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Objective: Various modalities are applied for pathological diagnosis of malignant biliary strictures (MBS), including brush cytology (BC), forceps biopsy (FB) and endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA). We aimed to assess the value of these modalities in a repeated tissue acquisition process for biliary strictures with initially inconclusive pathological outcomes. Methods: Patients who were suspected of having MBS and underwent a BC in two large teaching hospitals were retrospectively included. The sensitivity, specificity, positive and negative predictive values, and accuracy of the initial and repeated BC, FB and EUS‐FNA were analyzed. Their performances were compared to determine which modality was superior in repeated tissue acquisition. Results: In total, 476 patients were included. The sensitivity, specificity and accuracy in diagnosing MBS for the initial BC were 30.3%, 100% and 55.0%, respectively. Altogether 39, 27 and 44 patients underwent a repeat BC, FB and EUS‐FNA, respectively. The sensitivity for repeated BC, FB and EUS‐FNA was 41.2%, 61.1% and 44.4%, respectively, whereas their specificity all reached 100%. When comparing diagnostic accuracy, none of the modalities was superior (74.4% vs 74.1% vs 54.5%, P = 0.173). In the repeated process, one patient who underwent BC and two underwent FB developed mild pancreatitis. Conclusions: Repeated tissue acquisition achieves a conclusive diagnosis of MBS in nearly half patients who have an initially inconclusive cytological diagnosis. None of the tissue acquisition methods is significantly superior in the repeated process. [ABSTRACT FROM AUTHOR]

We describe a modified Z-scan technique for the case when nonlinear refraction is accompanied by nonlinear absorption to separately evaluate the nonlinear refraction and the nonlinear absorption by performing straightforward measurements with the aperture removed. We divide the closed aperture (S < 1) normalized Z-scan by a scan with an open aperture (S = 1). With nanosecond scale at a 532 nm wavelength, we first measured the nonlinear optical absorption and refraction coefficients of a solution of Ni(Ac)[SUB2][N-(8-quinolyl) pyridine-2-carboxamide] 4H[SUB2]O by using the modified Z-scan technique. The nonlinear absorption originates from the near resonant two-photon absorption while the mechanism of the nonlinear refraction is the near resonant two-photon absorption transition enhancement. The linear increasing dependences of the optical nonlinearities on the incident irradiance arise from the population redistribution due to the near resonant two-photon absorption. [ABSTRACT FROM AUTHOR]

The crystal structures of N, N′-(1,2-phenyl­ene)­bis­(pyridine-2-carbox­amide), C18H14N4O2, (I), and N, N′-(1,2-cyclo­hexane­diyl)­bis­(pyridine-2-carbox­amide) have been determined, the latter compound as the toluene hemisolvate, C18H20N4O2·0.5C7H8, (II). In (I), the benzene ring is nearly coplanar with one of the pyridine rings and forms a dihedral angle of 59.4 (1)° with the other. However, in (II), the dihedral angle of the two pyridine rings is 70.0 (1)°. [ABSTRACT FROM AUTHOR]

Background: The Methylenetetrahydrofolate Dehydrogenase (MTHFD) family plays an important role in the development and prognosis of a variety of tumors; however, the role of the MTHFD family in bladder cancer is unclear., Methods: R software, cBioPortal, GeneMANIA, and online sites such as String-LinkedOmics were used for bioinformatics analysis., Results: MTHFD1/1L/2 was significantly upregulated in bladder cancer tissues compared with normal tissues, high expression of the MTHFD family was strongly associated with poorer clinical grading and staging, and bladder cancer patients with upregulated expression of MTHFD1L/2 had a significantly worse prognosis. Gene function and PPI network analysis revealed that the MTHFD family and related genes play synergistic roles in the development of bladder cancer. 800 co-expressed genes related to the MTHFD family were used for functional enrichment analysis, and the results showed that many genes were associated with various oncogenic pathways such as cell cycle and DNA replication. More importantly, the MTHFD family was closely associated with multiple infiltrating immune lymphocytes, including Treg cells, and immune molecules such as TNFSF9, CD274, and PDCD1., Conclusion: Our study shows that MTHFD family genes may be potential prognostic markers and therapeutic targets for patients with bladder cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The aim of the present study was to evaluate the influence of tumor necrosis factor-alpha (TNF-α) -308 G > A polymorphism on hepatocellular carcinoma (HCC) risk., Methods: The present case-control study was conducted in a Han Chinese population consisting of 753 HCC patients and 760 controls from May 2010 to March 2013. The -308 TNF-a promoter polymorphisms were detected. Conditional logistic regression was performed to analyze the association between TNF-α -308 G > A polymorphism and the risk of HCC, which were estimated by odds ratios (ORs) and their 95% confidence intervals (95% CIs)., Results: The genotypic frequencies in the cases were not similar to that of the controls, differences being statistically significant (P = 0.002). Using the GG genotype as the reference genotype, AA was significantly associated with increased risk of HCC (adjusted OR = 5.12, 95% CI = 2.31-7.82). Similarly, AG + AA genotype showed 5.59-fold increased HCC risk in a dominant model. Furthermore, we found A allele was significantly associated with increased risk of HCC, compared with G allele (OR = 4.18, 95% CI = 1.76-6.97)., Conclusion: The present study showed that TNF-α -308 G > A polymorphism was associated with increased HCC risk in a Han Chinese population. Further prospective studies on large and different ethnic populations will be necessary to confirm our findings and elucidate the underlying molecular mechanism for the development of HCC., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000&#95;2014&#95;199.

Objective: To explore the effects of Huqi Extractum (HQE) on the viability and apoptosis in mouse thymic lymphocytes against 60Co radiation., Methods: Thymic lymphocytes were isolated from 4 -8 weeks healthy male Kunming mice and primarily cultured. Then they were divided into the control group, the irradiation group, the low dose HQE group, the medium dose HQE group, and the high dose HQE group. Equal volume of serum free RPMI-1640 culture solution was added in the control group and the irradiation group, while equal volume of HQE solution (at the daily dose of 25, 50, and 100 mg/mL) was respectively added in the low, medium, and high dose HQE groups. Except the control group, those in the rest groups were exposed radiation at a single dose of 5 Gy gamma-ray. Changes of the thymic lymphocytes' viability were measured by MTT colorimetric assay at 12, 24, 36, and 48 h after radiation. The early apoptosis rate was detected using flow cytometry (FCM) after 10-h radiation. The apoptosis was detected using agarose gel electrophoresis to observe the DNA injury after 24-h radiation., Results: The viability level decreased more obviously in the irradiation group than in the control group at 24 -48 h after radiation (P < 0.01, P < 0.05). The average viability level was obviously higher in the low, medium, and high dose HQE groups than in the irradiation group (P < 0.05) in a dose dependent manner. The early apoptosis rate was obviously lower in the low, medium, and high dose HQE groups than in the irradiation group, with statistical difference shown in the high dose HQE group (P < 0.01). Typical DNA ladder fragments were found in the electrophoresis in all groups except the control group. But the DNA injury was comparatively milder in the low, medium, and high dose HQE groups, with more obvious effects shown in the high dose HQE group., Conclusion: HQE showed protection for the viability of early thymic lymphocytes exposed to the 60CO radiation, and could lower the early apoptosis level.

Objective: To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) plus embolotherapy in the treatment of patients with gastroesophageal varices., Methods: A total of 36 patients with gastroesophageal varices underwent the therapies of TIPS plus embolotherapy from July 2005 to March 2011 at Provincial Hospital Affiliated to Shandong University. The rechecked items included abdominal ultrasound examination, liver function test and blood routine examination at Day 7 post-operation. All received endoscopic examinations at Month 1., Results: The technical success rate of TIPS plus embolotherapy was 100%. The portal vein pressures declined from (28 ± 8) mm Hg (1 mm Hg = 0.133 kPa) to (14 ± 7) mm Hg at post-operation. Angiography showed gastroesophageal varices disappeared in all patients. Both liver function and gastroesophageal varices markedly improved. During the follow-up period of 3 - 6 months, 4 cases had hepatic encephalopathy and 1 case stent restenosis at post-operation. And most cases were resolved after treatment. No rebleeding occurred during the follow-up period., Conclusions: The combined modality of TIPS plus embolotherapy can effectively lower portal vein pressure and cure esophageal and gastric varice bleeding. As a safe and excellent interventional procedure with fewer complications and a lower recurrence rate of portal hypertension, it has great clinical values in the treatment of portal hypertension and gastroesophageal varices.

To analyze the characteristics of serum sodium in decompensated cirrhosis and evaluate the prognostic ability of the model for end-stage liver disease (MELD) in Na-containing models. Patients diagnosed with decompensated cirrhosis at our hospital were enrolled for study between June 2005 and October 2010. Patients were classified among three groups, according to serum sodium concentration: less than 125 mmol/L, 125 to 135 mmol/L, and more than 135 mmol/L. Mortality rates among the three groups were compared by Kaplan-Meier survival analysis. In addition, the different serum sodium concentrations were analyzed for correlations between Child-Pugh score and complication incidence rates of portal hypertension. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare the predictive abilities of MELD, MELD-Na, and the integrated (i) MELD scores for 3-month, 6-month and 1-year mortalities. A total of 467 patients were analyzed, and 50.54% had hyponatremia ( less than 135 mmol/L). Sodium concentration was correlated with mortality, and Kaplan-Meier survival analysis indicated that mortality was significantly higher in each subgroup with lower sodium concentration (all, P = 0.000). Likewise, sodium concentration decreased in conjunction with increased severity of decompensation, as classified by Child-Pugh scoring (sodium: A more than B more than C; mortality: A less than B less than C). With the exception of digestive tract bleeding, complication incidence rates of hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome increased when sodium concentration decreased. For predicting 3-month mortality, the AUC scores of MELD were not significantly different from the MELD-Na and iMELD scores (P more than 0.05). For predicting 6-month and 1-year mortality, the AUC scores of MELD-Na and iMELD were significantly higher than those of MELD (P less than 0.05). Hyponatremia is correlated with mortality and complications in decompensated cirrhosis patients. Incorporation of Na into the MELD may enhance it's prognostic ability.

Objective: To evaluate the effect of portal hypertension on prognosis in patients with decompensated liver cirrhosis., Methods: The clinical data of decompensated cirrhosis patients in our hospital, between 2003 and 2006, were retrospected and followed up. Model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) classification was calculated using the standard formula. Kaplan-Meier survival analysis was used to compare the mortality in subgroups ranked by the syndromes. Cox proportional hazards regression was used to evaluate the effect of the syndromes on prognosis., Results: A cohort of 322 patients was admitted in this study at the end of the follow-up. The mortality of variceal bleeding, hepatic encephalopathy, a large volume ascites, spontaneous bacterial peritonitis, the type I and type II hepatorenal syndrome was 45.9%, 79.4%, 66.7%, 100%, 100% and 84.6% respectively. On the whole, the occurrence of all the syndromes was correlated with CTP classification and MELD score. Kaplan-Meier survival analysis showed that all of these syndromes, except for low to medium volume of ascites, significantly affected the survival rate (P<0.01). In Cox regression analysis, all the syndromes were the independent predictors of prognosis, the regression coefficient values of hepatic encephalopathy, spontaneous bacterial peritonitis, type I and type II hepatorenal syndrome, variceal bleeding and ascites were 0.973, 0.928, 0.935, 0.866, 0.464 and 0.369 respectively., Conclusions: The portal hypertensive syndromes have significant effect on the prognosis of the patients with decompensated cirrhosis, hepatic encephalopathy is the worst one.

Objective: To test the safety and validity of percutaneous transhepatic variceal embolization (PTVE) with tissue adhesive cyanoacrylate., Methods: PTVE with cyanoacrylate was performed on 92 patients with gastroesophageal varices, 53 males and 39 females, aged 62.5 (7-84): cyanoacrylate was injected into the varices and the afferent veins. Endoscopy and CT were performed to evaluate the embolization., Results: PTVE was successfully completed in 89 of the 92 patients with a technical success rate of 96.7%, and 3 patients died within 1 month. Among the other 86 patients 3 types of cyanoacrylate embolization were achieved: embolization of coronary vein, vessels around gastric fundus, and variceal lower esophagus veins in 40 patients, embolization of coronary vein, gastric fundus and pericardial varices in 33 patients, and embolization of sole gastric coronary vein stem in 13 patients. Acute variceal bleeding in 18 patients was immediately arrested after the procedure, with an acute bleeding control rate of 100%. Eighty-six patients were followed up for 31.5 (6-52) months. The general variceal recurrence rate was 14.1% (10/71), and the variceal recurrence rate of the coronary vein embolization group was 100% (2/2), significantly higher than those of the groups of esophagus and fundus embolization and gastric fundus and cardia varices embolization [7.5% (3/40) and 17.2% (5/29) respectively, P = 0.006]. The general rebleeding rate was 16.3% (14/86), and the rebleeding rates of the group of coronary vein embolization was 69.2% (9/13), significantly higher than those of the groups of esophagus and fundus embolization and gastric fundus and cardia varices embolization [7.5% (3/40) and 15. 2% (5/33) respectively, P = 0.0092]. No obvious ectopic embolization was found. The mortality was 24.7% (22/89). The cause of rebleeding in coronary vein embolization was mainly recurrent variceal bleeding, whereas that in the group of fundus and esophagus variceal embolization was mainly hypertensive gastropathy., Conclusion: PTVE with cyanoacrylate is safe and effective for the obliteration of gastroesophageal varices in cirrhotic patients.

Objective: To study the clinical efficacy of TH glue (cyanoacrylate) obliteration of esophageal varices and partial spleen embolization (PSE) in the treatment of esophageal varices bleeding., Methods: TH glue was injected into the gastroesophageal varices and their feeder veins in 84 patients. According to the size of the varices and their blood flow, the TH glue was injected alone or after a steel coil was placed at the ostium of the feeder vein. Sometimes absolute alcohol was also injected into the varices. PSE was performed after the TH glue obliteration in all patients., Results: (1) The TH glue obliteration was performed on 81 patients with a success rate of 96.4%. Three patients died from the procedure. (2) The left gastric vein coronary, gastric varices, pericardial varices, and lower esophageal veins were obliterated in 38 patients (group 1). Left gastric vein, gastric varices, and pericardial veins were obliterated in 31 patients (group 2). Only the main gastric coronary vein was obliterated in 9 patients (group 3). The disappearance rate of the esophageal varices was 71.1% (27/38), 35.5% (11/31) and 0% (0/9) in the three groups. (3) During a follow-up of 6-49 months, rebleeding occurred in 13 of all 78 (16.7%) patients, and it was 7.9% (3/38), 12.9% (4/31) and 66.7% (6/9) respectively in the three groups., Conclusion: Our results suggest percutaneous transhepatic TH glue obliteration of esophageal varices and PSE are safe and effective in treating gastroesophageal varicose bleeding.

It is very important to disrupt the stratum corneum structure and to create pathways allowing transport of macromolecules, as the traditional transdermal drug delivery has been severely limited by the skin barrier. With the development of the Micro Electro-Mechanical System (MEMS), it becomes possible for microneedles array to strengthen the transdermal drug delivery. In addition to the increase of the skin permeability, it can also be used to deliver drugs into skin, such as insulin and vaccine, providing a new direction for drug delivery systems. In this paper, we review the development and applications in transdermal drug delivery of microneedles' array. The commercial prospects and recommendations for the future research work are also represented.

Objectives: The prognostic ability of the model for end-stage liver disease (MELD) has been validated in many countries, but its abilities remain uncertain in China. Our aim is to evaluate the abilities of MELD in prognosis of liver cirrhosis., Methods: A cohort of 315 patients with liver cirrhosis were retrospectively studied and followed up at least for one year. MELD score was obtained for each patient according to the modified formula by Kamath P.S.. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare MELD and Child-Turcotte-Pugh (CTP) score and classification in predicting accuracy. Kaplan-Meier survival analysis was used to compare the mortality in subgroups ranked by the MELD score., Results: The AUC values generated by the ROC curves for the MELD were 0.95, 0.85 and 0.83 respectively in predicting 3, 6 month and 1 year survival, and were all more than 0.80 in predicting longer time survival, whereas the AUC was 0.82, 0.78, 0.74 for CTP score and 0.70, 0.66, 0.61 for CTP classification respectively in predicting 3, 6 month and 1 year survival. The differences of AUCs between the MELD and CTP classification were significant in predicting 6 month and 1, 3 and 4 year survival, but were not significant in predicting other time point survival. The differences of AUCs between the MELD and CTP score were not significant in predicting survival. In the subgroups of patients ranked by MELD score lower than 10, 10 to 20, 20 to 30, and more than 30, the survival rate was significant different (P = 0.000)., Conclusions: MELD is a useful prognosis indicator for the liver cirrhosis. The ability of prognosis by MELD is similar to Child-Turcotte-Pugh classification and score.

Background: The proportion of alcoholic liver disease among all kinds of liver diseases in China is increasing. Recent research has elucidated the mechanisms of alcohol-induced liver injury and offered the prospect of advances in the management of alcoholic liver disease., Data Resources: Searching MEDLINE (1982-July 2004) for papers on alcoholic liver disease, especially those on the treatment of alcoholic liver disease., Results: Abstinence remains the cornerstone of management of all forms of alcoholic liver disease. Nutritional support therapy is also a basal treatment. Corticosteroids may be benefitial for some severe alcoholic hepatitis. None of other measures including anti-inflammatory agents, antioxidants or colchicine has been shown consistently to improve the course of alcoholic liver damage. Ultimately, liver transplantation remains an option for selected patients with liver failure due to chronic alcoholic liver disease., Conclusions: Abstinence and nutritional support remain the base management of alcoholic liver disease. Corticosteroid is efficient for some severe alcoholic hepatitis. Anti-inflammatory agents and antioxidants may be of benefit but need further studies. The efficacy of other measures including the use of colchicine and propylthiouracil is controversial. Liver transplantation remains an option for selected patients with liver failure.