The PTGS1 (rs1330344) CC Genotype Contributes to Susceptibility to Kawasaki Disease in Southern Chinese Children.

Kawasaki disease (KD) is an acute systemic vascular disease complicated by coronary artery injury. Although polymorphisms in prostaglandin-endoperoxide synthase 1 (PTGS1) are being increasingly explored in cardiovascular diseases, little is known regarding the connection between PTGS1 polymorphisms and KD risk. We evaluated 834 KD patients and 1474 healthy controls to explore the relationship between PTGS1 polymorphisms (rs1330344 and rs5788) and KD risk. Our results showed that the rs1330344 CC genotype was significantly associated with KD risk and coronary artery injury in children with KD. In combined analysis, individuals with 1-2 unfavorable genotypes had an increased risk of KD, compared with those with no risk genotype. Stratified analysis indicated that the rs1330344 CC genotype is strongly associated with increased risk of KD in children aged ≤60 months and females. Moreover, carrying 1-2 of these SNP genotypes had a higher risk of KD than those who harbored none of them in children ≤60 months of age and females; the risk of coronary artery dilatations/small aneurysms and medium/giant aneurysms was also significantly increased in KD patients. In summary, the PTGS1 rs1330344 CC genotype is associated with increased susceptibility to KD, which may contribute to KD pathogenesis and serve as a genetic biomarker.

Myeloid signature reveals immune contexture and predicts the prognosis of hepatocellular carcinoma.

BACKGROUNDDespite an increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the tumor-associated myeloid response balance and its translational value. We aimed to construct a simple and reliable myeloid signature for hepatocellular carcinoma (HCC).METHODSUsing in situ immunohistochemistry, we assessed the distribution of major myeloid subtypes in both peri- and intratumoral regions of HCC. A 2-feature-based, myeloid-specific prognostic signature, named the myeloid response score (MRS), was constructed using an L1-penalized Cox regression model based on data from a training subset (n = 244), a test subset (n = 244), and an independent internal (n = 341) and 2 external (n = 94; n = 254) cohorts.RESULTSThe MRS and the MRS-based nomograms displayed remarkable discriminatory power, accuracy, and clinical usefulness for predicting recurrence and patient survival, superior to current staging algorithms. Moreover, an increase in MRS was associated with a shift in the myeloid response balance from antitumor to protumor activities, accompanied by enhanced CD8+ T cell exhaustion patterns. Additionally, we provide evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC.CONCLUSIONWe identified and validated a simple myeloid signature for HCC that showed remarkable prognostic potential and may serve as a basis for the stratification of HCC immune subtypes.FUNDINGThis work was supported by the National Science and Technology Major Project of China, the National Natural Science Foundation of China, the Science and Information Technology of Guangzhou, the Fundamental Research Funds for the Central Universities, the Guangdong Basic and Applied Basic Research Foundation, and the China Postdoctoral Science Foundation.

The anti-parasitic drug suramin potently inhibits formation of seminal amyloid fibrils and their interaction with HIV-1.

Seminal amyloid fibrils are made up of naturally occurring peptide fragments and are key targets for the development of combination microbicides or antiviral drugs. Previously, we reported that the polysulfonic compound ADS-J1 is a potential candidate microbicide that not only inhibits HIV-1 entry, but also seminal fibrils. However, the carcinogenic azo moieties in ADS-J1 preclude its clinical application. Here, we screened several ADS-J1-like analogs and found that the antiparasitic drug suramin most potently inhibited seminal amyloid fibrils. Using various biochemical methods, including Congo red staining, CD analysis, transmission EM, viral infection assays, surface plasmon resonance imaging, and molecular dynamics simulations, we investigated suramin's inhibitory effects and its putative mechanism of action. We found that by forming a multivalent interaction, suramin binds to proteolytic peptides and mature fibrils, thereby inhibiting seminal fibril formation and blocking fibril-mediated enhancement of viral infection. Of note, suramin exhibited potent anti-HIV activities, and combining suramin with several antiretroviral drugs produced synergistic effects against HIV-1 in semen. Suramin also displayed a good safety profile for vaginal application. Moreover, suramin inhibited the semen-derived enhancer of viral infection (SEVI)/semen-mediated enhancement of HIV-1 transcytosis through genital epithelial cells and the subsequent infection of target cells. Collectively, suramin has great potential for further development as a combination microbicide to reduce the spread of the AIDS pandemic by targeting both viral and host factors involved in HIV-1 sexual transmission.

Identification of molecular biomarkers for the diagnosis of gastric cancer and lymph-node metastasis.

BACKGROUND AND OBJECTIVE: Biomarkers are important tools for prompt diagnosis of cancer. This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node (LN) metastasis. METHODS: Between 1 December 2014 and 31 December 2015, we prospectively collected samples of gastric-cancer tissues, corresponding matched-pair normal gastric mucosa, and their peri-gastric metastatic and non-metastatic LNs to identify quantitatively reliable genes using quantitative real-time polymerase chain reaction. Relative quantity (RQ) was used to calculate the mRNA expression levels of our target genes. Statistics were calculated using one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Analytical graphs were plotted using GraphPad Prism. RESULTS: Of nine assessed genes, the mRNA levels of inhibin beta A (INHBA) and secreted phosphoprotein 1 (SPP1) were most consistently highly expressed in tumor tissues by 15.4- and 15.6-fold, respectively, as compared with normal tissues (P < 0.001), with 91.3% sensitivity and 95.7% specificity (receiver operating characteristic [ROC] curve area = 0.974) for the former and 82.6% sensitivity and 87.0% specificity (ROC curve area = 0.924) for the latter. Further analysis revealed no differentiating significance of SPP1 mRNA expression between metastatic and non-metastatic LNs (P = 0.470). In contrast, the INHBA mRNA level was up-regulated 4.1-fold in metastatic LNs (P < 0.001), with 80.0% sensitivity and 81.5% specificity (ROC curve area = 0.857), and was also able to successfully differentiate between more severe disease conditions, T3 and T4 (P = 0.003), M0 and M1 (P = 0.043) and different histological variants (intestinal type vs diffuse type, P = 0.019). CONCLUSIONS: Our results showed that INHBA was the most optimally reliable biomarker for diagnosing gastric cancer and LN metastasis.

Transplantation of lentiviral-transfected endothelial progenitor cells for pulmonary hypertension and the interventional effect of astragalosides / 中国组织工程研究

BACKGROUND: Activation of CD40 pathway negatively regulates the therapeutic effect of endothelial progenitor cells (EPCs), while inhibition of this pathway can enhance the biological function of the cells. OBJECTIVE: To compare the therapeutic effects of CD40-silenced EPCs (EPCs shRNA-CD40) and conventional EPCs transplantation in an animal model of pulmonary hypertension, and to explore the interventional effect of astragalosides on EPCs transplantation in the treatment of pulmonary hypertension. METHODS: Ninety SD rats were randomly divided into five groups: normal control group (n=24), model group (n=24), lentivirus transfection group (n=18), conventional transplantation group (n=18) and astragaloside group (n=6). Except the normal control group, the remaining four groups were given monocrotaline to induce pulmonary hypertension. Rats in the lentivirus transfection and conventional transplantation groups were given intravenous injection of Lv-shRNA-CD40-transfected EPCs and conventional EPCs respectively at 7, 14, 21 days after modeling (n=6 at each time point). Rats in the astragaloside group were given daily intraperitoneal injection of 80 mg/(kg?d) astragaloside within 1-21 days after modeling, and then Lv-shRNA-CD40-transfected EPCs were intravenously injected at 21 days after modeling. Hemodynamics, plasma endothelin-1 level and right ventricular hypertrophy index were detected at 28 days after modeling. RESULTS AND CONCLUSION: (1) After modeling, right ventricular pressure, mean pulmonary arterial pressure and right ventricular hypertrophy index were all increased compared with the normal control group (P < 0.05), while these indices were then decreased significantly after EPCs transplantation (P < 0.05). With the increasing of transplantation time, there was an increasing trend in the right ventricular pressure, mean pulmonary arterial pressure and right ventricular hypertrophy index in the two EPCs transplantation groups, but this trend was not remarkable in the lentivirus transfection group. (2) After modeling, the level of endothelin-1 was increased significantly compared with the normal control group (P < 0.05), and then decreased after EPCs transplantation (P < 0.05). The level of endothelin-1 in the lentivirus transfection group was significantly lower than that in the conventional transplantation group at the same time point (P < 0.05). (3) A significant improvement in hemodynamics, plasma endothelin-1 level and right ventricular hypertrophy index was observed in the astragaloside group as compared with the lentivirus transfection group (P < 0.05). Given the above findings, CD40-silenced EPCs transplantation is more effective and durable than the conventional transplantation in the treatment of pulmonary hypertension, and moreover, astragaloside can enhance the therapeutic effect.

[Lactic acid inhibits the formation of semen-derived amyloid fibrils].

OBJECTIVE: To investigate the inhibitory effect of lactic acid on semen-derived amyloid (SEVI) fibril formation. METHODS: PAP248-286 (2 mg/mL) was incubated with 4.0, 2.0, 1.0, 0.5, 0.25, and 0.125 mg/mL of lactic acid. After incubation for different times, aliquots were drawn from each sample for Thioflavin T (ThT) and Congo red staining to monitor semen-derived amyloid fibril formation. The ß sheet structure formation of PAP248-286 was measured by circular dichroism spectrum, and the morphology of amyloid fibrils incubated with or without lactic acid was observed with transmission electron microscopy (TEM). The enhancing effect of amyloid fibril incubated with lactic acid at different time points was determined using virus infection assay. PAP248-286 (2 mg/mL) was incubated with dilutions of vaginal secretion from healthy women, and amyloid fibril formation was detected with ThT and Congo red staining. RESULTS: Lactic acid inhibited SEVI fibril formation in a dose-dependent manner in vitro. Lactic acid at 0.5 mg/mL completely inhibited 2 mg/mL SEVI fibril formation within 48 h. After incubation for 48 h, lactic acid at 1 mg/mL inhibited the formation of ß-sheet structure of SEVI (2 mg/mL) and completely inhibited 2 mg/mL PAP248-286 aggregation as observed with TEM. In the presence of lactic acid, PAP248-286 lost the ability to enhance virus infection. Vaginal secretion inhibited SEVI fibril formation in a dose-dependent manner, and virtually no SEVI fibril occurred after incubation of 2 mg/mL PAP248-286 with 67% vaginal secretion. CONCLUSION: Lactic acid inhibits SEVI fibril formation in vitro.

Distinct patterns and prognostic values of tumor-infiltrating macrophages in hepatocellular carcinoma and gastric cancer.

BACKGROUND: Macrophages (Mφs) constitute a major component of the leukocyte infiltrate and perform distinct roles in different tumor microenvironments. This study aimed to characterize the distribution, composition and prognostic value of Mφs in hepatocellular carcinoma (HCC) and gastric cancer (GC). METHODS: Immunohistochemistry and immunofluorescence were used to identify Mφ subsets in HCC and GC tissues. Kaplan-Meier analysis and Cox regression models were applied to estimate the overall survival (OS) for HCC and GC patients. RESULTS: The results showed that the density of Mφs decreased in the intra-tumor region (IT) of HCC, but remarkably increased in the IT of GC, as compared with their non-tumor regions (NT). In HCC, most CD68+ Mφs were CD204+ and CD169+ cells in the NT region; however, there was a significant decrease in the percentage of CD169+ Mφ in the IT region. In contrast, CD68+ Mφs comprised a smaller percentage of CD204+ than the CD169+ subpopulation in the NT region, while more CD204+ but fewer CD169+ cells were present in the IT region of GC. The density of CD204+ Mφs correlated with poor prognosis in HCC, and CD169+ Mφs were associated with good survival in both HCC and GC. Moreover, the combination of low numbers of CD204+ and high numbers of CD169+ Mφs was associated with improved OS in both GC and HCC. CONCLUSIONS: Mφs display tissue-specific distributions and distinct composition patterns in HCC and GC tissues. Our results suggested that different types of tumors might use diverse strategies to reconstitute Mφ patterns to promote tumor progression.

CD169 identifies an activated CD8(+) T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients.

PURPOSE: CD169 was first identified on macrophages (Mϕ) and linked to antigen presentation. Here, we showed CD169 expression on some CD8(+) T lymphocytes in regional lymph nodes (LNs) and investigated the function and clinical relevance of CD169(+)CD8(+) T cells in tumor-draining LNs of colorectal cancer (CRC) patients. EXPERIMENTAL DESIGN: Fresh tumor-draining LN tissues from 39 randomly enrolled patients were assessed by flow cytometry for activation and differentiation of CD169(+)CD8(+) T cells and T cell-mediated killing of tumor cells. In total, 114 tumor-draining LN paraffin sections from CRC patients were analyzed by multiple-color immunofluorescence for CD169(+)CD8(+) T cell distribution and clinical values. The prognostic significance of CD169(+)CD8(+) T cells was evaluated by Kaplan-Meier analysis. RESULTS: A fraction of CD8(+) T cells in regional LNs, but not peripheral blood, tonsils, or tumors, expressed surface CD169. In situ detection of draining LNs revealed preferential localization of CD169(+)CD8(+) T cells to subcapsular sinus and interfollicular regions, closely associated with CD169(+) Mϕ. CD169(+)CD8(+) T cell ratios were significantly lower in peri-tumor LNs than distant-tumor LNs. CD169(+)CD8(+) T cells predominantly expressed activation markers (CD69, HLA-DR, PD-1) with slightly lower CD45RA and CD62L levels. They produced high granzyme B, perforin, TNF-α, and IFNγ levels, and promoted tumor-killing efficiency ex vitro. Moreover, CD169(+)CD8(+) T cells infiltrating tumor-draining LNs decreased with disease progression and were strongly associated with CRC patient survival. CONCLUSIONS: We identified novel activated/cytolytic CD169(+)CD8(+) T cells selectively present in regional LNs, potentially serving as a powerful prognostic factor and indicator for selecting patients for immunotherapy.

CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma.

Macrophages are a major component of most solid tumours and can exert both anti- and pro-tumourigenic functions. Although the immunosuppressive/pro-tumour roles of macrophages have been widely examined, significantly less is known about macrophage subpopulations that have potential anti-tumour properties in humans. In the present study, a population of CD169(+) macrophages with relatively high expression levels of HLA-DR and CD86 was identified in human hepatocellular carcinoma tissues. The frequency of CD169-expressing macrophages within cancer nests was significantly lower than that found in paired non-tumour areas. In vitro experiments revealed that in the presence of anti-CD3 stimulation, CD169(+) macrophages could significantly enhance the proliferation, cytotoxicity, and cytokine production capacity of CD8(+) T cells in a CD169 molecule-dependent manner. Autocrine TGF-ß produced by tumour-stimulated macrophages was involved in the down-regulation of CD169 expression on these cells. Moreover, the accumulation of CD169(+) macrophages in tumour tissues was negatively associated with disease progression and predicted favourable survival in hepatocellular carcinoma patients, which was in contrast to the trend observed for total CD68(+) macrophages. Therefore, CD169 might act as a co-stimulatory molecule for cytotoxic T-cell activation, and could define a population of tumour-infiltrating macrophages with potential anti-tumour properties in human hepatocellular carcinoma tissues. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

c-Met identifies a population of matrix metalloproteinase 9-producing monocytes in peritumoural stroma of hepatocellular carcinoma.

Macrophages (Mϕ) are prominent components of solid tumours and exhibit distinct phenotypes in different microenvironments. Previously, we found that tumours could alter the normal developmental process of Mϕ to trigger transient activation of monocytes in the peritumoural stroma of human hepatocellular carcinoma (HCC). In the present study, we showed that a fraction of monocytes in the peritumoural stroma, but not in HCC cancer nests, expressed surface c-Met molecules. Monocytes exposed to tumours strongly expressed c-Met proteins with kinetics similar to their activation status, and significant correlations were found between c-Met levels and HLA-DR expression on tumour-infiltrating monocytes. NF-κB-mediated autocrine TNF-α stimulated the expression of c-Met on activated monocytes, and by interacting with its ligand hepatocyte growth factor (HGF), c-Met increased the motility and matrix metalloproteinase (MMP) 9-producing capacity of tumour-associated monocytes. The intensity of c-Met expression on tumour-infiltrating monocytes was associated with high mortality and reduced survival of patients with HCC. Therefore, the expression of c-Met on activated monocytes/Mϕ may represent a novel mechanism by which a tumour actively and precisely regulates the distribution and functions of these cells to facilitate disease progression.

Determination of Carbon Dioxide in Refined Titanium Tetrachloride by Infrared Spectroscopy.

Refined TiCl4 is the key procedure in producing titanium sponge. Besides, the content of carbon and oxygen (C and O) impurities in titanium sponge and that of C and O impurities in refined TiCl4 presents the 4-times enrichment relationship. Therefore, the content control of the C and O impurities in refined TiCl4 becomes the key part for the quality control of titanium material. In order to control the oxygen and carbon, there is the need to analyze the source of C and O impurities so that strict control can be conducted over the impurities of refined TiCl4. Determination of CO2 in refined TiCl4 was significant for analysis of its impurities. CO2 could be determined by infrared spectroscopy due to its infrared characteristic spectrum line. However, normal infrared absorption cell was not fit for the sample analysis, because TiCl4 easily reacted with moisture in the air and immediately was hydrolyzed to form highly corrosive hydrochloric acid smoke. According to Lambert-Beer Law, which means the concentration (c(ξ)) and absorbance(A) - length (L) curve's slope have direct ratio. The infrared absorption cell with the window film of ZnSe (φ10 mm x 1 mm, wavenumers: 7 800 -440 cm(-1)) and the glass cell (optical path: 42, 22, 12, 7 and 4 mm) was assembled and utilized in determination of the CO2 in refined TiCl4 by standard addition method. The detection limit of CO2 was 0.92 mg x kg(-1), the regression equation was Y = 0.031 1X, R = 0.997 2; With standard addition method, the regression equation of CO2 was Y = 0.131 7X, R = 0.998 6, it's good in linearity relation, the CO2 content in refined TiCl4 is determined to be 1.53 mg x kg(-1) and SD up to 0.04 x mg x kg(-1). RSD of the method precision is between 0.53%-1.27%, while recovery rate is between 89.2%-96.8%. This infrared absorption device was safe, simple and convenient, easily removable and washable, and re-useable. The method could conduct the quantitative analysis over the CO2 content in refined TiCl4 through adding standard sample for one time, it could meet the requirement of determination of CO2 in refined TiCl4.

[A Set of Infrared Cells for the Determination of Titanium Oxychloride in Refined Titanium Tetrachloride].

The content control of the impurities in refined TiCl4 becomes the key part for the quality control of titanium material. Refined TiCl4 is the key procedure in producing titanium sponge. Besides, the content of the impurities in titanium sponge and that of the impurities in refined TiCl4 presents the 4-times enrichment relationship. Therefore, control the content of the oxygen, there is the need to analyze the source of oxygen impurities so that strict control can be conducted over the impurities of refined TiCl4. Determination of TiOCl2 in refined TiCl4 was significant for analysis of its impurities. TiOCl2 could be determined by infrared spectroscopy due to its infrared characteristic spectrum line. However, normal infrared absorption cell was not fit for the sample analysis, because TiCl4 easily reacted with moisture in the air and immediately was hydrolyzed to form highly corrosive hydrochloric acid smoke. According to Lambert-Beer Law, which means the concentration (c(x)) and absorbance (A)-length (L) curve's slope have direct ratio. The infrared absorption cell with the window film of ZnSe (Φ10 x 1 mm, wavenumers: 7800-440 cm⁻¹) and the glass cell (optical path: 22, 12, 7 and 4 mm) was assembled and utilized in determination of the TiOCl2 in refined TiCl4 by standard addition method. The detection limit of TiOCl2 was 17.8 mg · kg⁻¹, the regression equation was Y = 1.011 8X, R = 0.9963; With standard addition method, the regression equation of TiOCl2 was Y = 1.940 0X, R = 0.997 0, it' s good in linearity relation, the TiOCl2 content in refined TiCl4 is determined to be 833.8 mg · kg⁻¹ and SD up to 40.0 mg · kg⁻¹. RSD of the method precision is between 0.95%-1.94%, while recovery rate is between 88.5%-93.1%. This infrared absorption device was safe, simple and convenient, easily removable and washable, and re-useable. The method could conduct the quantitative analysis over the TiOCl2 content in refined TiCl4 through adding standard sample for one time, it could meet the requirement of determination of TiOCl2 in refined TiCl4.

Exploration of regulating blood lipids metabolism by integrative medicine / 中国中西医结合杂志

Hyperlipidemia is an important risk factor of cardio-/cerebrovascular disease, and reducing lipids has become an important project for itsclinical preventing and treating. Western medicine, with its confirmative efficacy and clear mechanism, has played an irreplaceable role. Along with the development of modern medicine, integrative medicine has gradually become a growing trend in regulating blood lipids metabolism. It not only could make up the insufficient power for Chinese medicine in lowering lipids, but also could reduce adverse reactions and economic costs brought by long-term administration of Western medicine. As a modern practitioner of Chinese medicine, we should keep clear that integrative medicine regulating blood lipids metabolism does not mean a simple combination of traditional Chinese medicine and Western medicine. We should treat it guided by systematic theories. We combine disease identification and syndrome differentiation, guide lipids lowering by integrative medicine including selecting Western drugs for blood lipids lowering, Chinese medical prescriptions for syndrome typing, and effective Chinese herbs based on modern pharmacologies.

Genistein sensitizes bladder cancer cells to HCPT treatment in vitro and in vivo via ATM/NF-κB/IKK pathway-induced apoptosis.

Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.

25(OH)D(3) affects the maturation and function of mouse bone marrow-derived dendritic cells stimulated by Mycobacterium bovis BCG.

It has been shown that vitamin D deficiency increases an individual's susceptibility to tuberculosis (TB). However, very little is known about the effect of vitamin D on the immune response to Mycobacterium tuberculosis (M. tb) in dendritic cells (DCs). Because DCs play an important role in TB infection, we investigated the phenotypic characteristics and functional capabilities of mouse bone marrow-derived dendritic cells (BMDCs) after stimulation with Bacillus Calmette-Guérin (BCG) in the presence or absence of 25(OH)D(3)(100 nM). Bone marrow cells from mice were cultured with GM-CSF (20 ng/ml) and were then treated with 25(OH)D(3) for 7 days. On day 6, 5 µg/ml of BCG (≥1.0×10(6) CFU/mg) was added to the cells for 24 hours, and on day 7, the non-adherent cells were harvested for phenotypic and functional analyses. After incubation with 25(OH)D(3), the expression levels of MHC-II and CD86 on the surface of the dendritic cells (DCs) and the ability of the DCs to stimulate proliferation of allogeneic mixed lymphocytes were lower than control cells (p<0.05). Furthermore, the level of Interleukin (IL) -4 secreted by the BMDCs in the 25(OH)D(3) culture was lower than that in the control culture (p<0.01). However, the BMDCs cultured with 25(OH)D(3) produced significantly higher levels of IL-2, IL-6, IL-10 and interferon gamma(IFN-γ) than those in the control culture (p<0.05). These findings suggest that 25(OH)D(3) modulates the immune response during mycobacterial infection by affecting the maturation and function of DCs.

Glenohumeral joint tuberculosis that mimics frozen shoulder: a retrospective analysis.

BACKGROUND: Although the incidence of osteoarticular tuberculosis is increasing, glenohumeral joint tuberculosis is rare and often misdiagnosed in its early stages. Our objective was to study the incidence of the initial misdiagnosis as frozen shoulder and the duration of the prediagnostic period among patients with glenohumeral joint tuberculosis. METHODS: The clinical records of 21 patients with tuberculosis of the shoulder joint were retrospectively analyzed. RESULTS: Among the 16 patients with glenohumeral joint tuberculosis, 14 (87.5%) were initially diagnosed as having frozen shoulder instead of glenohumeral joint tuberculosis at their primary care clinics. Two patients actually showed both shoulder pain and limited range of motion, although they did not have a record of initial diagnosis with frozen shoulder. Consequently, 14 (87.5%) of the patients in our study with glenohumeral joint tuberculosis were likely misdiagnosed as having frozen shoulder. On the other hand, this group accounted for 3.6% (n = 16) of 450 patients who, during the same period, had been initially diagnosed with frozen shoulder at our institution. The mean prediagnostic period to attain the final, correct diagnosis of glenohumeral joint tuberculosis for this group was 14.5 months. CONCLUSION: It appears that misdiagnosis is common and early diagnosis of tubercular infection in the glenohumeral joint has become increasingly difficult. Glenohumeral joint tuberculosis should be suspected in cases of longstanding pain in the shoulder. It is necessary to re-examine these frozen shoulder patients with repeated plain radiographs followed by further imaging studies, especially magnetic resonance imaging, if conservative therapy fails.

MRI findings for frozen shoulder evaluation: is the thickness of the coracohumeral ligament a valuable diagnostic tool?

BACKGROUND: Recent studies have demonstrated that the coracohumeral ligament (CHL) is shortened and thickened in a frozen shoulder. We analyzed the rate in CHL visualization between patients with frozen shoulder and normal volunteers using Magnetic Resonance Imaging (MRI) to determine the CHL thickness in the patients with a frozen shoulder. METHODS AND FINDINGS: There were 72 shoulder joints in 72 patients (50 femles and 22 males with a mean age of 53.5 years) with clinical evidence and MR imaging evidence of frozen shoulder. These were prospectively analyzed to identify and measure the maximum thickness of the CHL. The control group, which included 120 shoulder joints in 60 normal volunteer individuals (30 females and 30 males with a mean age of 50.5 years) was also referred for MR imaging. A chi-square test was used to analyze the data of the rate of CHL visualization between the patients with frozen shoulder and the control group. A two-way ANOVA was used to analyze the mean maximal thickness of CHL. The CHL was visualized in 110 out of 120 shoulders in the control group (91.7%), and in 57 out of 72 shoulders for the frozen shoulder group (79.2%), there was significant difference, using a chi-square test (P<0.05). The CHL was not visualized in 10 out of 120 shoulders in the control group (8.3%), and 15 out of 72 shoulders in the frozen shoulder group (20.8%), there was a significant difference (P<0.05). The CHL thickness (3.99±1.68 mm) in the patients with frozen shoulder was significantly greater than that thickness (3.08±1.32 mm) in the control group, using a two-way ANOVA (P<0.001). The CHL thickness (3.52±1.52 mm, n = 97) in the female shoulders was no significantly greater than that thickness (3.22±1.49 mm, n = 70) in the male shoulders, using a two-way ANOVA (P>0.05). CONCLUSIONS: MR Imaging is a satisfactory method for CHL depiction, and a thickened CHL is highly suggestive of frozen shoulder.

Preoperative levels of serum interleukin-6 in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: A high prevalence of serum IL-6 has been associated with the pathogenesis of hepatocellular carcinoma (HCC) in both animals and humans. However, it is not clear how the levels of serum IL-6 influence the prognosis of HCC patients. This study was carried out in order to attempt to answer this question. METHODOLOGY: A total of 156 adults were selected and categorized into four groups: healthy subjects (n=18), those with tumor recurrence (n=26), those initially diagnosed with HCC (n=32), and those with HCC (n=80) who received curative resection between 2002 and 2004 with five years of follow-up. Serum IL-6 levels were determined in all subjects by the same ELISA method. RESULTS: IL-6 was found in high levels in the serum of patients initially diagnosed with HCC (8.47±5.92, p<0.0001) and in patients with HCC and tumor recurrence (12±31.90, p=0.001) compared with healthy subjects (0.89±1.51). This includes all patients who received therapy between 2007 and 2008. The levels of serum IL-6 were positively correlated with tumor size (p=0.002) in the HCC patients who received curative resection between 2002 and 2004 with five years of follow-up. CONCLUSIONS: High levels of serum IL-6 correlated positively with tumor size and with poor prognosis in HCC patients.

Blood neutrophil-to-lymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization.

PURPOSE: To evaluate whether the neutrophil-to-lymphocyte ratio (NLR) predicts survival in patients with unresectable hepatocellular carcinoma (HCC) before and after transarterial chemoembolization treatment. MATERIALS AND METHODS: Clinical and laboratory data for 145 consecutive patients undergoing transarterial chemoembolization for unresectable HCC during 2001-2004 were analyzed retrospectively. The NLR was recorded before and 3 days after treatment. RESULTS: The pretreatment mean NLR was 3.3; 59 (40.7%) patients had an elevated NLR (≥ 3.3). The median survival of patients with a high NLR was 8 months (range 1-28 months) compared with 12 months (range 2-41 months) for patients with a normal NLR; a significant difference was found in overall survival (log-rank test, P = .001). The NLR was increased in 127 (87.6%) patients after transarterial chemoembolization and was decreased in 18 patients; the increase indicated better outcomes (log-rank test, P = .006). Age (≥ 49 y), high NLR, decreased NLR after treatment, large tumor (≥ 5 cm), vascular invasion, and elevated serum α-fetoprotein (AFP) level all were predictors of poor survival. Multivariate analysis showed that a high NLR (P = .041) and vascular invasion (P = .040) were independent factors for predicting worse survival. CONCLUSIONS: A high NLR independently predicts poor survival in patients with unresectable HCC undergoing transarterial chemoembolization treatment, and an increased NLR indicates a better outcome than a decreased NLR for patients after transarterial chemoembolization.