Development of a diagnostic model for pre-washout screening of primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

Liver injury induced by clomiphene citrate: A case report and literature reviews.

WHAT IS KNOWN AND OBJECTIVE: Clomiphene citrate is used to cause ovulation in females and to increase semen production in males. Clomiphene citrate is well tolerated in most patients and rarely induces liver injury. We report a case of liver injury which is associated with administration of clomiphene citrate in a male patient. CASE SUMMARY: A 31-year-old man who was treated by clomiphene citrate for 5 days was transferred to our emergency room with reddish-brown urine and upper abdominal pain. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were elevated. Based on the subsequent examination, he was diagnosed with liver injury and cholecystitis. The levels of AST and ALT returned to normal range after discontinuation of clomiphene citrate and symptomatic treatment. WHAT IS NEW AND CONCLUSION: The mechanism of liver injury caused by clomiphene citrate is still unclear. Polymorphism of CYP2D6 may have had an effect. Liver function tests should be performed when there is upper abdominal pain after administration of clomiphene citrate.

Genomic and phylogenetic evidence that Maize rough dwarf and Rice black-streaked dwarf fijiviruses should be classified as different geographic strains of a single species.

Maize rough dwarf disease (MRDD) has long been known as one of the most devastating viral diseases of maize worldwide and is caused by single or complex infection by four fijiviruses: Maize rough dwarf virus (MRDV) in Europe and the Middle East, Mal de Rio Cuarto virus (MRCV) in South America, rice black-streaked dwarf virus (RBSDV), and Southern rice black-streaked dwarf virus (SRBSDV or Rice black-streaked dwarf virus 2, RBSDV-2) in East Asia. These are currently classified as four distinct species in the genus Fijivirus, family Reoviridae, but their taxonomic status has been questioned. To help resolve this, the nucleotide sequences of the ten genomic segments of an Italian isolate of MRDV have been determined, providing the first complete genomic sequence of this virus. Its genome has 29144 nucleotides and is similar in organization to those of RBSDV, SRBSDV, and MRCV. The 13 ORFs always share highest identities (81.3-97.2%) with the corresponding ORFs of RBSDV and phylogenetic analyses of the different genome segments and ORFs all confirm that MRDV clusters most closely with RBSDV and that MRCV and SRBSDV are slightly more distantly related. The results suggest that MRDV and RBSDV should be classified as different geographic strains of the same virus species and we suggest the name cereal black-streaked dwarf fijivirus (CBSDV) for consideration.

Overwhelming postsplenectomy infection.

This report aims to deepen the understanding of the pathogenesis, diagnosis, clinical characteristics, and treatment of overwhelming postsplenectomy infection (OPSI). A patient treated at Taihe Hospital for tuberculous OPSI is described, and relevant literature is reviewed. Broad-spectrum antibiotics, suppression of the systemic inflammatory reaction, and anti-shock measures were the keys to the successful treatment of this condition. OPSI is a life-threatening condition and has a high mortality rate. Early diagnosis, use of anti-inflammatory glucocorticoids, and administration of high-dose gamma globulin and ulinastatin for the treatment of OPSI may improve outcomes.

Role of sphingosine-1-phosphate receptors in the tumor microenvironment: prospects for cancer immunotherapy.

OBJECTIVE: Sphingosine-1-phosphate (S1P) is a sphingolipid protein with anti-apoptotic and pro-survival effects on cancer cells via S1P receptors (S1PRs); however, the role of S1PRs in the tumor microenvironment and immune invasion is still unclear. This study investigated the relationship between S1PR expressions and patient survival and clinical manifestations with respect to the tumor microenvironment and immune infiltration. MATERIALS AND METHODS: The expression levels of five S1PRs were obtained from The Cancer Genome Atlas pan-cancer database and the Kaplan-Meier survival analysis was performed. We predicted the relationship between S1PRs expression levels and patient survival using the univariate Cox proportional hazard regression model. Subsequently, we analyzed correlations between S1PRs expression and infiltrating immune cell subtypes using the Kolmogorov-Smirnov test and the infiltration levels of immune and stromal cells in each tumor using the ESTIMATE algorithm and Spearman's test. RESULTS: The five S1PRs exhibited significant heterogeneity in their expression levels. The expression levels correlated with overall patient survival; however, anti-apoptotic or pro-apoptotic features varied depending on the cancer type. The variable effects of S1PRs on tumors may be related to TGF-ß levels. Our results suggest that S1PRs exert distinct influences on the tumor stem cell index and chemotherapeutic drug sensitivity. CONCLUSIONS: This research provides comprehensive information on the importance of S1PRs in the immune microenvironment, stemness score, sensitivity of human cancer drugs, and cancer prognosis. Interestingly, our findings indicate variations in the expression levels and functions of different S1PR family members. This study highlights S1PRs as potential new targets for antitumor (adjuvant) therapy.

Incidence and survival of symptomatic lacunar infarction in a Beijing population: a 6-year prospective study.

BACKGROUND AND PURPOSE: The incidence of ischaemic stroke has increased or remained high in China; however, little population-based evidence is available on the incidence and survival of lacunar infarction (LAC). We examined the incidence of LAC in a northern Chinese (Beijing) population and monitored survival. METHODS: A prospective registry population-based study was conducted over a 6-year period in a general, unselected, and representative community in Beijing with approximately 100,000 long-term permanent residents. All first-ever stroke cases were registered. RESULTS: A total of 1184 patients with ischaemic stroke were identified; 36.9% (437 cases) were classified as LAC. Age-standardized incidence rates of LAC ranged from 24.0 to 51.3/100,000 with an average rate of 35.3/100,000 during study period. The incidence of LAC increased with age before 70 years. The incidence of non-LAC increased with age. There were no significant differences in crude incidence of LAC between men and women (78.4/100,000 vs. 75.4/100,000). The incidence of non-LAC was significantly higher in men than in women (155/100,000 vs. 107/100,000, P < 0.001). The 28-day case fatality proportions were significantly lower in patients with LAC (0.5%) versus non-LAC (14.9%). One year after acute stroke onset, the survival rates between LAC and non-LAC were similar. CONCLUSION: LAC is a common stroke subtype in Northern China. Men or the elderly are more likely to have non-LAC. Long-term survival following LAC is similar to non-LAC patients.

Anlotinib inhibits the progress of colorectal cancer cells by antagonizing VEGFR/JAK2/STAT3 axis.

OBJECTIVE: Anlotinib, a novel tyrosine kinase receptor inhibitor (TKI), targets multi-targets, including vascular endothelial growth factor receptor (VEGFR). Increasing evidence suggests that anlotinib exhibits effective anti-tumor activity in various cancer types, such as liver cancer. However, the biological function of anlotinib in the treatment of colorectal cancer (CRC) remains largely unknown. This investigation aims to investigate the function and possible molecular mechanism of anlotinib in CRC therapy. MATERIALS AND METHODS: Human colorectal cancer cells (HCT-116 and LOVO) were cultured and treated with anlotinib alone or combined with cisplatin (DDP). Thereafter, CCK8 assay, CyQUANT NF assay, and colony formation were used to determine the cytotoxicity property and cell proliferation of colorectal cancer. To evaluate the invasion and metastasis of colorectal cancer cells, we conducted wound healing and trans-well assay. Hoechst33342 fluorescence staining and Flow Cytometry analysis were applied for apoptosis detection. Real-time qPCR and Western blot were used to measure the mRNA or protein level. RESULTS: Our results showed anlotinib alone or combined with cisplatin inhibited cell proliferation, migration, and invasion and activated apoptosis in colorectal cancer cells. Furthermore, we found that anlotinib inhibiting the phosphorylation level of VEGFR, Janus Kinase 2 (JAK2), and Signal Transducer and Activator of Transcription 3 (STAT3). Combination chemotherapy of anlotinib with cisplatin is more sensitive to colorectal cancer. CONCLUSIONS: These findings suggested that anlotinib might benefit colorectal cancer therapy by antagonizing VEGFR/JAK2/STAT3 signaling. Our study may provide new insights into novel molecular therapeutic strategies for colorectal cancer.

HSF1 promotes the viability of islet ß-cells via upregulating SIRPα expression.

OBJECTIVE: Increasing evidence has shown that HSF1 is involved in glycemia regulation, and SIRPα plays a pivotal role in islet ß-cell viability. However, it is still unknown whether SIRPα is associated with HSF1 in regulating the cell viability and cell death of islet ß-cells. MATERIALS AND METHODS: Western blot and qPCR were applied to determine protein and mRNA levels of HSF1 and SIRPα. Cell viability and death were investigated by cell counting kit-8 and trypan blue exclusion assay. Meanwhile, cell apoptosis was analyzed by detecting caspase3 activity. Moreover, luciferase reporter assay was applied to explore the mechanism by which HSF1 transcriptionally upregulated SIRPα expression. RESULTS: Our study reveals that HSF1 expression was lower in islets from T1DM compared to normal mice. We found that overexpression of HSF1 decreased the apoptosis of islet ß-cell lines. Moreover, we demonstrated that overexpression of HSF1 decreased the apoptosis of islet ß-cells through increasing the expression of SIRPα. In terms of mechanism, luciferase reporter assays showed that HSF1 upregulated SIRPα expression by activating its gene promoter region. The binding site (-1809 to -1795) was required for HSF1-induced increase of SIRPα gene promoter activity. CONCLUSIONS: These results indicate that the low expression of HSF1/SIRPα may be one of the mechanisms of islet ß-cell death and targeting HSF1/SIRPα may be a novel strategy for the treatment of T1DM.

Effects of activation of group III metabotropic glutamate receptors on spinal synaptic transmission in a rat model of neuropathic pain.

Chronic neuropathic pain remains an unmet clinical problem because it is often resistant to conventional analgesics. Metabotropic glutamate receptors (mGluRs) are involved in nociceptive processing at the spinal level, but their functions in neuropathic pain are not fully known. In this study, we investigated the role of group III mGluRs in the control of spinal excitatory and inhibitory synaptic transmission in a rat model of neuropathic pain induced by L5/L6 spinal nerve ligation. Whole-cell recording of lamina II neurons was performed in spinal cord slices from control and nerve-ligated rats. The baseline amplitude of glutamatergic EPSCs evoked from primary afferents was significantly larger in nerve-injured rats than in control rats. However, the baseline frequency of GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) was much lower in nerve-injured rats than in control rats. The group III mGluR agonist l(+)-2-amino-4-phosphonbutyric acid (l-AP4) produced a greater inhibition of the amplitude of monosynaptic and polysynaptic evoked EPSCs in nerve-injured rats than in control rats. l-AP4 inhibited the frequency of miniature EPSCs in 66.7% of neurons in control rats but its inhibitory effect was observed in all neurons tested in nerve-injured rats. Furthermore, l-AP4 similarly inhibited the frequency of GABAergic and glycinergic IPSCs in control and nerve-injured rats. Our study suggests that spinal nerve injury augments glutamatergic input from primary afferents but decreases GABAergic and glycinergic input to spinal dorsal horn neurons. Activation of group III mGluRs attenuates glutamatergic input from primary afferents in nerve-injured rats, which could explain the antinociceptive effect of group III mGluR agonists on neuropathic pain.

Signaling mechanisms mediating muscarinic enhancement of GABAergic synaptic transmission in the spinal cord.

Activation of muscarinic acetylcholine receptors (mAChRs) inhibits spinal nociceptive transmission by potentiation of GABAergic tone through M(2), M(3), and M(4) subtypes. To study the signaling mechanisms involved in this unique mAChR action, GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of lamina II neurons were recorded using whole-cell patch clamp techniques in rat spinal cord slices. The mAChR agonist oxotremorine-M caused a profound increase in the frequency of GABAergic sIPSCs, which was abolished in the Ca(2+)-free solution. Inhibition of voltage-gated Ca(2+) channels with Cd(2+) and Ni(2+) largely reduced the effect of oxotremorine-M on sIPSCs. Blocking nonselective cation channels (NSCCs) with SKF96365 or 2-APB also largely attenuated the effect of oxotremorine-M. However, the KCNQ channel blocker XE991 and the adenylyl cyclase inhibitor MDL12330A had no significant effect on oxotremorine-M-induced increases in sIPSCs. Furthermore, the phosphoinositide-3-kinase (PI3K) inhibitor wortmannin or LY294002 significantly reduced the potentiating effect of oxotremorine-M on sIPSCs. In the spinal cord in which the M(3) subtype was specifically knocked down by intrathecal small interfering RNA (siRNA) treatment, SKF96365 and wortmannin still significantly attenuated the effect of oxotremorine-M. In contrast, SKF96365 and wortmannin both failed to alter the effect of oxotremorine-M on sIPSCs when the M(2)/M(4) mAChRs were blocked. Therefore, our study provides new evidence that activation of mAChRs increases synaptic GABA release through Ca(2+) influx and voltage-gated Ca(2+) channels. The PI3K-NSCC signaling cascade is primarily involved in the excitation of GABAergic interneurons by the M(2)/M(4) mAChRs in the spinal dorsal horn.

Macrophage infiltrates with high levels of Toll-like receptor 4 expression in white adipose tissues of male Chinese.

BACKGROUND AND AIMS: Macrophages and Toll-like receptor 4 (TLR4) are involved in the inflammatory process of adipogenesis. This study aimed to characterize macrophage infiltrates and the associated TLR4 expression in different locations of white adipose tissues (WAT) of male Chinese and determine their correlations to adipocyte hypertrophy and hyperplasia. METHODS AND RESULTS: A total of 30 men, who were lean, overweight or with type 2 diabetes (T2D), were recruited. Their abdominal omental WAT (oWAT) and subcutaneous WAT (scWAT) were obtained. The contents of macrophages in oWAT and scWAT were quantified using anti-CD68 staining. The levels of TLR4 expression were analyzed by western blot assays and the adipocyte size was quantified, followed by linear regression analysis. Significantly higher numbers of macrophages (24.4+/-3.2 vs 6.1+/-2.9, p<0.001), associated with higher levels of TLR4 expression (0.59+/-0.19 vs 0.20+/-0.03, p<0.001), were observed in oWAT, as compared with that in scWAT. Furthermore, the levels of macrophage infiltrates and TLR4 expression in oWAT of subjects who were overweight or/and have T2D were significantly higher than that in the lean group. The average adipocyte diameters and cross-sectional areas in oWAT of subjects who were overweight were significantly greater than those in the lean group (p=0.003 and p=0.04, respectively). Importantly, the numbers of macrophage infiltrates were positively correlated to the levels of TLR4 expression, the sizes of adipocytes, the levels of body mass index and C-reactive protein, respectively. CONCLUSION: Our data suggest that macrophage-related TLR4 expression and inflammation contribute to the development of adipocyte hypertrophy in male Chinese.

Recent Rice stripe virus Epidemics in Zhejiang Province, China, and Experiments on Sowing Date, Disease-Yield Loss Relationships, and Seedling Susceptibility.

Rice stripe virus, transmitted by the small brown planthopper Laodelphax striatellus, has recently reemerged as a major disease in Zhejiang province, eastern China. Intensive surveys during 2003 to 2006 demonstrated how the disease has spread rapidly from the northern to central and eastern regions with increasing incidence each year. In bioassays, the highest proportions of viruliferous vectors were from regions where the disease was most severe. The greatest disease incidence was in the earliest sown plants, and substantial control could be achieved by delaying planting from late May to mid-June. In experiments where different proportions of infected plants were established (by inoculation or varying the sowing date), average yield losses were 0.8% for every 1% increase in disease incidence. In inoculation experiments, young seedlings, particularly those at the three- to five-leaf stage, were the most susceptible, whereas ≤1% of plants inoculated at or after the elongation stage developed symptoms. Recent epidemics appear to have resulted from large populations of viruliferous vectors colonizing rice seedlings at the most susceptible stage. This is probably because of changes in cropping practice, recent warmer winters in Zhejiang province, and the development of resistance or tolerance to the insecticides widely used (triazophos, synthetic pyrethroids, and Imidacloprid).

microRNA-199a-5p mediates high glucose-induced reactive oxygen species production and apoptosis in INS-1 pancreatic ß-cells by targeting SIRT1.

OBJECTIVE: Hyperglycemia-induced pancreatic ß-cell loss is a pathologic hallmark of type 2 diabetes mellitus (T2DM). This study was conducted to clarify the function of microRNA (miR)-199a-5p in high glucose-elicited ß-cell toxicity and associated molecular mechanisms. MATERIALS AND METHODS: INS-1 rat pancreatic ß-cells were cultured under normal (11 mM) or high (30 mM) glucose for 16-72 h and examined for miR-199a-5p expression. Gain and loss-of-function studies were performed to determine the role of miR-199a-5p in high glucose-induced apoptosis and reactive oxygen species (ROS) production. Additionally, the involvement of SIRT1 in the action of miR-199a-5p was checked. RESULTS: High glucose caused a significant upregulation of miR-199a-5p in INS-1 cells compared to cells under normal glucose conditions. Pre-transfection with anti-miR-199a-5p inhibitors prevented the reduction in cell viability and inhibited ROS generation in INS-1 cells after high glucose treatment. In contrast, overexpression of miR-199a-5p significantly reduced cell viability and promoted apoptosis and ROS formation in INS-1 cells, which was coupled with a downregulation of SIRT1. Knockdown of SIRT1 led to apoptotic death in INS-1 cells. Moreover, enforced expression of SIRT1 blocked miR-199a-5p-induced ROS generation and attenuated high glucose-mediated apoptosis in INS-1 cells. CONCLUSIONS: miR-199a-5p is upregulated in pancreatic ß-cells in response to high glucose and promotes apoptosis and ROS generation by targeting SIRT1. The miR-199a-5p/SIRT1 axis may represent a promising target for the treatment of T2DM.

Breast cancer metastasis suppressor 1 (BRMS1) suppresses prostate cancer progression by inducing apoptosis and regulating invasion.

OBJECTIVE: Breast cancer metastasis suppressor 1 (BRMS1) was originally identified as a metastasis suppressor gene in human breast cancer. MATERIALS AND METHODS: A recent study has established an association between BRMS1 with the clinical stage and different pathology grades of prostate cancer. However, whether BRMS1 plays a role in prostate cancer has not been elucidated. RESULTS: In this study, we found that overexpression of BRMS1 in PC-3 cells induced apoptosis and inhibited invasion; moreover, we found that overexpression BRMS1 was associated with the suppressed expression of EMMPRIN. CONCLUSIONS: Taken together, our results show that BRMS1 may suppress progression and metastasis of prostate cancer through modulating EMMPRIN expression.

Expressions and significances of TTF-1 and PTEN in early endometrial cancer.

OBJECTIVE: To analyze the expressions and significances of TTF-1 (Thyroid transcription factor-1) and PTEN (Phosphatase and tensin homolog) in early endometrial cancer. PATIENTS AND METHODS: 41 patients with endometrial cancer, 38 patients with proliferative endometrium and 13 patients with normal endometrium, were selected. The fluorescence quantitative PCR (polymerase chain reaction) was used to detect the expression levels of TFF-1 and PTEN mRNAs (Messenger ribonucleic acids) in the above three endometria, and their relations with clinical pathological characteristics were analyzed. The RT-PCR (reverse transcription-polymerase chain reaction) was employed to detect the expression levels of miR-135b, miR-125b and Snail mRNAs in the three endometria, and their correlations with the expressions of TTF-1 and PTEN mRNAs, were analyzed. RESULTS: The expression levels of TFF-1 and PTEN mRNAs in endometrial cancer tissues were significantly lower than those in the other two groups, while those in normal endometrium tissues were the highest, and the differences were statistically significant (p < 0.05). There were no significant differences in the menstruation status and the expression levels of TFF-1 and PTEN mRNAs between adenocarcinoma and squamous carcinoma (p > 0.05). With the increase of FIGO (International Federation of Gynecology and Obstetrics) stage and depth of invasion, as well as the metastasis of pelvic lymph nodes, the expression levels of TFF-1 and PTEN mRNAs were significantly decreased, and the differences were statistically significant (p < 0.05). The expression level of miR-135b mRNA in endometrial cancer was significantly higher than that in the other two groups, while that in normal endometrium was the lowest. The expression levels of miR-125b and Snail mRNAs were significantly lower than those in the other two groups, while those in normal endometrium were the highest; the differences were statistically significant (p < 0.05). Expression levels of TTF-1 and PTEN mRNAs were negatively correlated with the expression level of miR-135b mRNA, and positively associated with the expression levels of miR-125b and Snail mRNAs (p < 0.05). The results from the ROC (Receiver Operating Characteristic) model showed that, for the diagnosis of endometrial cancer with TTF-1 mRNA, the sensitivity was 86.5%, the specificity was 84.2%, the accuracy (area under curve - AUC) was 0.823, 95% CI (confidence intervals) = 0.762-0.921, p = 0.012. For the diagnosis of endometrial cancer with PTEN mRNA, the sensitivity was 85.3%, the specificity was 83.6%, the accuracy was 0.842, 95% CI = 0.785-0.936, p = 0.010. CONCLUSIONS: TTF-1 and PTEN can be used as molecular markers for the early diagnosis of endometrial cancer, which are closely related to clinical features and may affect tumor progression by regulating the proliferation activity of tumor cells.

Expression and clinical significance of aquaporin-1 and ET-1 in urine of children with congenital hydronephrosis.

OBJECTIVE: Congenital hydronephrosis is induced by congenital obstruction of uretero pelvic junction, bladder vesicoureteral reflux, posterior urethral valve, stricture of ureter end and ureterocyst, which is extremely apt to cause end-stage renal failure in children. It becomes significant to explore the expression profile and clinical significance of aquaporin-1 (AQP-1) and ET-1 (endothelin-1) in the urine of children with congenital hydronephrosis. PATIENTS AND METHODS: 80 cases of children with congenital hydronephrosis were selected to be the observation group and another 40 cases of children with other diseases were served as control group. Pre-operative morning urine, intra-operative renal pelvis urine and morning urine at the 7th day after the operation of all the children were collected for the detection of the level of ET-1, Cr level and AQP1 in the urine. Urine various indexes of different diseases stages in children of both groups were compared. RESULTS: There was no significant difference between children with mild and children in control group (p > 0.05). In the observation group, the AQP-1 level during the operation was significantly lower than that before operation, but it was significantly higher in post-operation than that during the operation, which was still lower than that in control group (p < 0.05). Urine ET-1 level in observation group and its positive rate were significantly higher than that in control group (p < 0.05). Serum stress indexes in each stage of the observation group were significantly higher than that in control group (p < 0.05). CONCLUSIONS: The expression levels of urine AQP-1 and ET-1 of children with congenital hydronephrosis were obviously increased. The AQP-1 level during the operation was lower than that before operation. This post-operation level was significantly higher than before the operation. The expression of AQP-1 and ET-1 could be used as important indexes for clinical diagnosis.

Human umbilical cord mesenchymal stem cells ameliorate experimental cirrhosis through activation of keratinocyte growth factor by suppressing microRNA-199.

OBJECTIVE: Keratinocyte growth factor (KGF) has a demonstrated role in the prevention of cirrhosis during liver regeneration. Previous studies have shown that transplantation of human umbilical cord mesenchymal stem cells (HUCMSCs) reduces the development of cirrhosis after liver injury. However, whether KGF may be involved in the underlying molecular mechanisms remains unknown. Here we addressed this question. MATERIALS AND METHODS: We did HUCMSC transplantation in mice that had developed cirrhosis by carbon tetrachloride (CCl4). The effects of UCMSC transplantation on KGF levels and liver damage were examined. The level of a KGF-targeting microRNA, miR-199, was examined. The regulation of KGF by miR-199 was studied by bioinformatics analyses and luciferase reporter assay. RESULTS: HUCMSC transplantation significantly ameliorated the severity of liver fibrosis, reduced portal hypertension and sodium retention that were induced by CCl4. HUCMSC transplantation significantly increased the levels of KGF in the injured liver, seemingly through suppression of miR-199, which targeted 3'-UTR of KGF mRNA to inhibit its protein translation. CONCLUSIONS: HUCMSCs may ameliorate cirrhosis through activation of KGF by suppressing miR-199.

Etiology of renal artery stenosis in 2047 patients: a single-center retrospective analysis during a 15-year period in China.

Systematic investigation with large sample size of the distribution of etiologies of renal artery stenosis (RAS) is scant in both Western countries and China. We retrospectively analyzed the etiology of RAS in 2047 consecutive inpatients diagnosed with RAS for hypertension at Fuwai Hospital between 1999 and 2014. The number of patients with atherosclerosis was 1668 (81.5%), 259 (12.7%) with Takayasu's arteritis (TA), 86 (4.2%) with fibromuscular dysplasia (FMD), 34 (1.6%) with other causes. There was an obvious increase with age in the proportion of atherosclerotic RAS (P<0.001). In patients aged ⩽40 years (n=319) the predominant etiology of RAS was TA (60.5%), followed by FMD (24.8%). In patients aged >40 years (n=1728) the major cause of RAS was atherosclerosis (94.7%), followed by TA (3.8%).The proportion of TA and FMD in female patients was significantly higher than that in male patients (P<0.001). In female patients aged ⩽40 years (n=215), the top three etiologies of RAS were TA (68.4%), FMD (27.9%) and atherosclerosis (1.4%). The present analysis showed that atherosclerosis, TA and FMD were sequentially the top three causes of RAS in the National Center of China. Age and gender had a significant effect on the distribution of etiologies of RAS.

Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature.

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.

Milan criteria, University of California, San Francisco, criteria, and model for end-stage liver disease score as predictors of salvage liver transplantation.

The selection criteria for salvage liver transplantation (SLT) candidates have not been previously established. A global analysis for the association between the criteria and prognosis is required. All of the adult patients who underwent liver transplantation with a diagnosis of hepatocellular carcinoma (HCC) from January 1, 2000, to December 31, 2011, were retrospectively analyzed. A total of 1,554 cases were involved, including 1,392 primary liver transplantation (PLT) and 162 SLT cases. All the cases were classified into 3 groups according to the Milan criteria combined with the University of California, San Francisco (UCSF), criteria, and significant differences were found between the 2 groups. The overall graft survival rate was lower in all cases of SLT than in PLT (P = .030). Within the Milan criteria, no significant difference in the graft survival rate was found between PLT and SLT. In a Cox regression analysis, the Model for End-Stage Liver Disease (MELD) score and tumor levels graded according to the Milan/UCSF criteria were found to be independent risk factors for the graft survival rate. Receiver operating characteristic (ROC) curves were generated by the fatality risk values calculated by means of the Cox model and the 1-year graft survival rates of all the patients and of the SLT patients. The areas under the ROC curves were 0.922 and 0.935, respectively. Compared with PLT, the global graft survival rate of SLT was compromised. The MELD score and Milan/UCSF criteria were effective in predicting the prognosis of PLT and SLT. Therefore, when the recurrent lesions of HCC are within the Milan criteria, SLT can be performed with a good prognosis.