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Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that CYP1A1, CYP3A4, CYP2B6, UGT2B17, UGT2B7, UGT1A8, UGT2B11, GAS5, SNHG6, XIST significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies.

Transformation of follicular lymphoma (FL) into B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare and results in greatly increased aggressiveness of clinical course. Here we present extensive molecular analysis of this unusual transformation, including immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole-exome sequencing (WES) of the patient's FL, B-ALL/LBL, and normal cells. Although FL showed marked somatic hypermutation (SHM) of the Ig genes, SHM appeared to be even more extensive in B-ALL/LBL. Cytogenetically, at least three translocations were identified in the B-ALL/LBL involving the BCL2, BCL6, and MYC genes; two of these, the BCL6 and BCL2 gene rearrangements, were already seen at the FL stage. WES identified 751 single-nucleotide variants with high allelic burden in the patient's cells, with the vast majority (575) present exclusively at the B-ALL/LBL stage. Of note, a TAF3 gene mutation was shared by normal, FL, and B-ALL/LBL tissue. A KMT2D nonsense mutation was identified in both FL and B-ALL/LBL and therefore may have contributed directly to lymphomagenesis. Mutations in KDM6A, SMARCA4, CBX1, and JMY were specific to the B-ALL/LBL stage, possibly contributing to the B-ALL/LBL transformation. Functionally, these identified mutations may lead to dysregulation of DNA repair, transcription, and cell differentiation. Thus, these genetic changes, together with the identified chromosomal translocations, may have contributed to lymphoma development and progression. Our findings may improve the mechanistic understanding of the FL-B-ALL/LBL transformation and may have therapeutic implications for this aggressive disease.

Our preliminary results show that huperzine A, an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD) patients in China, exhibits different pharmacokinetic features in elderly and young healthy subjects. However, its pharmacokinetic data in elderly subjects remains unavailable to date. Thus, we developed a population pharmacokinetic (PPK) model of huperzine A in elderly Chinese people, and identified the covariate affecting its pharmacokinetics for optimal individual administration.A total of 341 serum huperzine A concentration records was obtained from 2 completed clinical trials (14 elderly healthy subjects in a phase I pharmacokinetic study; 35 elderly AD patients in a phase II study). Population pharmacokinetic analysis was performed using the non-linear mixed-effect modeling software Phoenix NLME1.1.1. The effects of age, gender, body weight, height, creatinine, endogenous creatinine clearance rate as well as drugs administered concomitantly were analyzed. Bootstrap and visual predictive checks were used simultaneously to validate the final population pharmacokinetics models.The plasma concentration-time profile of huperzine A was best described by a one-compartment model with first-order absorption and elimination. Age was identified as the covariate having significant influence on huperzine A clearance. The final PPK model of huperzine A was: CL (L/h)=2.4649(*)(age/86)((-3.3856)), Ka=0.6750 h(-1), V (L)=104.216. The final PPK model was demonstrated to be suitable and effective by the bootstrap and visual predictive checks.A PPK model of huperzine A in elderly Chinese subjects is established, which can be used to predict PPK parameters of huperzine A in the treatment of elderly AD patients.

Anaplastic lymphoma kinase (ALK), physiologically expressed only by certain neural cells, becomes highly oncogenic, when aberrantly expressed in nonneural tissues as a fusion protein with nucleophosphin (NPM) and other partners. The reason why NPM-ALK succeeds in transforming specifically CD4 + T lymphocytes remains unknown. The IL-2R common γ-chain (IL-2Rγ) is shared by receptors for several cytokines that play key roles in the maturation and growth of normal CD4 + T lymphocytes and other immune cells. We show that IL-2Rγ expression is inhibited in T-cell lymphoma cells expressing NPM-ALK kinase as a result of DNA methylation of the IL-2Rγ gene promoter. IL-2Rγ promoter methylation is induced in malignant T cells by NPM-ALK. NPM-ALK acts through STAT3, a transcription factor that binds to the IL-2Rγ gene promoter and enhances binding of DNA methyltransferases (DNMTs) to the promoter. In addition, STAT3 suppresses expression of miR-21, which selectively inhibits DNMT1 mRNA expression. Reconstitution of IL-2Rγ expression leads to loss of the NPM-ALK protein and, consequently, apoptotic cell death of the lymphoma cells. These results demonstrate that the oncogenic tyrosine kinase NPM-ALK induces epigenetic silencing of the IL-2Rγ gene and that IL-2Rγ acts as a tumor suppressor by reciprocally inhibiting expression of NPM-ALK.

Purpose The present study aimed to confirm the efficacy and safety of topical and intravenous tranexamic acid (TXA) compared with that of topical placebo and to assess the noninferiority between the two application methods of TXA in patients undergoing unilateral primary total hip arthroplasty. Methods Our randomized controlled trial investigated 170 patients with 1:1:1 allocation to two doses of 10-mg/kg intravenous TXA, 3-g topical TXA, and topical placebo of 60-ml physiological saline groups. The primary outcome, total blood loss, was calculated with Nadler and Gross formula. The secondary outcomes included allogeneic blood transfusion requirement, drain blood loss, decreased hemoglobin level. Noninferiority would be established when the upper limit 95% CI is lower than 250 ml of the noninferiority margin for the mean difference of total blood loss between topical and intravenous TXA. Thromboembolic complication incidence was considered as a safety outcome. Results The total blood loss of patients administered intravenous (mean±standard deviation, 1125±514 ml) and topical TXA (1211±425 ml) was significantly reduced compared with that of those administered topical placebo (1464±556 ml) (p = 0.0012). Drain blood loss and hemoglobin level reduction in patients administered with TXA were also significantly lower than those in patients administered topical placebo. The mean difference of total blood loss between topical and intravenous TXA is 86 ml (95% CI, -88 to 260 ml). The complications were comparable between patients managed with TXA and patients with topical placebo. Conclusion The noninferiority of topical TXA to intravenous TXA can not be concluded. Considering no significant difference was found in all efficacy outcomes between the two administration methods. Any of the two TXA administration methods can be adopted for blood loss prevention in total hip arthroplasty.

In this study, we demonstrate that malignant mature CD4+ T lymphocytes derived from cutaneous T cell lymphomas (CTCL) variably display some aspects of the T regulatory phenotype. Whereas seven cell lines representing a spectrum of primary cutaneous T cell lymphoproliferative disorders expressed CD25 and TGF-β, the expression of FOXP3 and, to a lesser degree, IL-10 was restricted to two CTCL cell lines that are dependent on exogeneous IL-2. IL-2, IL-15, and IL-21, all of which signals through receptors containing the common γ chain, induced expression of IL-10 in the IL-2-dependent cell lines as well as primary leukemic CTCL cells. However, only IL-2 and IL-15, but not IL-21, induced expression of FOXP3. The IL-2-triggered induction of IL-10 and FOXP3 expression occurred by signaling through STAT3 and STAT5, respectively. Immunohistochemical analysis of the CTCL tissues revealed that FOXP3-expressing cells were common among the CD7-negative enlarged atypical and small lymphocytes at the early skin patch and plaque stages. Their frequency was profoundly diminished at the tumor stage and in the CTCL lymph node lesions with or without large cell transformation. These results indicate that the T regulatory cell features are induced in CTCL T cells by common γ chain signaling cytokines such as IL-2 and do not represent a fully predetermined, constitutive phenotype independent of the local environmental stimuli to which these malignant mature CD4+ T cells become exposed.

Objectives. To understand the current risk of HIV infection and transmission and further elucidate the underlying risk factors among men who have sex with men and women (MSMW) in China.Methods. Following PRISMA guidelines, we conducted a systematic review and meta-analysis of searching through Chinese and English available literature databases between January 2000 and June 2014 to identify articles.Results. Thirty-six articles (including 19,730 MSMW and 53,536 MSMO) met the selection criteria and the aggregated results found that MSMW have significantly higher HIV prevalence than MSMO (6.6% versus 5.4%, OR = 1.27, 95% CI = 1.01–1.58). A higher proportion of MSMW had commercial male partners in the past 6 months (18.3% versus 12.2%, OR = 1.56, 95% CI = 1.01–2.42). Additionally, substance use in the past 6 months was significantly more frequent among MSMW than MSMO (alcohol use: 27.1% versus 13.1%, OR = 2.53, 95% CI = 2.14–2.99; illicit drug use: 5.3% versus 2.5%, OR = 2.09, 95% CI = 1.48–2.95).Conclusion. A higher proportion of commercial sex and substance use among MSMW may be a potentially indicative factor for significantly higher HIV prevalence compared to MSMO. Targeted interventions should aim at increasing the frequency of HIV/STIs screening and preventing high risk commercial sex and substance use among MSMW to decrease their HIV transmission to the general population.

Surgeons often can contribute failure of sphincter-preserving procedure to a limitation of pelvis anatomy; however, they cannot determine definitely which anatomic diameter or spatial factor actually affected the success of the procedure. Colorectal surgeons, radiologists, and research fellows collaborated closely to establish a three-dimensional digital model of the pelvis with spiral computerized tomography scanning data of patients with rectal cancer. Retrospective analysis on data of 97 patients with low rectal cancer was performed with this model to identify geometric factors that might affect a successful sphincter preservation procedure for low rectal cancer. A digital pelvic model was established. Multivariate analysis demonstrated that distance from the anal verge, body mass index, and pelvic factors affected the success of sphincter preservation. Sphincter preservation was more likely to succeed when the distance from anal verge was ≥5 cm and body mass index was

To analyze the specific mechanism of Jinxueyuan granules, the relationship between the Jinxueyuan granules increased the saliva secretion of xerostomia model SD rats and excitement of receptors were studied in this experiment. In the study, three groups of xerostomia model rats were successfully established by using M-receptor blockers-4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP) and atropine, or adrenergic receptor blocker phentolamine; after the modeling, the medicine Jinxueyuan granules were gavaged. According to the clinical dose of Jinxueyuan granules and SD rats body surface area, the rats in atropine group were divided three dose groups respectively, namely low, medium and high dose of Jinxueyuan granules groups. The 4-DAMP group and phentolamine group were gavaged medium dose of Jinxueyuan granules. And the amount of salivary secretion for 150 minutes in all groups continuously were measured, and the effect of Jinxueyuan granules increased salivation and the relationship between characteristics and the receptors were observed; and submandibular gland tissue of the rats was isolated, then the effect of Jinxueyuan Granules for expression of the water channel protein aquaporin-5 (AQP5) in submandibular gland cells was analyzed by the Western blot technology. It was found that the saliva secretion of Jinxueyuan Granules groups was increased significantly, and compared with the saline control group, phentolamine group, 4-DAMP group and atropine group, difference was significant, P0.05. There was no significant difference between the low-dose of Jinxueyuan granules group and the saline group, but the medium dose of Jinxueyuan granules group had a significant difference, compared with the saline group (P0.05). In the time distribution of increasing saliva secretion, there was a significant difference between the saline and Jinxueyuan granules group in the saliva secretion (P0.05). After administration of Jinxueyuan granules, the expression of AQP5 protein in the submandibular gland cells expressing of treatment groups was increased, and compared with the blocker groups, there was a significant difference, P0.05. Except the atropine group, there was no significant difference in Jinxueyuan granules relieving the inhibition induced by blocks in phentolamine group and 4-DAMP group, compared with the saline group. Compared the AQP5 expression in three blockers groups, there was no significant difference in the efficacy of Jinxueyuan granules between phentolamine group and 4-DAMP group; but there was a significant difference between the atropine group and other groups (P0.05). Therefore, it was considered that the mechanism of Jinxueyuan granules increasing saliva secretion (effectiveness of nourishing Yin and generating body fluid ) possibly through the pathway mediated by muscarinic M receptor, especially M3 receptor, or adrenergic receptor, and increased expression of salivary gland AQP5 membrane, and then stimulate saliva production.

In this article, we report that cutaneous T cell lymphoma (CTCL) cells and tissues ubiquitously express the immunosuppressive cell surface protein CD80 (B7-1). CD80 expression in CTCL cells is strictly dependent on the expression of both members of the STAT5 family, STAT5a and STAT5b, as well as their joint ability to transcriptionally activate the CD80 gene. In IL-2–dependent CTCL cells, CD80 expression is induced by the cytokine in a Jak1/3- and STAT5a/b-dependent manner, whereas in the CTCL cells with constitutive STAT5 activation, CD80 expression is also STAT5a/b dependent but is independent of Jak activity. Although depletion of CD80 expression does not affect the proliferation rate and viability of CTCL cells, induced expression of the cell-inhibitory receptor of CD80, CD152 (CTLA-4), impairs growth of the cells. Coculture of CTCL cells with normal T lymphocytes consisting of both CD4+ and CD8+ populations or the CD4+ subset alone, transfected with CD152 mRNA, inhibits proliferation of normal T cells in a CD152- and CD80-dependent manner. These data identify a new mechanism of immune evasion in CTCL and suggest that the CD80–CD152 axis may become a therapeutic target in this type of lymphoma.

With this study we have demonstrated that in vitro transduction of normal human CD4(+) T lymphocytes with NPM-ALK results in their malignant transformation. The transformed cells become immortalized and display morphology and immunophenotype characteristic of patient-derived anaplastic large-cell lymphomas. These unique features, which are strictly dependent on NPM-ALK activity and expression, include perpetual cell growth, proliferation, and survival; activation of the key signal transduction pathways STAT3 and mTORC1; and expression of CD30 (the hallmark of anaplastic large-cell lymphoma) and of immunosuppressive cytokine IL-10 and cell-surface protein PD-L1/CD274. Implantation of NPM-ALK-transformed CD4(+) T lymphocytes into immunodeficient mice resulted in formation of tumors indistinguishable from patients' anaplastic large-cell lymphomas. Our findings demonstrate that the key aspects of human carcinogenesis closely recapitulating the features of the native tumors can be faithfully reproduced in vitro when an appropriate oncogene is used to transform its natural target cells; this in turn points to the fundamental role in malignant cell transformation of potent oncogenes expressed in the relevant target cells. Such transformed cells should permit study of the early stages of carcinogenesis, and in particular the initial oncogene-host cell interactions. This experimental design could also be useful for studies of the effects of early therapeutic intervention and likely also the mechanisms of malignant progression.

To explore the effects of different antihypertensive strategies on blood pressure and urinary albumin excretion in patients with hypertension and microalbuminuria.For this multi-center, randomized, positively controlled clinical trial, a total of 531 patients with mild-to-moderate essential hypertension and microalbuminuria were enrolled. They were divided randomly into calcium channel blocker (CCB), angiotensin II receptor antagonist (ARB) and CCB+ARB groups. The whole treatment period was 6 months.According to ANOVA analysis, the post-therapeutic urinary albumin level decreased 20.6, 27.6 and 30.9 mg/L in CCB, ARB and CCB+ARB groups respectively (P = 0.067). And the extents of urinary albumin reduction were 31.1 and 6.6 mg/L in patients with controlled and uncontrolled blood pressure respectively (P0.001).Effective antihypertensive therapy is a key for decreasing urinary albumin excretion in hypertensive patients. As compared with calcium antagonists, ARB-containing regimens appear to be better in reducing urinary albumin.

The management of patients with refractory immune thrombocytopenia (ITP) is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin (rhTPO) in combination with cyclosporin A (CsA) for the management of patients with corticosteroid-resistant primary ITP.Thirty-six patients with corticosteroid-resistant ITP were randomly divided into an observation group and control group. In the observation group, 19 patients received subcutaneous injection of rhTPO at a dose of 1 µg/kg (300 U/kg) once daily up to day 14. Simultaneously they also received oral CsA at a dose of 1.5-2.0 mg/kg twice daily for three months. In the control group, rhTPO alone was administered subcutaneously at 1 µg/kg once daily in the other 17 ITP patients for 14 consecutive days and then the treatment was withdrawn.There was no significant difference in the response rate at the end of the first week after treatment initiation between the observation group and the control group (63.2% vs. 58.8%, P0.05), neither was there at the end of the second week (89.5% vs. 94.1%, P0.05). However, the relapse rate in the observation group was significantly lower than that in control group at the end of the first (17.7% vs. 50.0%, P0.05), second (29.4% vs. 68.8%, P0.05) and the third month (29.4% vs. 87.5%, P0.01). In addition, rhTPO plus CsA were well tolerated and adverse events recorded were mild.Combination therapy with rhTPO and CsA was effective in the management of patients with corticosteroidresistant ITP, with a relatively short time to response and low recurrence rate. It might be considered as a potential secondline treatment regimen for ITP.

To investigate blood pressure control the glucose metabolism, cardiovascular risk factors of patients who were regularly followed up at professional hypertension clinics in China.A cross-sectional survey was conducted in 32 004 patients from 127 professional hypertension clinics across China. The questionnaires included case history and related treatment physical examination and laboratory biochemical tests were also taken at the same time.The mean blood pressure of overall population was (151 ± 13)/(92 ± 10) mm Hg(1 mm Hg = 0.133 kPa). Totally 3424 patients (10.7%) had never taken any anti-hypertension medicine. Among patients treated with anti-hypertension drugs, 19 818 were of mono-therapy (69.3%) and 8762 were of combination therapy. The most frequently used drug was renin-angiotensin system inhibitor, followed by calcium-channel blocker. Fixed compound preparations accounted for 15.6%. The overall blood pressure control rate (140/90 mm Hg ) was 26.8%, among them, 27.7%, 30.0%, 25.4% and 21.3% patients were complicated with coronary heart disease, diabetes mellitus, kidney diseases and cerebral stroke respectively. About 70.3% hypertensive patients had abnormal glucose metabolism whose mean glycosylated hemoglobin (GHbA1c) was 7.84%, which was significantly higher than 7.0% , the target value defined by ADA.Even among them, 20.2% patients have never received any anti-diabetic drugs.Low-risk and medium-risk patients accounted for 16.0%. Totally 48.0% patients were classified in high-risk group and 36.0% in very high risk group. About half of all patients had different target organ dysfunction. About 49.0% patients had associated comorbidities.Co-existence of hypertension and abnormal glucose metabolism is common in Chinese population. Among these patients, target organ dysfunction and comorbidities are prevalent, but blood pressure is only effectively controlled in less than 30% patients. Low proportion of combination therapy is one of the reasons for unsatisfied control of blood pressure.It indicates that effective management of hypertension is urgent.

To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients.Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent.(1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism.Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

To explore the characteristics and related risk factors of arterial elasticity in persons with prehypertension, high-normal blood lipid and(or) impaired glucose regulation(impaired fasting glucose and(or) impaired glucose tolerance).After receiving physical and biochemical examinations, a total of 1238 persons were enrolled. Among them, the etiologies were prehypertension (n = 65), high-normal blood lipid (n = 156), impaired glucose regulation (n = 159), prehypertension and high-normal blood lipid (n = 85), prehypertension and impaired glucose regulation (n = 77), high-normal blood lipid and impaired glucose regulation (n = 55) and prehypertension, high-normal blood lipid and impaired glucose regulation (n = 9). Also 332 healthy subjects, 113 hypertensive patients, 150 hyperlipidemics and 37 diabetics were enrolled as controls. Systemic vascular compliance (SVC), systemic vascular resistance (SVR), brachial artery distensibility (BAD) were measured with Dynapulse 200 M (Pulse Metric, Inc., USA).In persons with prehypertension, SVC was lower than healty group ((1.14 ± 0.20) ml vs (1.26 ± 0.23) ml, P0.01)and higher than hypertensive group ((1.11 ± 0.18) ml, P = 0.011), SVR higher than healty group (157 ± 29) kPa×s×L(-1) vs (148 ± 25) kPa×s×L(-1), P = 0.012) and lower than hypertensive group ((166 ± 36) kPa×s×L(-1), P0.01)and BAD lower than healty group(5.93% ± 1.14% vs 6.50% ± 1.30%, P0.01). Among different groups with prehypertension, high-normal blood lipid and(or) impaired glucose regulation, SVC, SVR and BAD had significant differences. As indicated by multiple linear regression analysis, blood pressure was an independent risk factor of arterial elasticity.Vascular function becomes damaged in prehypertensive stage. As an independent risk factor, blood pressure had more potent effect than lipid and blood glucose. Multiple cardiovascular risk factors with high-normal value may affect vascular function more strongly.

Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. The aim of this study was to assess the effect of aliskiren on arterial stiffness, compared with that of ramipril in mild to moderate essential hypertensive patients.Following a two week placebo run-in period, patients with a mean sitting diastolic blood pressure (ms-DBP) ≥ 95 and110 mmHg (1 mmHg = 0.133 kPa), and a mean sitting systolic blood pressure (ms-SBP)180 mmHg were randomly allocated to treatment with aliskiren (150 mg/d, n = 20) or ramipril (5 mg/d, n = 20) for eight weeks. Blood pressure, plasma renin activity, and the brachial-ankle pulse wave velocity (ba-PWV) were measured before and after eight weeks of treatment.Eight weeks of treatment significantly decreased systolic blood pressure and diastolic blood pressure in both the aliskiren group and ramipril group. The hypotensive effect did not differ between the two groups. Plasma renin activity decreased after aliskiren treatment and increased after ramipril treatment. There was no significant difference in baseline ba-PWV between the aliskiren and ramipril groups (P = 0.892). The ba-PWV was significantly reduced in both the aliskiren group (1535 (1405 - 1666) vs. 1464 (1360 - 1506) cm/s) (P0.01) and the ramipril group (1544 (1433 - 1673) vs. 1447 (1327 - 1549) cm/s) (P0.01). No statistically significant difference was found in the decline of ba-PWV between the two groups (P = 0.766).The current study revealed that aliskiren (150 mg/d) could ameliorate arterial stiffness and its effect was similar to ramipril (5 mg/d) in mild to moderate hypertensive patients, indicating that in addition to lowering blood pressure, aliskiren had beneficial effect on vascular protection.

To establish a three-dimensional image of the penile suspensory ligament, and explore a stereoscopic and multi angle observation method of patient' s penile suspensory ligament.This study selected the patients with small penis from our hospital as subjects. The participants were conducted on magnetic resonance imaging (MRI) examination before operation. Afterwards, the results of MRI were imported into 3D reconstruction software (MIMICS 10.0), and the suspensory ligament of penis, the pubic symphysis and other related structures were reconstructed for observation.The pubic symphysis, penis and corpus spongiosum can be quite clearly displayed in the thin-section MRI images. In addition, penile suspensory with patchy distribution can be visible between lower part of ligament pubic symphysis and corpus cavernosum. Finally, we can reconstruct the three-dimensional structures through MIMICS 10.0, and then precisely describe the suspensory ligament's start-stop point, the angle with cavernous body of penis and the attached area in the corpus cavernosum penis.Based on the MRI 3D reconstruction of deep penile suspensory ligament and adjacent structures, we can carry out dynamic, three-dimensional multi angle observation of patients deep penile suspensory ligament, and can use the reconstructed image to provide certain theory basis for the judgement of the corpus cavernosum penis extension length and penile suspensory ligament depth before penis extension operation.

This study was aimed to investigate the changes of the platelet particle membrane protein (GMP-140), platelet activating factor (PAF) and platelet parametes in the patients with hyperuricemia (HUA), ELISA was used to detect the levels of GMP-140 and PAF in 55 patients with HUA and 30 healthy individuals. Platelet parameters were measured with automatic blood cell analyzer, and the biochemical indexes were detected at the same time. The results showed that the levels of serum uric acid, triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in HUA patients were higher than that in the normal group (P0.01). Serum uric acid level of HUA group was higher in men than that in women. The levels of GMP-140 and PAF in HUA patients were much higher than that in the normal group (P0.01), the indexes of platelet distribution width (PDW) and platelet-large cell ratio (P-LCR) in HUA patients were higher than that in the normal group (P0.01), there was no statistically significant difference in platelet count, plateletcrit (PCT), mean platelet volume (MPV) between the two groups. There was positive correlation between serum uric acid and levels of GMP-140, PAF, P-LCR and PDW, respectively (r = 0.667, 0.879, 0.310, 0.460, P0.01 or P0.05). Multivariate stepwise regression analysis revealed that serum uric acid, creatinine, P-LCR, urea nitrogen contributed to GMP-140 level (adjusted R(2) = 0.822). Serum uric acid and LDL-C also contributed to PAF level (adjusted R(2) = 0.451). It is concluded that a close relationship exists between HUA and the change of platelet function, and HUA plays a certain role in cardiovascular disease thrombosis complications.

To establish a model of individually forecasting the penile length gained after penis lengthening.A total of 322 patients were diagnosed congenital penile shortness and received partial suspensory ligament release in our department from Oct. 1988 to Apr. 2011. The patients were divide into two groups as Modeling Group (n = 200) and Checking Group (n = 122). Then a two-dimensional model of the suspensory-ligament-release penis lengthening is established. In the Modeling Group, a statistical analysis of the penile length in flaccid and erectile state before and after penis lengthening was carried out, and a forecasting predictive function of increased penile length was derived. Then the predictive accurate rate was tested in the Checking Group.There was a significant linear correlation between the increased length in flaccid and erectile state (correlation coefficient = 0.921, P0.01), there was also a similar relationship between the extension rate of erection before and after the operation (correlation coefficient = 0.803, P0.01). According to the significant linear correlations showing above, two regression forecasting models were established. A predictive function of increased flaccid length was derived from the two regression forecasting models. The effectively forecasting rates were 84.5% (169/200, the Modeling Group) and 87.7% (107/122, the Checking Group) when the absolute value of forecasting error was less than 1.5 cm.The discovered significant correlation and the established forecasting function provide us a model of roughly and individually forecasting the penile length gained after penis lengthening.

To investigate the efficacy and safety of a schedule of 2 cycles' high-dose dexamethasone (HD-DXM) as an initial therapy in adults immune thrombocytopenia (ITP), and compare with conventional dose prednisone therapy.A total of 59 newly diagnosed ITP patients were divided into 2 groups randomly. In 30 patients (Dexamethasone group), oral HD-DXM was administered at 40 mg/d for 4 consecutive days, repeated one week later, and then failed to maintain. In the remaining 29 patients (Prednisone group), prednisone was administered orally at 1.0 - 1.5 mg×kg(-1)×d(-1) for 4 weeks, and then gradually tapered.For short-term efficacy, after 1 and 2 weeks of treatment, the response rate in Dexamethasone group was significantly higher than that in Prednisone group (50.0% vs 24.1%, P0.01; 73.3% vs 55.2%, P0.05), while 3 weeks later, there was no remarkable difference between the two groups (83.3% vs 68.9%, P0.05), though the response rate in Dexamethasone group remained higher. For long-term effect, at the end of the 2nd and 3rd months of follow-up, the relapse rate in Dexamethasone group was significantly lower than that in Prednisone group (24.0% vs 40.0%, P0.05; 32.0% vs 65.0%, P0.01), while at the end of the 1(st) month of follow-up, there was no significant difference (16.0% vs 20.0%, P0.05). In addition, it's well tolerated and no complications such as severe infection or Cushing syndrome were complained in Dexamethasone group.HD-DXM possesses an advantage over conventional dose prednisone therapy in efficacy and safety.

This study was aimed to explore the expression of erythropoietin receptor (EPOR) on acute leukemia cells and its clinical significance. Bone marrow of 40 patients with acute leukemia (AL) and 24 patients with normal bone marrow as control group were collected. Samples came from outpatients and inpatients in our hospital. EPOR mRNA was detected by reverse transcription-PCR. The results showed that there was EPOR expression on AL cells, the expression rate was 57.5%, and the average expression level (Gray value) was 0.3549 ± 0.2800, but both were lower than that in control group (p0.05). There was no significant statistic difference of expression rate between acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) (p0.05), and expression level of AML EPOR was higher than that of ALL (p0.05). It is concluded that there is EPOR expression on AL cells, while the expression rate and expression level are lower than those in control group (p0.05). There is no significant statistic difference of the expression rate between AML and ALL (p0.05), and the expression level of AML EPOR is higher than that of ALL (p0.05).

To investigate whether S100A14 and S100A4 expression correlates with metastatic potential and prognosis in colorectal cancer (CRC), we firstly used RT-PCR analysis to detect mRNA expression of S100A14 and S100A4 in 40 pairs of fresh tumor samples matched with adjacent normal tissues. We then evaluated the clinical significance of our findings with immunohistochemistry on 115 samples of formalin-fixed and paraffin-embedded tumors on tissue microarrays. Typically, we identified decreased S100A14 mRNA levels (52.5%, 21/40), and increased S100A4 mRNA levels (70.0%, 28/40) in primary CRC samples. In addition, down-regulated or absent S100A14 expression was detected in 56.5% of samples (65/115) and was correlated with poor differentiation (P=0.010). In contrast, overexpressed S100A4 was detected in 57.4% of samples (66/115) and was associated with lymph node metastasis (P=0.001). Simultaneous S100A14 low-expression and S100A4 high-expression was correlated with high CRC metastatic potential (P0.001). Taken together, the signature derived from the combined expression status of S100A14 and S100A4 could be a valuable prognostic indicator in CRC.

Among the many oncogenic variants of the anaplastic lymphoma kinase (ALK), nucleophosmin 1 (NPM)/ALK fusion protein expressed in the subset of T-cell lymphoma (ALK(+)TCL) is currently the best characterized. NPM/ALK activates several signal transduction pathways, including PI3K/AKT, MEK/ERK, mTORC1, STAT3, and STAT5b. In turn, the pathways modulate expression and function of many genes and proteins involved in the key cellular functions such as proliferation, growth, survival, metabolism, and angiogenesis. Recent data indicate that NPM/ALK also promotes immune evasion of the ALK(+)TCL by inducing through STAT3 activation the expression of immunosuppressive cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGFss) and cell surface protein CD274 (PD-L1, B7-H1). In addition, NPM/ALK protects its own expression by mediating via STAT3 and at least one member of the DNA methyltransferase family DNMT1 epigenetic silencing of the SHP-1 and STAT5a genes. In ALK+TCL cells, SHP-1 and STAT5a proteins act as potent tumor suppressors by promoting degradation of the NPM/ALK protein and inhibiting expression of the NPM/ALK gene, respectively. These findings provide further rationale to therapeutically target ALK and its effector proteins, foremost STAT3. They also suggest that immunotherapeutic approaches to ALK(+)TCL and, possibly, other ALK-driven malignancies may require inhibition of ALK and STAT3 to achieve the optimal clinical efficacy.

The mechanisms of malignant cell transformation caused by the oncogenic, chimeric nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) remain only partially understood, with most of the previous studies focusing mainly on the impact of NPM/ALK on cell survival and proliferation. Here we report that the NPM/ALK-carrying T cell lymphoma (ALK+TCL) cells strongly express the immunosuppressive cell-surface protein CD274 (PD-L1, B7-H1), as determined on the mRNA and protein level. The CD274 expression is strictly dependent on the expression and enzymatic activity of NPM/ALK, as demonstrated by inhibition of the NPM/ALK function in ALK+TCL cells by the small molecule ALK inhibitor CEP-14083 and by documenting CD274 expression in IL-3-depleted BaF3 cells transfected with the wild-type NPM/ALK, but not the kinase-inactive NPM/ALK K210R mutant or empty vector alone. NPM/ALK induces CD274 expression by activating its key signal transmitter, transcription factor STAT3. STAT3 binds to the CD274 gene promoter in vitro and in vivo , as shown in the gel electromobility shift and chromatin immunoprecipitation assays, and is required for the PD-L1 gene expression, as demonstrated by siRNA-mediated STAT3 depletion. These findings identify an additional cell-transforming property of NPM/ALK and describe a direct link between an oncoprotein and an immunosuppressive cell-surface protein. These results also provide an additional rationale to therapeutically target NPM/ALK and STAT3 in ALK+TCL. Finally, they suggest that future immunotherapeutic protocols for this type of lymphoma may need to include the inhibition of NPM/ALK and STAT3 to achieve optimal clinical efficacy.

To investigate the changes of plasma suPAR level in patients with multiple myeloma, ELISA was used to detect plasma suPAR level, and routine examination was performed for other clinical indexes in 26 multiple myeloma patients. The results showed that plasma suPAR level in patients was 4.31+/-1.67 ng/ml, which was obviously higher than that in control group (1.87+/-0.27 ng/ml) (p0.01). Plasma suPAR level in IgM subtype patients was 6.18+/-3.61 ng/ml, which was highest among all the subtypes; the plasma suPAR levels in non-secretion subtype, IgG and IgA subtype were 4.43+/-1.55 ng/ml, 4.00+/-0.95 ng/ml and 3.50+/-1.60 ng/ml respectively. The plasma suPAR levels in all subtypes were higher than that in control group, but there was no differences between these subtypes. SuPAR level was correlated with the blood sedimentation rate, creatinine level and hemoglobin level, plasma cell ratio and M protein level. It is concluded that the change of plasma suPAR level in multiple myeloma contributes to predict the development and prognosis of the disease.

To assess the correlation between micrometastasis in mesorectum and pathological factors after total mesorectal excision(TME) in lower rectal cancer.All lymph nodes were obtained by fat clearance from 31 lower rectal cancer patients with TME. The lymph nodes which had previously been considered negative of metastasis by conventional examination were submitted to immunohistochemical examination to identify the micrometastases using anti-cytokeratin antibody. The correlation between micrometastasis and pathological factors were analyzed.One thousand and seven LNs were collected from 31 patients. One hundred and five LNs were found positive by conventional examination, and the mean diameter was (5.5 +/- 3.1) mm. The mean diameter of conventional negative LNS was (2.8 +/- 1.5) mm. The diameter differed significantly between conventional positive and negative LNS (P0.05). In 902 conventional negative LNs, 26 contained micrometastasis (209%) and the mean diameter was (3.3 +/- 1.2) mm. The diameter of LNs with micrometastasis was significantly smaller than that of conventional positive LNs (P0.05). The diameter of most of the micrometastatic LNs(88.5%) was less than 5 mm. Fourteen patients (38.7%) contained micrometastasis. The pathological stage, serum carcinoembryonic antigen level and tumor differentiation were related to micrometastasis (P0.05).With the detection of micrometastasis after fat clearance, we can estimate the LN metastasis status more accurately. It can be useful in clinical staging and individual treatment of rectal cancer.

To obtain the glucose metabolic profile of patients with essential hypertension in China.This is an epidemiologic cross-sectional survey and screening study, 5 sites in China participated in. Patients with essential hypertension and without known diabetes mellitus(DM) answered the questionnaire and received in-site fasting blood glucose (FBG) determination and simple oral glucose tolerance test (OGTT).A total of 1,421 patients had the data of FBG and OGTT 2-hour glucose. Among them, The prevalence rates of newly diagnosed DM and impaired glucose regulation (IGR) were 22.9% and 64.4% respectively. Patients with newly diagnosed DM have higher systolic blood pressure, waistline, waist-to-hip ratio and plasma triglyceride.Newly diagnosed disturbed glucose metabolic status is common among patients with essential hypertension without DM history, which had very low diagnose rate in routine work. We must pay more attention to the glucose metabolic status of patients with hypertension, especially the one with metabolic syndrome, OGTT should be as a routine procedure in the diagnosis of such patients.

To evaluate the clinical characteristics and therapy conditions in hospitalized patients with essential hypertension in Beijing.Patients with essential hypertension hospitalized in 20 Beijing hospitals in recent 2 years were included in this epidemiologic retrospective survey. Data on age, blood pressure level, risk factors and complicated diseases, antihypertensive medication and heart structural and functional characteristics measured by echocardiography were collected.Total 5106 hospitalized patients (mean age 63.78 years) with essential hypertension were recorded. Mean blood pressure was 145.97/84.23 mm Hg (1 mm Hg = 0.133 kPa). Among them, 75.5% complicated with at least one risk factor, 30% suffered from heart failure. The atria enlargement and left ventricular diastolic dysfunction were the two most common echocardiographic pathological changes. Left ventricular hypertrophy is positively correlated with blood pressure. Logistic regression analysis showed that increased systolic blood pressure, diastolic blood pressure and plasma creatinine, old age and decreased HDL-cholesterol were risk factors of left ventricular hypertrophy. Only 32.1% patients achieved the goal blood pressure level (140/90 mm Hg) and 38.1% patients were treated with monotherapy. The most commonly used antihypertensive drugs were calcium channel blockers and diuretics.It is of importance to strictly follow the therapy guidelines on hypertension treatment and use combined drug therapy to increase the rate of patients reaching goal blood pressure level and reduce hypertensive complications.

To assess the efficacy and safety of valsartan/hydrochlorothiazide (HCTZ) 80/12.5 mg once daily (o.d.) in Chinese patients with mild to moderate essential hypertension who was not adequately controlled by valsartan 80 mg o.d. monotherapy.In this multi-center, double-blind, randomized, active controlled, parallel group trial, 1051 out of 1175 Chinese patients with mild to moderate essential hypertension [DBPor= 95 mm Hg and110 mm Hg (1 mm Hg = 0.133 kPa)] completed single-blind run-in period (valsartan 80 mg o.d. therapy for 4 weeks) after 2 week's wash-out period. At the end of the single-blind run-in period, those patients with DBPor= 95 mm Hg (n = 864) were randomized in 1:1 ratio to Valsartan and Valsartan 80 mg (n = 429)/HCTZ80/12.5 mg (n = 435) treatment o.d. for 8 weeks. Safety and efficacy was assessed every 4 weeks during double blind phase.At the end of study, valsartan/HCTZ 80/12.5 mg combination treatment further reduced systolic (-3.5 mm Hg) and diastolic (-2.2 mm Hg) pressures and increased the rate of patients reaching goal BP level (53.9% vs. 40.9%) compared to valsartan 80 mg o.d. monotherapy. Incidence of side effects was similar between the combination therapy and monotherapy groups (8.9% vs. 5.1%, P0.05).Efficacy of Valsartan 80 mg/HCTZ 12.5 mg compound was superior to valsartan 80 mg on BP reduction and goal BP control rate in Chinese patients with mild to moderate essential hypertension. The combination of Valsartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg provides a suitable treatment for Chinese patients who are not adequately controlled by valsartan 80 mg o.d. monotherapy.

To explore the relationship between the expression of CD133 and pathogenesis of leukemia and MDS, immunocytochemistry method was used to examine the expression of CD133 in bone marrow cells of patients with leukemia and MDS. The results showed that the positive rate of CD133 in 41 acute leukemia patients was 51.2%. The expression of CD133 in AML patients (16/29, 55.2%) was significantly higher than that in control group (2/15, 13.3%). There was no significant difference in CD133 expression between CML and control group. The positive rate of CD133 in 9 patients with MDS was 55.56% (5/9). There was no significant difference between MDS and normal control. The expression of CD133 in all leukemia cells with CD34(+) was higher than that in leukemia cells with CD34(-), and there was significant difference in expression of CD133 between them (P0.05). The expression of CD133 had no relationship with the clinical prognostic factors such as sex, age, the percentage of leukemic cells in peripheral blood and in bone marrow, WBC counts, hemoglobin concentration, platelet counts and LDH level. It is concluded that the expression of CD133 in bone marrow cells of patients with AML is higher than that in control group. The expression of CD133 is significantly correlated with the expression of CD34. The high expression of CD133 may be an adverse prognostic factor in acute leukemia.

To investigate the expression of pituitary tumor-transforming gene (PTTG) and basic fibroblast growth factor (b-FGF) in acute leukemia, as well as the relationship of their expression with prognosis in acute leukemia, expressions of PTTG and b-FGF in acute leukemia (AL) specimens were detected by immunocytochemical technique. The results showed that the expressions of PTTG and b-FGF in AL group were higher than that in the control group significantly (P0.01). In AL group, after chemotherapy, the expression of PTTG and b-FGF in de novo patients group was higher than in the complete remission patient group significantly (P0.01). The expressions of PTTG and b-FGF showed positive correlation (r = 0.61, P0.01). It is concluded that Up-regulation of PTTG and b-FGF expression may be involved in the progression of acute leukemia and correlated closely with therapeutic effect. Associated detection of PTTG and b-FGF may help to judge the malignancy degree and prognosis of acute leukemia.

To assess the indication and efficacy of surgical treatment for patients with hepatic metastases from gastric cancer.Clinical data of 43 patients with hepatic metastases from gastric cancer undergoing surgery from September 1995 to May 2002 were analyzed retrospectively.No relationships were found between the number of hepatic metastases and patient's gender, age, tumor invasion depth, lymphatic node metastases and differentiation P0.05. All of 43 patients underwent surgery. Four cases undergoing hepatic resection for metachronous hepatic metastases had a higher survival rate than those who had curative resections for synchronous hepatic metastases (median survival 35 months vs. 10 months) (P=0.0233). 39 patients had synchronous hepatic metastases, of whom 32 patients received gastric resection only and 7 patients received both gastric and hepatic resections, there was significant difference of median survival between synchronous group and metachronous group(median survival 6.0 vs. median survival 10.0 months)(P=0.2799). There was significant difference of the postoperative survival rate among H (1) (7.5 months), H (2) (6 months) and H (3) (4 months) in the patients with palliative gastric resections (P=0.0007).Hepatic resection for metachronous hepatic metastases from gastric cancer has a better prognosis. Resections of gastric and hepatic lesions at the same time may not benefit the patients with liver metastases from gastric cancer. H(3) is not feasible for palliative gastric resections.

To understand the epidemiological characteristics of essential hypertension in the northern and western areas of China.A community-based sampling survey.Rates of awareness, treatment and control were 78.6%, 59.7% and 5.9%, respectively. About half of the diagnosed and treated patients took antihypertensive medicine irregularly before the survey was carried out.It is necessary to carry out education, prevention and control on hypertension and to establish a series of standards for the management and treatment on cases of hypertension.