Electrochemically Driven Nickel-Catalyzed Halogenation of Unsaturated Halide and Triflate Derivatives.

A robust electrochemically driven nickel-catalyzed halogen exchange of unsaturated halides and triflates (Br to Cl, I to Cl, I to Br, and OTf to Cl) is reported. A combination of NiCl2 ⋅ glyme as the precatalyst, 2,2'-bipyridine as a ligand, NMP as the solvent, and electrochemistry allowed the generation of a nickel species that promotes reductive elimination of the desired product. This paired electrochemical halogenation is compatible with a range of unsaturated halides and triflates, including heterocycles, dihaloarenes, and alkenes with good functional-group tolerance. Joint experimental and theoretical mechanistic investigations highlighted three catalytic events: i) oxidative addition of the aryl halide to a Ni(0) species to deliver a Ni(II) intermediate; ii) halide metathesis at Ni(II); iii) electrochemical oxidation of Ni(II) to Ni(III) to enable the formation of the desired aryl halide upon reductive elimination. This methodology allows the replacement of heavy halogens (I or Br) or polar atoms (O) with the corresponding lighter and more lipophilic Cl group to block undesired reactivity or modify the properties of drug and agrochemical candidates.

Adhesive cryogel particles for bridging confined and irregular tissue defects.

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

Complications associated with irradiated homologous costal cartilage use in rhinoplasty: A systematic review and meta-analysis.

BACKGROUND: The use of irradiated homologous costal cartilage (IHCC) as an alternative source of graft material for rhinoplasty remains controversial because of the risk of complications. Herein, we aimed to perform a comprehensive assessment of complications associated with IHCC use in rhinoplasty through a meta-analysis of published studies. METHODS: We searched the PubMed, Embase, and Cochrane Library databases to identify eligible published studies, and we evaluated the complication rates of IHCC use in rhinoplasty. Published studies meeting the inclusion criteria included clinical studies involving at least 10 patients and assessing at least 1 postoperative long-term complication of rhinoplasty. Two investigators independently extracted data from the included studies using a standardized form. Meta-analysis was performed using a random-effects model. The main outcomes were the rates of various complications, including the need for revision surgery. RESULTS: Ten studies involving a total of 959 patients were analyzed. The complication rates were 2.07% (95% confidence interval [CI], 0.80%-5.23%) for warping, 1.77% (95% CI, 1.10%-2.83%) for infection, 1.34% (95% CI, 0.34%-5.16%) for resorption, 2.13% (95% CI, 0.86%-5.19%) for displacement, 2.99% (95% CI, 1.24%-7.03%) for revision, 0.16% (95% CI, 0.01%-3.25%) for extrusion, and 2.04% (95% CI, 1.02%-4.02%) for avulsion. All the included trials had moderate-to-high methodological quality except for small sample sizes and subjectively reporting of some complications. CONCLUSIONS: The overall long-term complication rates associated with IHCC use in rhinoplasty were low. Revision and displacement were the most common complications at the one-year follow-up; surgeons should pay special attention to the risk of these complications. IHCC can serve as a reliable material for rhinoplasty and achieve good patient satisfaction.

Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) sponges microRNA-124-3p to up-regulate phosphodiesterase 4B (PDE4B) to accelerate the progression of Parkinson's disease.

Reportedly, long non-coding RNA (lncRNA) are crucial modulators in neurodegenerative diseases. Herein, we investigated the role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in Parkinson's disease (PD). In-vitro PD model was established based on SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). NEAT1, microRNA (miR) -124-3p and phosphodiesterase 4B (PDE4B) expression levels were examined by qRT-PCR. CCK-8 assay and LDH release assay were adopted to delve into the cell viability and cytotoxicity, respectively. Besides, western blot was utilized to determine mTOR, p-mTOR and PDE4B expression levels. ELISA was executed to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). Dual-luciferase reporter assay and RIP assay were used to probe the relationship between miR-124-3p and NEAT1 or PDE4B. We demonstrated that, in SH-SY5Y cells treated with MPP+, NEAT1 and PDE4B expression levels were raised, while miR-124-3p expression was repressed; NEAT1 depletion or miR-124-3p overexpression increased the cell viability and suppressed cell injury. Besides, miR-124-3p was confirmed as the direct target of NEAT1, and its down-regulation counteracted the impact of NEAT1 depletion on SH-SY5Y cells. PDE4B was as the downstream target of miR-124-3p, and its overexpression weakens the impact of miR-124-3p on SH-SY5Y cells. Additionally, NEAT1 decoyed miR-124-3p to modulate PDE4B expression. Collectively, in MPP+-induced SH-SY5Y cells, NEAT1 depletion increases cell viability, represses cytotoxicity and reduces inflammatory response by regulating miR-124-3p and PDE4B expression levels, suggesting that NEAT1 may be a promising target for treating PD.

Novel biomarkers for the diagnosis and prognosis of gallbladder cancer.

Gallbladder cancer (GBC) is the most common form of biliary tract malignancy with a dismal prognosis. A poor outcome in patients with GBC is related to the aggressive nature of the tumor, delayed diagnosis, and a lack of reliable biomarkers and effective treatment. Therefore, early diagnosis and accurate disease assessment are crucial to prolonging the patient survival. Identification of novel prognostic and diagnostic biomarkers may help improve the early diagnostic rate and develop specific targeted treatments for patients with GBC. We herein review the novel biomarkers that may be associated with the diagnosis and prognosis in GBC and their potential clinical significance in the management of GBC.

Laparoscopic surgery for early gallbladder carcinoma: A systematic review and meta-analysis.

BACKGROUND: There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC). We hypothesized that the laparoscopic approach is an alternative for early GBC. AIM: To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early GBC. METHODS: A comprehensive search of online databases, including MEDLINE (PubMed), Cochrane libraries, and Web of Science, was performed to identify non-comparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019. A fixed-effects meta-analysis was performed for 1- and 5-year overall survival and postoperative complications, while 3-year overall survival, operation time, blood loss, the number of lymph node dissected, and postoperative hospital stay were analyzed by random-effects models. RESULTS: The review identified 7 comparative studies and 8 non-comparative studies. 1068 patients (laparoscopic surgery: 613; open surgery: 455) were included in the meta-analysis of 1-, 3-, and 5-year overall survival with no significant differences observed [(HR = 0.54; 95%CI: 0.29-1.00; I 2 = 0.0%; P = 0.051), (HR = 0.75; 95%CI: 0.34-1.65; I 2 = 60.7%; P = 0.474), (HR = 0.71; 95%CI: 0.47-1.08; I 2 = 49.6%; P = 0.107), respectively]. There were no significant differences in operation time [weighted mean difference (WMD) = 18.69; 95%CI: -19.98-57.36; I 2 = 81.4%; P = 0.343], intraoperative blood loss (WMD = -169.14; 95%CI: -377.86-39.57; I 2 = 89.5%; P = 0.112), the number of lymph nodes resected (WMD = 0.12; 95%CI: -2.95-3.18; I 2 = 73.4%; P = 0.940), and the complication rate (OR = 0.69; 95%CI: 0.30-1.58; I 2 = 0.0%; P = 0.377 ) between the two groups, while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD = -5.09; 95%CI: -8.74- -1.45; I 2 = 91.0%; P= 0.006). CONCLUSION: This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open surgery with comparable survival and operation-related outcomes for early GBC.

Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma.

BACKGROUND: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the prognostic and predictive factors remain unclear. AIM: To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC. METHODS: Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS. In order to assess the predictive factors of PA-TACE benefit, the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 378 patients (PA-TACE vs surgery alone, 189:189) from three centers were included after a propensity-score 1:1 matching analysis. Compared to the group receiving surgery alone, PA-TACE prolonged the OS rate in patients with resected HCC (P < 0.001). The Barcelona Clinic Liver Cancer system and ferritin-to-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups. Age (P = 0.023) and microscopic vascular invasion (MVI) (P = 0.002) were also identified in the PA-TACE group, while gender (P = 0.027), hepatitis B virus (P = 0.034) and albumin-bilirubin grade (P = 0.027) were also selected in the surgery alone group. In addition, PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone) < 1]. Notably, a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P = 0.038) and without MVI (P = 0.048). CONCLUSION: FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS. Moreover, high FHR and the absence of MVI were important predictive factors, which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.

Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma.

BACKGROUND: Despite significant advances in multimodality treatments, hepatocellular carcinoma (HCC) remains one of the most common malignant tumors. Identification of novel prognostic biomarkers and molecular targets is urgently needed. AIM: To identify potential key genes associated with tumor microenvironments and the prognosis of HCC. METHODS: The infiltration levels of immune cells and stromal cells were calculated and quantified based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) between high and low groups according to immune or stromal scores were screened using the gene expression profile of HCC patients in The Cancer Genome Atlas and were further linked to the prognosis of HCC. These genes were validated in four independent HCC cohorts. Survival-related key genes were identified by a LASSO Cox regression model. RESULTS: HCC patients with a high immune/stromal score had better survival benefits than patients with a low score. A total of 899 DEGs were identified and found to be involved in immune responses and extracellular matrices, 147 of which were associated with overall survival. Subsequently, 52 of 147 survival-related DEGs were validated in additional cohorts. Finally, ten key genes (STSL2, TMC5, DOK5, RASGRP2, NLRC3, KLRB1, CD5L, CFHR3, ADH1C, and UGT2B15) were selected and used to construct a prognostic gene signature, which presented a good performance in predicting overall survival. CONCLUSION: This study extracted a list of genes associated with tumor microenvironments and the prognosis of HCC, thereby providing several valuable directions for the prognostic prediction and molecular targeted therapy of HCC in the future.

Laparoscopic repair via the transabdominal preperitoneal procedure for bilateral lumbar hernia: Three cases report and review of literature.

A lumbar hernia is a rare entity, and a bilateral lumbar hernia is much rarer. From May 2015 to October 2017, we treated only three patients with bilateral lumbar hernias. One patient came to the hospital presenting with right-sided abdominal pain, and the other two patients presented with bilateral lumbar masses. The previous bilateral lumbar hernia reported in the literature was repaired by open surgery. The laparoscopic approach via the transabdominal preperitoneal (TAPP) procedure with the self-gripping Parietex ProGrip™ mesh was performed at our center. The laparoscopic repair was conducted by a skilled hernia surgeon, and was successfully performed in the three patients. The patients resumed a semi-liquid diet and had no activity restriction after six hours following the operation. No antibiotics were used after the surgery. The operative times of the three patients were 120 min, 85 min, and 130 min. The blood loss volumes of the three patients were 20 mL, 5 mL, and 5 mL. The visual analogue scale pain scores of the three patients were 1, 2, and 2 on postoperative day 1, and were 1, 2, and 1 on postoperative day 3. No perioperative complications, such as bulge, wound infection and hematoma, occurred after the surgery. All of the patients were discharged on the third day after the operation. There was no chronic pain and no hernia recurrence during the follow-up. This study showed that the laparoscopic TAPP approach with the self-gripping mesh is safe and feasible, and can be considered an alternative method for the treatment of bilateral lumbar hernias.

Laparoscopy-Assisted versus Open Hepatectomy for Live Liver Donor: Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the feasibility, safety, and potential benefits of laparoscopy-assisted living donor hepatectomy (LADH) in comparison with open living donor hepatectomy (ODH) for liver transplantation. BACKGROUND: LADH is becoming increasingly common for living donor liver transplant around the world. We aim to determine the efficacy of LADH and compare it with ODH. METHODS: A systematic search on PubMed, Embase, Cochrane Library, and Web of Science was conducted in May 2017. RESULTS: Nine studies were suitable for this analysis, involving 979 patients. LADH seemed to be associated with increased operation time (WMD = 24.85 min; 95% CI: -3.01~52.78, P = 0.08), less intraoperative blood loss (WMD = -59.92 ml; 95% CI: -94.58~-25.27, P = 0.0007), similar hospital stays (WMD = -0.47 d; 95% CI: -1.78~0.83, P = 0.47), less postoperative complications (RR = 0.70, 95% CI: 0.51~0.94, P = 0.02), less analgesic use (SMD = -0.22; 95% CI: -0.44~-0.11, P = 0.04), similar transfusion rates (RR = 0.82; 95% CI: 0.24~3.12, P = 0.82), and similar graft weights (WMD = 7.31 g; 95% CI: -23.45~38.07, P = 0.64). CONCLUSION: Our results indicate that LADH is a safe and effective technique and, when compared to ODH.

Lysine-specific demethylase 1 (LSD1) destabilizes p62 and inhibits autophagy in gynecologic malignancies.

Lysine-specific demethylase 1 (LSD1) - also known as KDM1A - is the first identified histone demethylase. LSD1 is highly expressed in numerous human malignancies and has recently emerged as a target for anticancer drugs. Owing to the presence of several functional domains, we speculated that LSD1 could have additional functions other than histone demethylation. P62 - also termed sequestasome 1 (SQSTM1) - plays a key role in malignant transformation, apoptosis, and autophagy. Here, we show that a high LSD1 expression promotes tumorigenesis in gynecologic malignancies. Notably, LSD1 inhibition with either siRNA or pharmacological agents activates autophagy. Mechanistically, LSD1 decreases p62 protein stability in a demethylation-independent manner. Inhibition of LSD1 reduces both tumor growth and p62 protein degradation in vivo. The combination of LSD1 inhibition and p62 knockdown exerts additive anticancer effects. We conclude that LSD1 destabilizes p62 and inhibits autophagy in gynecologic cancers. LSD1 inhibition reduces malignant cell growth and activates autophagy. The combinations of LSD1 inhibition and autophagy blockade display additive inhibitory effect on cancer cell viability. A better understanding of the role played by p62 will shed more light on the anticancer effects of LSD1 inhibitors.

Endothelial cells by inactivation of VHL gene direct angiogenesis, not vasculogenesis via Twist1 accumulation associated with hemangioblastoma neovascularization.

Inactivation of the VHL tumour suppressor gene is a highly frequent genetic event in the carcinogenesis of central nervous system-(CNS) hemangioblastomas (HBs). The patterning of the similar embryonic vasculogenesis is an increasing concern in HB-neovascularization, and the classic vascular endothelial growth factor (VEGF)-mediated angiogenesis driven by VHL loss-of-function from human endothelium have been questioned. With this regard, we identify a distinct, VHL silencing-driven mechanism in which human vascular endothelial cells by means of increasing cell proliferation and decreasing cell apoptosis, is concomitant with facilitating accumulation of Twist1 protein in vascular endothelial cells in vitro. Importantly, this molecular mechanism is also pinpointed in CNS-HBs, and associated with the process of HB-neovascularization. In contrast with recent studies of HB-neovascularization, these modified cells did not endow with the typical features of vasculogenesis, indicating that this is a common angiogenesis implementing the formation of the vascular network. Taken together, these findings suggest that vasculogenesis and angiogenesis may constitute complementary mechanisms for HB-neovascularization, and could provide a rational recognition of single anti-angiogenic intervention including targeting to the Twist1 signalling for HBs.

Efficacy of Magnetic Sphincter Augmentation versus Nissen Fundoplication for Gastroesophageal Reflux Disease in Short Term: A Meta-Analysis.

Background. The efficacy of Magnetic Sphincter Augmentation (MSA) and its outcomes for Gastroesophageal Reflux Disease (GERD) are uncertain. Therefore, we aimed to summarize and analyze the efficacy of two treatments for GERD. Methods. The meta-analysis search was performed, using four databases. All studies from 2005 to 2016 were included. Pooled effect was calculated using either the fixed or random effects model. Results. A total of 4 trials included 624 patients and aimed to evaluate the differences in proton-pump inhibitor use, complications, and adverse events. MSA had a shorter operative time (MSA and NF: RR = -18.80, 95% CI: -24.57 to -13.04, and P = 0.001) and length of stay (RR = -14.21, 95% CI: -24.18 to -4.23, and P = 0.005). Similar proton-pump inhibitor use, complication (P = 0.19), and severe dysphagia for dilation were shown in both groups. Although there is no difference between the MSA and NF in the number of adverse events, the incidence of postoperative gas or bloating (RR = 0.71, 95% CI: 0.54-0.94, and P = 0.02) showed significantly different results. However, there is no significant difference in ability to belch and ability to vomit. Conclusions. MSA can be recommended as an alternative treatment for GERD according to their short-term studies, especially in main-features of gas-bloating, due to shorter operative time and less complication of gas or bloating.

Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology.

OBJECTIVES: Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas. METHODS: Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays. RESULTS: Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors. CONCLUSION: Our findings support a recent paradigm-shifting concept that most SEOCs originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy.

Covered Stents versus Uncovered Stents for Unresectable Malignant Biliary Strictures: A Meta-Analysis.

AIM: To summarize the covered or uncovered SEMS for treatment of unresectable malignant distal biliary obstruction, comparing the stent patency, patient survival, and incidence of adverse events between the two SEMSs. METHODS: The meta-analysis search was performed independently by two of the authors, using MEDLINE, EMBASE, OVID, and Cochrane databases on all studies between 2010 and 2015. Pooled effect was calculated using either the fixed or the random effects model. RESULTS: Statistics shows that there is no difference between SEMSs in the hazard ratio for patient survival (HR 1.04; 95% CI, 0.92-1.17; P = 0.55) and stent patency (HR 0.87, 95% CI: 0.58 to 1.30, P = 0.5). However, incidence of adverse events (OR: 0.74, 95% CI: 0.57 to 0.97, P = 0.03) showed significant different results in the covered SEMS, with dysfunctions events (OR: 0.75, 95% CI: 0.56 to 1.00, P = 0.05) playing a more important role than complications (OR: 0.87, 95% CI: 0.58 to 1.30, P = 0.50). CONCLUSIONS: Covered SEMS group had lower incidence of adverse events. There is no significant difference in dysfunctions, but covered SEMS trends to be better, with no difference in stent patency, patient survival, and complications.

PP4 is essential for germinal center formation and class switch recombination in mice.

PP4 is a serine/threonine phosphatase required for immunoglobulin (Ig) VDJ recombination and pro-B/pre-B cell development in mice. To elucidate the role of PP4 in mature B cells, we ablated the catalytic subunit of murine PP4 in vivo utilizing the CD23 promoter and cre-loxP recombination and generated CD23(cre)PP4(F/F) mice. The development of follicular and marginal zone B cells was unaffected in these mutants, but the proliferation of mature PP4-deficient B cells stimulated by in vitro treatment with either anti-IgM antibody (Ab) or LPS was partially impaired. Interestingly, the induction of CD80 and CD86 expression on these stimulated B cells was normal. Basal levels of serum Igs of all isotypes were strongly reduced in CD23(cre)PP4(F/F) mice, and their B cells showed a reduced efficiency of class switch recombination (CSR) in vitro upon stimulation by LPS or LPS plus IL-4. When CD23(cre)PP4(F/F) mice were challenged with either the T cell-dependent antigen TNP-KLH or the T cell-independent antigen TNP-Ficoll, or by H1N1 virus infection, the mutant animals failed to form germinal centers (GCs) in the spleen and the draining mediastinal lymph nodes, and did not efficiently mount antigen-specific humoral responses. In the resting state, PP4-deficient B cells exhibited pre-existing DNA fragmentation. Upon stimulation by DNA-damaging drug etoposide in vitro, mutant B cells showed increased cleavage of caspase 3. In addition, the mutant B cells displayed impaired CD40-mediated MAPK activation, abnormal IgM-mediated NF-κB activation, and reduced S phase entry upon IgM/CD40-stimulation. Taken together, our results establish a novel role for PP4 in CSR, and reveal crucial functions for PP4 in the maintenance of genomic stability, GC formation, and B cell-mediated immune responses.

(18)F-FDG PET in stage IB/IIB cervical adenocarcinoma/adenosquamous carcinoma.

PURPOSE: The diagnostic and prognostic value of (18)F-FDG PET in cervical adenocarcinoma/adenosquamous carcinoma (AC/ASC) is unclear. The aim of this study was to assess the value of PET in the management of cervical AC/ASC. METHODS: Patients with resectable FIGO stage IB/IIB cervical AC/ASC receiving a preoperative MRI scan and a PET or PET/CT scan before radical surgery were eligible. Diagnostic efficacy was compared by receiver operating characteristic (ROC) analysis. Correlations between clinicopathological parameters and outcome and maximum standardized uptake values (SUVmax) of FDG uptake were evaluated. RESULTS: The study group comprised 83 patients (mean age 48.3 + or - 9.7 years) Five-year overall survival was 85.5%, with a median follow-up time of 38.6 months (range 2.8-87.2 months). Pelvic lymph node (PLN) and paraaortic lymph node (PALN) metastases were seen in 32.5% and 8.4% of patients, respectively. The difference in diagnostic efficacy in identifying metastatic PALN between PET and MRI was significant (PET versus MRI, area under the curve 0.832 versus 0.607, p=0.039). SUVmax in primary tumour was correlated with LN metastasis and deep stromal invasion. Overall survival was significantly related to FIGO stage, PLN metastasis, deep cervical stromal invasion, tumour size measured by MRI, and SUVmax of the primary cervical tumour. CONCLUSION: PET provided significantly better diagnostic efficacy than MRI in detecting PALN metastasis. Poor prognostic factors in cervical AC/ASC were SUVmax of the primary cervical tumour >5.3, stage IIB, deep cervical stromal invasion, tumour size measured by MRI > or = 40 mm, and PLN metastasis.

A dual-functional E. coli vector for expressing recombinant protein with high solubility and antigen presentation ability.

A dual-functional Escherichia coli expression vector capable of producing soluble recombinant proteins with high immunogenicity in animals is introduced. This vector expresses polypeptides fused to a PTD-J-domain peptide. The J-domain peptide is derived from murine Hsp40 by using optimized codons for E. coli. The association of the J-domain to the nucleotide binding domain of the DnaK chaperone increases the probability that the fused polypeptide will be folded by the DnaK and hence increases the solubility of the recombinant protein. The PTD-J-domain can also enhance the immunogenicity of the fused chicken IGF-I polypeptide as well as an oligo-peptide derived from haptoglobin in rodents, possibly via the association with either the extracellular or intracellular Hsp70 proteins.