Search

Previous studies have demonstrated residual complement-mediated deposits in repeat kidney biopsies of C3 glomerulopathies (C3G) (dense deposit disease (DDD) and C3 glomerulonephritis) following eculizumab treatment, despite some clinical improvement. With residual complement deposition, it is difficult to determine whether there is a reduced complement-mediated endothelial cell injury. We validated that myeloperoxidase (MPO) immunohistochemical staining identified glomerular endothelial cell injury in crescentic glomerulonephritis and C3G. We report that MPO staining in the glomerular endothelium of the post-treatment kidney biopsy was significantly reduced after 3 years of eculizumab treatment and clinical improvement in a 5-year-old boy with initial DDD and secondary crescent formation. We find that immunostaining for MPO is a useful method to compare glomerular endothelial injury in C3G following eculizumab treatment. This finding also supports the notion that eculizumab, a C5 blocker, may not mainly block C3 deposits in the glomeruli but significantly blocks final activation of the complement cascade, thus reducing glomerular endothelial cell injury.

Objective The objective of this study was to describe the different components of left atrial (LA) dysfunction predictors in nonobstructive and occult obstructive hypertrophy cardiomyopathy (HCM) patients especially with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (D) longitudinal and circumferential strains. Methods Twenty-eight nonobstructive HCM patients and 30 occult obstructive HCM patients according to LV outflow tract gradient at rest and after exercise were prospectively enrolled. 4D echocardiographic evaluation was performed in 58 HCM patients, both nonobstructive and occult obstructive, and 38 control subjects. LA reservoir, conduit, contractile functions were performed by 4D volume-strain with volumes and longitudinal, circumferential strains. Results Optimal correlation coefficients obtained between LV 4D mass (index) and LA 4D longitudinal/circumferential strain (r=-0.860 to 0.518, all P 0.75 and >0.85, respectively. Conclusions LA volumes were significantly increased and LA reservoir, conduit, and contractile functions were significantly impaired in HCM patients. Furthermore, different performances of LA functional analyses in nonobstruction and occult obstruction patients with 4D volume-strain echocardiography may facilitate the recognition of subtle LA dysfunctional differentiation in HCM patients.

Aims Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease characterized by abdominal pain. Our recent study has shown that the acid‐sensitive ion channel 1 (ASIC1) in dorsal root ganglion (DRG) is involved in stomachache of adult offspring rats subjected with prenatal maternal stress (PMS). MiR‐485 is predicted to target the expression of ASIC1. The aim of the present study was designed to determine whether miR‐485/ASIC1 signaling participates in enterodynia in the spinal dorsal horn of adult offspring rats with PMS. Methods Enterodynia was measured by colorectal distension (CRD). Western blotting, qPCR, and in situ hybridization were performed to detect the expression of ASICs and related miRNAs. Spinal synaptic transmission was also recorded by patch clamping. Results PMS offspring rats showed that spinal ASIC1 protein expression and synaptic transmission were significantly enhanced. Administration of ASICs antagonist amiloride suppressed the synaptic transmission and enterodynia. Besides, PMS induced a significant reduction in the expression of miR‐485. Upregulating the expression markedly attenuated enterodynia, reversed the increase in ASIC1 protein and synaptic transmission. Furthermore, ASIC1 and miR‐485 were co‐expressed in NeuN‐positive spinal dorsal horn neurons. Conclusions Overall, these data suggested that miR‐485 participated in enterodynia in PMS offspring, which is likely mediated by the enhanced ASIC1 activities., The present study has shown that miR‐485 negatively regulates ASIC1 expression and synaptic transmission in the spinal dorsal horn, thus eventually contributing to enterodynia of PMS offspring. It tips us to prevent the adverse effects on offspring induced by environmental stressors during pregnancy.

Constipation is a common gastrointestinal complication during pregnancy. The prevalence of constipation is higher in pregnant women compared to the general population owing to the physiological changes that occur throughout pregnancy. Lactulose and polyethylene glycol belong to a class of medications known as osmotic laxatives. The purpose of this study is to compare the safety and efficacy of polyethylene glycol and lactulose in pregnant women with constipation.In this study, we selected 113 pregnant women with constipation who attended the Department of Gastroenterology, Affiliated Hospital of Jiangnan University from May 1, 2017 to April 30, 2020. The included patients were randomly divided into two groups. The observation group used polyethylene glycol 4000 (manufactured by Beau four Ipsen Industry, France, National Medicine Standard: H20130145), 10 g, twice daily. The control group used lactulose (manufactured by Abbott Biologicals BV, Netherlands, National Medicine Standard: H20120387) 15 mL, twice daily. Both groups were given a 3-week course of treatment, and were observed for any adverse drug reactions. The clinical effects were compared every week during the 3-week treatment.Treatment was found to be effective in both the observation and control groups, as measured by a significant difference in the Wexner constipation scores of patients before and after treatment (P0.05). Although no significant differences in the final effect of treatment were observed between the two groups (P0.05), analysis of the Wexner scores at the first and second week of treatment indicated that polyethylene glycol had a faster therapeutic effect than lactulose (P=0.06, P=0.029).Compared with lactulose, Polyethylene glycol 4000 can significantly shorten the treatment course for constipation during pregnancy.

The overlap syndromes of anti-neutrophil cytoplasmic antibodies (ANCA)-associated crescentic glomerulonephritis (AACGN) and variants of immune complex medicated glomerulopathy (ICMGN) have been reported. But very few have compared AACGN alone with the overlap syndromes (AACGN plus ICMGN). The aim of this retrospective study was to make that comparison, following serum creatinine (sCr) to determine whether the two groups (AACGN-only group versus overlap group) would behave differently over time. We identified 14 cases with dual diagnoses of AACGN and various ICMGN in the overlap group. Data were collected and compared with 15 randomly selected AACGN-only cases over the similar period of time. The overlap syndrome represented 0.35% of our overall biopsies (14/4049). All 14 patients were ANCA positive and had crescentic formation. The percentage of crescents in the biopsies ranged from 10 to 78%. ICMGN included the following: membranoproliferative glomerulonephritis, post-infectious glomerulonephritis, membranous glomerulopathies, idiopathic mesangial proliferative glomerulonephritis, lupus nephritis, and IgA nephropathy. With the exception one biopsy revealing lupus nephritis class III, most of the ICMGN were mild. When compared to the AACGN-only group, there were no significant differences in clinical and histologic indices including age, percent of crescents, and sCr (on biopsy days, and over the follow-up periods), although the numbers of follow-up cases were limited over time. Our findings suggest that AACGN was the dominant disease process in the majority of overlap syndromes between AACGN and ICMGN, similar to the clinical processes of AACGN-only disease, therefore, the AACGN in overlap syndrome cases should be the main target for clinical management.

We try to investigate whether the values of three-dimensional principal longitudinal strain present differently between the left and right ventricles in patients with long-time follow-ups after heart transplantation (HTx).Transthoracic echocardiography with three-dimensional speckle tracking was performed at one-, five- and ten-year follow-ups in 62 "healthy" HTx patients together with routine echocardiographic evaluation in 32 control group (CG) individuals. Longitudinal strain was applied in all subjects assessing without myocardium wall motion abnormality. Firstly, left ventricular ejection fraction preserved in HTx and had no significant difference in comparison with the controls (p .05). 3D measurement showed obvious reduction in global (%: CG: -20.5 ± 3.5 vs. HT1y: -13.7 ± 4.6, HT5y: -14.4 ± 4.5, HT10y: -14.6 ± 4.7. p .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p .01) strain values of the left compared HTx with control subjects. Secondly, tissue Doppler imaging s' velocity and tricuspid annular plane systolic excursion reduced in HTx as compared to the controls in right ventricle (p .01). Longitudinal strain presented a more distinctive reduction in global (%: CG: -24.5 ± 4.6 vs. HT1y:-14.8 ± 7.5, HT5y: -15.5 ± 6.4, HT10y: -15.9 ± 6.8. p .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p .01) average values of the right compared HTx with control subjects. Thirdly, there weren't any significant changes between one-, five- and ten-year of all the values with HTx inter-group comparison in both the left and right ventricles (p .05). Fourthly, the global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, with the global decreased differentiation rates of 7%, 7%, 6%, respectively.Compared HTx with control subjects in both ventricles, conventional evaluation showed preserved or decreased functions in the left and right separately. Myocardial function evaluating by 3D longitudinal strain reduced after HTx, but the deformation of the right ventricle reduced more than those of the left ventricle. Additionally, 3D strain values almost remained with stable decreased differentiation rates during the long-time follow-ups.

Chronic visceral pain is one of the primary symptoms of patients with irritable bowel syndrome (IBS), which affects up to 15% of the population world-wide. The detailed mechanisms of visceral pain remain largely unclear. Our previous studies have shown that neonatal maternal deprivation (NMD) followed by adult multiple stress (AMS) advances the occurrence of visceral pain, likely due to enhanced norepinephrine (NE)-β2 adrenergic signaling. This study was designed to explore the roles of P2X3 receptors (P2X3Rs) in the chronic visceral pain induced by combined stress. Here, we showed that P2X3Rs were co-expressed in β2 adrenergic receptor (β2-AR)-positive dorsal root ganglion neurons and that NE significantly enhanced ATP-induced Ca2+ signals. NMD and AMS not only significantly increased the protein expression of P2X3Rs, but also greatly enhanced the ATP-evoked current density, number of action potentials, and intracellular Ca2+ concentration of colon-related DRG neurons. Intrathecal injection of the P2X3R inhibitor A317491 greatly attenuated the visceral pain and the ATP-induced Ca2+ signals in NMD and AMS rats. Furthermore, the β2-AR antagonist butoxamine significantly reversed the expression of P2X3Rs, the ATP-induced current density, and the number of action potentials of DRG neurons. Overall, our data demonstrate that NMD followed by AMS leads to P2X3R activation, which is most likely mediated by upregulation of β2 adrenergic signaling in primary sensory neurons, thus contributing to visceral hypersensitivity.

OBJECTIVES The lack of risk profile data on changes in multiple polyps identified by a colonoscopy constrains the creation of evidence-based guidelines. Our study aimed to investigate the relationship between size, location and histology of multiple polyps and patients' characteristics in a large teaching hospital-based Chinese population. METHODS We conducted a large, case-control, retrospective analysis on polyps obtained from 8308 patients who presented at the Digestive Endoscopy Center, Changhai Hospital (Shanghai, China) from January 2013 to August 2015. In total 10572 polyps were analyzed, with risk factors extrapolated through chart reviews of patients' electronic medical records. RESULTS Single polyps were identified in 6843 (82.4%) patients while multiple polyps were found in 1465 (17.6%). A multivariate analysis indicated that men were more likely than women to have multiple polyps (P < 0.001). Compared with the single polyps group, the numbers of patients with multiple polyps increased significantly with age (P < 0.001). Multiple small (6-9 mm) non-advanced adenomas were more likely to be found than were diminutive (

Purinergic receptors have been reported to be involved in brain disorders. In this study, we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus (T2DM). T2DM rats exhibited a worse performance in the T-maze and Morris water maze (MWM) than controls. Microglia positive for P2X purinoceptor 4 (P2X4R) in the hippocampus were reduced and activated microglia were increased in T2DM rats. Long Amplicon PCR (LA-PCR) showed that DNA amplification of the p2x4r gene in the hippocampus was lower in T2DM rats. Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2DM rats in the MWM. Most importantly, P2X4R overexpression suppressed the activated microglia and rescued the memory impairment of T2DM rats. Overall, T2DM led to excessive activation of microglia in the hippocampus, partly through the DNA damage-mediated downregulation of P2X4Rs, thus contributing to memory impairment. Electronic supplementary material The online version of this article (10.1007/s12264-020-00478-7) contains supplementary material, which is available to authorized users.

Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What’s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.

Objective: The purpose of this study was to evaluate the different components of left atrial (LA) dysfunction predictors in asymptomatic primary systemic hypertension patients with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (4D) longitudinal and circumferential strain values. Methods and Results: Patients with no left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) are all asymptomatic regarding primary blood hypertension. Thirty NLVH patients and 30 LVH patients according to LV mass index and 40 controls analyzed by 4D echocardiography were prospectively enrolled. LA volumes and longitudinal and circumferential strains were measured using 4D volume-strain echocardiography with a Vivid E95 Version 203 instrument. Correlation analysis indicated a significant relation between LV 4D mass index and LA 4D longitudinal/circumferential strain (r = –0.446 to 0.381, p = 0.000–0.042). LVH patients had a reduced LA emptying fraction compared with NLVH patients and control subjects (p < 0.01). NLVH patients had an impaired LA conduit function and increased contractile function compared with the control group (p < 0.01). LVH patients had increased LA volumes and significantly decreased reservoir, conduit and contractile functions compared with the controls (p < 0.01). LVH patients had increased LA volumes and decreased reservoir and contractile functions compared with NLVH patients (p < 0.01). The clinical utility of LA 4D volume-strain measurement was verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with NLVH, LVH and control group comparisons. Interclass correlation coefficients of interobserver and intraobserver assessments in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. Conclusions: LVH patients showed increased LA volumes and decreased LA emptying fractions. LA reservoir, conduit and contractile functions were significantly impaired in LVH patients. Decreased LA conduit function and increased contractile function were revealed in NLVH patients. LA volumetric and functional analyses with 4D volume-strain echocardiography may facilitate the recognition of subtle LA and LV dysfunctions in asymptomatic systemic hypertension patients.

Despite advancements in diagnosis and therapy, relapse of rectal cancer after clinical complete remission (cCR) remains a frequent event. The key factors influencing the treatment strategy for the management of patients achieving cCR following neoadjuvant chemoradiotherapy (Neo-CRT) remain to be identified. We present the case of a 64-year-old man with rectal cancer. The patient was initially admitted to the hospital in September 2011 with a 3-month history of change in his stools. Following his re-hospitalization in November 2011, a biopsy specimen of the neoplasm suggested the presence of rectal adenocarcinoma; laboratory investigations also revealed elevated levels of carcinoembryonic antigens (CEA; carbohydrate antigen 199) in the serum. Subsequently, the patient received Neo-CRT, as well as symptomatic and supportive treatment. The level of serum CEA returned to normal, without signs of swollen lymph nodes in the pelvic cavity. The patient was diagnosed with rectal cancer based on the elevated level of serum CEA, colonoscopy, and contrast-enhanced magnetic resonance imaging. He relapsed 4 months after cCR following Neo-CRT and underwent laparoscopic Miles' surgery in April 2013. The relapse may have been mainly attributed to residual tumor cells. This case report and literature review may contribute to the clinical recognition of treatment for patients with rectal cancer achieving cCR following Neo-CRT.

Introduction and aims Age-related severity and distribution of haemophilic arthropathy (HA) among Chinese patients with haemophilia using the Haemophilia Early Detection with Ultrasound (HEAD-US) system have not been extensively studied. Methods In our study, 89 patients with moderate and severe haemophilia were recruited. A total of 534 joints (knees, ankles and elbows on both sides included) were evaluated using musculoskeletal ultrasound (MSKUS) and scored using the HEAD-US system. Results Prevalence and average number of HA were 39.1% and 0.7, 90.6% and 3.2, 94.1% and 4.5, and 100% and 4.3 for ages ≤10, 11-20, 21-30 and 31-40 years, respectively. Prevalence and mean number of knee, ankle and elbow arthropathies also increased with age, although joint damages progressed in unparallel patterns. A significant difference in synovium subscores was observed between patients aged 10 years. An increasing tendency was observed in cartilage and subchondral bone subscores along with age before 30 years. No significant difference in mean joint scores was found between patients receiving on-demand therapy and those receiving on-demand to low-dose prophylactic therapy. Conclusions Haemophilic arthropathy developed in early childhood and progressed mainly before 30 years of age among Chinese patients with haemophilia, although in different ways among the knee, ankle and elbow.

Kidney injury molecule-1 (KIM-1) staining has been shown to be very useful in identifying acute proximal tubular injury, but its sensitivity, specificity and predicting values for the recovery of renal function after injury in renal biopsies have not been well established. In the first study, we randomly selected 184 renal biopsies from a wide age range of patients (children to elderly) with various renal diseases. KIM-1 staining scores were significantly correlated with serum creatinine (sCr) levels (P

Multiple sclerosis (MS) is a chronic and incurable autoimmune neurodegenerative disease of the central nervous system. Although the symptoms of MS can be managed by vitamin D3 treatment alone, this condition cannot be completely eradicated. Thus, there might be unknown factors capable of regulating the vitamin D receptor (VDR). Genome-wide analysis showed that miRNAs were associated with VDRs. We sought to determine the role and mechanism of action of miRNA-125a-5p and VDRs in a model of MS, mice with experimental autoimmune encephalomyelitis (EAE), which was induced by myelin oligodendrocyte glycoprotein 35–55 peptides. EAE mice showed decreased mean body weight but increased mean clinical scores compared with vehicle or control mice. And inflammatory infiltration was found in the lumbosacral spinal cord of EAE mice. In addition, VDR expression was significantly lower while the expression of miR-125a-5p was markedly higher in the spinal ventral horn of EAE mice than in vehicle or control mice. Importantly, activation of VDRs by paricalcitol or inhibition of miR-125a-5p by its antagomir markedly decreased the mean clinical scores in EAE mice. Interestingly, VDR and miR-125a-5p were co-localized in the same neurons of the ventral horn. More importantly, inhibition of miR-125a-5p remarkably blocked the decrease of VDRs in EAE mice. These results support a critical role for miR-125a-5p in modulating VDR activity in EAE and suggest potential novel therapeutic interventions.

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-019-00372-x) contains supplementary material, which is available to authorized users.

Tumor thrombosis is a poor prognostic feature and an exceptionally rare occurrence in salivary gland malignancies. We present a case of primary parotid myoepithelial carcinoma (MC) with tumor thrombosis in the external jugular vein (EJV). An 82-year-old man presented with a right-sided facial mass. MRI with and without gadolinium demonstrated a mass of the right parotid gland with a filling defect of the right EJV. The patient underwent right parotidectomy and selective neck dissection. Tumor thrombosis was found intraoperatively within the EJV. Final pathology demonstrated a poorly differentiated MC. Adjuvant radiation therapy without concurrent systemic therapy was administered. Three months later, restaging positron emission tomography (PET) with CT revealed numerous bilateral pulmonary nodules with biopsy, demonstrating poorly differentiated MC without locoregional relapse. Given that primary parotid tumor thrombosis is associated with a poor prognosis, the use of early systemic therapy should be investigated.

Background:. Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. Methods:. The clinical data of EPI (gestational age [GA]

Irritable bowel syndrome (IBS) is one of the most common challenging diseases for clinical treatment. The aim of this study is to investigate whether transcranial direct current stimulation (tDCS) has analgesic effect on visceral hypersensitivity (VH) in an animal model of IBS as well as the underlying mechanism. As the activation of GluN2B in anterior cingulate cortex (ACC) takes part in VH, we examined whether and how GluN2B in ACC takes part in the effect of tDCS. Neonatal maternal deprivation (NMD), a valuable experimental model to study the IBS pathophysiology, was used to induce visceral hypersensitivity of rats. We quantified VH as colorectal distention threshold and performed patch-clamp recordings of ACC neurons. The expression of GluN2B were determined by RT-qPCR and Western blotting. The GluN2B antagonist Ro 25-6981 was microinjected into the rostral and caudal ACC. tDCS was performed for 7 consecutive days. It was found that NMD decreased expression of GluN2B, which could be obviously reversed by tDCS. Injection of Ro 25-6981 into rostral and caudal ACC of normal rats induced VH and also reversed the analgesic effect of tDCS. Our data sheds light on the nonpharmacological therapy for chronic VH in pathological states such as IBS. NEW & NOTEWORTHY Irritable bowel syndrome (IBS) is a gastrointestinal disease characterized by visceral hypersensitivity. This study showed a decrease of GluN2B expression and neural activity in ACC of IBS-model rats, which could be obviously reversed by tDCS. In addition, blockade of GluN2B in rostral and caudal ACC induced VH of normal rats. Furthermore, analgesic effect of tDCS on NMD rats was reversed by GluN2B antagonist.

Introduction/Objective Collapsing glomerulopathy (CGN) mainly occurs in patients of African descent because a majority of these patients have APOL-1 gene mutations that results in damage of terminally differentiated podocytes, diffuse fusion of foot processes, and podocyte hyperplasia. Idiopathic FSGS is associated with high rates of recurrent FSGS in renal transplants and can be seen in patients with APOL-1 gene mutations as well, but recurrent FSGS progressing to CGN is not reported. Here we report an autopsy case with renal transplant showing recurrent FSGS progressing to CGN. Methods/Case Report Our patient was a 32 year old African American man who had a native renal biopsy which showed primary FSGS (with no infectious history) 8 years ago. Last year he received a renal transplantation (complex donor kidney from a deceased 25 year old man with pre-mortem serum creatinine (sCr) at 0.7 mg/dl). His initial post- transplant sCr level was as low as 1.17 mg/dl. However, in 4 months his sCr went up and he began to have higher levels of proteinuria. Sequential biopsies indicated that the patient developed a recurrent FSGS that progressed to show features of CGN. In his autopsy kidney graft, approximately 50% of glomeruli show collapsed loops with various degrees of hyperplasic podocytes, confirmed by positive CD133 staining (a progenitor cell marker). In addition, the hyperplastic podocytes lost WT-1 expression and were positive for Ki-67 staining. Distal tubules showed obvious cystic dilation. Overall findings were consistent with a severe form of CGN. Results (if a Case Study enter NA) NA Conclusion The clinical presentation of recurrent FSGS progressing to collapsing FSGS in our patient suggests that CGN and idiopathic FSGS may share a common pathophysiologic mechanism of disease.

Introduction/Objective GATA3 is found in glomerular mesangial cells, and the distal tubules & collecting ducts in metanephros and eventual kidneys, but not associated with the proximal tubules and loops of Henle. We hypothesize that GATA3 can be used as a marker to identify the origin of tubular differentiation in most renal tumors. Methods/Case Report Ten negative controls and 43 renal mass lesions (RCC, papillary, clear cell papillary, and chromophobe carcinomas, oncocytoma, and polycystic kidney disease). GATA3 nuclear stain was graded as negative (absent stain), equivocal and positive (< 5 and > 5% cells, respectively). Details of their GATA3 nuclear expression was analyzed for identifying their tubular segmental origins. Results (if a Case Study enter NA) In 10 normal renal parenchyma, GATA3 was positive in mesangial cells, distal tubules, and collecting ducts, but was negative in the proximal tubules and loop of Henle. The cystic lining of glomerulocystic renal disease was stained negatively for GATA3 (proximal tubular origin), whereas pediatric and adult variants of polycystic kidney diseases was positive for GATA3 staining (distal tubular origin). 1/10 ten clear cell RCC and papillary RCC showed focal positive GATA3 stain. GATA3 showed weakly positive staining in some oncocytomas (4/11) and some chromophobe RCC (4/11), indicating that they might be derived from the junctional segment between the loop of Henle and the distal tubules. By contrast, all clear cell papillary RCC (distal tubule origin) were diffusely positive. Conclusion Our results indicate that GATA3 is a useful immunohistochemical marker to determine the developmental origin in the specific renal tubular segment for the majority of renal mass lesions. Thus, it may be useful for routine differential diagnosis of these lesions.

Introduction/Objective IgG4 related disease, a systemic autoimmune inflammatory disorders, can be identified by high% of IgG4 positive plasma cells, thus IgG4 staining in paraffin embedded tissue is widely available in the most of pathology labs. IgG4 staining has been found useful to identify primary MGN (PLA2R and/or THSD7A positive) by others and us. This study was to scrutinize the findings of primary vs secondary MGN needed for IgG4 staining as a screening tool in our renal pathology practice over pasts 5 years Methods/Case Report IgG4 staining in paraffin embedded tissue was performed in 45 primary MGN and 43 secondary MGN after the clinical history was reviewed and a possibility of primary MGN cannot be excluded. In addition, both groups of cases were also stained for PLA2R. Detail correlation with clinical history was analyzed. Results (if a Case Study enter NA) Totally 82 % (37/45) of primary MGN was found diffuse positive for IgG4 staining at 2+ intensity in the glomeruli. Seven out of eight remaining primary MGN cases with either negative or weak IgG4 stained MGN were found to have diffuse resolving features by electron microscopy but there was still positive PLA2R staining in the glomeruli. All secondary MGN were stained negatively for both IgG4 and PLA2R and we found that etiologies of the secondary MGN included membranous lupus nephritis, infection, GVHD, or variants of cancers. Conclusion Our data indicate that IgG4 staining along (without IgG1-3 staining) is a reliable screening tool to confirm the majority of primary MGN vs secondary MGN in paraffin embedded tissue. As both PLA2R+ and THSD7A+ primary MGN are both IgG4 related, the IgG4 staining may potentially represent a wider range of scope in identifying primary MGN. In addition, negative/weak IgG4 staining in PLA2R-positive MGN most likely represents a primary MGN with resolving features.

Aims: To determine whether acid-sensing ion channel 1 (ASIC1)–sodium-potassium-chloride cotransporter 1 (NKCC1) signaling pathway participates in chronic visceral pain of adult rats with neonatal maternal deprivation (NMD).Methods: Chronic visceral pain was detected by colorectal distension (CRD). Western blotting and Immunofluorescence were performed to detect the expression and location of ASIC1 and NKCC1. Whole-cell patch-clamp recordings were performed to record spinal synaptic transmission.Results: The excitatory synaptic transmission was enhanced and the inhibitory synaptic transmission was weakened in the spinal dorsal horn of NMD rats. ASIC1 and NKCC1 protein expression in the spinal dorsal horn was significantly up-regulated in NMD rats. Incubation of Amiloride reduced the amplitude of mEPSCs. Incubation of Bumetanide (BMT) increased the amplitude of mIPSCs. Intrathecal injection of ASIC1 or NKCC1 inhibitors reversed the threshold of CRD in NMD rats. Also, Amiloride treatment significantly reversed the expression of NKCC1 in the spinal dorsal horn of NMD rats.Conclusion: Our data suggest that the ASIC1-NKCC1 signaling pathway is involved in chronic visceral pain in NMD rats.

Objective Metabolic disturbance of lysophosphatidylcholine (LPC) is related with dyslipidemia. Therefore, eight single-nucleotide polymorphisms (SNPs) were selected from LPC metabolic enzymes to study their associations with obesity and serum levels of lipids. Methods A total of 3305 children were recruited from four independent studies. Eight SNPs of LPC metabolic enzymes were selected and genotyped with the matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The multivariable linear regression model was applied to detect the associations of eight SNPs with obesity-related phenotypes and levels of lipids in each study. Meta-analyses were used to combine the results of four studies. Results Only SNP rs4420638 of APOC-1 gene was associated with serum lipids even after Bonferroni correction. The rs4420638 was positively associated with TC (β = 0.15, P = 8.59 × 10-9) and low-density-lipoprotein-cholesterol (LDL-C, β = 0.16, P = 9.98 × 10-14) individually. Conclusion The study firstly revealed the association between APOC-1/rs4420638 and levels of serum lipids in Chinese children, providing evidence for susceptible gene variants of dyslipidemia.

Electron microscopy (EM) has been mainly used for identifying ultrastructural abnormalities such as fusion of foot processes and immune complex deposits in glomeruli. However, electron microscopic findings in renal tubules can provide either diagnostic evidence (unique finding) or supportive evidence (additional finding) for final diagnosis. Here we present multiple situations that EM can be used for drawing conclusions of various drug-associated nephrotoxicity. Multiple cases with drug-induced nephrotoxicity are reviewed, including clinical history, EM findings, and serum creatinine (sCr) levels, prior to renal biopsy and during follow-up. Two cases with nephrotoxicity by aminoglycoside antibiotics showed acute tubular injury with EM findings of myeloid bodies, characterized by laminated dense materials in lysosomes in both proximal and distal tubular epithelium (diagnostic evidence). Five cases of vancomycin associated nephrotoxicity presented with acute tubular injury and vancomycin casts in distal tubules, characterized by central laminated casts in the lumina of distal tubules (supportive evidence). Vedolizumab, a humanized monoclonal antibody used in treating Crohn's disease, can cause T-cell dominant acute interstitial nephritis, with EM revealing lymphocytic infiltration into tubules as tubulitis (supportive evidence). Four of Seven cases (5/8) cases had renal functional recovery upon follow-up check for sCr. EM findings of characteristic changes in renal tubules can be particularly useful as either diagnostic or supportive evidence, in correlation with clinical history and etiologies of nephrotoxicity. Therefore, EM should not only focus on glomerular changes, but renal tubular changes as well.

Introduction: Pathological scar is the abnormal manifestation of skin fiber hyperplasia caused by the failure of normal healing after skin damage. At present, there are many clinical treatments for pathological scars. However, there is no cure for clinically effective pathological scars with high recurrence rate. In this study, we will use a combination of Chinese and western medicine treatment methods to evaluate the clinical efficacy and related indicators of young and middle-aged female patients who meet pathological scars, looking for an objective and effective treatment method for pathological scars. Methods/design: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for pathological scars. The untreated pathological scars of the enrolled patients will be used as blank controls. The intervention group will be given conventional western medicine treatment and combined Chinese and western medicine treatment. The assessment of scar area, color, hardness, thickness, itching, and pain was recorded for 8 weeks of treatment. Discussion: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of traditional Chinese medicine for patients with pathological scars. Trial registration: ClinicalTrials.gov, ChiCTR2000032187, Registered on April 22, 2020.

The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β2 adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β2 adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β2 adrenergic signaling in DRGs.

There is currently no technique to unambiguously diagnose antemortem kidney injury on postmortem examination since postmortem tissue damage and autolysis are common. We assessed the ability to detect kidney injury molecule-1 (KIM-1) expression in adult and fetal kidneys examined at autopsy. In adult kidneys ( n = 52 subjects), we found that the intensity of KIM-1 staining significantly correlated with the antemortem level of serum creatinine, and this was independent of the extent of tissue autolysis. In addition, kidneys from a total of 52 fetal/neonatal subjects, 30 stillborns and 22 liveborns, were assessed for KIM-1 staining. Given that serum creatinine is unreliable and often unavailable in fetuses and newborns, we assessed preterminal hypoxia in fetuses by the presence of squames in pulmonary alveoli and by required intubation. KIM-1 expression correlated with these clinical indexes of hypoxia. The expression of KIM-1 was seen in a majority of the fetal and neonatal autopsy kidneys (77%, 40/52) as early as 16 wk of gestation, even in the presence of autolysis. Thus KIM-1 is a specific and stable marker of antemortem tubular injury in kidneys of adults and fetuses despite postmortem autolysis.

Introduction/Objective Only one prior case report indicates that mixed positive cryoglobulin in serum can be associated with intestinal vasculitis (Annals of Internal Medicine, 1974). Methods/Case Report We report a 63-year old man with history of positive serum cryoglobulin and hepatitis-C 4 years ago and membranoproliferative pattern of glomerulonephritis with possible cryoglobulin type of deposits by electron microscopy on renal biopsy. After treatment, his hepatitis C became negative. But he was recently found to have monoclonal IgM-kappa and positive cryoglobulin in his serum, and the concurrent renal biopsy showed membranoproliferative pattern of glomerulopathy with many hyaline-thrombi (eosinophilic vascular occlusions with no lamination, inflammatory cells or nuclear debris) in the glomerular capillary loops (Figure, left panel). Both immunofluorescent and electron microscopy confirmed a mixed IgG polyclonal and IgM monoclonal type 2 cryglobulinemic glomerulonephritis. The patient also developed abdominal pain and underwent intestinal endoscopy with biopsy. His jejunal biopsy revealed neutrophil infiltration into glands and surface epithelium, with superficial sloughed epithelial cells, consistent with acute jejunitis with features of ischemic etiology. In addition, hyaline-thrombi were identified in the submucosal vessels with surrounding vasculitis (Figure, right panel); the central part of thrombi was morphologically similar to that found in glomerular capillary loops. Therefore, we conclude that cryoglobulin associated hyaline-thrombi were the most likely etiology to cause the acute ischemic jejunitis in this patient. Results (if a Case Study enter NA) NA Conclusion NA

Introduction/Objective Inflammatory bowel disease (IBD) and acute ischemic colitis can both be involved by active colitis. IBD is characterized by crypt architectural distortion, basal lymphoplasmacytosis, and occasional granulomatous changes. However, diagnosis of IBDs is still largely by exclusion of other types of active colitis with similar changes. We previously demonstrated that glucose regulated protein 94 (grp94) is mainly expressed by activated plasma cells. We postulate that increased numbers of grp94-positive plasma cells may support diagnosis of IBDs. Here, we compared IBD and active ischemic colitis for grp94 expression in mucosal plasma cells of colectomy specimens Methods/Case Report Tissue sections from colectomy specimens with active IBD (n = 8) and ischemic colitis (n = 7) were examined for grp94 expression by immunohistochemistry (monoclonal antibody clone 9G10 at dilution of 1:200, Enzo Life Science, Inc Farmindale, NY). The staining intensity and highest number of grp94 in plasma cells per high power field was counted and recorded for each case, and combined scores were calculated as # of plasma cells multiplied by staining intensity (ranging from 0 to 3+). Unpaired student T tests were used to compare these indices between the two groups for statistical significance (p value < 0.05 was considered significantly different) Results (if a Case Study enter NA) Plasma cells in lamina propria identified by grp94 staining showed higher intensity in IBD than ischemic groups. The number of plasma cells and combined scores were also significantly higher in the IBC group than that of ischemic group Conclusion Our data indicates that active plasma cells are much more numerous in IBD than ischemic colitis, supporting the notion that active plasma cells are involved in the development of this disease process. Morphologically, active colitis with increased number of plasma cells appears to be another index favoring the diagnosis of IBD.

Background/aims Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. Methods DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension. Results Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89. Conclusions Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.

Background In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. Methods Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis. Results Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs. Conclusions Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3451-x) contains supplementary material, which is available to authorized users.

To investigate the relationship between left ventricular (LV) myocardial mechanics evaluated by three-dimensional speckle tracking echocardiography (3D-STE) and degree of coronary artery stenosis in patients with coronary artery disease (CAD). Ninety-seven suspected CAD patients without LV regional wall motion abnormality (RWMA) observed visually form traditional echocardiography were divided into four groups according to coronary artery angiography (CAG): 23 patients in slight stenosis group [stenosis rate (SR) ≤25%], 26 patients in mild stenosis group (25 SR ≤50%), 28 patients in moderate stenosis group (50 SR ≤75%), and 20 patients in severe stenosis group (SR 75%). Global longitudinal strain (GLS), circumferential strain (GCS), radial strain (GRS), area strain (AS) and three dimensional strain (3D-Strain) were obtained. The parameters from 3D-STE were compared between different groups and then the diagnostic value of global strains indicating different graded coronary artery stenosis was analyzed by the receiver operating characteristic curve. (1) There were significant difference in GLS, GCS, GRS, GAS and 3D-Strain between the severe stenosis group and any other group while all 3D-STE parameters except GCS in the moderate stenosis group were remarkably different from those respectively in mild group. (2) Receiver operator characteristic curve (ROC) analysis showed that the area under the curve of GLS, GRS, GCS, GAS, 3D-Strain were 0.899, 0.873, 0.723, 0.856 and 0.863 respectively for the identification of stenosis rate 50%, and 0.896, 0.866, 0.797, 0.909 and 0.899 respectively for the identification of severe stenosis. GAS less than -29.13% allowed a sensitivity of 95% and a specificity of 71.4%, while 3D strain less than 41.35% allowed a sensitivity of 90% and a specificity of 80.5% for evaluating serve coronary artery stenosis. The myocardial mechanics from 3D-STE in the CAD patients were characteristic. It could be expected to identify serve coronary stenosis with a good sensitivity and an acceptable specificity by using GAS or 3D-strain especially in the suspected CAD patients without RWMA on conventional echocardiography.

Introduction/Objective Differentiating low-grade SIL from reactive changes on light microscopy has remained controversial. P16 immunostaining is widely accepted in high-grade SIL unlike in low-grade SIL. We focused on the use of p16 immunostaining in eliminating inaccurate diagnosis of low-grade SIL on light microscopy. Methods A retrospective study on 60 cervical biopsies results over a 2 year-period was conducted using 35 suspicious cases for low-grade SIL (bi-nucleation and some nuclear atypia) and 25 low suspicion cases (enlarged nuclei but nuclear atypia cannot differentiate from reactive changes). All cases were stained for p16, significant nuclear expression of p16 was determined as low- grade SIL. Results After p16 immunostaining, 30/35 (85%) cervical biopsies from the suspicious group were found to be truly positive for low-grade SIL while 5/35 (15%) biopsies negative for p16 immunostaining were regarded as reactive changes. In the low suspicious group, 7/25 (28%) were found to be positive for low-grade SIL and 18/25 (72%) biopsies were negative, favoring reactive changes. The overall percentage of all 60 biopsies that showed a changed diagnosis based on p16 immunostaining was 20% (5 were truly negative in the suspicious group and 7 were truly positive in the low suspicious group). Using a 2 x 2 table with p16 as a gold standard for all biopsies, sensitivity and specificity of light microscopy for low-grade SIL were only 81% and 78% respectively. Conclusion Our study showed that p16 immunostaining can also be utilized to eliminate inaccurate diagnosis of low- grade SIL up to 20% in cervical biopsies.

Functional dyspepsia is a common functional gastrointestinal disorder. Gastric hypersensitivity (GHS) is a hallmark of this disorder, but the cellular mechanisms remain largely unknown. Stressors during gestational period could have effects on the offspring's tissue structure and function, which may predispose to gastrointestinal diseases. The aim of this study was to test whether prenatal maternal stress (PMS) induces GHS and to investigate role of acid-sensing ion channel (ASIC)/nuclear factor-κB (NF-κB) signaling by examining Asic1 methylation status in adult offspring rats. Gastric hypersensitivity in response to gastric distension was examined by electromyography recordings. Changes in neuronal excitability were determined by whole-cell patch-clamp recording techniques. Demethylation of CpG islands of Asic1 was determined by methylation-specific PCR and bisulfite sequencing assay. Prenatal maternal stress produced GHS in adult offspring rats. Treatment with amiloride, an inhibitor of ASICs, significantly attenuated GHS and reversed hyperexcitability of gastric-specific dorsal root ganglion (DRG) neurons labeled by the dye DiI. Expression of ASIC1 and NF-κBp65 was markedly enhanced in T7 to T10 DRGs. Furthermore, PMS led to a significant demethylation of CpG islands in the Asic1 promoter. A chromatin immunoprecipitation assay showed that PMS also enhanced the ability of NF-κBp65 to bind the promoter of Asic1 gene. Blockade of NF-κB using lentiviral-p65shRNA reversed upregulation of ASIC1 expression, GHS, and the hyperexcitability of DRG neurons. These data suggest that upregulation of ASIC1 expression is attributed to Asic1 promoter DNA demethylation and NF-κB activation, and that the enhanced interaction of the Asic1 and NF-κBp65 contributes to GHS induced by PMS.

Background Muscle-invasive bladder cancer (MIBC) is originated in the muscle wall of the bladder, and is the ninth most common malignancy worldwide. However, there are no reliable, accurate and robust gene signatures for MIBC prognosis prediction, which is of the importance in assisting oncologists to make a more accurate evaluation in clinical practice. Methods This study used univariable and multivariable Cox regression models to select gene signatures and build risk prediction model, respectively. The t-test and fold change methods were used to perform the differential expression analysis. The hypergeometric test was used to test the enrichment of the differentially expressed genes in GO terms or KEGG pathways. Results In the present study, we identified three prognostic genes, KLK6, TNS1, and TRIM56, as the best subset of genes for muscle-invasive bladder cancer (MIBC) risk prediction. The validation of this stratification method on two datasets demonstrated that the stratified patients exhibited significant difference in overall survival, and our stratification was superior to three other stratifications. Consistently, the high-risk group exhibited worse prognosis than low-risk group in samples with and without lymph node metastasis, distant metastasis, and radiation treatment. Moreover, the upregulated genes in high-risk MIBC were significantly enriched in several cancer-related pathways. Notably, PDGFRB, a receptor for platelet-derived growth factor of PI3K-Akt signaling pathway, and TUBA1A were identified as two targets of multiple drugs. In addition, the angiogenesis-related genes, as well as two marker genes of M2 macrophage, CD163 and MRC1, were highly upregulated in high-risk MIBC. Conclusions In summary, this study investigated the underlying molecular mechanism and potential therapeutic targets associated with worse prognosis of high-risk MIBC, which could improve our understanding of progression of MIBC and provide new therapeutic strategies for the MIBC patients.

Despite rapid advances in diagnostic and therapeutic medicine, renal cell carcinoma (RCC) continues to cause significant morbidity and mortality in patients. While there has been a shift towards earlier detection, approximately 16% of patients present with metastatic disease at the time of diagnosis. Kidney injury molecule-1 (KIM-1) is a glycoprotein that has been shown to be a robust and reliable biomarker of acute proximal tubular injury. As KIM-1 is mainly expressed in RCC derived from the proximal tubules, it is a reliable marker to differentiate between proximal tubular primary RCC and distal nephron primary RCC. Several studies have investigated urinary KIM-1 (uKIM-1) in RCC and demonstrated that it is a sensitive and specific marker for detecting localized RCC, as patients had markedly reduced uKIM-1 levels following nephrectomy, with uKIM-1 levels correlating with tumor size and grade. In addition, levels of KIM-1 present in plasma have also shown utility as a biomarker of RCC with levels being elevated in RCC cases at least 5 years before diagnosis. This review focuses on a progressive understanding of KIM-1 in the diagnosis of RCC using biopsies, urine, and plasma samples, and it will also provide some insight into potential roles of KIM-1 in the growth and spread of RCC.

Objectives Our study investigated left ventricular dyssynchrony (LVD) in coronary artery disease (CAD) patients without regional wall-motion abnormality (RWMA) by three-dimensional echocardiography (3-DE) and explored the relationship between LVD and severity of CAD as assessed by the Gensini score (GS). Methods Sixty-one patients with a confirmed diagnosis of CAD by coronary angiography (CAG) were enrolled. We quantified LVD parameters, including the left ventricular segments (16, 12, and 6) standard deviation of the time to minimum systolic volume (TmsvSD-16, TmsvSD-12, and TmsvSD-6) and the systolic dyssynchrony index in regions 16, 12, and 6 (16R-SDI, 12R-SDI, 6R-SDI) using 3-DE. The severity of coronary atherosclerotic lesions was evaluated by the GS system on the basis of CAG findings. We further divided all patients into three groups according to the tertiles of GS: low-GS ≤20, mid-GS >20 and ≤48, and high-GS >48. The differences of LVD values among the three groups were compared, and the associations between LVD parameters and GS were analyzed. Results Coronary artery disease patients demonstrated increased LVD parameters compared with healthy controls. TmsvSD12, 16R-SDI, and 6R-SDI were prolonged in the high-GS group compared with the low- and mid-GS groups. 16R-SDI was positively correlated with the GS, and multivariate regression analysis showed that 16R-SDI was an independent predictor of the GS. 16R-SDI above 10.7% had a sensitivity of 84.21% and a specificity of 92.86% for identifying high-GS. Conclusion Three-dimensional echocardiography is a noninvasive technique to detect LVD in non-RWMA CAD patients, and the parameter 16R-SDI was significantly correlated with CAD severity.

Background and aim Diabetic neuropathic pain is a refractory and disabling complication of diabetes mellitus. The pathogenesis of the diabetic neuropathic pain is still unclear, and treatment is insufficient. The aim of this study is to investigate the roles of glucose-6-phosphate dehydrogenase (G6PD) and toll-like receptor 4 (TLR4) in neuropathic pain in rats with diabetes. Methods Type 1 diabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 75 mg/kg) in adult female Sprague-Dawley rats. Paw withdrawal threshold and paw withdrawal latency of rats were measured by von Frey filaments and thermal radiation, respectively. The expressions of G6PD and TLR4 in L4-L6 dorsal root ganglions (DRGs) were measured by western blotting and quantitative real-time polymerase chain reaction analysis. Fluorescent immunohistochemistry was employed to detect expressions of G6PD and TLR4 and co-location of G6PD with TLR4. Results The mRNA and protein expression levels of G6PD in DRGs were significantly decreased in diabetic rats when compared with age-matched control rats. Upregulation of G6PD by intrathecal injection of G6PD overexpression adenovirus markedly attenuated hindpaw pain hypersensitivity of diabetic rats. The mRNA and protein expression levels of TLR4 in DRGs of diabetic rats were significantly increased when compared with control rats. Intrathecal injection of TLR4-selective inhibitor CLI-095 attenuated diabetic pain in dose- and time-dependent manners. Furthermore, G6PD and TLR4 were co-localized in DRG neurons. Intrathecal injection of G6PD overexpression adenovirus greatly reduced TLR4 expression, while intrathecal injection of CLI-095 had no significant effect on G6PD expression in diabetic rats. Conclusions Our results suggest that decrease in G6PD expression was involved in diabetic peripheral neuropathic pain, which was most likely through upregulation of TLR4 expression in the DRGs of rats.

Objectives To determine whether 3-dimensional (3D) speckle-tracking echocardiography could provide a new way to assess myocardial viability in patients with myocardial infarction (MI). Methods Forty-five patients with MI underwent routine echocardiography, 2-dimensional (2D) speckle-tracking echocardiography, and 3D speckle-tracking echocardiography. Radionuclide myocardial perfusion/metabolic imaging was used as a reference standard to define viable and nonviable myocardia. Results Among 720 myocardial segments in 45 patients, 368 showed abnormal motion on routine echocardiography; 204 of 368 were categorized as viable on single-photon emission computed tomography/positron emission tomography (SPECT/PET), whereas 164 were defined as nonviable; 300 normal segments on SPECT/PET among 352 segments without abnormal motion on routine echocardiography were categorized as a control group. The radial, longitudinal, 3D, and area strain on 3D speckle-tracking echocardiography had significant differences between control and nonviable groups (P < .001), whereas none of the parameters had significant differences between control and viable groups. There were no significant differences in circumferential, radial, and longitudinal peak systolic strain from 2D speckle-tracking echocardiography between viable and nonviable groups. Although there was no significant difference in circumferential strain between the groups, radial and longitudinal strain from 3D speckle-tracking echocardiography decreased significantly in the nonviable group. Moreover, 3D and area strain values were lower in the nonviable segments than the viable segments. By receiver operating characteristic analysis, radial strain from 3D speckle-tracking echocardiography with a cutoff of 11.1% had sensitivity of 95.1% and specificity of 53.4% for viable segments; longitudinal strain with a cutoff of 14.3% had sensitivity of 65.2% and specificity of 65.7%; 3D strain with a cutoff of 17.4% had sensitivity of 70.6% and specificity of 77.2%; and area strain with a cutoff of 23.2% had sensitivity of 91.5% and specificity of 82.8%. Conclusions Three-dimensional speckle-tracking echocardiography might have potential for detection of myocardial viability in patients with cardiac dysfunction due to MI.

Introduction: Hypertrophic scars are a common disease in plastic surgery, which is the reaction of skin connective tissue to trauma beyond the normal range. Although scholars around the world have explored the tissue structure and formation mechanism of HS for decades, they are not satisfactory the result of. No effective treatment has been found. Therefore, the search for safe and effective treatments for HS has always been the focus of medical attention and research. Acupuncture therapy has a definite effect on HS and has unique advantages. Methods/design: In this study, we will use our own front-to-back clinical research method. We plan to include 120 young and middle-aged female patients who meet the diagnostic criteria for HS. The untreated HS of the enrolled patients will be used as blank controls. The intervention group will be given acupuncture treatment. The assessment of scar area, color, hardness, thickness, itching and pain will be recorded for 30 days of treatment. Discussion: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of Acupuncture for patients with HS. Trial registration: ClinicalTrials.gov, ChiCTR2000032624, Registered on 04 May 2020.

Coronavirus disease in 2019 (COVID-19) has spread around the world and caused significantly pandemic mobility and mortality. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) usually infects lungs first and involves other organs including kidneys subsequently. Acute kidney injury and proteinuria in patients with COVID19 are resulted from the direct infection of the spikycrowned viruses to proximal tubules and podocytes, leading to acute tubular injury and collapsing focal segmental glomerulosclerosis. Therefore treatment strategy should target against the direct infection of SARS-CoV2 to the renal tissue.

Background: Diabetes is associated with an increased risk of heart failure, cardiac arrhythmias and sudden cardiac death. We previously showed that ROCK2 expression is elevated in diabetic rat hearts, and that ROCK inhibition acutely improves their contractile function. In the present study we investigated whether inhibition of ROCK or partial deletion of ROCK2 improves impaired Ca handling in the diabetic heart. Methods: Contractile properties and Ca transients were measured before and after treatment with the ROCK inhibitor Y-27632 (1 μM) in fluo-4-loaded cardiomyocytes isolated from streptozotocin (STZ)-diabetic or non-diabetic rats. Cardiac function was determined in vivo, and contractile properties and Ca transients also measured in cardiomyocytes from non-diabetic and STZ-diabetic wild-type (WT) and ROCK2+/− mice. Results: ROCK inhibition improved some parameters of contractile function and Ca handling in cardiomyocytes from diabetic rat hearts. In addition, ROCK inhibition attenuated the diabetes-induced delayed aftercontractions (DACs) and associated irregular Ca transients induced by increased [Ca]o. Although no overt cardiac dysfunction was detected in diabetic WT mice, cardiomyocytes from these mice also developed arrhythmic Ca transients in response to increased [Ca]. These were attenuated in cardiomyocytes from diabetic ROCK2+/− mice, in association with decreased diastolic Ca leak and with reduction of the diabetes-induced increased phosphorylation of both CaMKII and the ryanodine receptor (RyR). Conclusions: These data suggest that ROCK2 contributes to diabetes-induced impaired cardiac Ca homeostasis, at least in part by promoting CaMKII-mediated phosphorylation of RyR. This may have important clinical implications for the treatment of the increased incidence of dysrhythmias in diabetes., This study was supported by operating grants from the Canadian Institutes of Health Research (MOP 97861) and Diabetes Canada (KMM), and Spanish Ministry of Economy and Competitiveness SAF2014-58286-C2-1R (LHM).

OBJECTIVE This observational cross-sectional study evaluated the distribution of ultrasound (US) features of lower-limb joints and the risk factors of tophus in gout patients. METHODS We examined 588 joints including the bilateral knee, ankle, and first metatarsophalangeal (MTP) joints in 98 gout patients by US between March to August in 2017. The distribution of double-contour (DC), tophus, aggregates, synovitis, effusion and erosion in different joint, course, and age groups were investigated by Cochran Q and χ test. The risk factors of tophus were analyzed using logistic regression method. RESULTS Double-contour was most commonly observed in the knee (p = 0.005). Tophus, aggregates, synovitis, and erosion were mostly detected in the first MTP (p < 0.001, p = 0.01, p = 0.001, p < 0.001, respectively). The prevalence rates of DC, tophus, and erosion in patients with a longer course were significantly higher (p = 0.029, p = 0.002, p < 0.001, respectively). Older patients had more detectable tophus and erosion than younger patients (p = 0.028, p = 0.021). Patients of older age (odds ratio [OR], 3.83; 95% confidence interval [CI], 1.27-11.48), with frequent attacks (OR, 3.80; 95% CI, 1.10-13.15), and with longer course (OR, 6.52; 95% CI, 1.37-30.96) had higher risks of tophus. CONCLUSIONS Most signs were detected by US in the first MTP, except that DC was most commonly observed in the knees. Patients of older age with frequent attacks and longer course may experience higher risks for tophus. Comprehensive assessment of the lower limbs, particularly the knee and first MTP, can significantly help diagnosis.

Introduction Frozen sections have been used for evaluating tumors and margins during daily practice in pathology with high specificity and sensitivity (>90% for both indices both at national level and in our department). The correlation between frozen section tissue for immunofluorescent (IF) studies and permanent sections for light microscopy, along with electron microscopy, is critical for constructing a final renal pathology diagnosis. Methods We studied the correlation between the frozen sections for IF studies and separate fragments of tissue for permanent light microscopic sections in our renal transplant biopsies for purposes of quality control. Frozen sections for IF sections were compared with permanent sections for light microscopy in 122 renal transplant biopsies, using inflammation as the key criterion (63 with no inflammation and 59 with inflammation) to determine the correlation. Results There was high sensitivity (94.9%) and specificity (92.1%) for the correlation between the frozen section and permanent sections. Conclusions Our data suggest that parts of renal transplant biopsy tissue dissected to freeze for IF studies and for light microscopy were highly correlated to ensure a high quality of renal tissue dissection for the final diagnosis in renal transplant biopsies.