Assessment of different modalities for repeated tissue acquisition in diagnosing malignant biliary strictures: A two-center retrospective study.

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.

[Correlation of serum androgen levels with lipid metabolism in middle-aged and elderly men in Zunyi, Guizhou].

OBJECTIVE: To investigate the relationship of the levels of serum androgens with lipid metabolism in middle-aged and elderly men in Zunyi, Guizhou. METHODS: Using the stratified cluster sampling method, we conducted a questionnaire investigation and physical examinations among 437 men in Zunyi City. We divided the subjects into a middle-aged (40－64 ï¼»53.20 ± 7.41ï¼½ years, n = 269) and an elderly group (=≥65 ï¼»70.63 ± 4.66ï¼½ years, n = 168) and collected fasting elbow venous blood samples from them for measuring the levels of total testosterone (TT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), total cholesterol (TCH), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), calculated free testosterone (cFT), free testosterone index (FTI), and testosterone secretion index (TSI). RESULTS: Compared with the elderly group, the middle-aged males showed significantly lower SHBG, LH, HDL and LDL, and higher cFT, FTI, TSI, TG and TCH (all P < 0.05). TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, while cFT was positively correlated with TCH, and so was FTI with TG, TCH with LDL, and TSI with TCH, HDL and LDL (all P < 0.05), but LH was negatively correlated with TG, TCH and LDL (all P < 0.05). Multivariate linear regression analysis showed that TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, and so was LH with TCH, HDL and LDL (all P < 0.05). CONCLUSIONS: In the middle-aged and elderly men in Zunyi, low concentrations of TT, SHBG and LH were associated with the increased risk of high-TCH and -LDL dyslipidemia, low concentrations of TT and SHBG with that of high-TG dyslipidemia, while high concentrations of TT, SHBG and LH with that of low-HDL dyslipidemia.

[Vasectomy has no obvious longterm influence on the levels of serum androgens in aging males].

OBJECTIVE: To explore the longterm influence of vasectomy on the levels of serum androgens in aging males. METHODS: Using stratified random sampling, we conducted a questionnaire survey and physical examinations among 437 adult males aged ≥40 years, 232 with and 205 without the history of vasectomy. In addition, we measured the levels of serum total testosterone (TT), sexhormone binding globulin (SHBG), calculated free testosterone (cFT), testosterone secreting index (TSI), free testosterone index (FTI), and luteinizing hormone (LH). RESULTS: Compared with the nonvasectomy group, the vasectomy group showed significantly increased levels of serum TT (ï¼»16.01±5.41ï¼½ vs ï¼»17.39±6.57ï¼½ nmol/L), SHBG (ï¼»58.91±36.89ï¼½ vs ï¼»70.28±40.90ï¼½ nmol/L), and LH (ï¼»8.86±6.49ï¼½ vs ï¼»10.85±11.73ï¼½ IU/L) (all P< 0.05) and a decreased level of FTI (0.33±0.15 vs 0.30±0.12, P< 0.05). There were no statistically significant differences between the nonvasectomy and vasectomy groups in cFT (ï¼»0.24±0.07ï¼½ vs ï¼»0.23±0.09ï¼½ nmol/L) or TSI (ï¼»2.42±1.34ï¼½ vs ï¼»2.46±1.51ï¼½ nmol/IU) (both P>0.05), nor after adjustment for relevant factors in TT (ß: 1.015, 95% CI: －0.180－2.210), SHBG (ß: 5.118, 95% CI: －2.069－12.305), cFT (ß: 0.003, 95% CI: －0.011－0.018), FTI (ß: －0.012, 95% CI: －0.035－0.011), TSI (ß: 0.138, 95% CI: －0.131－0.407), and LH (ß: 1.011, 95% CI: －0.811－2.834) (all P>0.05). CONCLUSIONS: Vasectomy has no obvious longterm influence on the levels of serum androgens in aging males.

[Effect and safety of testosterone undecanoate in the treatment of late-onset hypogonadism: a meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of testosterone undecanoate (TU) in the treatment of late-onset hypogonadism (LOH) by meta-analysis. METHODS: We searched Pubmed (until April 1, 2014), Embase (until March 28, 2014), Cochrane Library (until April 17, 2014), CBM (from January 1, 2001 to February 2, 2014), CNKI (from January 1, 2001 to February 2, 2014), Wanfang Database (from January 1, 2000 to February 2, 2014), and VIP Database (from January 1, 2000 to Febru ary 2, 2014) for randomized controlled trials of TU for the treatment of LOH. We evaluated the quality of the identified literature and performed meta-analysis on the included studies using the Rveman5. 2 software. RESULTS: Totally, 14 studies were included after screening, which involved 1 686 cases. Compared with the placebo and blank control groups, TU treatment significantly increased the levels of serum total testosterone (SMD = 6.22, 95% CI 3.99 to 8.45, P < 0.05) and serum free testosterone (SMD = 4.35, 95% CI 1.86 to 6. 85, P < 0.05) but decreased the contents of luteinizing hormone (WMD = -2.23, 95% CI -4.03 to -0.42, P < 0.05), sex hormone binding globulin (WMD = 2.00, 95% CI 1.38 to 2.63, P < 0.05). TU also remarkably reduced the scores of Partial Androgen Deficiency of the Aging Males (WMD = -9.49, 95% CI -12.96 to -6.03, P < 0.05) and Aging Males Symptoms rating scale (WMD = -2.76, 95% CI -4.85 to -0.66, P <0.05) but increased the hemoglobin level (SMD = 2.35, 95% CI 0.29 to 4.41, P < 0.05) and packed-cell volume (SMD = 4.35, 95% CI 1.36 to 7.33, P < 0.05). However, no significant changes were shown in aspertate aminotransferase, alanine transaminase, prostate-specific antigen, or prostate volume after TU treatment (P > 0.05). CONCLUSION: TU could significantly increase the serum testosterone level and improve the clinical symptoms of LOH patients without inducing serious adverse reactions. However, due to the limited number and relatively low quality of the included studies, the above conclusion could be cautiously applied to clinical practice.

Tumor necrosis factor-alpha gene -308G > A polymorphism alters the risk of hepatocellular carcinoma in a Han Chinese population.

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_2014_199.

Smad7 inhibits AngII-mediated hypertensive nephropathy in a mouse model of hypertension.

The TGFß (transforming growth factor ß)/SMAD and NF-κB (nuclear factor κB) signalling pathways play a key role in hypertensive nephropathy. The present study examined whether targeting these pathways by SMAD7, a downstream inhibitor of both pathways, blocks AngII (angiotensin II)-induced hypertensive kidney disease in mice. A doxycycline-inducible SMAD7-expressing plasmid was delivered into the kidney by a non-invasive ultrasound-microbubble technique before and after AngII infusion. Results showed that pre-treatment with SMAD7 prevented AngII-induced progressive renal injury by inhibiting an increase in proteinuria and serum creatinine while improving the glomerular filtration rate. Similarly, treatment with SMAD7 in the established hypertensive nephropathy at day 14 after AngII infusion halted the progressive renal injury. These preventive and therapeutic effects of SMAD7 on hypertensive kidney injury were associated with inhibition of AngII-induced up-regulation of SMURF2 (SMAD-specific E3 ubiquitin protein ligase 2) and Sp1 (specificity protein 1), blockade of TGFß/Smad3-mediated renal fibrosis and suppression of NF-κB-driven renal inflammation. Moreover, overexpression of SMAD7 also prevented AngII-induced loss of renal miR-29b, an miRNA with an inhibitory role in both TGFß/Smad3 and NF-κB pathways. In conclusion, SMAD7 may be a therapeutic agent for AngII-mediated hypertensive nephropathy. Inhibition of the Sp1/SMAD3/NF-κB/miR-29b regulatory network may be a mechanism by which SMAD7 inhibits hypertensive nephropathy.

MDCT angiography to evaluate the therapeutic effect of PTVE for esophageal varices.

AIM: To evaluate the role of multi-detector row computed tomography (MDCT) angiography for assessing the therapeutic effects of percutaneous transhepatic variceal embolization (PTVE) for esophageal varices (EVs). METHODS: The subjects of this prospective study were 156 patients who underwent PTVE with cyanoacrylate for EVs. Patients were divided into three groups according to the filling range of cyanoacrylate in EVs and their feeding vessels: (1) group A, complete obliteration, with at least 3 cm of the lower EVs and peri-/EVs, as well as the adventitial plexus of the gastric cardia and fundus filled with cyanoacrylate; (2) group B, partial obliteration of varices surrounding the gastric cardia and fundus, with their feeding vessels being obliterated with cyanoacrylate, but without reaching lower EVs; and (3) group C, trunk obliteration, with the main branch of the left gastric vein being filled with cyanoacrylate, but without reaching varices surrounding the gastric cardia or fundus. We performed chart reviews and a prospective follow-up using MDCT images, angiography, and gastrointestinal endoscopy. RESULTS: The median follow-up period was 34 mo. The rate of eradication of varices for all patients was 56.4% (88/156) and the rate of relapse was 31.3% (41/131). The rates of variceal eradication at 1, 3, and 5 years after PTVE were 90.2%, 84.1% and 81.7%, respectively, for the complete group; 61.2%, 49% and 42.9%, respectively, for the partial group; with no varices disappearing in the trunk group. The relapse-free rates at 1, 3 and 5 years after PTVE were 91.5%, 86.6% and 81.7%, respectively, for the complete group; 71.1%, 55.6% and 51.1%, respectively, for the partial group; and all EVs recurred in the trunk group. Kaplan-Meier analysis showed P values of 0.000 and 0.000, and odds ratios of 3.824 and 3.603 for the rates of variceal eradication and relapse free rates, respectively. Cyanoacrylate in EVs disappeared with time, but those in the EVs and other feeding vessels remained permanently in the vessels without a decrease with time, which is important for the continued obliteration of the feeding vessels and prevention of EV relapse. CONCLUSION: MDCT provides excellent visualization of cyanoacrylate obliteration in EV and their feeding veins after PTVE. It confirms that PTVE is effective for treating EVs.

Disruption of Smad7 promotes ANG II-mediated renal inflammation and fibrosis via Sp1-TGF-ß/Smad3-NF.κB-dependent mechanisms in mice.

Smad7 is an inhibitory Smad and plays a protective role in obstructive and diabetic kidney disease. However, the role and mechanisms of Smad7 in hypertensive nephropathy remains unexplored. Thus, the aim of this study was to investigate the role and regulatory mechanisms of Smad7 in ANG II-induced hypertensive nephropathy. Smad7 gene knockout (KO) and wild-type (WT) mice received a subcutaneous infusion of ANG II or control saline for 4 weeks via osmotic mini-pumps. ANG II infusion produced equivalent hypertension in Smad7 KO and WT mice; however, Smad7 KO mice exhibited more severe renal functional injury as shown by increased proteinuria and reduced renal function (both p<0.05) when compared with Smad7 WT mice. Enhanced renal injury in Smad7 KO mice was associated with more progressive renal fibrosis with elevated TGF-ß/Smad3 signalling. Smad7 KO mice also showed more profound renal inflammation including increased macrophage infiltration, enhanced IL-1ß and TNF-α expression, and a marked activation of NF-κB signaling (all p<0.01). Further studies revealed that enhanced ANG II-mediated renal inflammation and fibrosis in Smad7 KO mice were also associated with up-regulation of Sp1 but downregulation of miR-29b expression. Taken together, the present study revealed that enhanced Sp1-TGF-ß1/Smad3-NF-κB signaling and loss of miR-29 may be mechanisms by which deletion of Smad7 promotes ANG II-mediated renal fibrosis and inflammation. Thus, Smad7 may play a protective role in ANG II-induced hypertensive kidney disease.

[Changes of reflectance spectra of pine needles in different stage after being infected by pine wood nematode].

In the present study, seedlings of Pinus Thunbergii and Pinus Massoniana were planted and used for reflectance spectrum measurement. In different stage after being infected by pine wood nematode, reflectance spectra were measured by ASD spectrometer and the features of spectral parameters and the change of chlorophyll were analyzed. The results showed that (1) Disease could be estimated in the early stage according to the curve of mid-infrared reflectance; (2) Dynamic parameters such as the position of red edge, green peak height, reflectance of red band, slope of red edge and reflectance of water-stressed wave band were consistent with the disease features of two pine species after being infected by pine wood nematode; (3) To both of two pine species, content of chlorophyll tended to reduce with the development of disease and obvious linear relationship was observed between chlorophyll content and spectral parameters. There results might be able to provide some theoretical basis for the application of remote sensing technology in monitoring of pine wood disease. In addition, it might be also used as theoretical support for the controlling measures in different stage after being infected by pine wood nematode.

[Construction and application of probability distribution model for mixed forests measurement factors].

Aiming at the deficiencies in the researches about the probability distribution model for mixed forests tree measurement factors, a joint maximum entropy probability density function was put forward, based on the maximum entropy principle. This function had the characteristics of 1) each element of the function was linked to the maximum entropy function, and hence, could integrate the information about the probability distribution of measurement factors of main tree species in mixed forests, 2) the function had a probability expression of double-weight, being possible to reflect the characteristics of the complex structure of mixed forests, and accurately and completely reflect the probability distribution of tree measurement factors of mixed forests based on the fully use of the information about the probability distribution of measurement factors of main tree species in mixed forests, and 3) the joint maximum entropy probability density function was succinct in structure and excellent in performance. The model was applied and tested in two sampling plots in Tianmu Mountain Nature Reserve. The fitting precision (R2 = 0.9655) and testing accuracy (R2 = 0.9772) were both high, suggesting that this model could be used as a probability distribution model for mixed forests tree measurement factors, and provided a feasible method to fully understand the comprehensive structure of mixed forests.

[Integrated Chinese and western medicinal treatment on systemic lupus erythematosus characterized by hypoplastic bone marrow].

OBJECTIVE: To study the clinical effect of combined treatment with gamma-globulin, corticosteroids, immunosuppressor and Chinese medicines on systemic lupus erythematosus (SLE) patients characterized by hypoplastic bone marrow (HBM). METHODS: Nineteen patients were randomly assigned to two groups, the treated group (10 cases) received combined therapy of prednisone and cyclophosphamide (CTX) plus Chinese medicine Langchuang Recipe after being treated impactively with gamma-globulin. The control group (9 cases) was treated with prednisone and CTX. Changes of hypoplastic bone marrow, peripheral white blood cell (WBC), complement C3, 24 h urinary protein excretion, and lupus activity index (LAI) were observed, and a follow-up was carried out for one year. RESULTS: After one-month treatment, the bone marrow hypoplasia was relieved significantly in the treated group (P < 0.05, P < 0.01), showing an improvement superior to that in the control group (P < 0.05, P < 0.01); after three months treatment, the level of complement C3 increased (P < 0.01), while the 24 h urinary protein excretion and LAI decreased in the treated group (P < 0.05), showing significant difference as compared with those in the control group (P < 0.05, P < 0.01). In the follow-up period, 3 cases withdrew from the trial because of infection and 4 cases manifested full moon-face and acne in the control group, while no adverse reaction was found in the treated group. CONCLUSION: Treatment with integrated Chinese and Western medicine could effectively improve bone marrow hypoplasia, alleviate the clinical symptoms, suppress the activity of lupus in patients, and reduce the adverse reaction of treatment, showing a superiority to the treatment with prednisone combining with CTX.