatic angiography were consistent with hepatocellular carcinoma.A right posterior segmentectomy was performed,and the lesions were microscopically diagnosed as pseudolymphoma.To the best of our knowledge,only 31 other cases of this disease have ever been reported,with a highly asymmetrical male:female ratio of 1:9.7.Although we could find only one case of transformation of hepaticpseudolymphoma into lymphoma in the liver,the exact nature of development from benign pseudolymphoma to malignant lymphoma is still not fully understood and cases of hepatic lymphoma need to be followed carefully.

Breast cancer resistance protein(BCRP/ABCG2):its role in multidrug resistance and regulation of its gene expression

Breast cancer resistance protein(BCRP)/ATP-binding cassette subfamily G member 2(ABCG2) is an ATP-binding cassette(ABC) transporter identified as a molecular cause of multidrug resistance(MDR) in diverse cancer cells.BCRP physiologically functions as a part of a self-defense mechanism for the organism;it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract,as well as through the blood-brain,placental,and possibly blood-testis barriers.BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use.Thus,BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs.Because BCRP is also known to be a stem cell marker,its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance,self-renewal(stemness),and invasiveness(aggressiveness),and thereby impart a poor prognosis.Therefore,blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers.Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR.Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1α,estrogen receptor,and peroxisome proliferator-activated receptor.Furthermore,alternative promoter usage,demethylation of the BCRP promoter,and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells.Finally,PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions.These biological events seem involved in a complicated manner.Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer.This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells,and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers.

Hepatitis C-related liver cirrhosis-strategies for the prevention of hepatic decompensation,hepatocarcinogenesis,and mortality

Liver cirrhosis(LC)is a critical stage of chronic liver disease,including that caused by hepatitis C virus(HCV).In the absence of antiviral therapy,67%-91%of patients with HCV-related LC patients die of liver-related causes,including hepatocellular carcinoma(HCC)and liver failure.Among the therapeutic strategies used to prevent liver-related complications in these patients is standard therapy with pegylated interferon and ribavirin,which induces a sustained virological response(SVR)in 25%of HCV genotype 1-infected patients and in 69% of patients infected with genotypes 2 and 3.SVR in patients with HCV-related LC has been associated with reduced rates of hepatic decompensation,HCC,and mortality.More recently developed direct-acting antiviral agents have shown excellent antiviral efficacy,with preliminary data demonstrating that an interferon-free regimen that includes these direct-acting antiviral agents achieved SVR in more than 50%of patients with HCV genotype 1 LC.Branched-chain amino acid supplementation,improvement of insulin resistance,and the use ofβ-blockers for portal hypertension may also reduce liverrelated complications.Here,we review advances in antiviral and adjunctive therapies for improved outcomes in patients with HCV-associated LC.