Minimal change disease associated with gastrointestinal stromal tumor accompanied by significantly elevated serum IgE level: a case report.

BACKGROUND: Minimal change disease (MCD) is a common cause of the nephrotic syndrome. Several studies have shown an increased incidence of cancer in patients with MCD. However, there are no reports on the association between MCD and gastrointestinal stromal tumor (GIST). CASE PRESENTATION: We report a case of a 66-year-old female with severe nephrotic syndrome and concomitant duodenal GIST. Immunoglobulin test showed a significant increase of IgE levels. The diagnosis of renal histopathology was MCD with subacute tubulointerstitial injury. The combination of preoperative Imatinib mesylate chemotherapy and tumor excision was accompanied by significant remission of proteinuria, and IgE level decreasing, without immunosuppressivetherapy. CONCLUSIONS: It is the first case report that MCD was associated with GIST and elevated IgE level. Clinically, in patients with elevated IgE level associated with nephrotic syndrome, the possibility of tumor must be taken into account when allergic factors are excluded.

[Homozygous CFAP65 mutation induces multiple morphological abnormalities of sperm flagella: A preliminary genetic study].

OBJECTIVE: To search for the possible pathogenic genes for multiple morphological anomalies of sperm flagella (MMAF). METHODS: We performed whole exome sequencing (WES) of a typical case of MMAF and analyzed its possible pathogenic genes. We examined the semen sample from the patient and identified the ultrastructural characteristics of the sperm flagella under the scanning electron and transmission electron microscopes, and analyzed the expression pattern of cilia and flagela-associated protein 65 (CFAP65) in spermatogenesis by immunofluorescence assay. RESULTS: The MMAF patient was found with a homozygous pathogenic mutation of the CFAP65 gene c.2675G>A(p.Trp892*). Scanning electron microscopy showed that the sperm of the patient had typical characteristics of MMAF, that is, without tails or with folded tails, curly tails, short tails or irregular tails. Transmission electron microscopy revealed the loss and disorder of the "9+2" structure in the sperm flagellum, with abnormal assembly of the fibrous sheath, accompanied by loss of central microtubules and dynamin arms. Cellular immunofluorescence assay suggested that the CFAP65 gene was expressed at all levels of mouse germ cells. CONCLUSIONS: The CFAP65 gene is involved in the assembly of the sperm flagellum structure, and its mutation can cause the phenotype of MMAF, leading to male infertility.

Intravenous Administration of Vitamin C in the Treatment of Herpes Zoster-Associated Pain: Two Case Reports and Literature Review.

Background: Herpes zoster (HZ) is an acute inflammatory neurocutaneous disease caused by the reactivation of varicella-zoster virus. It is estimated that the incidence of postherpetic neuralgia following HZ is 10-20%. The leading risk factors of the prognosis are aging and immunity dysfunction. Vitamin C plays a pivoted role in enhancing white blood cell function. Epidemiological evidence and clinical studies have indicated an association between pain and suboptimal vitamin C status. At present, vitamin C has been used as an additional option in the treatment of HZ-associated pain. Despite the current controversy, case reports and randomized controlled studies have indicated that both acute- and postherpetic neuralgia can be dramatically alleviated following intravenous vitamin C infusions. Case Presentation. Two patients (male aged 72 and female 78 years) with HZ did not respond well to antiviral therapy and analgesics. Skin lesions in the right groin and front thigh healed after early antiviral therapy, but the outbreak of pain persisted in the male patient. The female patient presented to our clinic with clusters of rashes in the right forehead with severe edema of her right upper eyelid. Because nerve blockade could not be conducted for both patients, intravenous infusion of vitamin C was applied and resulted in an immediate remission of the breakthrough pain in the male patient and cutaneous lesions in the female patient. Conclusions: The use of vitamin C appears to be an emerging treatment alternative for attenuating HZ and PHN pain. Hence, we recommend the addition of concomitant use of intravenously administered vitamin C into therapeutic strategies in the treatment of HZ-associated pain, especially for therapy-resistant cases. Furthermore, animal studies are required to determine analgesic mechanisms of vitamin C, and more randomized clinical trials are essential to further determine the optimal dose and timing of administration of vitamin C.

Blockade of insulin receptor substrate-1 inhibits biological behavior of choroidal endothelial cells.

AIM: To investigate the effects of blockade of insulin receptor substrate-1 (IRS-1) on the bio-function of tube formation of human choroidal endothelial cells (HCECs). METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to determine the expression level of IRS-1 and phospho-IRS-1 in HCECs. Tube formation of HCECs was analyzed using three dimensional in vitro Matrigel assay with or without IRS-1 blockage via IRS-1 inhibitor (GS-101) and vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor. In addition, cell counting kit (CCK)-8 and Transwell migration assay were exerted to analyze the effects of blockade of IRS-1 on the bio-function of proliferation and migration of HCECs, respectively. The apoptosis of HCECs was examined using flow cytometry (FCM). RESULTS: RT-PCR and Western blot revealed that IRS-1 phospho-IRS-1 were expressed in HCECs and the expression level was enhanced by stimulation of VEGF-A. The number of tube formation was decreased significantly in GS-101 treated groups compared to phosphate buffered saline (PBS) treated control groups. Furthermore, both cell proliferation and migration of HCECs were decreased in the presence of GS-101. FCM analysis showed that the apoptosis of HCECs was enhanced when the cells were treated with GS-101. Western blot also showed that the expression level of cleaved-caspase 3 in GS-101 treated group was higher than that in control group. CONCLUSION: Blockade of IRS-1 can inhibit tube formation of HCECs through reducing cell proliferation and migration and promoting cell apoptosis.

Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy.

BACKGROUND/AIMS: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. METHODS: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). RESULTS: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21-0.74; Oxford classification 0.48, 95% CI 0.28-0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23-0.92; Oxford classification 0.59, 95% CI 0.10-0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. CONCLUSIONS: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

Urinary angiostatin: a novel biomarker of kidney disease associated with disease severity and progression.

BACKGROUND: This study aimed to evaluate the value of urinary angiostatin levels for assessing disease severity and progression of IgA nephropathy (IgAN). METHODS: Urinary angiostatin was identified as one of the distinct proteins in samples of patients with IgAN analyzed by Raybiotech protein array, and further confirmed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Urinary angiostatin levels were significantly higher in IgAN patients than that in healthy controls (HC) subjects and lower than in disease controls (DC) patients. The concentrations of angiostatin in urine normalized to urinary creatinine (angiostatin/Cr) were positively associated with proteinuria level. With advancing chronic kidney disease (CKD) stage, urinary angiostatin/Cr levels were gradually increased. Urinary angiostatin/Cr levels in patients with Lee's grade IV-V were significantly higher than those in Lee's grade I-II and III. We further compared urinary angiostatin/Cr levels by using Oxford classification and found the expression in patients with mesangial proliferative score 1(M1) was significantly higher than that in M0 (P < 0.001). In addition, the levels of urinary angiostatin/Cr in patients with tubular atrophy/interstitial fibrosis score 1(T1) and T2 were significantly higher than those in T0 (P < 0.01, P < 0.001, respectively). After follow-up, renal survival was significantly worse in patients with higher levels of urinary angiostatin (P < 0.05). CONCLUSIONS: Urinary angiostatin may be a useful novel noninvasive biomarker to evaluate disease severity and progression of IgAN.

EGFL6 promotes breast cancer by simultaneously enhancing cancer cell metastasis and stimulating tumor angiogenesis.

EGFL6, a member of the EGF-like superfamily, plays an important role during embryonic development and has been implicated in promotion of tumor angiogenesis without affecting wound healing. There is very little known about the function of EGFL6 in cancer cells. Here, we investigated whether EGFL6 plays a direct role in cancer cells in addition to the promotion of tumor angiogenesis. Our study showed that EGFL6 promoted epithelial-mesenchymal transition (EMT) and stemness of breast cancer cells and increased cell migration and invasion in cell culture studies. We also found that EGFL6 reduced apoptotic signaling in cancer cells and promoted tumor growth in vivo. Importantly, expression of EGFL6 in cancer cells and tumor endothelial cells not only increased tumor angiogenesis but also promoted migration of cancer cells. Such dual engagement of cancer and stromal cells suggests crosstalk mediated by EGFL6 in the tumor microenvironment. Blockade of EGFL6 using our novel anti-EGFL6 monoclonal antibody significantly reduced cancer cell migration, tumor angiogenesis, and tumor growth in mouse xenograft tumor models. Silencing EGFL6 mRNA by shRNA transfection of cancer cells also significantly reduced cancer cell migration, tumor angiogenesis, and tumor growth in mouse xenograft tumor models. Taken together, the results of this study indicate that targeting EGFL6 is a unique strategy for inhibiting both cancer cell metastasis and tumor angiogenesis.

Discrepant Clinical Significance of CD28+CD8- and CD4+CD25high Regulatory T Cells During the Progression of Hepatitis B Virus Infection.

Accumulating evidence demonstrates that CD8+CD28- regulatory T cells increase in chronic viral infection as well as tumorigenesis. However, it is still not clear about their characteristics in hepatitis B virus (HBV) infection. In addition, it is not understood whether this regulatory immune subset is distinct from CD4+CD25high regulatory T cells in the aspect of impact on or relationship to the progression of HBV infection. Hence, we investigated their dynamics and compared their correlations with clinical parameters in the chronic and advanced phases of HBV infection. The data showed that compared with healthy controls, the frequencies of CD28+CD8- and CD4+CD25high T cells increased in both chronic and advanced phases, while there is no significant difference between the two case groups. Interestingly, we found that in chronic phase, the frequency of CD8+CD28- subset was negatively correlated with the levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST), respectively, and did not present association with HBV DNA load, whereas that of CD4+CD25high T cells was positively correlated with HBV DNA load and the levels of ALT and AST, respectively. Amazingly, in advanced phase, the frequency of CD4+CD25high T cells was negatively correlated with HBV DNA load and the levels of ALT, respectively, while there is no significant correlation between the frequency of CD8+CD28- subset and those clinical parameters. Thereby, our findings demonstrated that CD28+CD8- and CD4+CD25high regulatory T cells might exert distinct effect on modulating antiviral immune responses and mitigate immunomediated liver damage in different phases of HBV infection, which represent potential prognostic markers and therapeutic targets for HBV-infected patients based on further exploration of detailed mechanism.

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells.

BACKGROUND: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. METHODS: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. RESULTS: Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-γ, TNF-α, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8+ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1+CD8+T cells. CONCLUSION: We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.

Minimally invasive thalamic hematoma drainage can improve the six-month outcome of thalamic hemorrhage.

OBJECTIVE: To explore predictors of the 6-month clinical outcome of thalamic hemorrhage, and evaluate if minimally invasive thalamic hematoma drainage (THD) could improve its prognosis. METHODS: A total of 54 patients with spontaneous thalamic hemorrhage were evaluated retrospectively. Clinical data, including demographics, stroke risk factors, neuroimaging variables, Glasgow Coma Score (GCS) on admission, surgical strategy, and outcome, were collected. Clinical outcome was assessed using a modified Rankin Scale, six months after onset. Univariate analysis and multivariate logistic regression analysis were performed to determine predictors of a poor outcome. RESULTS: Conservative treatment was performed for five patients (9.3%), external ventricular drainage (EVD) for 20 patients (37.0%), THD for four patients (7.4%), and EVD combined with THD for 25 patients (46.3%). At six months after onset, 21 (38.9%) patients achieved a favorable outcome, while 33 (61.1%) had a poor outcome. In the univariate analysis, predictors of poor 6-month outcome were lower GCS on admission (P = 0.001), larger hematoma volume (P < 0.001), midline shift (P = 0.035), acute hydrocephalus (P = 0.039), and no THD (P = 0.037). The independent predictors of poor outcome, according to the multivariate logistic regression analysis, were no THD and larger hematoma volume. CONCLUSIONS: Minimally invasive THD, which removes most of the hematoma within a few days, with limited damage to perihematomal brain tissue, improved the 6-month outcome of thalamic hemorrhage. Thus, THD can be widely applied to treat patients with thalamic hemorrhage.

Serum is an indispensable factor in the maintenance of the biological characteristics of sweat gland cells.

The tolerance of sweat gland cells for in vitro amplification and subcultivation is low as they are somatic cells. The present study aimed to formulate an optimal medium for the culture of human eccrine sweat gland cells (HESGCs) and to establish a method for induction of HESGCs proliferation, whilst maintaining the characteristics of sweat gland cells. HESGCs cultured in sweat gland (SG):keratinocyte growth medium­2 (KGM­2) (1:1) medium had a higher proliferation rate and a stable morphology compared with cells cultured in SG and KGM­2 medium only. Reverse transcription­quantitative polymerase chain reaction indicated that cells cultured in the SG:KGM­2 (1:1) medium exhibited higher expression levels of α­smooth muscle actin, keratin (K)77, carcinoembryonic antigen, K8, K18, ectodysplasin A receptor, c­Myc, Kruppel­like factor 4 and octamer­binding transcription factor 4 compared with cells cultured in SG only or KGM­2 only medium. Three­dimensional culture analysis revealed that HESGCs cultured in SG:KGM­2 1:1 medium differentiated into sweat gland­like structures, whereas cells cultured in KGM­2 only medium underwent cornification. The present study also determined that the maintenance of the biological characteristics of HESGCs occurred due to the presence of fetal bovine serum (FBS). Cells cultured in medium without FBS differentiated into keratinocytes. Therefore, the SG:KGM­2 (1:1) medium may be a suitable culture medium for HESGCs. In conclusion, this mixed medium is a valuable compound and should be considered to be a potential supplemental medium for HESGCs.

Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The clinical spectrum of IgAN varies from minor urinary abnormalities to rapidly progressive renal failure. Evaluation of the disease by repeated renal biopsy is not practical due to its invasive procedure. Urinary sediment miRNAs promise to serve as non-invasive biomarkers to assess kidney injury of IgAN. METHODS: Fifty two biopsy-proven IgAN patients and twenty five healthy controls were enrolled in the study. Urinary sediment miRNAs were extracted. Expressions of miR-34a, miR-205, miR-21, miR-146a and miR-155 were quantified by real-time quantitative polymerase chain reaction (RT-QPCR). The receiver operating characteristic (ROC) curve was used to investigate the value of the miRNAs for predicting diagnosis of IgAN and evaluating histopathological injury. The patients were treated according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and followed up. The roles of miRNAs in reflecting therapeutic efficacy and disease progression were analyzed. RESULTS: 1. The IgAN group had significantly lower urinary miR-34a, miR-205, and miR-155, but higher miR-21 levels than controls. The ROC revealed that urinary miR-34a ≤ 0.047, miR-205 ≤ 0.209, miR-21 ≥ 0.461 and miR-155 ≤ 0.002 could distinguish patients with IgAN from healthy ones. In addition, miR-205 ≤ 0.125 and miR-21 ≥ 0.891 can distinguish IgAN patients with severe tubular atrophy/interstitial fibrosis from those with mild tubular atrophy/interstitial fibrosis. 2. After a mean 15.19 months follow-up, the reduction of proteinuria (g/24 h/year) was positively correlated with baseline urinary miR-21 and inversely correlated with miR-205. The levels of baseline eGFR and miR-205 in the complete remission group were significantly higher than non-complete remission group (p < 0.001; p = 0.018), while proteinuria, miR-21 and miR-146a were lower than non-complete remission group (p = 0.002; p = 0.021; p = 0.009). But multivariate analysis revealed that only baseline eGFR correlated with the remission of IgAN (p = 0.001, OR = 1.042). CONCLUSIONS: The levels of some urinary sediment miRNAs, especially baseline miR-21 and miR-205, may be used as potential prognostic markers for evaluating the tubulointerstitial damage of IgAN. Furthermore, baseline levels of urinary miRNAs may be predictors of therapeutic efficacy and disease progression.

Clinical Significance of Dynamics of Programmed Death Ligand-1 Expression on Circulating CD14+ Monocytes and CD19+ B Cells with the Progression of Hepatitis B Virus Infection.

Programmed death-1 (PD-1) expression has been revealed to be upregulated on T cells and contributes to T cell exhaustion in patients with hepatitis B virus (HBV) infection. In this study, we investigated the dynamic expression of programmed death ligand-1 (PD-L1), the ligand of PD-1, on circulating CD14+ monocytes and CD19+ B cells of HBV-infected patients at the stages of chronic HBV (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC), respectively. The results showed that compared with healthy controls, the levels of PD-L1 expression on CD14+ and CD19+ populations were both upregulated in CHB, LC, and HCC groups. Although there was no significant difference of PD-L1 expression on CD14+ population among three disease groups, further analysis demonstrated that the frequency of CD14+PD-L1+ population was negatively correlated with HBV DNA load, the levels of alanine aminotransaminase (ALT), and the levels of aspartate aminotransferase (AST), respectively, at CHB stage, while it did not present significant correlation with such parameters at LC stage and was only positively correlated with HBV DNA load at HCC stage. Similarly, the levels of PD-L1 expression on CD19+ population also did not present much difference among three disease groups. Intriguingly, the frequencies of CD19+PD-L1+ population at CHB and LCC stages were both positively correlated with the levels of ALT and AST, but they were not significantly correlated with HBV DNA load. Thereby, the current study elucidated the dynamics of PD-L1 expression on monocytes and B cells, along with the dynamic regulation of PD-1 on T cells, which had a close relationship during the progression of HBV infection. Collectively, our findings demonstrated that in the course of HBV infection development, PD-L1 expression on CD14+ monocytes and CD19+ B cells varied and significantly correlated with clinical parameters, which could be utilized as a potential clinical indicator.

Assessment of plasma B7-H3 levels in pediatric patients with different degrees of surgical stress.

BACKGROUND: Surgical stress initiates a series of host hormone, metabolism and immune responses, which predominantly affect the homeostatic mechanism of patients with major surgery. B7-H3 is a co-stimulatory molecule and has been shown to participate in both adaptive and innate immune responses. In this study we evaluated the clinical significance of plasma B7-H3 levels in pediatric patients with different types of operation and degrees of surgical stress. METHODS: A total of 48 children received pediatric general and cardiac surgery were recruited into this study. Based on the surgical stress scoring, children were divided into moderate stress (n = 14) and severe stress (n = 34) groups. Plasma B7-H3 levels were assessed at selected time points: before surgery, immediately after surgery, at day 1, day 3, and day 7 after surgery. Correlations between plasma B7-H3 levels and surgical stress scores were also examined. RESULTS: Plasma B7-H3 levels were significantly decreased in all 48 pediatric patients after surgery compared to the B7-H3 level before surgery (p < 0.01). Children with general surgery showed significant decreases in plasma B7-H3 immediately after surgery, and at day 3 and day 7 after surgery (p < 0.05, p < 0.01), whereas children with cardiac surgery showed reduced plasma B7-H3 immediately after surgery and at day 3 after surgery (p < 0.05). Plasma B7-H3 in cardiac surgery group was dropped much lower than that in general surgery group at day 1 (p < 0.05) and day 3 (p < 0.01) after surgery. Significantly reduced plasma B7-H3 was observed in the severe stress group, but not in the moderate stress group, immediately after surgery and at day 3 after surgery (p < 0.05), and severe stress group had significantly lower plasma B7-H3 levels than moderate stress group at day 1, day 3, and day 7 after surgery (p < 0.05). Furthermore, plasma B7-H3 levels at day 1 (p = 0.01) and day 3 (p = 0.025) after surgery correlated negatively with surgical stress scores. CONCLUSIONS: Plasma B7-H3 levels were decreased significantly in children subjected to pediatric general and cardiac surgery, which is closely associated with the severity of surgical stress. The negative correlation of plasma B7-H3 levels at day 1 and day 3 after surgery with surgical stress scoring implicates that the plasma B7-H3 level might be a useful biomarker for monitoring stress intensity during pediatric surgery.

[Therapeutic Effect of Combined Cytokines on Nonhuman Primate Model of Severe Haemopoietic Acute Radiation Sickness].

OBJECTIVE: To evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment. METHODS: Seventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation. RESULTS: After 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated. CONCLUSION: rhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.

Enhancement of CD4(+) T cell response and survival via coexpressed OX40/OX40L in Graves' disease.

OX40/OX40L pathway plays a very important role in the antigen priming T cells and effector T cells. In the present study, we aimed to examine the involvement of OX40/OX40L pathway in the activation of autoreactive T cells in patients with Grave's disease (GD). We found that OX40 and OX40L were constitutively coexpressed on peripheral CD4(+) T cells from GD patients using flow cytometry analysis. The levels of OX40 and OX40L coexpression on CD4(+) T cells were shown to be correlated with TRAbs. Cell proliferation assay showed that blocking OX40/OX40L signal inhibited T cell proliferation and survival, which suggested that OX40/OX40L could enhance CD4(+) T cell proliferation and maintain their long-term survival in GD by self-enhancing loop of T cell activation independent of APCs. Confocal microscopy and coimmunoprecipitation analysis further revealed that OX40 and OX40L formed a functional complex, which may facilitate signal transduction from OX40L to OX40 and contribute to the pathogenesis of GD.

Renal Light Chain Deposition Associated with the Formation of Intracellular Crystalline Inclusion Bodies in Podocytes: A Rare Case Report.

We herein report the case of an elderly woman with bone pain and proteinuria as the main clinical manifestations. The patient was diagnosed with the IgG κ type of multiple myeloma. Her renal pathology consisted of widespread κ light chain protein deposition associated with the formation of large quantities of rod-like crystals in podocytes. This phenomenon is very rare. We explored the significance of this crystal formation via a detailed and descriptive analysis and also performed a literature review, thus providing data to increase the available information about this type of disease.

Dysmorphic erythrocytes are superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics.

AIMS/INTRODUCTION: There are sparse and limited studies on erythrocyte morphology in renal biopsy identifying nephropathic patients among type 2 diabetics. The present study sought to clarify the predictive value of dysmorphic erythrocytes in type 2 diabetics with non-diabetic renal disease and influences on hematuria. MATERIALS AND METHODS: We examined 198 patients with type 2 diabetes who underwent kidney biopsies between 2012 and 2013. Hematuria was defined as >3 or >10 red blood cells per high-power field (RBCs/hpf) in urine sediment. If >80% of the erythrocytes were dysmorphic, glomerular hematuria was diagnosed. Clinical findings and predictive value of dysmorphic erythrocytes were compared between patients with hematuria (n = 19) and those without (n = 61). The potential risk factors for hematuria among diabetic nephropathy patients were also screened. RESULTS: There was a statistically significant difference between the diabetic nephropathy group and the non-diabetic renal disease group (6.6 vs 16.8%; P = 0.04) when the demarcation point of hematuria was 10 RBCs/hpf. When the definition of hematuria was based on an examination of urinary erythrocyte morphology, a marked difference was seen (3.3 vs 24.8%; P < 0.001). Glomerular hematuria showed high specificity and a positive predictive value (0.97 and 0.94, respectively) in non-diabetic renal disease. A multivariate analysis showed that nephrotic syndrome was significantly associated with hematuria (odds ratio 3.636; P = 0.034). CONCLUSIONS: Dysmorphic erythrocytes were superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics. Nephrotic syndrome was an independent risk factor for hematuria.

The increase of circulating PD-L1-expressing CD68(+) macrophage in ovarian cancer.

Tumor-associated macrophages (TAMs) have been characterized as a critical population of immunosuppressive cells in a variety of tumor types. PD-L1 (also termed B7-H1) has been described to exert co-inhibitory and immune regulatory functions. Here, in ovarian cancer, PD-L1 is selectively overexpressed on some TAM compared that of benign ovarian disease. When expanding the data in peripheral blood, the proportion of PD-L1(+)CD68(+) cell among CD68(+) cells and the intensity of PD-L1 staining on CD68(+) cell in healthy group were similar to that observed in ovarian cyst group; instead, these two measures were significantly higher in ovarian cancer group, thereafter related to TNM stage. Interestingly, intracellular levels of IL-10, IL-6, TNF-α, and IFN-γ in PD-L1(+)CD68(+) macrophage were higher than those in PD-L1(-)CD68(+) macrophage, especially IL-6 expression. Based on the PD-L1 receptor PD-1 expression on tumor-infiltrating cytotoxic cells, our data supported that expression of PD-L1 on TAM promoted apoptosis of T cells via interaction with PD-1 on CD8(+)T cells. Taken together, these results suggested that PD-L1-expressing macrophage represents a novel suppressor cell population in ovarian cancer, which contributes immune escape of ovarian cancer.