25-OH-vitamin D deficiency identifies poor tumor response in hepatocellular carcinoma treated with transarterial chemoembolization.

PURPOSE: Vitamin D is implicated linked to liver cancer and chronic liver diseases, but its association with tumor response in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) remains unclear. This study aimed to determine whether vitamin D levels influence tumor response in HCC patients treated with TACE. METHODS: A total of 58 HCC patients undergoing TACE were enrolled in the study. Serum 25-hydroxyvitamin D (25-OHD) levels were determined at baseline and 1 day after TACE using electrochemiluminescence immunoassay. Response to TACE was evaluated after a 4-6 week interval. Univariate and multivariate analyses with Cox regression model were performed to determine the risk factors associated with tumor response. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of baseline 25-OHD levels on tumor response in HCC patients undergoing TACE. RESULTS: 43.1% of HCC patients showed 25-OHD deficiency. Baseline 25-OHD level was associated with liver cirrhosis (P = 0.025), vascular invasion (P = 0.031), Barcelona Clinic Liver Cancer stage (P = 0.002) and an alanine aminotransferase increase after TACE (P = 0.021). Serum 25-OHD level was significantly decreased 1 day after TACE (P = 0.045). Multiple tumor numbers (P = 0.034) and low baseline 25-OHD levels (P = 0.040) were independently correlated with poor tumor response after TACE. ROC curve analysis showed that baseline 25-OHD levels present better predictive performance for OR in those patients, compared with other current clinical test pointers. CONCLUSION: Our study suggested that 25-OHD deficiency at baseline is a prognostic indicator for a poor tumor response in hepatocellular carcinoma treated with TACE.

Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

Mitochondrial dysfunction in resveratrol-induced apoptosis in QGY-7701 cells.

This study aims to evaluate the cytotoxicity of resveratrol on QGY-7701 cells via a cell viability assay, and determine the cytological alterations and damages that result. Resveratrol was found to inhibit QGY-7701 cell growth and decrease their viability in a remarkably dose-dependent manner. Resveratrol exposure also induced an increase in Caspase-3 activity and a decrease in Bcl-2, which caused an increase in membrane permeability, and the opening of mitochondrial permeability transition pores and mitochondrial depolarization. Cellular ATP is thus exhausted, and apoptosis is induced via the change in mitochondrial membrane permeability and mitochondrial dysfunction.

Association of IL-18 polymorphisms with rheumatoid arthritis: a meta-analysis.

Interleukin-18 (IL-18), an important proinflammatory cytokine, has been reported to play a potential pathological role in rheumatoid arthritis (RA). Results from previous studies on the association between IL-18 polymorphisms and RA are conflicting. To clarify this, an updated meta-analysis of all available studies on IL-18 polymorphisms and RA was conducted. Eligible articles were identified by searching databases, including PubMed, Ovid, Cochrane Library, EMBASE, and China Knowledge Resource Integrated Database, for the period up to May 1, 2015. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were used to assess the strength of association in the homozygote, heterozygote, dominant, recessive, and additive models. The software STATA (Version 13.0) was used for statistical analysis. Finally, 14 articles were included in the present meta-analysis. The IL-18 -607C/A polymorphism showed pooled ORs and 95%CIs for the homozygote model (AA vs CC: OR = 0.598; 95%CI = 0.395-0.907), and the association between the IL-18 -137G/C polymorphism and RA showed pooled ORs and 95%CIs for the homozygote (CC vs GG: OR = 0.699; 95%CI = 0.364-1.342) and heterozygote (CG vs GG: OR = 0.924; 95%CI = 0.803-1.064) models. In summary, the current meta-analysis, which was based on the most current studies, showed that the -607A/C, -920C/T, and -105A/C polymorphisms in IL-18 were significantly associated with increased RA risk. However, the -137C/G polymorphism was not associated with RA risk under any genetic model. More evidence is needed to support or deny such a conclusion.

Transplantation of erythropoietin gene-transfected umbilical cord mesenchymal stem cells as a treatment for limb ischemia in rats.

The aim of this study was to investigate the mechanisms of erythropoietin (EPO)-transfected umbilical cord mesenchymal stem cells (UC-MSCs) in the treatment of rats with ischemic limb and provide a theoretical basis for optimization of UC-MSC transplantation. Sixty SD rats were randomly divided into four groups: ischemia control group, EPO treatment group, UC-MSCs treatment group, EPO gene transfected UC-MSC treatment groups (15 rats in each group). The left femoral hind artery and its branches were ligated to develop hind limb ischemia in male SD rats. Five points were injected in the adductor and gastrocnemius muscles with medium, cDNA3-EPO gene DNA-liposome complex solution or UC-MSCs in control groups and EPO-transfected-UC-MSCs in the experimental group. Western blot confirmed in vitro EPO expression in EPO gene-transfected human UC-MSCs. Arterial angiography at 4 weeks post-transplantation showed no development of blood vessels in the control group and moderate angiogenesis in the EPO- and UC-MSC-treated groups. However, a large number of freshmen angiogenesis and abundant collateral circulation was observed in the EPO-transfected-UC-MSC-treated experimental group. Rat capillary density measurement results confirmed the angiographs quantitatively and showed no statistically significant difference between EPO- and UC-MSC-treated groups (P > 0.05). CM-Dil-positive cell numbers were (0 ± 0.00), (0 ± 0.00), (32.46 ± 6.68), (59.64 ± 10.38)/HP (P < 0.05). RT-PCR detected that the in vivo mRNA expression of the EPO gene was relatively higher in the EPO-transfected-UC-MSC-treated group than the EPO-treated group (0.79 ± 0.06 vs 0.19 ± 0.04, P < 0.05). Thus, this study revealed that using UC-MSCs as vector in gene therapy for limb ischemia facilitates stable and effective expression of EPO compared to direct gene injection.

Growth and viability of Liaoning Cashmere goat hair follicles during the annual hair follicle cycle.

Here, we studied hair follicle development of Liaoning Cashmere goats. Every month for 1 year, skin samples were collected from five 1.5-year-old female goats, and made into paraffin sections. A number of parameters were measured of primary and secondary hair follicles via microscopic observation including follicle depth, hair bulb width, dermis and epidermis thickness, changes in follicle activity, and histology. The results showed the presence of three phases in the annual hair cycle: anagen, catagen, and telogen. Primary and secondary hair follicle depth varied across the months; however, no significant difference was obtained between adjacent months (P>0.05). Primary hair follicles had a bigger hair bulb width compared to secondary hair follicles; however, this difference declined during hair follicle developed in anagen. As hair follicle growth slowed, the hair bulb broadened, and hair root depth became shallower. During the entire hair cycle, hair follicle depth and dermis thickness were positively correlated; however, this relationship was not significant (P>0.05) for primary and secondary hair follicle density and the ratio of secondary hair follicle density and primary hair follicle density (S/P ratio). In addition, new and old primary hair follicles coexisted with secondary hair follicles. Finally, secondary hair follicles had a higher activity rate compared to primary hair follicle in adult Liaoning Cashmere goats in certain months.

Expression and localization of the vascular endothelial growth factor and changes of microvessel density during hair follicle development of Liaoning cashmere goats.

Vascular endothelial growth factors (VEGFs) play important roles in neovascularization, tissue development, and angiogenesis. In this study, changes in VEGF expression patterns and microvessel density (MVD), and their correlations, were investigated during hair follicle development in epidermal appendages of Liaoning cashmere goats. Polyclonal antibodies to VEGF and microvessels were used for monthly immunohistochemical examinations of normal skin specimens from adult female goats for one year. VEGF was expressed in the hair bulb of primary and secondary hair follicles, the outer and inner root sheaths, sebaceous glands (ductal and secretory portions), eccrine sweat glands (ductal and secretory portions), and the epidermis. Abundant expression of VEGF was observed in the follicular basement membrane zone surrounding the bulb matrix and in ductal and secretory portions of eccrine sweat glands. The change in VEGFs in primary hair follicles showed a bimodal pattern, with the first peak observed from March to May, and the second in August. Maximal expression in secondary hair follicles occurred in May and August. Therefore, VEGF expression in primary and secondary hair follicles is synchronized throughout the year, and is correlated to hair development. In the later telogen and anagen phases, VEGF expression was higher in the secondary, compared to the primary, hair follicle. Changes in MVD also showed a bimodal pattern with peaks in May and August. VEGF expression and MVD showed moderate and strongly positive correlation in the primary and secondary hair follicles, respectively. Therefore, MVD and VEGF are closely related to the processes involved in hair cycle regulation.

Controle de arrtmias atriais com período refratário atrial controlado por sensor e mudança automática de modo em pacientes portadores de marcapasso dupla-câmara com sensor de ventilação por minuto / Atrial arrhythmia management with sensor controlled atrial refractory period and automatic mode switching in patients with minute ventilation sensing dual chamber rate adaptive pacemakers

Apesar de um longo período refratário atrial pós evento ventricular (PVARP) pode prevenir a ocorrência de taquicardias mediadas pelo marcapasso e também o sincronismo inapropriado com arrtmias atriais na estimulação dupla-câmara(DDD) a limitação da freqüência máxima será necessariamente comprometida. Testamos a possibilidade de utilizar um marcapasso dupla-câmara com sensor de ventilação por minuto (DDDR) e com capacidade de encurtar o PVARP durante o exercício em 13 pacientes com bradicardia (PVARP em repouso = 463 + - 29 ms) a fim de prevenir a limitação prematura da freqüência máxima. O teste de esforço em esteira nos modos DDD e DDDR com este PVARP resultou em freqüências máximas de 98 bpm + - 8 bpm e 142 bpm + - 3 bpm respectivamente (P < 0,0001). Estes resultados foram obtidos graças à incompetênciacronotrópica e à limitação da freqüência máxima no modo DDD, ambas contornadas pelo uso do sensor. Com a finalidade de simular arritmias atriais, foi aplicada estimulação na parece torácica por 30 segundos, a uma freqüência de 250 bpm e com uma sensibilidade atrial unipolar média de 0,82 mV. No modo DDD, ocorreu uma resposta ventricular irregular (as freqüências com um PVARP de 280 ms e 463 ms + - 29 ms foram respectivamente 92 bpm + - 5 bpm e 66 bpm + - 3 bpm (P < 0,0001). No modo DDDR, com PVARP de 463 ms + - 29 ms, ocorreu uma estimulação ventricular regular a 53 bpm + - 2 bpm devida à mudança de modo para VVIR, na presença de eventos repetitivos captados dentro do PVARP. Um paciente desenvolveu fibrilação atrial espontânea durante o seguimento, que foi corretamente identificada pelo algoritmo do marcapasso, resultando na mudança de modo DDDR para VVIR e na preservação da resposta em freqüência. Em conclusão, o PVARP controlado pelo sensor permite a utilização de um PVARP mais longo durante o repouso, sem comprometer a freqüência máxima durante o exercício. Adicionalmente, ao oferecer em proteção contra retrógrada, o PVARP longo e a mudança automática de modo também limitam a freqüência durante as arritmias atriais, permitindo uma resposta ventricular de acordo com a demanda fisiológica...

3-Amino-2-piperidinone-6-carboxylic acid. Molecular structures of cis and trans benzoyl derivatives.

The cis (2a) and trans (2b) isomers of methyl 3-benzamido-2-piperidinone-6-carboxylate (Apca) were prepared and separated by fractional recrystallizations. Proton n.m.r. studies in dimethylsulfoxide solution indicate that the six-membered lactam ring adopts a distorted chair conformation with an equatorially oriented benzamido substituent in both 2a and 2b. The carboxyl function also is equatorially oriented in the trans isomer 2b, but is disposed axially in the cis isomer 2a. In the crystal structure, the six-membered lactam ring of 2a is clearly in a boat conformation with the benzamido and carboxyl functions attached to the two apex carbon atoms equatorially. The trans isomer, 2b, exists as two crystallographically independent, conformationally distinct molecules in one unit cell. The lactam ring in both molecules adopts a distorted chair conformation, as is the case in solution, with both the benazamido and carboxyl functions attached equatorially. The rotameric orientation for the endocyclic lactam differs between the two molecules. Both structures show evidence of C-H...O hydrogen bond formation intermolecularly in the solid state. This ability, along with the distinctive conformational features of Apca, may be exploitable in the design of unique features of polypeptides.