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Background: Although the primary malignant spleen tumor is relatively rare, lymphoma is the most common splenic malignancy. It can have quite different clinical manifestations that usually lead to relatively poor outcomes, and thus early and accurate diagnosis are of utmost importance., Case Presentation: The present study reports a case of a 67-year-old female with high fever, abnormal spleen (diagnosed by PET/CT) and no obvious lymph node enlargement. After being subjected to splenectomy, the patient was diagnosed with splenic diffuse large B cell lymphoma coexisting with gastrointestinal stromal tumor in the stomach., Conclusions: To our knowledge, splenic lymphoma accompanied by gastrointestinal stromal tumor in the stomach is rarely reported. This case report discusses the diagnosis and case management of a patient referring to the existing literature.

Aims/introduction: Patients with diabetes frequently develop orthostatic hypotension (OH). The present study was designed to examine the relationship of blood pressure (BP) circadian rhythms and outcomes in diabetes with OH., Materials and Methods: In the present study, 173 inpatients with type 2 diabetes were enrolled. Patients were divided into an OH group and a non-OH group according to the BP changes detected in the supine and standing position. Then, 24-h ambulatory BP was monitored. Patients were followed up for an average of 45 ± 10 months post-discharge. Outcomes - death and major adverse cardiac and cerebrovascular events, including heart failure, myocardial infarction and stroke - were recorded., Results: There were 61 patients (35.26%) in the OH group and 112 patients (64.74%) in the non-OH group. In the OH group, the night-time systolic BP and night-time diastolic BP were higher, the blood BP rhythms were predominantly of the riser type (67.21%). OH was as an independent marker of riser type circadian rhythm (adjusted odds ratio 4.532, 95% confidence interval 2.579-7.966). In the OH group, the incidence rates of mortality, and major adverse cardiac and cerebrovascular events were increased significantly compared with those in the non-OH group (11.48 vs 2.68%, P = 0.014; 37.70 vs 8.93%, P < 0.01)., Conclusions: In patients who had type 2 diabetes diagnosed with OH, the BP circadian rhythm usually showed riser patterns, and they had increased rates of mortality, and major adverse cardiac and cerebrovascular events., (© 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The effects of long non-coding RNAs (lncRNAs) on hepatocellular carcinoma (HCC) remain largely unclear. In this study, we identified an interferon (IFN)-γ-induced LncRNA, LncRNA00364, in HCC by microarray. LncRNA00364 displays lower expression in HCC tumor samples compared to paired normal controls. Overexpression of LncRNA00364 inhibits cell proliferation, G1/S cell cycle progression and promotes apoptosis in HCC cell lines. Consistently, LncRNA00364 overexpression leads to decreased HCC tumor formation in vivo . Mechanistically, LncRNA00364 specifically binds with STAT3, resulting in inhibition of STAT3 phosphorylation and therefore leads to upregulation of IFIT2. In a clinical setting, LncRNA00364 shows an independent prognostic indicator for overall survival and cumulative recurrence in HCC patients, and correlates with IFIT2. Therefore, our study provides new insights into a novel therapeutic avenue targeting the LncRNA00364 signaling axis in HCC., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objectives: In this study, we aimed at investigating the preoperatively available prognostic factors for intrahepatic cholangiocarcinoma (ICC) patients and proposing a new preoperative prognostic scoring system for ICC., Methods: A total of 246 consecutive ICC patients who underwent curative hepatectomy were enrolled retrospectively and were randomly divided into training (n=164) and validation cohorts (n=82) at a ratio of 2:1. The prognostic factors were investigated in both cohorts using multivariate Cox's proportional hazards regression model., Results: Multivariate analyses identified that two preoperative factors (serum C-reactive protein (CRP) levels >4.1 mg/l (hazard ratio (HR): 2.75, 95% CI: 1.65-4.73, P<0.001) and carbohydrate antigen 19-9 (CA19-9) levels >300 mg/ml (HR: 3.76, 95% CI: 2.18-6.49)) were independent prognostic factors for postoperative survival in the training cohort. The results were further confirmed in the validation cohort. On the basis of these data, a preoperative prognostic score (PPS) was established by allocating 0 or 1 point to the two factors, respectively. Then, both in the training and validation cohorts, the PPS showed the power to stratify patients into three distinct groups (groups with scores 2, 1, and 0) with significant difference in the risk of postoperative death., Conclusions: A new preoperative scoring system consisting of preoperative CRP and CA19-9 levels could effectively predict postoperative survival of ICC patients.

Aim: The association between parity and rheumatoid arthritis (RA) risk has been investigated, but results are controversial. Thus, our aim was to systematically analyze the effect of number of parity on the risk of RA in women., Methods: Relevant published studies were identified using PubMed and embase databases through 1 April 2016. We pooled the relative risks (RR) and 95% confidence intervals (CI) using random-effects models., Results: In all, 12 studies with a total of 2 497 580 participants and 11 521 RA cases were included. A borderline significant inverse association was observed when we compared parity with nulliparity for RA, with summarized RR = 0.90 (95%CI: 0.79-1.02; I 2  = 58.5%, P heterogeneity  = 0.010). In dose-response analysis, we observed a significant nonlinear (P nonlinearity  = 0.000) relation between parity number and the risk of RA. Compared with null parity, the pooled RR of RA were 0.89 (95%CI: 0.86-0.93), 0.84 (95%CI: 0.79-0.89), 0.85 (95%CI: 0.79-0.90), 0.88 (95%CI: 0.81-0.95), 0.90 (95%CI: 0.83-0.97), 0.92 (95%CI: 0.84-1.02), and 0.94 (95%CI: 0.83-1.07) for 1, 2, 3, 4, 5, 6, and 7 live births, respectively. Subgroup and sensitivity analyses showed similar associations. No publication bias was found., Conclusion: The findings from the current meta-analysis indicate that parity was related to decreased risk of RA. The greatest risk reduction appeared when the parity number reached two. Further studies are warranted to confirm our findings., (© 2017 Japan Society of Obstetrics and Gynecology.)

Background: Percutaneous cervical pedicle screw fixation has been proven to be an effective method of cervical screw instrumentation, which has the advantages of less invasiveness and low blood loss. Emerging evidence has indicated that the cervical spinous process plays an important role in percutaneous spine surgery. However, there is a limited amount of information on the fundamental research of pedicle and its associated imaging parameter measurement. The purpose of this study was to measure the anatomic data of the pedicle screw channel (PSC) using reverse engineering and three-dimensional reconstruction, and also to discuss the three-dimensional relationship between the cervical spinous process and the pedicle screw channel., Methods: Twenty adult subjects (10 males, 10 females, age range 19-46 years) were studied using the method of three-dimensional CT reconstruction and reverse engineering. The centrum was divided into 10 equal parts from front to back. The bisectors were defined as borderline depths of the centrum, from front to back, 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 0% of borderline depths were presented. Then, a 3D coordinate system was constructed to measure all the data, including the radius of the inscribed circle, the length of the PSC, the insertion angle, the distances from entry point to cervical spinous process and skin depth. All the indexes were measured from 70% to 90% borderline depth., Results: The radius of the inscribed circles from C 3 to C 7 at 90% borderline depth were 2.94 ± 0.55 mm, 3.04 ± 0.40 mm, 3.15 ± 0.36 mm, 3.28 ± 0.47 mm, 3.89 ± 0.54 mm, respectively. The lengths of the PSC were between 25 and 32 mm. The insertion angles for 70% to 90% borderline depth were 28.33°, 34.28°, 37.92°, respectively. The relationship between the PSC and spinous process was measured as the distance from the entry point to the end of the spinous process, which were, respectively, 26.91 mm, 28.18 mm, 30.03 mm, 35.67 mm, 41.99 mm from C 3 to C 7 .The distance from the skin to the entry point of C 3-7 increased gradually., Conclusions: The measurements of this study could provide detailed information for percutaneous cervical screw fixation. The data of the relationship between the cervical spinous process and the pedicle screw channel present valuable technical information for the design, optimization and clinical application of the aiming device for percutaneous cervical pedicle screw fixation. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background & Aims: Identifying target genetic mutations in hepatocellular carcinoma (HCC) for therapy is made challenging by intratumoral heterogeneity. Circulating cell-free DNAs (cfDNA) may contain a more complete mutational spectrum compared to a single tumor sample. This study aimed to identify the most efficient strategy to identify all the mutations within heterogeneous HCCs., Methods: Whole exome sequencing (WES) and targeted deep sequencing (TDS) were carried out in 32 multi-regional tumor samples from five patients. Matched preoperative cfDNAs were sequenced accordingly. Intratumoral heterogeneity was measured using the average percentage of non-ubiquitous mutations (present in parts of tumor regions). Profiling efficiencies of single tumor specimen and cfDNA were compared. The strategy with the highest performance was used to screen for actionable mutations., Results: Variable levels of heterogeneity with branched and parallel evolution patterns were observed. The heterogeneity decreased at higher sequencing depth of TDS compared to measurements by WES (28.1% vs. 34.9%, p<0.01) but remained unchanged when additional samples were analyzed. TDS of single tumor specimen identified an average of 70% of the total mutations from multi-regional tissues. Although genome profiling efficiency of cfDNA increased with sequencing depth, an average of 47.2% total mutations were identified using TDS, suggesting that tissue samples outperformed it. TDS of single tumor specimen in 66 patients and cfDNAs in four unresectable HCCs showed that 38.6% (26/66 and 1/4) of patients carried mutations that were potential therapeutic targets., Conclusions: TDS of single tumor specimen could identify actionable mutations targets for therapy in HCC. cfDNA may serve as secondary alternative in profiling HCC genome., Lay Summary: Targeted deep sequencing of single tumor specimen is a more efficient method to identify mutations in hepatocellular carcinoma made from mixed subtypes compared to circulating cell-free DNA in blood. cfDNA may serve as secondary alternative in profiling HCC genome. Identifying mutations may help clinicians choose targeted therapy for better individual treatments., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Chronic spontaneous urticaria (CSU) is a common skin disease characterized by recurrent itchy wheals with or without angioedema that lasts longer than 6 weeks. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that plays critical roles in angiogenesis and endothelial permeability., Objective: To investigate serum levels of soluble VE (sVE)-cadherin in patients with CSU., Methods: Serum levels of sVE-cadherin in patients with CSU, patients with atopic dermatitis, and healthy controls were determined by enzyme-linked immunosorbent assay. In addition, changes in sVE-cadherin serum levels were compared in patients with CSU before and after H 1 antihistamine treatment. Furthermore, the effects of histamine on sVE-cadherin release by HMEC-1 cells were determined by enzyme-linked immunosorbent assay. The inhibition effects of H 1 antihistamine and H 2 antihistamine on sVE-cadherin release, VE-cadherin phosphorylation, and VE-cadherin disruption were evaluated in histamine-treated HMEC-1 cells by western blot and immunofluorescence., Results: Serum levels of sVE-cadherin in patients with CSU were significantly higher than those in patients with atopic dermatitis and healthy controls. Serum sVE-cadherin levels in patients with CSU were correlated with the severity of CSU according to Urticaria Activity Scores. Furthermore, serum sVE-cadherin levels in patients with CSU at pretreatment decreased after H 1 antihistamine treatment. In addition, histamine markedly induced sVE-cadherin release in HMEC-1 cells. Moreover, H 1 antihistamine, but not H 2 antihistamine, significantly inhibited sVE-cadherin release in histamine-treated HMEC-1 cells. Western blot data showed that histamine induced phosphorylation of VE-cadherin in HMEC-1 cells, which was blocked by H 1 antihistamine., Conclusion: The present data showed serum levels of sVE-cadherin are increased in patients with CSU. Histamine-induced sVE-cadherin release from endothelial cells could play a role in the pathogenesis of CSU., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background. Yiqi Huayu Jiedu Decoction (YHJD) can obviously improve the quality of life of those patients with gastric cancer and prolong their survival. Methods . In vitro experiments, we observe YHJD's effect on the cells' proliferation by MTT assay. Cell adhesion assay, wound-healing assay, and Transwell invasion assay serve to detect its influence on cells' adhesion, migration, and invasion, respectively. Inhibitor (10  μ M/L of SB431542) and activator (10 ng/mL of TGF- β ) of TGF- β /Smad pathway were used to estimate whether YHJD's impact on the biological behavior of gastric cancer cells was related to TGF- β /Smad pathway. In in vivo studies, YHJD was administered to the nude mice transplanted with gastric cancer to observe its effect on the tumor. Western blotting and immunohistochemical assay were used to test relevant cytokines of TGF- β /Smad pathway and epithelial-mesenchymal transition (EMT) in MGC-803 cells and the tumor bearing nude mice. Results. YHJD inhibited proliferation, adhesion, migration, and invasion of MGC-803 gastric cancer cells in vitro. In in vivo studies, YHJD reduced the volume of the transplanted tumors. It also enhanced the expression of E-cadherin and decreased the levels of N-cadherin, TGF- β , Snail, and Slug in both MGC-803 cells and the transplanted tumor by western blot assay. The immunohistochemical assay revealed that YHJD raised E-cadherin in the tumors of the mice; on the contrary, the expression of N-cadherin, Twist, vimentin, TGF- β R I, p-Smad2, p-Smad3, Snail, and Slug reduced. Conclusion . YHJD can effectively inhibit the invasion and metastasis of gastric cancer cells. The mechanism may be related to TGF- β /Smad pathway.

The HLA-I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The loss of surface expression of HLA-I molecules is particularly important as this enables tumor cells to evade recognition and lysis by cytotoxic T-lymphocytes. Transcriptional control of the APM genes is regulated by the nuclear factor kappa B (NF-κB). BCRFl is an Epstein-Barr virus homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). vIL-10 shares many immunosuppressive effects with hIL-10 but lacks the immunostimulatory effect of hIL-10. The aim of this study was to assess whether vIL-10 inhibits APM components (TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I) through the NF-κB signaling pathway in nasopharyngeal carcinoma. This work demonstrated that vIL-10 inhibited NF-κB activation by blocking IKK phosphorylation and promoting the expression of IKB. TNF-α treatment led to a strong translocation of NF-κB p65, whereas pretreatment with vIL-10 before TNF-α treatment blocked NF-κB p65 translocation. vIL-10 also inhibited TNF-α-induced DNA-binding of NF-κB p65 in the nucleus. Furthermore, chromatin immunoprecipitation analysis demonstrated that NF-κB p65 could bind to the TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I gene promoters, and after TNF-α stimulation, the down-regulation of TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I transcription by vIL-10 correlated with the suppression of NF-κB in CNE-2 cells. Surprisingly, vIL-10 inhibits only TAP-1 and LMP-7 transcription in CNE-1 cells. Taken together, these results suggest that the inhibition of NF-κB activity may be an important mechanism for vIL-10 suppression of APM (TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I) gene transcription in CNE-2 cells.

Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7(+) cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7(+) mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7(+) cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7(+) cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7(+) mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P < 0.001, r = 0.391). High density of CCR7(+) mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P < 0.05). Survival analyses revealed that increased number of CCR7(+) mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7(+) mononuclear cells featured a naive Treg-like phenotype (CD45RA(+)CD25(+)FOXP3(+)) and possessed tumor-promoting potential by producing TGF-β1. Moreover, CCR7(+) cells were also composed of several immunocytes, a third of which were CD8(+) T cells. CCR7(+) Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1.

Aim: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide (APS) against experimental colitis., Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colitis was induced with 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The rats with colitis were treated with 400 mg/kg of APS for 7 d. The therapeutic effect was evaluated by colonic weight, weight index of the colon, colonic length, and macroscopic and histological scores. The levels of regulatory T (Treg) cells in Peyer's patches were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed using enzyme-linked immunosorbent assay. The expression of related orphan receptor-γt (ROR-γt), IL-23 and STAT-5a was measured by Western blot., Results: After 7-d treatment with APS, the weight index of the colon, colonic weight, macroscopical and histological scores were decreased, while the colonic length was increased compared with the model group. The expression of interleukin (IL)-2, IL-6, IL-17, IL-23 and ROR-γt in the colonic tissues was down-regulated, but Treg cells in Peyer's patches, TGF-β and STAT5a in the colonic tissues were up-regulated., Conclusion: APS effectively ameliorates TNBS-induced experimental colitis in rats, probably through restoring the number of Treg cells, and inhibiting IL-17 levels in Peyer's patches.

BACKGROUND Impaired renal function is common among older patients. Deficiency of vitamin D is a frequent phenomenon among patients with impaired renal function, who are likely to develop cardiovascular diseases. This study aimed to explore the association of 25 (OH) D levels with left ventricular mass and arterial stiffness in older patients with impaired renal function. MATERIAL AND METHODS Based on their admission estimate glomerular filtration rate (eGFR), 273 inpatients (≥65 years) were allocated into a normal eGFR group (≥60 ml/min) and an impaired eGFR group (<60 ml/min). The 25 (OH) D levels were measured and the left ventricular mass index (LVMI) was estimated. Pulse wave velocity (PWV) was used to explore arterial stiffness. RESULTS The 25 (OH) D levels of patients in the impaired eGFR group were significantly lower than in the normal eGFR group [(11.92±6.01) μg/L vs. (18.14±8.07) μg/L, p<0.05). LVMI and PWV were both significantly higher in the impaired eGFR group than in the normal eGFR group [(104.89±33.50) g/m2 vs. (92.95±18.95) g/m2, P<0.05; (15.99±3.10) m/s vs. (13.62±2.90) m/s, P<0.05]. After adjusting for age, sex, eGFR, cardiovascular risk factors, serum calcium, and iPTH levels, the inverse association between LVMI and 25 (OH) D, PWV, and 25 (OH) D were statistically significant. CONCLUSIONS Vitamin D level is lower in older patients with impaired renal function. Lower vitamin D levels were correlated with higher left ventricular mass and increased arterial stiffness in older patients.

Objective: To study the clinical and pathological characteristics of sporadic cutaneous infections due to nontuberculous mycobacteria (NTM), and investigate the diagnostic criteria and therapeutic principal., Methods: Totally 37 cases of sporadic cutaneous infections due to NTM were confirmed in the Department of Dermatology, Peking University People's Hospital from January 2000 to March 2014. The microbiologic and clinical data were reviewed, and their skin biopsy specimens were reassessed., Results: Of all the 37 patients, 30 cases were Mycobacterium marinum infection, 6 were Mycobacterium abscessus infection, and one was Mycobacterium chelonea and Mycobacterium fortuitum infection. Identification of mycobacterial species by analysis of hsp65 gene in tissue DNA was more sensitive than traditional bacterial culture. The most common risk factors were traumatic injuries (21 of 37) and aquarium or fish-related job (21 of 37). One case of Mycobacterium abscessus infection occurred after autologous fat filling. Nodule and plaque were most common lesions in Mycobacterium marinum infection. Twenty-four of the 30 cases of Mycobacterium marinum infection presented with multiple lesions or sporotrichoid spread lesions. Ulceration, papules, abscess, and purulent discharge were observed in cases of Mycobacterium abscessus infection. Infective granuloma was most common histopathological appearance. For the treatment of Mycobacterium marinum infection, rifampin, ethambutol, and clarithromycin were commonly used (combination of two antibiotics, or three antibiotics), with the cure rate 90.00%. Four of the six Mycobacterium abscessus infections cases were cured, and one patient died., Conclusion: The most common species of sporadic cutaneous infections due to NTM is Mycobacterium marinum. Traumatic injuries, aquarium or fish-related job, and cosmetic surgeries are common risk factors. Mycobacterium marinum infection often presents with nodules, plaques, and sometimes sporotrichoid spread lesions. Lesions of Mycobacterium abscessus infection may vary. Pathological changes were not species specific, final diagnosis must be made depending on the identification of the microorganism. For the treatment of Mycobacterium marinum infection, excellent outcomes can be achieved by the combination of rifampin and ethambutol, and the combination of clarithromycin and rifampin or ethambutoland. Treatment regimens of Mycobacterium abscessus infection should be decided according to the results of antibiotic susceptibility testing.

Acute ischemic stroke (AIS) has become a serious health problem in many countries because of its poor outcome and worsening epidemic trend. Early identification of genetic risk factors and physiological indicators for stroke occurrence may help to reduce the incidence of stroke. Therefore, we conducted a case-control study including 50 AIS patients and 50 healthy individuals from a Chinese population to explore the association between AIS and patient complete blood profiles and the association between AIS and the genetic polymorphism K469E in intercellular adhesion molecule-1 (ICAM-1). Compared to the control group, AIS patients showed a high percentage of mononuclear cells, low platelet count, low ratio of platelet to lymphocyte count, high frequency of the 469K allele, and low frequency of the 469E allele. White blood cell count, percentage of neutrophils, percentage of lymphatic cells, platelet distribution width, mean platelet volume, and platelet hematocrit levels showed no significant differences between the 2 groups and between different genotypes. Our results suggested an association of elevated levels of mononuclear cells and reduced platelet count with higher AIS risk. Our results also supported the hypothesis that the KK genotype at the K469E locus in ICAM-1 is a risk factor for AIS.

β-Asarone is the main volatile oil of Chinese herb Rhizoma Acori Tatarinowii. It exhibits a wide range of biological activities in many human organs. However, few studies have investigated the effect of β-asarone on gastric cancer. The present study investigated the effect of β-asarone on the proliferation and apoptosis of three types of differentiated human gastric cancer cell lines (SGC-7901, BGC-823 and MKN-28) in vitro as well as the related molecular mechanisms. Methyl thiazolyl tetrazolium assay, Annexin V/PI double staining, immunofluorescence test and transmission electron microscopy all confirmed that β-asarone had an obvious dose-dependent inhibitive effect on the proliferation of human gastric cancer cells and induced apoptosis of the cell lines. Transwell invasion, wound-healing and matrix‑cell adhesion experiments confirmed that β-asarone inhibited the invasion, migration and adhesion of human gastric cancer BGC-823 cells. Quantitative real-time PCR and western blotting found that β-asarone significantly activated caspase-3, caspase-8, caspase-9, Bax, Bak and suppressed Bcl-2, Bcl-xL and survivin activity. Moreover, β-asarone increased the expression of RECK, E-cadherin and decreased the expression of MMP-2, MMP-9, MMP-14 and N-cadherin. The present study demonstrated that β-asarone effectively inhibits the proliferation of human gastric cancer cells, induces their apoptosis and decreased the invasive, migratory and adhesive abilities.

Background: Tie2-expressing monocytes (TEMs) are found in various tumors, involved in forming tumor blood vessels and expressing several important proangiogenic factors. The goals of this study were to evaluate the value of TEMs in diagnosing and predicting the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)., Methods: Flow cytometry was performed to identify and count TEMs in peripheral blood monocytes from HCC patients (n = 84) receiving hepatectomy, HBV cirrhotic patients (n = 21), benign tumors patients (n = 15) and healthy volunteers (n = 23). Angiopoietin-2 (Ang-2) levels in the plasma were determined by enzyme linked immunosorbent assay. The distribution of TEMs in tumor tissue was observed by immunofluorescence staining. Then we determined the vascular area as a percentage of tumor area (vascular area/tumor area) by immunohistochemical staining. Finally the prognostic significance of TEMs and other clinicopathologic factors was evaluated., Results: Percentage of TEMs in peripheral blood monocytes significantly increased in HCC patients compared with HBV cirrhotic patients and healthy donors (both P< 0.001). However there was no significance in benign liver tumor (P = 0.482). In addition, the percentage of circulating TEMs was positively correlated with plasma Ang-2 concentration (P<0.001, r2 = 0.294) and vascular area/tumor area (P<0.001, r2 = 0.126). Furthermore the percentage of intratumoral TEMs was significantly higher than that of paratumoral TEMs (P<0.001). Increased circulating TEMs was associated with poor overall survival (P = 0.043) and a shorter time to recurrence (P = 0.041). Multivariate Cox analysis also revealed that the percentage of TEMs in peripheral blood was an independent factor for HCC patients' prognosis., Conclusions: TEMs may promote angiogenesis in HCC regarding the angiopoietin/Tie2 signal pathway. Percentage of TEMs in peripheral blood monocytes may be applied as a biomarker for identifying HBV-related HCC and predicting the prognosis of these patients after resection.

Laggera pterodonta is commonly used for treating influenza in Southwest China, especially in Yunnnan province. The main clinical effects of L. pterodonta include anti-influenza, anti-microbial, anti-inflammatory. To investigate the anti-influenza A (H1N1) virus effect of L. pterodonta, neutralization inhibition and proliferation inhibition tests were performed. MDCK culture method was used to observe the cytopathic effect (CPE) of extracts from L. pterodonta in inhibiting influenza A (H1N1) virus and haemagglutination titre of H1N1 virus in vitro. The culture medium were collected at 24 h, 48 h, 72 h, 96 h, and detected by Real time RT-PCR, in order to compare the effect of different extracts from L. pterodonta on in vitro proliferation of H1N1, virus. The result of neutralization inhibition test showed that hemagglutination titer of ethyl acetate extract were 8 times lower at 72 h; in proliferation inhibition test, hemagglutination titer of ethyl acetate extracts reduced by 2 and 4 times. According to the results of Real time RT-PCR test, the H1N1 inhibition ratio of ethyl acetate extract was 72.5%, while the proliferation inhibition ratio of ethyl acetate extract was 25.3%; as for petroleum ether extracts, the H1N1 inhibition ratio was 60.2%, while the proliferation inhibition ratio was 81.4%. In conclusion, both ethyl acetate extract and petroleum ether extract of L. pterodonta have significant neutralization and direct proliferation inhibition effects on influenza A virus.

Interleukin-9 receptor (IL-9R) overexpression has a pivotal role in human hematological malignancies. However, the expression of IL-9R and its biological role in human solid tumors remains elusive. In the present study, western blot analysis and RT-qPCR were used to determine the expression of IL-9R in hepatocellular carcinoma (HCC) cell lines and tumor tissues. Proliferation, cell cycle, apoptosis and Transwell assays were used to examine the biological role of IL-9R in HCC cells. The results showed that IL-9R and its ligand IL-9 were constitutively expressed in HCC cells and tissues. Moreover, the expression levels of IL-9R and IL-9 were significantly higher in tumor tissues compared to the peritumor liver tissues. Functional experiments suggested that IL-9R significantly promoted HCC cell proliferation, invasion and inhibited apoptosis, possibly by acting through the IL-9/IL-9R axis. After silencing IL-9R, the expression of VEGF, p-p38, p-STAT3 and MMP9, markedly decreased suggesting the potential involvement of these molecules in IL-9R activity. Immunohistochemistry‑based survival analysis revealed that a differential expression of IL-9R in HCC tissue was a significant and independent prognostic factor for survival [HR, 1.66; 95% confidence interval (CI), 1.17-2.36; P=0.005] and recurrence [HR, 1.50; 95%CI, 1.04‑2.17; P=0.03]. In addition, a high IL-9R expression positively and significantly correlated with larger (P=0.012) and advanced tumor stage (P=0.018). The findings indicated that IL-9R was constitutively expressed and exerted a tumor-promoting effect in HCC, whose expression level may be a useful biomarker of tumor invasiveness and patient clinical outcome.

Two new heterodimeric sesquiterpenes, sterhirsutins C (1) and D (2), along with eight new sesquiterpenoid derivatives, sterhirsutins E--L (3-10), were isolated from the culture of Stereum hirsutum. The absolute configuration of 1 was assigned by a single-crystal X-ray diffraction experiment. Compounds 1 and 2 possessed an unprecedented chemical skeleton with a 5/5/5/6/9/4 fused ring system. Compound 10 is the first sesquiterpene coupled with a xanthine moiety. Compounds 1-10 showed cytotoxicity against K562 and HCT116 cell lines. Compound 9 induced autophagy in HeLa cells. Compound 5 inhibited the activation of IFNβ promoter in Sendai virus infected cells.

Chronic renal insufficiency and osteoporosis have become very common among old people in China. Hyperparathyroidism caused by renal insufficiency would result in turbulence of bone metabolism and unbalance between serum calcium and phosphorus. The aim of this study is to investigate the BMD, PTH, CT and 25(OH)-Vit's significance for screening and diagnosing chronic renal insufficiency. In this study, seventy cases with chronic renal insufficiency from Jun. 2010 to Oct. 2013 were selected as the observation group. Meanwhile, another 70 volunteers with normal renal functions were set as the control group. The level of BMD, PTH, CT and 25(OH)-Vit were detected by using ELISA assay. DPX bone density meters (UNIGAMMA X-RAY PLUS) were used for the detection of BMD. The results indicated that BMD levels of the proximal femur (include Troch, Shaft, Total, Neck, Ward) and lumbar vertebra in the observation group were significantly lower while the PTH and CT were significantly higher compared with the control group (P<0.05). A positive correlation was identified between the serum creatinine (Scr) concentrations and CT, PTH, while the correlation with 25(OH)-Vit was considered to be negative. In conclusion, the BMD, PTH, CT, and 25 (OH)-Vit would provide reference in diagnosing and treatment for chronic renal insufficiency. These indexes would be important clinical significance for screening and early diagnose of osteoporosis in these patients.

To investigate the nanoscale mechanical properties of exfoliated cervical epithelial cells from patients to further reveal the pathogenesis of cervical cancer and help early diagnose. Exfoliated cells were collected from nine patients with chronic cervicitis or CIN1(control group), 30 patients with CIN2-3 (CIN 2-3 group), and 13 patients with cervical cancer (cervical cancer group). Stiffness of the cells was determined by atomic force microscope (AFM). Expression of P16INK4A was studied by immunocytochemistry. Environmental scanning electron microscopy was performed to observe the surface microtopography of the exfoliated cells. Young's modulus was measured for cells exfoliated from control and patients with CIN 2-3 and cervical cancer by AFM. The results showed that with increasing cervical lesions, the Young's modulus of the exfoliated cervical cells increased (P < 0.05). The modulus of the exfoliated cells was significantly decreased in the three patients 1 year after the surgery compared with the value before the surgery. Expression of P16INK4A in the exfoliated cells had not been statistically significant. Squamous cells from cervical cancer group had dense and disordered microvilli without clear microridges compare to other groups. The Young's modulus is increased from the control group, to CIN2-3 and cervical cancer groups, suggesting that the stiffness of cervical epithelial cells increases gradually with increasing cervical lesions. The changes in the mechanical properties of the exfoliated cells occur earlier than the changes in cell morphology. Therefore, analysis of mechanical properties of the exfoliated cells may be used to aid early diagnosis of the cancer.

Macrophages are a major component of the leukocyte infiltrate of tumors and play a pivotal role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which macrophages promote HCC invasion are poorly understood. The present study was undertaken to investigate the relationship between macrophages and epithelial-mesenchymal transition (EMT) of HCC. Double-staining immunohistochemistry was used to observe the association between macrophages and EMT markers in clinical HCC samples and it showed that EMT primarily occurred at the edge of the tumor nest, in which infiltrating macrophages were always observed. This indicated that CD68 which is a marker of macrophages, was correlated with EMT marker levels. In addition, after being cultured with macrophages for 24 h, the ability of HCC cells to migrate and invade increased, Snail and N-Cadherin expression was upregulated, and E-Cadherin was downregulated. An antibody array assay was applied to analyze the supernatant of these cultures and it demonstrated IL-8 increased significantly in the macrophage co-culture system. Finally, the role of macrophage-derived IL-8 in the invasion of HCC cells was assayed, and downstream signaling pathways were also investigated. We found that IL-8: i) may induce EMT and promote HCC cell migration and invasion and ii) is associated with the JAK2/STAT3/Snail signaling pathway. Taking together, these findings revealed that macrophages that have infiltrated tumors may induce epithelial-mesenchymal transition of HCC cells via the IL-8 activated JAK2/STAT3/Snail pathway. Thus, this may offer a potential target for developing new HCC therapies.

Objective: To explore the inhibitory effect of cinnamaldehyde on invasion capacities of human breast cancer cell line MDA-MB-435S and its relation with regulating the expression of miR-27a., Methods: The effect of cinnamaldehyde on invasive capacities of MDA-MB-435S was measured by Transwell matrigel invasion assay. The effect of miR-27a expression on invasive capabilities of MDA-MB-435S, the intervention of cinnamaldehyde in the miR-27a expression, and its relation with its effect on invasive capabilities were defected with liposome 2000 transinfection miRNA27a mimics/inhibitors, real time-polymerase chain reaction (Real-time PCR), and Transwell chamber model., Results: Compared with the control group, the number of cells passing through the transwell chamber was more significantly reduced after treated by cinnamaldehyde for 12 h (P < 0.05). The miR-27a expression was 962.07 times and 40% of that of the control group after transinfected by miR-27a mimics and miR-27a inhibitors. After transinfected by miR-27a inhibitors, the number of cells passing through the transwell chamber was more significantly reduced (P < 0.05). The miR-27a expression of MDA-MB-435S was down-regulated by 12-h treatment of cinnamaldehyde (2(-deltaCt) = 0.56, 0.18, 0.18, respectively). The number of miR-27a mimics transinfection pretreated MDA-MB-435S cells passing through the transwell chamber increased more obviously than the number of un-pretreated MDA-MB-435S cells in the control group (P < 0.05)., Conclusions: Cinnamaldehyde could inhibit invasive capabilities of human breast cancer cell line MDA-MB-435S. The over-expression of miR-27a played an important role in the invasive capability of MDA-MB-435S. The inhibition of cinnamaldehyde on invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a.

miRNAs are endogenous 19- to 25-nt noncoding RNAs that can negatively regulate gene expression by directly cleaving target mRNA or by inhibiting its translation. Recent studies have revealed that miRNA plays a significant role in gastric cancer development either as a tumor suppressor gene or oncogene. miRNA-single-nucleotide polymorphisms (SNPs), as a novel class of functional SNPs/polymorphisms, have been identified as candidate biomarkers for gastric cancer susceptibility. On the basis of recent data, the present review summarizes current knowledge of the functional effects of miRNA-SNPs and their importance as candidate gastric cancer biomarkers. Additionally, this review also includes a meta-analysis of the most frequently studied miRNA-SNPs in gastric cancer.

The human leukocyte antigen (HLA)-I and antigen-processing machinery (APM) are crucial in the anti-cancer immune response. The aim of this study was to assess the clinical significance of the APM components [transporters associated with antigen processing (TAP)-1 and -2 and HLA-I] in nasopharyngeal carcinoma (NPC). A total of 58 NPC specimens and 20 healthy specimens used as control were evaluated by semiquantitative immunohistochemistry for three APM components (TAP-1, TAP-2 and HLA-I). The expression of the APM components in NPC was downregulated. CD4 + and CD8 + T cells were measured by flow cytometry and IL-10 was measured by ELISA. The number of CD8 + T cells and the expression of IL-10 were higher and the number of CD4 + T cells was lower in NPC, compared to the controls. The number of CD8 + T cells and the expression of IL-10 were negatively correlated with TAP-1, TAP-2 and HLA-I expression. The clinical phase, lymph node metastasis, distant metastasis, pathological type, TAP-1 expression, TAP-2 expression and HLA-I expression were identified as prognostic factors by the Kaplan-Meier analysis. A multivariate analysis using a Cox regression model indicated that distant metastasis and the downregulation of HLA-I expression were independent unfavorable prognostic factors. In conclusion, the lower expression of HLA-I induced immunosuppression in NPC patients and was associated with a poor prognosis.

To select the adaptive strain of Dengue-III virus D9964 strain (China strain) in KMB17 cells, elucidate the biological characteristics and proliferation kinetics of adapted strain,and to lay the foundation for the development dengue inactivated vaccine and attenuated live vaccine. Dengue-III virus D9964 strain was firstly identified by amplification of the type-specific gene segment of dengue virus by RT-PCR, and the titer was determined. The virus was then subcultured in KMB17 cells with 4.0 MOI till completely adaptive to multiply in cell S. After subculturing in KMB17 cells for 10 consecutive passages, the adapted strain was screened, and purified through plaque. Virus titer of each passage was measured by microtitrimetry, and the antigenicity was detected by IFA. The purified virus RNA extraction of 3-8 day cultured from KMB17 cells, was performed to detect the proliferation kinetics of adapted strain. The results showed that after continuous subculture, dengue-III virus D9964 (China) strain could stably proliferate in KMB17 cells, a highly puried virus adapted strain was obtained through plaque purification. Purified strain maintained the good antigenicity with a highest replicating activity during the 5th-6th day.

Background: Acute rejection (AR) of an organ transplant is a life-threatening complication. Currently, there are few diagnostic biomarkers suitable for clinical application. We aim to determine the potential of plasma microRNAs as biomarkers for AR., Methods: Using rat orthotopic liver transplantation model and microarrays, we compared the difference in the spectrum and levels of microRNAs in both plasma and grafts between AR rats and control. AR-related plasma microRNAs were selected and validated using real-time quantification polymerase chain reaction. Plasma from AR rats with or without tacrolimus treatment was used for microRNA dynamic monitoring. To clarify the origin of AR-related plasma microRNAs, drug-induced liver damage rat model were performed and in situ hybridization was used to detect and localize the specific microRNA in allografts., Results: We found that plasma miR-122, miR-192, and miR-146a was significantly up-regulated when AR occur (fold change>2; P<0.05) and the elevation could be repressed by immunosuppression. In liver injury rat model, up-regulated plasma miR-122 (fold change=22.126; P=0.002) and miR-192 (fold change=8.833; P<0.001) rather than miR-146a (fold change=1.181; P=0.594) were observed. Further study demonstrated that miR-146a was up-regulated by sixfold in microvesicles isolated from AR plasma, whereas miR-122 and miR-192 showed no distinct change. In situ hybridization revealed that the portal areas of the AR graft were brimming with lymphocytes, which showed highly intense staining for miR-146a., Conclusions: Our study provides the global fingerprint of plasma microRNAs in AR rats and suggests that plasma miR-122 and miR-192 reflect liver injury, whereas miR-146a may associate with cellular rejection.

To analyze the genomic sequence characteristics of a human Echovirus 9(ECHO-9) strain isolated from a child with Hand-foot-mouth disease (HFMD) in Kunming, Yunnan Province, in 2010. The complete genome sequence of a human echovirus 9 strain, MSH-KM812-2010 was determined. As other human enterovirus, its genome was 7,424 nucleotides (nts) in length and encoded for 2,203 amino acids (aas). In comparison to other human enteroviruses, MSH-KM812-2010 strain had the highest homology with other strains of human echovirus 9 in structural genomic regions and more homologous to other serotypes of B specie than to human echovirus 9 in non-structural genomic regions. Phylogenetic analysis based on complete VP1 gene revealed that the sequences of human echovirus 9 segregated into three distinct clades A, B and C with more than 15. 0% diversity between clades. All Chinese isolates belonged to the same clade. RDP3 and Blast revealed evident recombination in non-structural genomic regions. This report is the first to, describe the complete genome of the human echovirus 9 in China and provide an overview of the diversity of genetic characteristics of a circulating human echovirus 9.

Background: Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). We explored the relationship between CVD, plasma brain natriuretic peptide (BNP) and copeptin in non-dialysis patients with chronic kidney disease (CKD)., Methods: BNP and copeptin were measured using ELISA in 86 non-dialysis patients with different degrees of CKD and in 20 control patients. The effects of BNP, copeptin levels and other biochemical indices on carotid ultrasound echocardiography and CVD history were determined using correlation analysis., Results: BNP and copeptin levels were significantly higher in the CKD group than in the control group. Both indices increased progressively, in parallel with the decline in glomerular filtration rate (GFR). BNP levels were (184.25 ± 65.18) ng/L in early phase CKD, (975.245 ± 354.09) ng/L in middle phase CKD, and (1463.51 ± 614.92) ng/ml in end phase CKD compared with levels of (101.56 ± 42.76) ng/L in the control group (all P < 0.01). Copeptin levels in the middle phase ((20.36 ± 9.47) pmol/L) and end phase groups ((54.26 ± 18.23) pmol/L were significantly higher than in the control group ((9.21 ± 2.64) pmol/L; both P < 0.01). There was no difference in copeptin levels between early phase CKD ((10.09 ± 5.23) pmol/L) and control patients. Stepwise multiple regression analysis identified GFR, intima-media thickness (IMT), left ventricular hypertrophy (LVH), and previous history of CVD as independent risk factors for elevated BNP and copeptin levels., Conclusion: BNP and copeptin appear to provide sensitive biological markers for the evaluation of atherosclerosis in non-dialysis patients with CKD.

To investigate E6 and E7 gene variations of human papillomavirus type 16 in Yunnan Province, DNA was extracted from 2000 gynecological outpatient samples. For Human papillomavirus (HPV) genotyping, the genomic DNA was first amplified by the consensus MY09/MY11 primer pair followed by nested PCR with GP5+/GP6+ primers, then the PCR products were subjected to direct DNA sequencing. A total of 20 HPV-16 viral DNAs were identified. E6 and E7 genes of HPV-16 viral DNA were then amplified using E6 and E7 specific primers, the PCR products were purified and sequenced. The results showed that mutations were found at nucleotide position 178 of HPV-16 E6 gene in 10 cases,the mutation rate was 50%; For HPV-16 E7 gene, the mutations were found at nucleotide position 647 in 10 cases; the mutation rate was 50%. Phylogenetic analysis showed that Asian (As) variants of HPV-16 were predominated in Yunnan, China. None of African-1, African-2 variants of HPV-16 was found in this region.

Objective: To investigate the role of aeroallergen and food allergen IgE in the pathogenesis of allergen diseases and the relationship between environments, diet, exposed factors and prevalence rate in allergic skin diseases., Methods: Food allergen specific IgE (sIgE) antibody quantitative detection kit was used to detect 142 allergen cases, including artemisia, mixture of epithelia, mixed molds, mixed botany, mixed pollens, willow, poplar, egg, milk, shrimp, mutton, beef, fish, crab, staple foods, etc., Results: Mixed molds and mixed botany were the most common allergens in the allergy dermatitis group (positive rate 60%), eczema group (43%), urticaria group (46%), and allergic purpuria group (71%). The milk revealed that it was the most common allergen in the allerge dermatitis group and eczema group (42% and 56%, respectively). While seafood was the most common allergen in the urticaria group (34%). There was no significant relationship between the exposure and prevalence rate., Conclusion: The detection of allergen IgE provides valuable basis for analysis of the cause in allergic disease.

Background: Glycoprotein non-metastatic melanoma protein B (GPNMB) plays an important role in the pathogenesis of inflammatory and malignant diseases. We investigated the expression of GPNMB in benign and malignant skin diseases., Methods: Tissue microarray was performed in the skin tissues of 102 cases including malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and benign dermatosis. The expression of GPNMB in the tissues was detected by immunohistochemistry. Twenty cases of normal skin and adjacent neoplastic normal skin tissues were selected as controls., Results: GPNMB was positively stained in skin malignancies (38/50, 76%), which was significantly higher than that in the control and the benign skin tissues (P = 0.001 and < 0.001 respectively). GPNMB was positively stained in MM (13/15, 87%) and SCC (16/20, 80%) (P < 0.001). Significant higher expression of GPNMB was observed in patients aged ≥ 65 years than those less than 65 years (n = 11 and n = 9 respectively, P = 0.027). No significant difference of the expression rates was observed between normal control and BCC; however, stronger intensity was detected in the latter. Negative or weak expression was observed in the controls., Conclusion: Over-expression of GPNMB correlated strongly and might play an important role in the pathogenesis of MM and SCC.

Objective: To describe the genetic characterization of complete genome from a human coxsackievirus A16 (CA16) strain KMM08, isolated in Yunnan, China, in 2008., Methods: By using RT-PCR, the seven fragments contained about 1000 nucleotides in the complete genome were sequenced. The sequences were aligned with other enterovirus sequences downloaded from GenBank using Mega 4.1, RDP3 and SimPlot 3.5.1 software., Results: As in other human enterovirus, its genome was 7409 nucleotides in length, encoding for 2193 amino acids. KMM08 strain was closely related to other reference strains of B genotype. In the complete genome, the homology of nucleotide and amino acid among the eleven CA16 isolated strains were 79.0% - 98.2% and 94.5% - 99.3%, respectively. The rates of homology were 79.1% and 94.8% when comparing with that of G10 strains and 78.7% and 89.0% comparing with that of BrCr strains, respectively. SZ-HK08-3 strain had high homology when compared to other strains. In different segment of genome, the rates of homology were 97.0% - 99.0% and 98.0% - 100.0% when compared with that of SZ-HK08-3 strains, respectively. The rates of homology were 74.2% - 86.9% and 90.9% - 97.0% when compared with that of G10 strains, respectively and were 65.0% - 84.9% and 71.0% - 95.2% when compared with that of BrCr strains. Data from Phylogenetic analysis showed that KMM08 belong to genotype B. The putative recombinant Tainan-5079-98 was detected positive with RDP3 and SimPlot 3.5.1., Conclusion: KMM08 strains isolated in Yunnan in 2008 belonged to B genotype of coxsackievirus A16. The possible occurrence of inter-typic recombination would involve EV71 and CA16.

Littoral cell angioma (LCA) is a rare splenic vascular neoplasm that arises from the cells lining the red pulp sinuses. It is deemed to be a benign and incidental lesion. The earliest literature report of littoral cell angioma has been described by Falk. The examination of samples after splenectomy reveals similar pathological change and its change rule is summarized. However, many recent reports have described it to be a malignant tumor with congenital and immunological associations. Generally speaking, the definitive diagnosis can only be made after histological and immunohistochemical profiles. In this case report, we presented the case of a 48-year-old woman with multiple splenic LCAs. Initially, the patient was characteristics of abdominal distension, weakness and fatigue. Multiple hemangiomas were observed in the spleen through abdominal ultrasonic diagnosis. Computed tomography (CT) scans revealed the splenomegaly with multiple round and hyperdense lesions. The patient subsequently underwent splenectomy. Postoperative histological and immunohistochemical studies confirmed the diagnosis of LCA. Based on the presentation of this case, clinical, radiographic and pathological results of LCA as well as recent advances in our understanding of this uncommon splenic lesion were reviewed. LCA is an uncommon splenic tumor diagnosed in patients with or without abdominal discomfort. Only a few case reports regarding this kind of tumor have been published as inconsistent results. In the present paper, we have reported a case of LCA and reviewed the literature.

Glycosylated natural products are reliable platforms for the development of anticancer drugs, simply due to the important features added by sugar appendages to the shape and the stereoelectronic properties of natural scaffolds. Herein, we indentified D11, a novel diphyllin glycoside with acetylated D-quinovose sugar moiety, as a potent topoisomerase IIα (Topo IIα) inhibitior. This peculiar sugar moiety endows D11 an optimal conformation with a high binding affinity for Topo IIα via hydrogen bonding to the entrance of ATPase pocket, thereby helping achieve more potent Topo II inhibition activity compared to the aglycon diphyllin. Further biochemical insights manifested that D11 significantly inhibited Topo IIα ATPase-catalyzed ATP hydrolysis in an ATP-dependent, but a DNA-independent manner. All these underlie the consequent superiority of D11 in the in vitro proliferation inhibition, apoptosis induction and the in vivo remarkable antitumor potency in xenograft mouse model. Moreover, D11 treatment also displayed no obvious body weight loss and other apparent toxicities, indicative of the restricted side effects by the virtue of sugar attachment. Taken together, a defined glycosylated manipulation of diphyllin may be a promising alternative approach in the development of novel Topo II inhibitors.

Background and Aims: Intense research has been performed to identify the genetic risk factors in type 2 diabetes, and a single nucleotide polymorphism (SNP) in SLC30A8 (rs13266634) was reported to be associated with type 2 diabetes mellitus. However, published data on the association between SLC30A8 polymorphism and the risk of type 2 diabetes were inconsistent. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship., Methods and Results: We searched PubMed through October 2009 to identify all relevant papers. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted under an additive genetic model. In the current meta-analysis, we identified a total of 27 groups including 42,609 cases and 69,564 controls. In analyses of the case-control studies by ethnicity, the results indicated that SLC30A8 polymorphism was related to elevate risks of type 2 diabetes both in Europeans (OR=1.15, 95% CI 1.11-1.18, P<0.001) and Asians (OR=1.15, 95% CI 1.11-1.19, P<0.001). Next, we separated hospital-based case-control studies from population-based case-control studies, however, there was no apparent difference between population-based case-control study groups (OR=1.15, 95% CI 1.12-1.17, P<0.001) and hospital-based case-control study groups (OR=1.16, 95% CI 1.07-1.25, P<0.001)., Conclusion: Our present meta-analysis provided evidence that SLC30A8 (rs13266634) C allele carriers could elevate the risk of type 2 diabetes, especially in Europeans and Asians., (Copyright © 2009 Elsevier B.V. All rights reserved.)

Objective: To analyze genetic characterization of the small hydrophobic and hemagglutinin-neuraminidase genes of mumps virus (MuV) isolated in Yunnan province, China from 2007 to 2009., Methods: Fourteen MuV strains were isolated in Yunnan, China from 2007 to 2009. Using RT-PCR, the SH gene fragments contained 316 nucleotides in all strains and HN gene of six strains were sequenced. The sequences were aligned with other mumps virus sequences downloaded from GenBank using Mega 4.1 software., Results: Fourteen isolated strains were closely related to other reference strains of F genotypes. In SH gene, the homology of nucleotide and amino acid among the fourteen isolated strains were 98.3% - 100.0% and 96.5% - 100.0%, respectively, and 92.6% - 99.4% and 87.7% - 100.0% of homology when compared with that of strains isolated from other provinces in China, respectively. Wsh1 and Wsh2 strains had less homology when compared to other strains of F genotypes. The fourteen strains had homology of 84.5% - 85.1% and 77.2% compared to vaccine strains on nucleotide and amino acid, respectively, and had homology of 83.4% - 90.9% and 70.1% - 86.0% compared to that of other genotypes. In HN gene, the homology of nucleotide and amino acid among the six isolated strains were 99.3% - 99.5% and 99.1% - 99.7%, respectively, and also 99.8% and 99.8% of homology respectively when compared to the SP strain in China. All the six strains had homology of 92.4% - 93.2% and 95.5% - 96.4% when compared to the vaccine strains on nucleotide and amino acid, respectively, and had homology of 94.7% - 96.8% and 95.5% - 99.1% compared to other genotypes., Conclusion: Fourteen strains isolated in Yunnan from 2007 to 2009 belonged to F genotype of MuV while the HN gene seemed more conservative than SH gene.

A case of hereditary benign telangiectasia without family history was reported. A 39-year-old woman presented with small and tiny telangiectases on the face, neck, upper trunk and forearms at birth. The numbers and sizes of the lesions increased gradually and she had no hemorrhagic diathesis and systemic diseases. No similar patients were found in her family. Upon physical examination, telangiectases were found on the face, neck, upper trunk and forearms; and a telangiectatic erythema was found on the right forearm 25 mm × 40 mm in size. Histopathology examination showed a normal epidermis and dilation of the capillaries at upper dermis. Hereditary benign telangiectasia without family history was diagnosed.

Background: Recurrence prediction of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) present a great challenge because of a lack of biomarkers. Genetic variations play an important role in tumor development and metastasis., Methods: Oligonucleotide microarrays were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent LT. Recurrence-related single-nucleotide polymorphism were selected, and their prognostic value was assessed and validated in two independent cohorts of HCC patients (N = 102 and N = 77), using pretransplant plasma circulating DNA. Prognostic significance was assessed by Kaplan-Meier survival estimates and log-rank tests. Multivariate analyses were performed to evaluate prognosis-related factors., Results: rs894151 and rs12438080 were significantly associated with recurrence (P = .003 and P = .004, respectively). Multivariate analyses demonstrated that the co-index of the 2 SNPs was an independent prognostic factor for recurrence (P = .040). Similar results were obtained in the third cohort (N = 77). Furthermore, for HCC patients (all the 3 cohorts) exceeding Milan criteria, the co-index was a prognostic factor for recurrence and survival (P<.001 and P = .002, respectively)., Conclusions: Our study demonstrated first that genetic variations of rs894151 and rs12438080 in pretransplant plasma circulating DNA are promising prognostic markers for tumor recurrence in HCC patients undergoing LT and identify a subgroup of patients who, despite having HCC exceeding Milan criteria, have a low risk of post-transplant recurrence.

Mammalian cochlear hair cells don't regenerate naturally after injury, which usually leave permanent hearing loss. Math1 gene is a positive regulator of hair cell differentiation during cochlear development and was proved to be very critical in hair cell regeneration in deaf animals. Generating new cochlear hair cells by forced Math1 expression may be a cure for hearing loss. However, satisfying gene delivering vectors in gene therapy are not available. We combined quaternized chitosan (QCS) with Na-carboxymethyl-beta-cyclodextrin (CM-beta-CD) as novel non-viral vector, which adsorbs pRK5-Math1-EGFP perfectly at the mass ratio of 4:1. In vitro cell transfection can reach a 40% transfect efficiency and relatively low cytotoxity than liposomes. These results suggest that QCS/CM-beta-CD nanoparticle complexes could be a novel non-viral gene carrier in further clinical application.

Aim: To investigate the association between pre-miR-146a C/G polymorphism and gastric cancer risk., Methods: We performed a hospital-based, case-control study using polymerase chain reaction-restriction fragment length polymorphism method in 608 individuals (304 gastric cancer patients and 304 age and sex matched cancer-free controls)., Results: The frequencies of pre-miR-146a C/G genotypes in the case group were significantly different from those in the control groups (P = 0.037). Compared with CC genotype carriers, subjects with the variant genotypes (GC + GG) had a 58% increased risk of gastric cancer (adjusted OR = 1.58, 95% CI: 1.11-2.20, P = 0.009). Moreover, a higher gastric cancer risk was especially evident in younger individuals aged < or =58 years, nonsmokers, and males (adjusted OR = 1.76, 95% CI: 1.08-2.87, P = 0.024; adjusted OR = 1.55, 95% CI: 1.06-2.28, P = 0.025; adjusted OR = 1.53, 95% CI: 1.04-2.27, P = 0.033; respectively)., Conclusion: Pre-miR-146a C/G polymorphism might be associated with an elevated risk of gastric cancer in Chinese population.

Aberrant activation of the epidermal growth factor receptor (EGFR) is closely associated with malignant progression of tumors. EGFR inhibitors have been used successfully in clinic in the treatment of solid tumors. In the present study, we revealed that BB, a new synthetic quinonazoline derivative, was a potent EGFR inhibitor. BB selectively inhibited EGFR with a IC(50) value of 50 +/- 37 nM, at least 32-fold more potent than suppressed all other ten tested receptor tyrosine kinases including the same family member ErbB2 (IC(50) = 5.6 +/- 3.2 microM). BB effectively abrogated autophosphorylation of the EGF-stimulated EGFR and phosphorylation of its key downstream signaling molecules ERK and AKT in A549 cells. BB was shown to suppress EGF-stimulated proliferation of A549 cells with an apparently lower IC(50) value (0.33 +/- 0.07 microM) than that (2.7 +/- 0.4 microM) for the serum-stimulated cells. BB also inhibited the EGF-independent proliferation of a panel of tumor cells. In addition, BB exhibited anti-angiogenesis activity, as evidenced by antagonizing EGF-induced HMEC-1 migration in vitro, blocking HMEC-1 tube formation, and inhibiting microvessel sprouting from rat aortic rings. Most importantly, BB prominently inhibited in vivo tumorigenesis of NIH3T3 cells specifically driven by the activation-mutated EGFR genes. As reported, normal NIH3T3 cells lack tumorigenicity in nude mice. NIH3T3 cells transfected with the EGFR gene with activating mutation (A750P or L858R) produced rapidly growing xenografts in nude mice. BB, when given orally at 100 mg/kg consecutively for 2 w, prominently inhibited the growth of the xenografts and reduced the number of microvessels. Taken together, the data indicate that BB is a new selective EGFR inhibitor with potent antitumor activity, revealing its potential as a promising anticancer candidate.

The frequency and distribution of the major vernalization requirement genes and their effects on growth habits were studied. Of the 551 bread wheat genotypes tested, seven allelic combinations of the three Vrn-1 genes were found to be responsible for the spring habit, three for the facultative habit and one for the winter habit. The three Vrn-1 genes behaved additively with the dominant allele of Vrn-A1 exerting the strongest effect. The allele combinations of the facultative genotypes and the discovery of spring genotypes with "winter" allele of Vrn-1 implied the presence of as yet unidentified alleles/genes for vernalization response. The dominant alleles of the three Vrn-1 genes were found in all ten ecological regions where wheat is cultivated in China, with Vrn-D1 as the most common allele in nine and Vrn-A1 in one. The combination of vrn-A1vrn-B1Vrn-D1 was the predominant genotype in seven of the regions. Compared with landraces, improved varieties contain a higher proportion of the spring type. This was attributed by a higher frequency of the dominant Vrn-A1 and Vrn-B1 alleles in the latter. Correlations between Vrn-1 allelic constitutions and heading date, spike length, plant type as well as cold tolerance were established.

Background: Glutathione peroxidase 1 (GPX1), the key antioxidant enzyme in vascular endothelial cells, has been shown to exert a protective effect against the presence of coronary artery disease (CAD). The 198Pro/leu variant, located at codon 198 of GPX1 gene, has recently been linked to cardiovascular disease, but data were inconsistent. We investigated the association between the occurrence of CAD and the 198Pro/leu variant in a Chinese population., Methods: A total of 265 unrelated CAD patients and 265 age- and sex-matched control subjects were recruited in this study. The GPX1 198Pro/leu genotype was determined using polymerase chain reaction-restriction fragment length polymorphism., Results: Compared to the 198Pro/Pro carriers, subjects with the variant genotypes (198Pro/leu and 198Leu/leu) had a significantly higher risk of CAD (adjusted OR=2.02, 95%CI=1.27-3.22). In stratified analyses, the variant genotypes were significantly associated with increased CAD risk in subjects <64 y (adjusted OR=2.41, 95%CI=1.16-4.98), males (adjusted OR=1.86, 95%CI=1.09-3.18) and non-smokers (adjusted OR=2.40, 95%CI=1.15-5.01). However, no significant association was observed between this variant and the severity of CAD., Conclusion: These data provide evidence that GPX1 198Pro/leu variant genotypes are significantly associated with CAD risk in this Chinese population.

Objective: To examine how the thymidine phosphorylase (TP) gene expression is upregulated by interferon-alpha (IFN-alpha) in human hepatocellular carcinoma SMMC-7721 cells., Methods: TP mRNA levels were determined by RT-PCR. Whether the JAK-STAT cascade mediates IFN-alpha-induced TP mRNA expression was studied by pretreatment with Janus Kinase (JAK) inhibitor, AG-490. Effects of IFN-alpha on TP mRNA stability were detected with additional actinomycin D., Results: The expression of TP mRNA was induced by IFN-alpha in a dose- and time-dependent manner in SMMC-7721 (human hepatocellular carcinoma) cells. TP mRNA levels rose at 8 h, reached the peak value at 12 h, and remained at a high level up to 72 h in SMMC-7721 cells treated with IFN-alpha 10000 U/ml. IFN-alpha at a dose of 5000 or 10000 U/ml up-regulated TP expression about 3 fold compared with that of non-treated cells (P < 0.05). Induction of TP mRNA expression by IFN-alpha was significantly inhibited in SMMC-7721 cells by pretreatment with AG-490, in comparison with that treated with IFN-alpha alone. Pretreatment of SMMC-7721 cells with IFN-alpha 10000 U/ml for 24 h caused a substantial stabilization of TP mRNA, with a half-live of 35.8 h, compared with 8.5 hr in the control SMMC-7721 cells., Conclusion: IFN-alpha at certain doses upregulates TP mRNA expression via both JAK-STAT transcriptional activation and post-transcriptional mRNA stabilization in human hepatocellular carcinoma SMMC-7721 cells.

Aims: To examine the effect of the TIMP-2 G-418C polymorphism on gastric cancer risk., Methods: We conducted a hospital-based, case-control study using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 412 individuals (206 gastric cancer patients and 206 age, sex matched cancer-free controls)., Results: The genotype and allele frequencies were significantly different (P = 0.007 and 0.005, respectively) between cases and controls. Further analysis showed that the variant TIMP-2 genotypes (CC+GC) had a 51% increased risk of gastric cancer compared with GG [adjusted odds ratio (OR) 1.51, 95% confidence interval (CI) 1.00-2.26, P = 0.049]. The elevated gastric cancer risk was especially evident in younger individuals (age < 58 years old) (adjusted OR 2.21, 95% CI 1.18-4.16) and smokers (adjusted OR 2.61, 95% CI 1.01-6.72). However, no significant association was observed between the variant genotypes and clinicopathological features of gastric cancer., Conclusions: These findings suggest that the TIMP-2 G-418C polymorphism is a genetic predisposing factor for gastric cancer.

The aim of the present study was to assess the influence of the endothelial lipase (EL) gene 584C/T variant, which results in a change at codon 111 of the EL gene from threonine to isoleucine, on the risk of coronary artery disease (CAD) in a Chinese population. The study population consisted of 265 CAD patients and 265 age- and sex-matched control subjects. The T allele frequency was significantly lower among CAD patients than among control subjects (18.3% vs. 29.8%; P < 0.001). In both the CAD and control groups, the T allele carriers had higher high density lipoprotein cholesterol (HDL-C) levels than homozygote C allele carriers. In a multiple logistic regression model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, hyperlipidemia, and low density lipoprotein cholesterol, a significantly decreased risk of developing CAD was found in subjects carrying a variant CT or TT genotype (odds ratio = 0.496, 95% confidence interval = 0.341-0.723; P < 0.001), and the significance persisted after further adjustment for HDL-C. In conclusion, our observation that the EL 584T allele was associated with protection from CAD in this Chinese population replicates the findings in a Japanese study, which found a similar association of this allele with acute myocardial infarction, independent of HDL-C levels.