Multiway Junction Conditions for Spacetimes with Multiple Boundaries.

We explore the construction of gluing together an arbitrary number of spacetimes along a common interface. This provides a general tool to construct new gravitational backgrounds with multiple boundaries. We derive junction conditions across the interface, in both Einstein gravity and dilaton gravity, using two methods (1) by developing a geometrical technique of introducing an auxiliary reverse extension manifold and (2) by the variational principle. Our junction condition works for both spacelike and timelike interfaces. We illustrate applications of the junction conditions in Jackiw-Teitelboim gravity and analyze their constraints on the allowed dilaton profile. We further comment on the geometry of a web of spacetime in the presence of multiple interfaces and its resemblance to Feynman diagrams.

MTHFR C677T、MTHFR A1298C、MTRR A66G and MTR A2756G polymorphisms and male infertility risk: a systematic review and meta-analysis.

BACKGROUND: Epidemiological studies have reported that polymorphisms of folate-metabolizing genes have a significant impact on male infertility. However, the results of published studies have come to different conclusions. OBJECTIVE: To determine an association between folate-metabolizing gene polymorphisms and the risk of male infertility. METHODS: The meta-analysis was conducted according to the PRISMA 2020 statement. The protocol was registered with PROSPERO (CRD42023412251). Studies were searched from PubMed, Google Scholar, Embase, Scopus, and the Cochrane Library up to 24st October2023. Articles that satisfied the inclusion criteria were evaluated for their quality using the Newcastle-Ottawa Scale. Data were extracted from the eligible studies and were analyzed for pooled up odds ratio (OR) with 95% confidence interval (CI). Meta-analysis was conducted using STATA 12. RESULTS: Forty-six case-control studies were included in the meta-analysis which comprised 20,639 participants. The pooled analysis revealed that the MTHFR C677T polymorphism was significantly associated with male infertility and abnormospermia.Three-fifths of the model showed there was a significant association between the MTR A2756G polymorphism and male infertility. Both MTHFR A1298C and MTRR A66G polymorphisms were not significantly associated with male fertility. Furthermore, subgroup analysis revealed a significant association between the MTHFR C677T polymorphism and male fertility in Asian countries. CONCLUSION: This meta-analysis suggests that the MTHFR C677T and MTR A2756G polymorphisms may be a potential risk factor for male infertility.

Leukocyte immunoglobulin-like receptor A3 gene deletion in five Chinese populations and protective association with nasopharyngeal carcinoma.

Among the thirteen leukocyte Ig-like receptor (LILR) loci located at 19q13.4, LILRA3 is unique in that it encodes a soluble protein lacking the transmembrane and cytoplasmic domains, and a 6.7 kb deletion spanning the first seven exons has been detected in some human individuals. Presently, there is a lack of data about the distribution of LILRA3 gene deletion in more diverse ethnic groups. Also, no previous studies have investigated the correlation between copy number variation (CNV) of LILRA3 and nasopharyngeal carcinoma (NPC). In this study, five populations from China mainland: two Southern Han populations, Hunan (N = 1478) and Guandong (N = 107); one Southeastern Han population, Fujian (N = 439); and two Northern populations, Inner Mongolia Han (N = 104) and Mongol population from Inner Mongolia (N = 158) were investigated for CNV of LILRA3 using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. LILRA3 variants were also examined in a cohort of NPC cases (N = 1142) in Hunan Han population. The five Chinese populations demonstrated northward increase in frequency of the deleted form of LILRA3 gene (LILRA3*Del) (all corrected p values < 0.05). Inter-population comparison also uncovered significant differentiation in the distribution of CNV of LILRA3 among modern human populations. LILRA3*Del was found to confer significantly reduced risk to NPC in Hunan Han population (at allelic level: OR = 0.79, 95% CI = 0.71-0.89, p < 0.0001; at genotype level: OR = 0.63, 95% CI = 0.51-0.79, p < 0.0001). No interaction was found between LILRA3 variants and HLA-A*02:07, HLA-A*11:01, HLA-B*13 and HLA-B*46:01 alleles in susceptibility to NPC. Our study constitutes the first demonstration of LILRA3 gene as a locus linked to NPC susceptibility in a southern Chinese population. Future independent studies in other populations are warranted to confirm the findings reported in this study.

Development of a reverse transcription recombinase-aided amplification assay for the detection of coxsackievirus A10 and coxsackievirus A6 RNA.

Hand, foot and mouth disease (HFMD) is a serious public health problem, and coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) are two of the major causative pathogens, in addition to enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). A simple and rapid reverse transcription recombinase-aided amplification assay (RT-RAA) was developed for the detection of CVA10 and CVA6 in this study. The analytical sensitivity for detection of CVA10 and CVA6 at 95% probability by probit regression analysis was 35 copies per reaction and 38 copies per reaction, respectively, with 100% specificity. Compared with commercial RT-qPCR assays, when testing 455 fecal specimens, the kappa value of the RT-RAA assay for CVA10 and CVA6 was 0.920 (p < 0.001) and 0.952 (p < 0.001), respectively. Moreover, four samples that were positive for CVA10 and five that were positive for CVA6 by RT-RAA but negative by RT-qPCR were further determined to be true positives. These results demonstrate that the proposed RT-RAA assays are very valuable tools for the detection of CVA10 and CVA6 and have potential for use in resource-limited settings.

Anti-Tumor Effects of Paeoniflorin on Epithelial-To-Mesenchymal Transition in Human Colorectal Cancer Cells.

BACKGROUND Colorectal cancer is one of the leading causes of death in China, and the development of effective drugs is urgently needed. Here, we report on Paeoniflorin (PF), a product isolated from the roots of the peony plant, as a possible candidate because of its anti-tumor effects on epithelial-to-mesenchymal transition (EMT) of PF in human colorectal cancer (CRC). MATERIAL AND METHODS Cell proliferation, wound healing, and Transwell assays were used to analyze the effects of PF on in vitro cell migration and invasion of HCT116 and SW480, 2 colorectal cancer cell lines. The tumor xenograft model was used to verify the anti-metastasis effects of PF in vivo. The RNA and protein levels of epithelia-cadherin (E-cadherin), Vimentin, and histone deacetylase2 (HDAC2) were measured by qPCR and Western blot analysis to explore the mechanism involved. RESULTS Our results showed that PF inhibited colorectal cancer cell migration and invasion and suppressed the metastatic potential of the cancer cells in vivo. Moreover, PF significantly decreased the expression of HDAC2 and Vimentin, while increasing the expression of E-cadherin. CONCLUSIONS These results suggest that PF inhibits colorectal cancer cell migration and invasion ability and reverses the EMT process, through inhibiting the expression of HDAC2, and then affects the expression level of E-cadherin and Vimentin at the cell level. Our results were also verified in the tumor xenograft model. This indicates that PF may be a candidate for colorectal cancer treatment.

Venous anastomosis using a non-penetrating vascular closure system in orthotopic liver transplantation.

BACKGROUND: A non-penetrating vessel closure system (VCS-AnastoClip® ) may facilitate vascular anastomosis. The purpose of this study is to explore the utilization of a non-penetrating VCS in orthotopic liver transplantation (OLT). METHODS: From January 2015 to February 2017, patients who underwent OLT were divided into two groups, ie, those who underwent non-penetrating VCS application for inferior vena cava (IVC) and portal vein (PV) reconstructions and those who underwent hand sewing for these purposes. Clinical data, venous anastomotic times, anhepatic phases, and the recovery of liver function were compared between the groups. RESULTS: One hundred and fifteen patients underwent OLT (63 in the VCS group and 52 in the suture group). No differences between the two groups were observed in the baseline characteristics. The venous anastomotic time and anhepatic phase in the VCS group were significantly shorter than those in the suture group (P < .01). The alanine transaminase and total bilirubin levels in the VCS group were comparable to those in the suture group (P = .39 and P = .06, respectively). The complication, mortality, and patency rates of the PV reconstructions did not differ significantly between the two groups. CONCLUSIONS: In OLT, the reconstruction of the PV and IVC with a non-penetrating VCS system is a safe alternative method that has the advantage of shortening the anastomotic time and the anhepatic phase compared to the results of conventional hand suturing. However, the use of this VCS system had no influence on the recovery of graft function.

[Diagnostic Value of Immunofixation Electrophoresis and KAP/LAM Ratio in Multiple Myeloma Patients with Renal Injury].

OBJECTIVES: To explore the diagnostic value of immunofixation electrophoresis and Kappa/Lambda (KAP/LAM) ratio in multiple myeloma patients with renal injury. METHODS: The serum of 822 patients of renal disease were collected for the examnation of immunofixation electrophoresis, KAP/LAM ratio, serum immunoglobulin levels and renal function, including serum urea nitrogen (BUN), serum creatinine (Crea), cystatin C (Cys-C) and estimated glomerular filtration rate (eGFR). To analyze the diagnostic value of immunofixation and KAP/LAM ratio in the differentiation of renal injury of multiple myeloma from primary renal injury diseases. RESULTS: M protein was observed in 75 patients (9.1%). The ratio of each type was IgG 49.3%(37/75), IgA 34.7%(26/75), IgM 5.3%(4/75) and LAM 10.7%(8/75). There was significant difference of KAP/LAM ratio between M protein group and non-M protein group. The KAP/LAM ratio was significant higher in KAP group, compared to non-M protein group. Reverse result was obtained in LAM group. There were higher Crea level and lower eGFR value in pure LAM light chain group, compared with IgG, IgA and IgM groups. CONCLUSIONS: Immunofixation electrophoresis and KAP/LAM ratio may play an important role in the diagnosis of multiple myeloma patients with renal injury, so could be early screening markers.

MiR-133b Promotes neurite outgrowth by targeting RhoA expression.

BACKGROUND: MicroRNA-133b (miR-133b) has been shown to play a critical role in spinal cord regeneration. The aim of this study was to investigate the cellular role of miR-133b in neural cells. METHODS: PC12 cells and primary cortical neurons (PCNs) were transfected with lenti-miR-133b, lenti-miR-133b inhibitor, plasmid-shRNA-RhoA, plasmid-RhoA and their negative controls. After 48 hours of transfection, the levels of proteins and mRNA or miRNA were evaluated by Western blotting and qRT-PCR, respectively. Moreover, the neurite outgrowth was analyzed by Image J. For pharmacological experiments, inhibitors of MEK1/2 kinase (PD98059), phosphoinositide-3 kinase (PI3K) (LY294002) and ROCK (Y27632) were added into the culture medium. RESULTS: Overexpression of miR-133b in PC12 cells enhanced neurite outgrowth. Conversely, inhibition of miR-133b reduced neurite length. We further identified RhoA as a target and mediator of mir-133b for neurite extension by Western blot and knockdown experiment. Moreover, overexpression of RhoA could attenuate the neurite growth effects of miR-133b. Also, we observed that miR-133b activated MEK/ERK and PI3K/Akt signaling pathway by targeting RhoA. Finally, in PCNs, miR-133b also increased axon growth and attenuated axon growth restrictions from chondroitin sulfate proteoglycans (CSPG). CONCLUSIONS: In summary, our study suggested that miR-133b regulated neurite outgrowth via ERK1/2 and PI3K/Akt signaling pathway by RhoA suppression.

Contribution of transforming growth factor α polymorphisms to nonsyndromic orofacial clefts: a HuGE review and meta-analysis.

We performed a meta-analysis of the association of transforming growth factor α gene (TGFA) polymorphisms with the risk of cleft lip with or without cleft palate (CL/P) or cleft palate (CP). In total, data from 29 studies were pooled for the following 3 polymorphisms: TGFA/TaqI, TGFA/BamHI, and TGFA/RasI in the TGFA gene. A fixed-effects or random-effects model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. A significantly increased CL/P or CP risk was observed in persons carrying a C2 allele at the TaqI polymorphism (odds ratio (OR) = 1.70, 95% confidence interval (CI): 1.41, 2.05) compared with those with a C1 allele (OR = 1.57, 95% CI: 1.23, 2.01). For the TGFA/BamHI polymorphism, carriers of the minor A1 allele had an estimated relative decrease in CL/P risk (OR = 0.44, 95% CI: 0.30, 0.64). These associations remained significant when only high-quality studies were included. However, no significant association was observed between the TGFA/RasI variant and CL/P risk. In summary, this meta-analysis provided a robust estimate of the positive association of the TGFA/TaqI polymorphism with both CL/P and CP and suggests that persons with an A1 allele may have a markedly decreased risk of CL/P.

Neurogenin 2 converts mesenchymal stem cells into a neural precursor fate and improves functional recovery after experimental stroke.

BACKGROUND: Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. Here, we investigated whether Ngn2 can reprogram MSCs to adopt a neural precursor fate and enhance the therapeutic effects of MSCs after experimental stroke. METHODS: In vitro, MSCs were transfected with lenti-GFP or lenti-Ngn2. Following neuronal induction, cells were identified by immunocytochemistry, Western blot and electrophysiological analyses. In a stroke model induced by transient right middle cerebral artery occlusion (MCAO), PBS, GFP-MSCs or Ngn2-MSCs were injected 1 day after MCAO. Behavioral tests, neurological and immunohistochemical assessments were performed. RESULTS: In vitro, Ngn2-MSCs expressed neural stem cells markers (Pax6 and nestin) and lost the potential to differentiate into mesodermal cell types. Following neural induction, Ngn2-MSCs expressed higher levels of neuron-specific proteins MAP2, Tuj1 and NeuN, and also expressed voltage-gated Na+ channel, which was absent in GFP-MSCs. In vivo, after transplantation, Ngn2-MSCs significantly reduced apoptotic cells, decreased infarct volume, and increased the expression of VEGF and BDNF. Finally, Ngn2-MSCs treated animals showed the highest functional recovery among the three groups. CONCLUSIONS: Ngn2 was sufficient to convert MSCs into a neural precursor fate and transplantation of Ngn2-MSCs was advantageous for the treatment of stroke rats.

Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma.

BACKGROUND: This study was designed to evaluate the effectiveness of radiofrequency ablation in patients with intermediate (BCLC B) stage hepatocellular carcinoma who underwent transcatheter arterial chemoembolization. METHODS: Included in this study were 211 patients with intermediate stage HCC who underwent initial transcatheter arterial chemoembolization and were potentially amendable for radiofrequency ablation (single tumor with diameter 5-8 cm, median 6.0 cm; 2-5 multiple nodules with diameter less than 5 cm) between January 2005 and December 2011. According to the inclusion and exclusion criteria, 55 patients were treated with following radiofrequency ablation, and the remaining 156 patients were treated with transcatheter arterial chemoembolization alone. The treatment effectiveness, local tumor control and survival outcome between the two groups were compared. RESULTS: The complete tumor necrosis rate after treatment was 76.9% in combination group vs. 46.5% in transcatheter arterial chemoembolization alone group (P = 0.02). The major complication rate was 1.8% in combination group vs. 2.6% in transcatheter arterial chemoembolization alone group. Follow-up observation showed that the total tumor control rate was 74.5% in combination group versus 54.5% in transcatheter arterial chemoembolization alone group (P < 0.001). The 1-, 3- and 5-year survival rates in combination group were significantly higher than those in TACE alone group (P = 0.01). CONCLUSIONS: Radiofrequency ablation following initial transcatheter arterial chemoembolization delays tumor progression and prolongs overall survival of patients with intermediate stage HCC tumors.

Impact of insulin resistance on IVF/ICSI outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of insulin resistance (IR) on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: PubMed, Google Scholar,Web of Science, Embase, Scopus and the Cochrane Library were searched to identify relevant studies. A total of 6,137 PCOS women undergoing IVF/ICSI with or without IR were included in the systematic review and meta-analysis. RESULTS: The systematic review and meta-analysis included twelve observational studies that were free from inherent bias. When comparing PCOS women undergoing IVF/ICSI, the IR and non-IR groups did not show significant differences in oocytes retrieved (WMD = -0.63, 95 % CI: -2.37 to 1.12, P = 0. 483), fertilization rate (WMD = 1.01, 95 % CI: -0.66 to 2.67, P = 0.236; OR = 0.97, 95 % CI: 0.79 to 1.19, P = 0.783), and live birth rate (OR = 1.02, 95 % CI: 0.78 to 1.33, P = 0.892). However, the group with IR had a lower number of MII oocytes (WMD = -1.07, 95 % CI: -1.54 to -0.59, P < 0.001), total embryos (WMD = -1.37, 95 % CI: -1. 78 to -0.95, P < 0.001), and clinical pregnancy rate (OR = 0.77, 95 % CI: 0.59 to 0.99, P = 0.042), as well as a higher miscarriage rate (OR = 1.11, 95 % CI: 1.02 to 1.22, P = 0.017) compared to the non-IR group. CONCLUSION: In women with PCOS, IR had a negative impact on IVF/ICSI outcomes. To obtain more favourable empirical support, larger studies are necessary.

Photoredox/Copper-Catalyzed One-Pot Aminoalkylation/Cyclization of Alkenes with Primary Amines to Synthesize Polysubstituted γ-Lactams.

Visible-light-driven chemical transformation has emerged as a powerful tool for the synthesis of γ-lactams. However, during this transformation, the α-bromoimides need to be pre-prepared. Herein, we report a photoreodox/copper-catalyzed one-pot three-component reaction of alkenes with primary amines for the construction of γ-lactams. In this transformation, the orthoquinones were generated via a photocatalytic pathway, followed by attack by Cu-amido complexes and intramolecular cyclization to give the γ-lactams. This method represents a simple synthetic route displaying broad functional group tolerance, including substrates bearing alcohols, ketones, heterocycles, esters, halides, alkynes, nitriles, ethers, etc.

Photoinduced Palladium-Catalyzed 1,2-Aminoalkylation of Aromatic Alkenes with Hydroxyl as the Directing Group.

The hybrid nature of Pd(I)-alkyl radical species has enabled a wide array of radical-based transformations. However, in this transformation, the secondary Pd(I)-alkyl radical species are prone to recombining into Pd(II)-alkyl species to give Heck-type products via ß-H loss. Herein, we report a visible-light-induced, three-component Pd-catalyzed 1,2-aminoalkylation of alkenes with readily available alkyl halides and amines to construct C-C and C-N bonds simultaneously. Mechanistic investigation shows that the intermediate of o-quinone methide produced is the key factor in the transformation.

[Clinical significance for monitoring of serum ghrelin in acute pancreatitis severity assessment].

OBJECTIVE: To explore the value of altered serum level of Ghrelin for severity assessment in patients with acute pancreatitis (AP). METHODS: Peripheral blood samples were collected from 47 AP patients at admission, 48 hours post-admission and at discharge. According to the criteria of APACHEII score ≥ 8, RANSON ≥ 3, CT ≥ 4, they were divided into mild (n = 17) and severe (n = 30) groups. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of Ghrelin. And correlation analysis was made with the score of APACHEII and the level of C reactive protein (CRP). Also the serum level of Ghrelin was analyzed with receiver operating characteristic (ROC) curve. RESULTS: The serum levels of Ghrelin after 24 h were 358.6 ± 119.3 vs 212.1 ± 42.7 ng/L (P < 0.001); after 48 hours, 253.1 ± 71.2 vs 275.5 ± 73.6 ng/L (P = 0.572); at discharge, 327.8 ± 103.8 vs 319.4 ± 87.1 ng/L respectively (P = 0.816). And serum level of Ghrelin was positively correlated with APACHEII and CRP. ROC area under curve was 0.841 ± 0.057 and 95% confidence interval 0.729-0.952 (P < 0.001). CONCLUSION: The serum level of Ghrelin during early-stage AP has significant differences between two groups. And it may become an early predictor of pancreatic necrosis and a degree marker of clinical severity.

[Determination of catecholamines in urine by disperse solid-phase extraction-liquid chromatography based on Ti3C2Tx/polyimide composites].

Neurotransmitters (NTs) are basic signaling chemicals used for communication between cells. The most well-known catecholamines (CAs) are epinephrine, norepinephrine, and dopamine. CAs are an important class of monoamine NTs that contain catechins and amine groups. The accurate determination of CAs in biological samples can provide essential information on potential pathogenic mechanisms. However, biological samples generally contain only trace levels of CAs. Therefore, sample pretreatment is necessary to separate and enrich CAs before instrument analysis. Dispersive solid-phase extraction (DSPE) technology combines the principles of liquid-liquid extraction and solid-phase extraction and is a useful method for purifying and enriching the target analytes in complex matrices. This method has the advantages of low solvent consumption, environmental safety, and high sensitivity and efficiency. In addition, the adsorbents used in DSPE do not need to be packed into a column and can simply be completely dispersed in the sample solution; this excellent feature greatly improves the extraction efficiency and simplifies the extraction process. Therefore, the development of new DSPE materials with high efficiency and adsorption capacity using simple preparation procedures has received wide attention from the research community. Carbon nitrides (MXenes) are a class of two-dimensional layered materials that possess good hydrophilicity, a large number of functional groups (-O, -OH, and -F), large layer spacing, different elemental compositions, excellent biocompatibility, and environmental friendliness. However, these materials have a small specific surface area and poor adsorption selectivity, which limits their applications in SPE. The separation selectivity of MXenes can be significantly improved by functional modification. Polyimide (PI) is a crosslinking product that is mainly formed by the condensation polymerization of binary anhydride and diamine. It has a unique crosslinked network structure, as well as a large number of carboxyl groups, and shows excellent characteristics. Therefore, the synthesis of new PI-functionalized Ti3C2Tx (Ti3C2Tx/PI) composites by growing a PI layer on the surface of two-dimensional MXene nanosheets in situ may not only overcome the adsorptive limitations of MXenes but also effectively improve their specific surface area and porous structure, thereby enhancing their mass transfer capacity, adsorption capacity, and selectivity. In this study, a Ti3C2Tx/PI nanocomposite was fabricated and successfully applied as a DSPE sorbent to enrich and concentrate trace CAs in urine samples. The prepared nanocomposite was examined using various characterization methods, including scanning electron microscopy, Fourier transform-infrared spectroscopy, X-ray diffraction, and zeta potential analysis. The effects of the extraction parameters on the extraction efficiency of Ti3C2Tx/PI were also investigated in detail. The adsorption performance of Ti3C2Tx/PI can be described by pseudo-second-order kinetics and the Freundlich isotherm model. The adsorption process appeared to occur on the outer surface, as well as surface voids, of the nanocomposite. The adsorption mechanism of Ti3C2Tx/PI indicated a chemical adsorption process based on multiple electrostatic, π-π, and hydrogen-bonding interactions. The optimal adsorption conditions included an adsorbent dosage of 20 mg, sample pH of 8, adsorption and elution times of 10 and 15 min, respectively, and eluent composed of acetic acid-acetonitrile-water (5∶47.5∶47.5, v/v/v). A sensitive method for detecting CAs in urine was subsequently developed by coupling Ti3C2Tx/PI as a DSPE sorbent with HPLC-FLD analysis. The CAs were separated on an Agilent ZORBAX ODS analytical column (250 mm×4.6 mm, 5 µm). Methanol and an aqueous solution of 20 mmol/L acetic acid were used as the mobile phases for isocratic elution. Under optimal conditions, the proposed DSPE-HPLC-FLD method exhibited good linearity in the range of 1-250 ng/mL with correlation coefficients >0.99. The limits of detection (LODs) and limits of quantification (LOQs) were calculated based on signal-to-noise ratios of 3 and 10 and found to be in the range of 0.20-0.32 and 0.7-1.0 ng/mL, respectively. The recoveries of the method were in the range of 82.50%-96.85% with RSDs≤9.96%. Finally, the proposed method was successfully applied to the quantification of CAs in urine samples from smokers and nonsmokers, thereby indicating its applicability for determining trace CAs.

TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs.

The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR's downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein-protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4's promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.

Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients.

BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+IL-17+ cells were measured by flow cytometry. The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes. Percentages of circulating Th17 cells were compared between the two groups and controls. RESULTS: The levels of circulating CD4+IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56+/-0.43% versus 1.79+/-0.44%, P<0.001). The frequency of CD4+IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002). CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

[Function of SM protein in vesicle transport].

Most cells contain various transport vesicles that target to different destinations. The underlying molecular mechanisms are highly conserved in evolution. Sec1/Munc-18 (SM) proteins play an important role on regulating vesicle transport by interacting with soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) at each vesicle fusion sites. SM proteins interact with syntaxin, an important component in SNARE complex, to regulate the assembly of SNARE complex, and promote overall membrane fusion process together with SNARE complex. This review summaries new research progresses of structure and function of SM protein.

[Diagnostic values of procalcitonin, interleukin-6, C reactive protein and serum amyloid A in sepsis].

OBJECTIVE: To evaluate the diagnostic values of procalcitonin (PCT), C reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA) in septic patients. METHODS: This study totally enrolled 390 patients who were admitted to West China Hospital, Sichuan University from March to November 2011 with septic manifestation. The patients were divided into sepsis group (n = 203) and non-sepsis group (n = 187) according to clinical infectious disease standard. PCT and IL-6 were measured by automatic electrochemiluminescence (ECL) analyser. CRP was measured by rate immunonephelometric analyser, SAA was measured by fixed time nephelometric method. The diagnostic powers of these four biomakers were constructed by receiver operating characteristics (ROC) curves. RESULTS: There were statistically significant differences on the values of PCT, CRP, IL-6, SAA between sepsis group and non-sepsis group. PCT had an AUC value of 0. 919 (P < 0.05) which was higher than that of CRP, IL-6, and SAA (P < 0.05). CRP performed with an AUC of 0.755 (P < 0.05), IL-6 with an AUC of 0.786 (P < 0.05), and SAA with the lowest AUC of 0.645 (P < 0.05). The combination AUC was 0.892 (P < 0.05) and there was no statistically significant difference when compared to PCT. As an early diagnostic indicator of sepsis, the cut-off value of PCT was 1.18 ng/mL, with sensitivity of 84.7%, specific of 83.4%, while Youden index was 0.681, positive predict value was 64.1%, negative predict value was 75.8%, positive likelihood ratio was 5.10, negative likelihood ratio was 0.18, respectively. A statistically significant difference was available on the value of PCT in septic patients between ICU and non-ICU. CONCLUSION: PCT as an early independent biomarker for sepsis is superior to immune inflammatory biomarkers (CRP, IL-6, SAA), also is better than the combination of these four biomarkers for economic effect.