Prognostic and therapeutic potential of imbalance between PD-1+CD8 and ICOS+Treg cells in advanced HBV-HCC.

Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOShi) and low-ratio (PD-1/ICOSlo) groups according to ratio median. Compared with PD-1/ICOSlo patients, the PD-1/ICOShi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOShi patients exhibited a higher proportion of tissue-resident memory T (TRM) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOSlo advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.

Astragaloside IV attenuates high glucose-induced NF-κB-mediated inflammation through activation of PI3K/AKT-ERK-dependent Nrf2/ARE signaling pathway in glomerular mesangial cells.

Inflammation is a key contributor to diabetic kidney disease pathogenesis, including reactive oxidation stress (ROS)-mediated nuclear factor-κB (NF-κB) signaling pathway. In this study, we examined the effect of Astragaloside IV (AS-IV) on anti-inflammatory and anti-oxidative properties under high glucose (HG) condition and the potential mechanism in glomerular mesangial cells (GMCs). We showed that AS-IV concentration-dependently reduced GMCs proliferation, restrained ROS release and hydrogen peroxide content, and suppressed pro-inflammatory cytokines as well as pro-fibrotic factors expression, which were associated with the inhibition of NF-κB and nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling activation. Accordingly, both NF-κB overexpression by using RNA plasmid and Nrf2 gene silencing by using RNA interference weakened the ability of AS-IV to ameliorate HG-induced oxidative stress, inflammation, and cell proliferation. Furthermore, phosphatidylinositide 3-kinases (PI3K)/serine/threonine protein kinase (Akt) and extracellular regulated protein kinases (ERK) signaling pathway regulated the process of AS-IV-induced Nrf2 activation and antioxidant capacity, which evidenced by using PI3K inhibitor LY294002 or ERK inhibitor PD98059 that largely abolished the AS-IV efficacy. Taken together, these results indicated that AS-IV protected against HG-induced GMCs damage by inhibiting ROS/NF-kB-induced increases of inflammatory cytokines, fibrosis biomarkers, and cell proliferation via up-regulation of Nrf2-dependent antioxidant enzyme expression, which were mediated by PI3K/Akt and ERK signaling pathway activation.

Spatially homogeneous few-cycle compression of Yb lasers via all-solid-state free-space soliton management.

The high power and variable repetition-rate of Yb femtosecond lasers makes them very attractive for ultrafast science. However, for capturing sub-200 fs dynamics, efficient, high-fidelity and high-stability pulse compression techniques are essential. Spectral broadening using an all-solid-state free-space geometry is particularly attractive, as it is simple, robust and low-cost. However, spatial and temporal losses caused by spatio-spectral inhomogeneities have been a major challenge to date, due to coupled space-time dynamics associated with unguided nonlinear propagation. In this work, we use all-solid-state free-space compressors to demonstrate compression of 170 fs pulses at a wavelength of 1030nm from a Yb:KGW laser to ∼9.2 fs, with a highly spatially homogeneous mode. This is achieved by ensuring that the nonlinear beam propagation in periodic layered Kerr media occurs in spatial soliton modes, and by confining the nonlinear phase through each material layer to less than 1.0 rad. A remarkable spatio-spectral homogeneity of ∼0.87 can be realized, which yields a high efficiency of >50% for few-cycle compression. The universality of the method is demonstrated by implementing high-quality pulse compression under a wide range of laser conditions. The high spatiotemporal quality and the exceptional stability of the compressed pulses are further verified by high-harmonic generation. Our predictive method offers a compact and cost-effective solution for high-quality few-cycle-pulse generation from Yb femtosecond lasers, and will enable broad applications in ultrafast science and extreme nonlinear optics.

Serum chromogranin A correlated with albuminuria in diabetic patients and is associated with early diabetic nephropathy.

BACKGROUND: The kidney is the main site for the removal of chromogranin A (CgA). Previous studies have found that patients with renal impairment displayed elevated concentrations of CgA in plasma and that CgA concentrations reflect a deterioration of renal function. In this study, we aimed to estimate serum CgA levels and to evaluate the role of serum CgA in the early diagnosis of diabetic nephropathy (DN). METHODS: A total of 219 patients with type 2 diabetes mellitus (T2DM) were included in this cross-sectional study. These patients were classified into normoalbuminuria (n = 121), microalbuminuria (n = 73), or macroalbuminuria (n = 25) groups based on their urine albumin to creatinine ratios (UACRs). The degree of DN is reflected by UACR. A control group consisted of 45 healthy subjects. The serum CgA levels were measured by ELISA, and other key parameters were assayed. RESULTS: Serum CgA levels were higher in patients with T2DM than in control subjects, and a statistically significant difference among the studied subgroups regarding CgA was found (P < 0.05). The levels of serum CgA increased gradually with the degree of DN (P < 0.001). Serum CgA levels showed a moderate-intensity positive correlation with UACRs (P < 0.001). A cutoff level of 3.46 ng/ml CgA showed 69.86% sensitivity and 66.12% specificity to detect DN in the early stage. CONCLUSION: The levels of serum CgA increased gradually with the degree of DN and can be used as a biomarker in the early detection of DN.

[Association between tea drinking and the risk of type 2 diabetes mellitus among rural adults in Deqing County:a prospective cohort study].

OBJECTIVE: To explore the associations between tea drinking and the incident risk of type 2 diabetes mellitus(T2 DM). METHODS: A dynamic prospective cohort study among a total of 27 841 diabetes-free permanent adult residents randomly selected from 2, 6 and 7 rural communities between 2006-2008, 2011-2012 and 2013-2014, respectively. Questionnaire survey, physical examination, and laboratory test were carried out among the participants. In 2018, we conducted a follow-up through the electronic health records of residents. Cox regression model were applied to explore the association between tea drinking and the incident risk of T2 DM and estimate the hazard ratio(HR), and its 95%CI. RESULTS: Among the 27 841 rural community residents in Deqing County, there were 10 726(38.53%) were tea drinkers, 8215 of which were green tea drinkers, accounting for 76.59%. Totally 883 new T2 DM incidents were identified until December 31, 2018, and the incidence density was 4.43 per 1000 person years(PYs). The incidence density was 4.07/1000 PYs in those with tea drinking habits and 4.71/1000 PYs in those without tea drinking habits, among which the incidence density was 3.79/1000 PYs in those with green tea drinking habits. After controlling for sex, age, education, farming, smoking, alcohol consumption, dietary preference, body mass index, hypertension, impaired fasting glucose, family history of diabetes, the risk of T2 DM among rural residents with tea drinking habits in Deqing County was 0.79 times higher than that among residents without tea drinking habits(HR=0.79, 95%CI 0.65-0.96), and the risk of T2 DM among residents with green tea drinking habits was 0.72 times higher than that among residents without tea drinking habits(HR=0.72, 95%CI 0.58-0.89). However, no significant associations were found between other kinds of tea and the risk of T2 DM, nor the amount of green tea to drink. CONCLUSION: Drinking green tea may reduce the risk of T2 DM among adult population in rural China.

Klotho ameliorates diabetic nephropathy by activating Nrf2 signaling pathway in podocytes.

Oxidative stress plays a key role in the pathogenesis of diabetic nephropathy (DN). The anti-aging protein Klotho has been demonstrated to have antioxidant capacity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a central transcription factor regulating antioxidant responses. The present study aimed to explore the effects of Klotho on DN and the underlying mechanisms related to Nrf2. Low glucose (LG) or high glucose (HG) medium-cultured podocytes and diabetic db/db mice were overexpressed with Klotho via adenoviral transfer to evaluate the effects of Klotho on Nrf2 signaling, oxidative stress, podocyte apoptosis, and renal function and histopathology. Klotho overexpression significantly induced the expression and activation of Nrf2 as well as its downstream targets SOD2 and NQO1 in podocytes. Moreover, Klotho overexpression inhibited HG-induced oxidative stress and apoptosis in podocytes. Co-treatment with Nrf2 inhibitor trigonelline prevented Klotho-induced expression of SOD2 and NQO1, and abolished Klotho-conferred antioxidant and anti-apoptotic effects. In db/db mice, Klotho overexpression also activated Nrf2 signaling, and suppressed diabetes-induced oxidative stress and podocyte apoptosis, which were accompanied by improved renal function and decreased glomerulosclerosis. Our data highlight a novel Nrf2-mediated antioxidant mechanism underlying the protective effects of Klotho in podocytes and indicate the therapeutic potential of targeting Klotho to activate Nrf2 in DN.

ApoL1 induces kidney inflammation through RIG-I/NF-κB activation.

The genetic variations of the apolipoprotein L1 (APOL1) gene are associated with non-diabetic kidney diseases. However, very little is known about the role of ApoL1 in glomerular damage. Here, we aimed to identify the function and mechanism of ApoL1 in glomerular damage. The mice were randomly divided into two groups: one group was intraperitoneally injected with phosphate buffer saline (PBS), while the other group was intraperitoneally injected with recombinant ApoL1 every other day for 3 months. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were used to demonstrate the effects of ApoL1 on kidney inflammation and injury. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses revealed that ApoL1-treated mice exhibited enhanced expression of various inflammation markers in the kidney and serum compared to the PBS-treated mice. Immunofluorescence staining revealed that ApoL1 accumulated in kidney podocytes. Treatment with ApoL1 dose-dependently increased the expression of inflammation markers and apoptotic markers. The abnormal gene expression associated with ApoL1-mediated podocyte inflammation was evaluated using microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the upregulated genes were enriched in the inflammation-related processes, such as the RIG-I/NF-κB signaling pathway. Consistently, the knockdown of RIG-I significantly mitigated the ApoL1-induced upregulation of inflammatory and apoptotic markers in the human podocytes. Additionally, the ApoL1-induced glomerular damage was attenuated in AAV-shRIG-I mice. Therefore, the effects of ApoL1 on glomerular damage may be, at least partially, through inducing abnormal expression of inflammatory molecules, which may have important implications for treatment of kidney diseases.

Protective Effect of Probiotics against Esophagogastric Variceal Rebleeding in Patients with Liver Cirrhosis after Endoscopic Therapy.

BACKGROUND Probiotic therapy has been shown to be beneficial against some liver diseases. However, there is still uncertainty regarding the clinical efficacy of probiotics for the treatment of variceal rebleeding. This research explored the efficacy of probiotics in variceal rebleeding. MATERIAL AND METHODS This was a retrospective study of 704 consecutive patients with liver cirrhosis who recovered from esophagogastric variceal bleeding after endoscopic treatment. Patients were subdivided into a probiotics cohort (n=214) and a non-probiotics cohort (n=490) based on the cumulative defined daily dose (cDDD) of probiotics received during follow-up. Propensity score matching was utilized to obtain a relatively balanced cohort of 200 patients per group for the analysis. Patients were monitored for rebleeding during the one-year follow-up. RESULTS Multivariate Cox regression analysis revealed that probiotic therapy (≥28cDDD) was an independent protector against rebleeding (AHR=0.623; 95% CI=0.488-0.795; P<0.001). After propensity score matching, Kaplan-Meier analysis revealed that the rebleeding rate was higher in the non-probiotics cohort (n=200) than in the probiotics cohort (n=200) (56.0% vs. 44.0%, P=0.002). The incidence of rebleeding decreased with increased probiotic dosage (56.0%, 48.5%, 43.3%, and 38.1% in <28 cDDD, 28-60 cDDD, 61-90 cDDD, and >90 cDDD groups, respectively; P=0.011). The median rebleeding interval in the probiotics cohort (n=95) was significantly longer than that in the non-probiotics cohort (n=261) (147.0 vs. 91.0 days; P<0.001). CONCLUSIONS Adjuvant probiotic therapy significantly reduced the incidence of variceal rebleeding and delayed rebleeding after endotherapy in patients with cirrhosis.

Endothelin-1 rs9296344 associates with the susceptibility of childhood primary nephrotic syndrome.

BACKGROUND: Recently, the rs5370 single nucleotide polymorphisms (SNPs) of Endothelin-1 (EDN1) showed association with the susceptibility of childhood primary nephrotic syndrome (CPNS). This study aims to investigate potential relationships between other EDN1 SNPs and CPNS. METHODS: Seven SNPs (rs5370, rs10478723, rs1476046, rs1800541, rs2070698, rs2071942, and rs9296344) of the EDN1 gene were genotyped in 579 CPNS patients and 586 age-matched healthy children. Then, we analyzed potential associations of the six SNPs with susceptibility of CPNS by using rs5370 as a conditional variant in a logistic regression model. SNP-SNP interaction analysis was performed to investigate the joint effects of the seven SNPs in the pathogenesis of CPNS. RESULTS: Independent with rs5370, only rs9296344 significantly associated (T vs C, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.57-0.88, P = .001) with the susceptibility of CPNS. Meanwhile, no joint effect among the analyzed seven SNPs was discovered in this study. CONCLUSIONS: This study discovered that C allele of rs9296344 on EDN1 is a novel independent risk factor for CPNS.

Disruption of MAGI2-RapGEF2-Rap1 signaling contributes to podocyte dysfunction in congenital nephrotic syndrome caused by mutations in MAGI2.

The essential role of membrane associated guanylate kinase 2 (MAGI2) in podocytes is indicated by the phenotypes of severe glomerulosclerosis of both MAGI2 knockout mice and in patients with congenital nephrotic syndrome (CNS) caused by mutations in MAGI2. Here, we show that MAGI2 forms a complex with the Rap1 guanine nucleotide exchange factor, RapGEF2, and that this complex is lost when expressing MAGI2 CNS variants. Co-expression of RapGEF2 with wild-type MAGI2, but not MAGI2 CNS variants, enhanced activation of the small GTPase Rap1, a central signaling node in podocytes. In mice, podocyte-specific RapGEF2 deletion resulted in spontaneous glomerulosclerosis, with qualitative glomerular features comparable to MAGI2 knockout mice. Knockdown of RapGEF2 or MAGI2 in human podocytes caused similar reductions in levels of Rap1 activation and Rap1-mediated downstream signaling. Furthermore, human podocytes expressing MAGI2 CNS variants show severe abnormalities of cellular morphology and dramatic loss of actin cytoskeletal organization, features completely rescued by pharmacological activation of Rap1 via a non-MAGI2 dependent upstream pathway. Finally, immunostaining of kidney sections from patients with congenital nephrotic syndrome and MAGI2 mutations showed reduced podocyte Rap1-mediated signaling. Thus, MAGI2-RapGEF2-Rap1 signaling is essential for normal podocyte function. Hence, disruption of this pathway is an important cause of the renal phenotype induced by MAGI2 CNS mutations.

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population.

BACKGROUND: The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS. METHODS: In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clinical features in primary nephrotic syndrome of children in Chinese population. RESULTS: Significant associations with PNS were found on missense SNP rs1129740 (GG vs AA, odds ratio (OR) = 1.987, 95% confidence interval (CI) = 1.468-2.652, P = 0.00177049) and rs1047992 (AA vs GG, OR = 1.857, 95% CI = 1.325-2.391, P = 1.1073E-10) of the HLA-DQA1 gene. CONCLUSIONS: This work suggests SNPs of HLA-DQA1 are risk factors for PNS in Chinese population, which implies roles of immune response in the pathogenesis of PNS.

MAGI-1 Interacts with Nephrin to Maintain Slit Diaphragm Structure through Enhanced Rap1 Activation in Podocytes.

MAGI-1 is a multidomain cytosolic scaffolding protein that in the kidney is specifically located at the podocyte slit diaphragm, a specialized junction that is universally injured in proteinuric diseases. There it interacts with several essential molecules, including nephrin and neph1, which are required for slit diaphragm formation and as an intracellular signaling hub. Here, we show that diminished MAGI-1 expression in cultured podocytes reduced nephrin and neph1 membrane localization and weakened tight junction integrity. Global magi1 knock-out mice, however, demonstrated normal glomerular histology and function into adulthood. We hypothesized that a second mild but complementary genetic insult might induce glomerular disease susceptibility in these mice. To identify such a gene, we utilized the developing fly eye to test for functional complementation between MAGI and its binding partners. In this way, we identified diminished expression of fly Hibris (nephrin) or Roughest (neph1) as dramatically exacerbating the effects of MAGI depletion. Indeed, when these combinations were studied in mice, the addition of nephrin, but not neph1, heterozygosity to homozygous deletion of MAGI-1 resulted in spontaneous glomerulosclerosis. In cultured podocytes, MAGI-1 depletion reduced intercellular contact-induced Rap1 activation, a pathway critical for proper podocyte function. Similarly, magi1 knock-out mice showed diminished glomerular Rap1 activation, an effect dramatically enhanced by concomitant nephrin haploinsufficiency. Finally, combined overexpression of MAGI-1 and nephrin increased Rap1 activation, but not when substituting a mutant MAGI-1 that cannot bind nephrin. We conclude that the interaction between nephrin and MAGI-1 regulates Rap1 activation in podocytes to maintain long term slit diaphragm structure.

Neonate acute kidney injury.

Acute kidney injury (AKI) is characterized by the abrupt inability of the kidneys to adequately excrete waste products and regulate fluid and electrolyte homeostasis appropriately. This results in an at least partially reversible increase in the blood concentration of creatinine and nitrogenous waste products. Moreover, medication eliminated via renal routes will accumulate that in turn result in a "second hit" to the already injured kidneys. Furthermore, fluid management and nutrition will be hampered by oliguria. Neonatal AKI is a frequent complication in children admitted to an ICU and is associated with significant morbidity and mortality. Moreover, in newborns the diagnosis of AKI is more difficult since at birth serum creatinine (SCr) predominantly reflects maternal renal function. Furthermore, neonates are especially susceptible to hypovolemic kidney injury due to an inadequate renal auto regulation Thus, accurate assessment of renal function in children is important in numerous clinical situations including screening and/or monitoring of renal disease. The present narrative review article will deal with the latest innovations in diagnostic as well as management options available for AKI in children.

Case report: Urachal perivascular epithelioid cell tumor.

Background: Urachal tumors are rare in clinical practice, among which urachal adenocarcinoma is the most common. In this study, we report a rare case of urachal perivascular epithelioid cell tumor to improve our understanding of the disease. Case presentation: A 26-year-old male patient was hospitalized for lower abdominal pain. The US showed a hypoechoic mass measuring 26mm × 18mm in the superior aspect of the bladder. MRI showed an irregular mass located anterior to the bladder roof, near the midline. The tumor exhibited hypointense on T1WI and heterogeneous hyperintense on T2WI. Additionally, contrast-enhanced T1-weighted imaging revealed obvious ring enhancement of the tumor. The patient underwent surgical resection of the urachal tumor, with subsequent pathological examination revealing a diagnosis of urachal PEComa. Following surgery, the patient underwent regular follow-up assessments, with no evidence of recurrence or metastasis observed after three and a half years. Conclusions: Urachal PEComa is a rare mesenchymal tumor that presents challenges in diagnosis through imaging and clinical symptoms. Definitive diagnosis relies on pathological and immunohistochemical analysis. Due to the rarity of urachal PEComa, prognosis assessment necessitates long-term follow-up and evaluation of more cases.

Exploring the application of sildenafil for high-fat diet-induced erectile dysfunction based on interleukin-18-mediated NLRP3/Caspase-1 signaling pathway.

Background: Inflammation is a key risk factor for heart disease and has also been linked to erectile dysfunction (ED). Sildenafil is a phosphodiesterase type 5 inhibitor with a strong antioxidant effect. Interleukin (IL)-18 is a proinflammatory factor. Excessive production and release of IL-18 disrupt the balance between IL-18 and IL-18 binding proteins in certain inflammatory diseases, leading to the occurrence of pathological inflammation. Aim: We evaluated the effects of sildenafil on erectile function in a rat model of high-fat diet-induced ED. Methods: Male Sprague Dawley rats (6 weeks old) were divided into 5 groups: control, ED, sildenafil, IL-18, and IL-18 + sildenafil. Subsequently, intracavernous pressure and mean arterial pressure were used to assess the erectile function of these rats. The expression of endothelial nitric oxide synthase, pyroptosis factors, and the ratio of smooth muscle cells and collagen fibers were evaluated in the serum and corpora tissue. Outcomes: Exploring the role and mechanism of sildenafil in ED through NLRP3-mediated pyroptosis pathway. Results: In comparison to the ED and IL-18 groups, there were statistically significant increases in the ratio of intracavernous pressure to mean arterial pressure, endothelial nitric oxide synthase expression, and the ratio of smooth muscle cells to collagen fibers following sildenafil intervention (P < .05). The sildenafil group and IL-18 + sildenafil group also showed statistically significant decreases the expression of NLRP3, caspase-1, and gasdermin D (P < .05). Clinical Implications: Sildenafil can improve erectile dysfunction by inhibiting inflammation. Strengths and Limitations: Strengths are that the relationship between pyroptosis and ED has been verified through in vitro and in vivo experiments. The limitation is that the conclusions drawn from animal and cells experiments need to be confirmed in clinical research. Conclusion: Sildenafil may reduce the effect of IL-18-induced inflammation in high-fat diet-induced ED rats through NLRP3/caspase-1 pyroptosis pathway.

Pyroptosis and inflammation­mediated endothelial dysfunction may act as key factors in the development of erectile dysfunction (Review).

Erectile dysfunction (ED) is a prevalent disease that causes sexual dysfunction in males. Inflammation­induced endothelial dysfunction is a fundamental pathophysiological symptom of ED, which is impacted by cell death. Pyroptosis is a type of programmed cell death mediated by the inflammasome that was discovered in inflammatory disorders. The activation of nucleotide­binding oligomerization domain­like receptors, particularly downstream inflammatory factors, such as IL­1ß and IL­18, is indicative of caspase­dependent pyroptosis. Although the underlying mechanisms of pyroptosis have been investigated in several disorders, the role of pyroptosis in ED remains to be fully elucidated. At present, studies on pyroptosis have focused on improving the understanding of ED pathogenesis and promoting the development of novel therapeutic options. The present review article aimed to discuss the literature surrounding the mechanisms underlying pyroptosis, and summarize the role of pyroptosis in the development and progression of inflammation­mediated ED.

Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway.

PURPOSE: This study aims to investigate the mechanism underlying the beneficial effects of Huangqi decoction (HQD) on Diabetic kidney disease (DKD) in diabetic db/db mice. METHODS: Eight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg), HQD-M (0.36 g/kg), and HQD-H (1.08 g/kg) groups. Non-diabetic db/m mice were served as the control group. These mice received HQD treatment for 8 weeks. After treatment, the kidney function, histopathology, micro-assay, and protein expression levels were assessed. RESULTS: HQD treatment improved the albumin/creatine ratio (ACR) and 24 h urinary albumin excretion, prevented the pathological phenotypes of increased glomerular volume, widened mesangial areas, the of mesangial matrix proliferation, foot process effacement, decreased nephrin expression and reduced number of podocytes. Expression profiling analysis revealed global transcriptional changes that predicted related functions, diseases and pathways. HQD treatment activated protein expressions of BMP2, BMP7, BMPR2, and active-Rap1, while inhibiting Smad1 and phospho-ERK. In addition, HQD was associated with improvements in lipid deposition in the kidneys of db/db mice. CONCLUSION: HQD ameliorated the progression of DKD in db/db mice by regulating BMP transcription and downstream targets, inhibiting the phosphorylation of ERK and the expression of Smad1, promoting Rap1 binding to GTP, and regulating the lipid metabolism. These findings provide a potential therapeutic approach for treating DKD.

Inflammatory myofibroblastic tumor of the bladder: Computed tomographic features.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with intermediate biologic potential, in which lack of understanding often poses difficulties in preoperative diagnosis and treatment. The aim of the present study was to characterize the computed tomography (CT) features of the bladder IMT. The CT images of nine pathologically confirmed bladder IMT were retrospectively reviewed. All patients underwent both unenhanced CT and contrast-enhanced CT. The diameter, location, contour, growth pattern, margin, boundary, density and enhancement pattern of the lesions were assessed. The mean Ki67 value of an irregular blood clot was 18% and that of no blood clot was 12%. A total of eight (89%) patients had one tumor and 1 (11%) patient had multiple tumors. An endophytic growth pattern was observed in 4 (44%) patients, an exophytic growth pattern in 2 (22%) patients, and a mixed growth pattern in 3 (33%) patients. The tumor manifests morphologically as either polypoid (n=5), or cauliflower-like (n=1) soft-tissue mass with a wide base in the cavity, or a limited thick-walled (n=3). The tumor margins were smooth (n=8) or lobulated (n=1), and the tumor boundaries were either clear (n=7) or ill-defined (n=2). The lesions showed either ring-shaped (n=3) or heterogeneous (n=6). The polypoid and cauliflower-like soft-tissue mass showed a symmetrical change in the center of the lesion after enhancement. The bladder IMT is mostly a single polypoid nodule in the superior wall, mostly endophytic growth, with ring-haped enhancement and symmetrical change after enhancement as its characteristic manifestations.

Gastric morphological type: A supplementary addition for the evaluation of gastric cancer.

Clinical and pathological features are important factors that affect the prognosis and treatment strategies of patients with gastric cancer (GC). An upper gastrointestinal barium X-ray examination is commonly used to show gastric mucosa and morphological changes. The aim of the present study was to evaluate the association between gastric morphological type and the clinicopathological features of patients with GC, based on double-contrast barium X-ray imaging. A total of 329 patients with GC who underwent upper gastrointestinal barium X-ray examination were analyzed. The gastric morphological type was divided into four types on barium X-ray images: Horn-type, hook-type, weak-type and waterfall-type stomach. The χ2 test or Fisher's exact test was used to assess the association between gastric morphological type and the clinicopathological features. There was a statistically significant difference in the location of GC between different types of gastric morphology. Hook-type and horn-type GC were commonly present in the lower region of the stomach, while waterfall-type GC was mainly located in the upper region of the stomach. The incidence of waterfall-type non-poorly differentiated GC was higher than that of other gastric types. The incidence of waterfall-type intestinal-type GC was higher than that of other gastric types, and horn-type GC was more common in mixed-type GC. There was a statistically significant difference in the T-staging of GC between different types of gastric morphology. In conclusion, gastric morphological type correlates with the location and T-stage distribution of GC.

Titanium surface-grafted zwitterionic polymers with an anti-polyelectrolyte effect enhances osteogenesis.

Zwitterionic polymers have attracted considerable attention because of their anti-adsorption and unique anti-polyelectrolyte effects and was widely used in surface modification. In this study, zwitterionic copolymers (poly (sulfobetaine methacrylate-co-butyl acrylate) (pSB) coating on the surface of a hydroxylated titanium sheet using surface-initiated atom transfer radical polymerization (SI-ATRP) was successfully constructed. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Water contact angle (WCA) analysis proved the successful preparation of the coating. The swelling effect caused by the anti-polyelectrolyte effect was reflected in the simulation experiment in vitro, and this coating can promote the proliferation and osteogenesis of MC3T3-E1. Therefore, this study provides a new strategy for designing multifunctional biomaterials for implant surface modifications.