Coexistence of primary clear cell subtype of hepatocellular carcinoma, cholangiocarcinoma, and ordinary type hepatocellular carcinoma: A case report.

INTRODUCTION AND IMPORTANCE: Primary Clear Cell subtype of Hepatocellular Carcinoma (PCHCC) is a rare kind of Hepatocellular Carcinoma (HCC). The coexistence of PCHCC, Intrahepatic Cholangiocarcinoma (ICC), and ordinary-type HCC(OHCC) in different parts of the liver is seldom reported in the literature. CASE PRESENTATION: A 66 years old man with three masses in his liver was admitted. Positron emission tomography-computed tomography suggested that 2 of the lesions were low-density and likely malignant, while the 3rd lesion was considered benign. Magnetic Resonance Imaging indicated all were malignant tumors. Minor hepatectomies were underwent respectively, and the pathology indicated the 3 tumors were PCHCC, ICC, and OHCC. Twelve months post operation, the patient was readmitted because of the recurrence of a 10.2 × 9.2 × 8.9 cm hepatic tumor. Transarterial chemoembolization and three courses of systemic chemotherapy were carried out, but the effectiveness was limited. The patient passed away 20 months after surgery. CLINICAL DISCUSSION: Surgical resection is the primary treatment of CHCC and minor hepatectomy should be considered especially when complicated with cirrhosis. Considering the poor prognosis and the high recurrence rate, sequential treatments like hepatectomy, targeted therapy, and TACE are recommended. CONCLUSION: PCHCC, ICC, and OHCC coexisted in a different part of one liver is particularly rare, comprehensive treatment with minor hepatectomy should be recommended, but the prognosis is poor.

Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation.

To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL-1ß was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor-α (TNF-α) and IL-6 were measured by ELISA kit, and Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were performed to test the expression of related proteins. The STRING database was used to predict the relationship between LASP1 and DNA methyltransferase 1 (DNMT1). The tight junction protein 2 (TJP2) and Gene Expression Omnibus data were analyzed for differential OA genes. Methylation-specific PCR detected methylation of the TJP2 promoter region, and chromatin immunoprecipitation detected the enrichment of DNMT1 in the TJP2 promoter region. Safranin O-Fast Green staining and hematoxylin and eosin staining were used to determine the OARSI score and evaluate the pathological conditions of the joint tissues. LASP1 was highly expressed in IL-1ß-induced cell models. Silencing of LASP1 promoted chondrocyte proliferation and expression of Collagen II and Aggrecan and inhibited chondrocyte apoptosis, inflammatory factors, and matrix metalloprotein expression. TJP2 is weakly expressed in OA models, and LASP1 promotes methylation of the TJP2 promoter region by interacting with DNMT1. Silencing of LASP1 attenuated IL-1ß-induced chondrocyte degeneration by promoting TJP2 expression. Similarly, silencing LASP1 promotes TJP2 expression to alleviate articular cartilage injury in mice with OA. Silencing of LASP1 inhibited the methylation of the TJP2 promoter region by interacting with DNMT1, thereby alleviating articular cartilage damage in OA mice.

High-quality color image restoration from a disturbed graded-index imaging system by deep neural networks.

Imaging transmission plays an important role in endoscopic clinical diagnosis involved in modern medical treatment. However, image distortion due to various reasons has been a major obstacle to state-of-art endoscopic development. Here, as a preliminary study we demonstrate ultra-efficient recovery of exemplary 2D color images transmitted by a disturbed graded-index (GRIN) imaging system through the deep neural networks (DNNs). Indeed, the GRIN imaging system can preserve analog images through the GRIN waveguides with high quality, while the DNNs serve as an efficient tool for imaging distortion correction. Combining GRIN imaging systems and DNNs can greatly reduce the training process and achieve ideal imaging transmission. We consider imaging distortion under different realistic conditions and use both pix2pix and U-net type DNNs to restore the images, indicating the suitable network in each condition. This method can automatically cleanse the distorted images with superior robustness and accuracy, which can potentially be used in minimally invasive medical applications.

Gene variation profile and it's potential correlation with clinical characteristics in HBV-associated HCC patients of Sichuan Han nationality in China.

OBJECTIVE: To explore the correlation between hepatocellular carcinoma (HCC) gene variation profile and clinical characteristics in Han nationality with HBV infection in Sichuan province. METHODS: The clinical data and HCC tissues were obtained from the enrolled patients. Whole exome sequencing and bioinformatics analysis were performed on formalin-fixed and paraffin-embedded samples from HCC. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. RESULTS: Sixteen high-frequency mutated genes with differential expressions were identified by WES. SMG1 gene variation could be positively correlated with satellite lesions. AMY2B and RGPD4 gene mutation seemed to have a greater chance of vascular invasion. The patients with TATDN1 variation have bigger diameters and greater chances of vascular and microvascular invasion (all P < 0.05). Univariate analysis indicated patients with gene TATDN1 variation had worse prognoses both in disease free survival (DFS) and overall survival (OS). In addition, the enrichment analysis showed many pathways, including the cell cycle pathway, viral oncogene pathway, MAPK pathway, PI3K-AKT pathway, etc., may be associated with HCC. CONCLUSION: This study explores the gene variation profile of HCC patients with HBV infection in Han nationality of Sichuan Province for the first time, which confirmed the existence of some high-frequency mutated genes and the possibility that the gene variations are involved in the tumorigenesis of HCC through multiple signal pathways. Also, patients with TATDN1 wild type showed a trend of better prognosis both in DFS and OS.

Comparison Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients with Unstable Angina with Preserved Left Ventricular Systolic Function.

The present study evaluated the clinical results of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) treatment in patients with unstable angina (UA) with preserved left ventricular systolic function who underwent percutaneous coronary intervention (PCI) due to uncertainty regarding the long-term prognosis using ACEI or ARB. A total of 1627 UA patients with preserved left ventricular systolic function after PCI were enrolled. After propensity score matching, there were no differences in major adverse cardiovascular and cerebrovascular events (MACCEs) (hazard ratio (HR) = .860, 95% confidence interval (CI): .465-1.590, P = .630), all-cause death (HR = .334, 95% CI: .090-1.238, P = .101), nonfatal myocardial infarction (HR = 4.929, 95% CI: .576-42.195, P = .145), stroke (HR = 1.049, 95% CI: .208-5.290, P = .954) and target vessel revascularization (TVR) (HR = 1.276, 95% CI: .537-3.031, P = .581) between the ACEI and ARB groups. In conclusion, prognoses were comparable between ACEI or ARB treatment in UA patients who had preserved left ventricular systolic function after PCI.

[Single-Center Experience of Treating Chronic Limb-Threatening Ischemia of Lower Limbs Combined with Diabetes].

Objective: To summarize our hospital's single-center experience of and reflections on the treatment of chronic limb-threatening ischemia (CLTI) of lower limbs combined with diabetes in the past 5 years. Methods: We retrospectively analyzed cases of lower limb CLTI combined with diabetes diagnosed at our hospital from March 2017 to June 2021. The baseline data, surgical information, and follow-up results of the patients were collected. The primary outcome indicator was the patency rate of lower limb target artery within 1 year post-op, and the secondary indicators were the reoperation rate within 1 year post-op and the amputation rate within 1 year post-op. Results: A total of 89 patients with lower limb CLTI combined with diabetes were included in the study. A total of 85 patients underwent percutaneous transluminal angioplasty and the operation of 7 patients ended in failure, with the operation success rate reaching 91.76% (78/85). Three patients underwent femoral popliteal artery bypass grafting with artificial blood vessels and one patient underwent iliac femoral artery bypass grafting with artificial blood vessels, with the success rate of the operations reachign 100% (4/4). Among 78 patients who successfully underwent percutaneous transluminal angioplasty, the median follow-up time was 33 months (13, 64). Two patients died within one year after operation, with the post-op one-year survival rate being 97.44% (76/78). The post-op 1-year reoperation rate was 19.23% (15/78), the 1-year target vascular patency rate (deaths not included) was 85.53% (65/76), and the 1-year amputation rate was 3.85% (3/78). Among the patients who underwent bypass surgery, the follow-up period was 13-48 months. No thrombosis in or re-occlusion of the artificial blood vessels were observed during the follow-up period, and the artificial blood vessels remained unoccluded. Conclusion: Transluminal angioplasty has a relatively ideal rate of postoperative vascular patency. In addition, it is a minimally invasive procedure involving low perioperative risks and is performed under local anesthesia. Therefore, it can be used as the preferred treatment for patients with CLTI. On the other hand, bypass surgery has good long-term patency rate, but it involves higher perioperative risks and the procedure is more invasive. Therefore, bypass surgery can be used as an alternative when transluminal angioplasty ends in failure.

Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production.

BACKGROUND: Hepatitis B surface antigen (HBsAg) is one of the important clinical indexes for hepatitis B virus (HBV) infection diagnosis and sustained seroconversion of HBsAg is an indicator for functional cure. However, the level of HBsAg could not be reduced by interferons and nucleoside analogs effectively. Therefore, identification of a new drug targeting HBsAg is urgently needed. METHODS: In this study, 6-AN was screened out from 1500 compounds due to its low cytotoxicity and high antiviral activity. The effect of 6-AN on HBV was examined in HepAD38, HepG2-NTCP and PHHs cells. In addition, the antivirus effect of 6-AN was also identified in mouse model. FINDINGS: 6-AN treatment resulted in a significant decrease of HBsAg and other viral markers both in vitro and in vivo. Furthermore, we found that 6-AN inhibited the activities of HBV SpI, SpII and core promoter by decreasing transcription factor PPARα, subsequently reduced HBV RNAs transcription and HBsAg production. INTERPRETATION: We have identified a novel small molecule to inhibit HBV core DNA, HBV RNAs, HBsAg production, as well as cccDNA to a minor degree both in vitro and in vivo. This study may shed light on the development of a novel class of anti-HBV agent.

PBK overexpression promotes metastasis of hepatocellular carcinoma via activating ETV4-uPAR signaling pathway.

Invasion and metastasis are the predominant causes of lethal outcomes in patients with hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the invasive or metastatic process are still insufficiently understood. Here, we first integrated several public databases and identified a novel protein kinase, PDZ-binding kinase (PBK) that was frequently upregulated and correlated with poor prognosis in patients with HCC. Gain- or loss-of-function analysis revealed that PBK promoted migration and invasion of HCC cells both in vitro and in vivo. Mechanistically, PBK enhanced uPAR expression by activating its promoter activity. Chromatin immunoprecipitation (ChIP) assay showed that ETV4 directly bound to the core region of uPAR promoter while PBK could enhance the binding of ETV4 to uPAR promoter. In orthotopic mouse model, PBK knockdown markedly inhibited the lung metastasis of HCC cells, while this effect was significantly restored by uPAR overexpression. Finally, there was a positive correlation between PBK and uPAR, ETV4 and uPAR in HCC clinical samples. Collectively, these findings revealed that PBK acted as a crucial kinase by promoting invasion and migration via the ETV4-uPAR signaling pathway, and it therefore could be a promising diagnostic biomarker and therapeutic target for HCC metastasis.

Clinical characteristics and prognostic factors of gastroenteropancreatic neuroendocrine tumors: a single center experience in China.

BACKGROUND/AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a unique subgroup of tumors in the digestive system but with great clinical heterogeneity. The information on clinical characteristics and prognostic factors of Chinese patients is rather limited. METHODOLOGY: We retrospectively analyzed the clinical features, prognostic factors of this disease in a consecutive cohort (N=294) between January 2007 and December 2012. RESULTS: Functioning tumors accounted for 9.2%. Rectum was the most predominant GEP-NETs locations. Abdominal pain occurred in 46.5% patients which was the most common initial symptom. G1, G2 and G3 tumors accounted for 41.5%, 34.7% and 23.8%, respectively. Endoscopy provided the highest detection rate of 95.7%. Consistence between endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNAB) and surgically obtained histological Ki-67 index was 36.4%. Serum CgA test showed a 80.0% consistence with the tissue biopsy. The median follow up duration was 2.8 years (0.02-5.90 years), the median survival was 4.8 years, overall 5-year survival rate was 69.6%. We found colonic localization, tumor size larger than 20 mm, G3 tumor and metastasis were associated with worse outcome (p<0.05). CONCLUSION: We found both consistence and differences in GEP-NETs characteristics between our study and previous reports.

Proteomic analysis of the effect of diclazuril on second-generation merozoites of Eimeria tenella.

Diclazuril has long been used as an effective benzeneacetonitrile anticoccidial for the control of Eimeria tenella that causes coccidiosis. However, the molecular mechanism underlying the anticoccidial effects of diclazuril remains elusive. In this study, a proteomic analysis of the effect of diclazuril on second-generation merozoites of E. tenella was performed. Using two-dimensional gel electrophoresis and real-time quantitative polymerase chain reaction (RT-PCR), 13 target proteins were found to be significantly affected by diclazuril treatment, with 11 of these proteins being identified as annotated proteins from E. tenella or other Apicomplexa parasites. These proteins contribute to various functions, including metabolism, protein synthesis, and host cell invasion. Using RT-PCR, we identified the potential pattern of transcriptional regulation induced by diclazuril, and we suggest some promising targets for the intervention of E. tenella infection.

A minimally invasive management for abdominal compartment syndrome in severe acute pancreatitis.

Three patients with severe acute pancreatitis (SAP) developed into overt abdominal compartment syndrome (ACS) and confirmed or suspected infection of necrotic tissue. We successfully treated these patients by minimally invasive decompression with the assist of laparoscope after the failures of intensive care treatments. This technique we report here may be another safe and effective management for ACS in SAP.

Clinical study on Suspension Pancreatic-Duct-Jejunum End-to-Side Continuous Suture Anastomosis in pancreaticoduodenectomy.

OBJECTIVE: To study the influence of Suspension Pancreatic-Duct-Jejunum End-to-Side Continuous Suture Anastomosis (SPDJCS) on the incidence of pancreatic fistula after pancreaticoduodenectomy, and to analyze its applicability, safety, and efficacies. METHODS: A prospective controlled trial was conducted with 165 cases receiving pancreaticoduodenectomy in the Department of Hepatopancreatobiliary Surgery from January 2010 to May 2012. The patients were divided into Group A (end-to-end/end-to-side invaginated anastomosis, n=52), Group B (end-to-side mucosal anastomosis, n=48), and Group C (SPDJCS, n=65). The preoperative data, intraoperative data, and operative outcomes (incidence of pancreatic fistula, operation time, intraoperative blood loss, peritoneal drainage, peritoneal hemorrhage, peritoneal abscess, delayed gastric emptying, pulmonary infection, postoperative infection, blood transfusion, and perioperative mortality) were compared among the 3 groups. RESULTS: The total incidence of pancreatic fistula was 13.9% (23/165) in all the 165 patients. The incidence in Group A and Group B was 23.1% (12/52) and 18.8% (9/48), both higher than that in Group C [3.1% (2/65), both P<0.05]. Group C showed significantly better outcomes than group A and B in terms of the operation time (5.5±1.2 hours vs. 6.1±1.1 hours, 5.5±1.2 hours vs. 6.3±1.5 hours), volume of blood loss (412.0±205.0 mL vs. 525.0±217.0 mL, 412.0±205.0 mL vs. 514.0±217.0 mL), and postoperative drainage amount of plasma tubes (175.0±65.0 mL vs. 275.0±80.0 mL, 175.0±65.0 mL vs. 255.0±75.0 mL) (all P<0.05), while Group A and Group B displayed no difference in these aspects (P>0.05). As complications other than pancreatic fistula were concerned, the three groups were not different from each other (P>0.05). CONCLUSIONS: SPDJCS may have the effect of reducing the incidence of pancreatic fistula after pancreaticoduodenectomy. It could be safe, practical and convenient technique of anastomosis for pancreaticojejunostomy.

Roles of histone hypoacetylation in LAT expression on T cells and Th2 polarization in allergic asthma.

BACKGROUND: Linker for activation of T cells (LAT), a transmembrane adaptor protein, plays a role in T cell and mast cell function, while it remains unclear how histone modifications mediate LAT expression in allergic asthma. The present study aimed at understanding alterations of lymphocyte LAT in patients with asthma and potential mechanisms by which histone modulation may be involved in. METHOD: The expression of LAT mRNA was checked by Quantitative real-time PCR and histone hypoacetylation on LAT promoter was detected by Chromatin Immunoprecipitation. RESULTS: Our results demonstrated that the expression of LAT mRNA in peripheral blood T cells from patients with asthma decreased, as compared to healthy controls. Peripheral blood T cells were treated with pCMV-myc-LAT, pCMV-myc or LAT-siRNA plasmid. Over-expression of LAT mRNA and decrease of Th2 cytokine production were noted, which could be prevented by the inhibition of LAT. The further investigation of the role of histone was performed in an asthma model induced by allergen. Histone hypoacetylation on LAT promoter could inhibit LAT expression and enhanced Th2 differentiation, while trichostatin A, a histone deacetylase inhibitor, promoted LAT expression and inhibited Th2 cytokine production. CONCLUSION: Our results indicate that histone hypoacetylation may regulate LAT expression on T cells and modify Th2 polarization in allergic asthma.

Clinical study on Suspension Pancreatic-Duct-Jejunum End-to-Side Continuous Suture Anastomosis in pancreaticoduodenectomy / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the influence of Suspension Pancreatic-Duct-Jejunum End-to-Side Continuous Suture Anastomosis (SPDJCS) on the incidence of pancreatic fistula after pancreaticoduodenectomy, and to analyze its applicability, safety, and efficacies.</p><p><b>METHODS</b>A prospective controlled trial was conducted with 165 cases receiving pancreaticoduodenectomy in the Department of Hepatopancreatobiliary Surgery from January 2010 to May 2012. The patients were divided into Group A (end-to-end/end-to-side invaginated anastomosis, n=52), Group B (end-to-side mucosal anastomosis, n=48), and Group C (SPDJCS, n=65). The preoperative data, intraoperative data, and operative outcomes (incidence of pancreatic fistula, operation time, intraoperative blood loss, peritoneal drainage, peritoneal hemorrhage, peritoneal abscess, delayed gastric emptying, pulmonary infection, postoperative infection, blood transfusion, and perioperative mortality) were compared among the 3 groups.</p><p><b>RESULTS</b>The total incidence of pancreatic fistula was 13.9% (23/165) in all the 165 patients. The incidence in Group A and Group B was 23.1% (12/52) and 18.8% (9/48), both higher than that in Group C [3.1% (2/65), both P<0.05]. Group C showed significantly better outcomes than group A and B in terms of the operation time (5.5±1.2 hours vs. 6.1±1.1 hours, 5.5±1.2 hours vs. 6.3±1.5 hours), volume of blood loss (412.0±205.0 mL vs. 525.0±217.0 mL, 412.0±205.0 mL vs. 514.0±217.0 mL), and postoperative drainage amount of plasma tubes (175.0±65.0 mL vs. 275.0±80.0 mL, 175.0±65.0 mL vs. 255.0±75.0 mL) (all P<0.05), while Group A and Group B displayed no difference in these aspects (P>0.05). As complications other than pancreatic fistula were concerned, the three groups were not different from each other (P>0.05).</p><p><b>CONCLUSIONS</b>SPDJCS may have the effect of reducing the incidence of pancreatic fistula after pancreaticoduodenectomy. It could be safe, practical and convenient technique of anastomosis for pancreaticojejunostomy.</p>

Receptor for activated C kinase ortholog of second-generation merozoite in Eimeria tenella: clone, characterization, and diclazuril-induced mRNA expression.

The receptor for activated C kinase (RACK) cDNA of second-generation merozoites of Eimeria tenella was cloned using reverse transcriptase polymerase chain reaction and rapid amplification of cDNA ends, compared with other species, and then successfully expressed using the pET-28a vector in Escherichia coli BL21 (DE3) (EtRACK). Nucleotide sequence analysis revealed that the full length of the cloned cDNA (1,264 bp) encompassed a 957-bp open reading frame encoding a polypeptide of 318 residues with an estimated molecular mass of 34.94 kDa and a theoretical isoelectric point of 5.97. Molecular analysis of EtRACK reveals the presence of seven WD40 repeat motifs. EtRACK localizes to the cytoplasm and nucleus in second-generation merozoites of E. tenella. The cDNA sequence has been submitted to the GenBank Database with accession number JQ292804. EtRACK shared 98% homology with the published sequence of a RACK protein from Toxoplasma gondii at the amino acid level (GenBank XP_002370996.1). Recombinant protein expression was induced using 1 mM of isopropyl ß-D-1-thiogalactopyranoside in vitro at 30 °C. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that the 39.79-kDa fusion protein existed in unsolvable form. Quantitative real-time PCR analysis showed that compared with the control group, the level of EtRACK mRNA expression in the treatment group was downregulated by 81.3% by diclazuril treatment. The high similarity of EtRACK to previously described RACKs of other organisms, as well as its downregulated expression in second-generation merozoites induced by diclazuril, suggests that it could play a key role in the signaling event that precedes protein secretion and parasite invasion. Moreover, the downregulation of EtRACK mRNA expression also enriches studies on the mechanism of action of diclazuril on E. tenella.

[The expressions and correlation of bcl-2 and Beclin-1 in pancreatic cancer].

OBJECTIVE: To investigate the expressions of Bcl-2 and Beclin-1 in pancreatic cancer and analyze the correlation between them. METHODS: The pancreatic tissue samples were collected from each 6 cases of pancreatic cancer, pancreatic exocrine benign tumor, chronic pancreatitis and normal pancreas and marked as group A, group B, group C and group D, respectively. The mRNA expression levels of Bcl-2 and Beclin-1 were detected by real-time fluorescence quantitative PCR and the protein expression levels of Bcl-2 and Beclin-1 were detected through immunohistochemistry. RESULTS: The expression levels of Bcl-2 mRNA and protein, were the lowest in group D and the highest in group A (P < 0.05). The expression levels of Beclin-1 mRNA and protein in group A were significantly lower than those in group B and group D (P < 0.05). However, the expression levels of Beclin-1 between group A and group C were not significantly different (P > 0.05). The correlation coefficient between Bcl-2 and Beclin-1 protein expression in pancreatic cancer is--0.827 (P = 0. 042). CONCLUSION: Compared with normal pancreatic tissue, pancreatic cancer had Bcl-2 expression upregulated and Beclin-1 expression downregulated. The increased anti-apoptotic effect of Bcl-2 and the decreased autophagic effect of Beclin-1 may collaboratively contribute to the occurrence of pancreatic cancer.

Hydroxyethyl starch resuscitation reduces the risk of intra-abdominal hypertension in severe acute pancreatitis.

OBJECTIVES: This study aimed to address whether hydroxyethyl starch (HES) is beneficial for intra-abdominal pressure (IAP) in severe acute pancreatitis (SAP) in early stages. METHODS: Forty-one patients with SAP were randomized to HES group (n = 20) and the Ringer's lactate (RL) group (n = 21). The groups received 6% HES 130/0.4 for 8 days and RL solution without colloid, respectively. The primary end point was the IAP. The secondary end points were fluid balance, major organ complications, the Acute Physiology and Chronic Heath Evaluation II score, and the serum levels of C-reactive protein, interleukin-6, and interleukin-8. RESULTS: The characteristics of baseline data were similar in the 2 groups. In the HES group, the IAP was significantly lower in 2 to 7 days, and fewer patients received mechanical ventilation (15.0% vs 47.6%). A negative fluid balance was observed earlier in the HES group than in the RL group (2.5 ± 2.2 vs 4.0 ± 2.5 days). CONCLUSIONS: Fluid resuscitation with HES in the early stages of SAP can decrease the risk of intra-abdominal hypertension and reduce the use of mechanical ventilation.

[Study on the role of Th17 cells in the islet transplantation].

OBJECTIVE: To study the role of Th17 cells in the Immune rejection of islet transplantation, explore the feasibility of immune tolerance of islet transplantation induced by the combination applying of IL-23R antibody and Anti-CD154mAb. METHODS: The in vitro experiments were divided into 5 groups: Blank control group, SD rat islet cells were cultured alone; A group, co-culture of rat pancreatic islet cells and lymphocytes, without IL-23R antibodies; B, C, D groups, co-culture of rat pancreatic islet cells and lymphocytes, respectively with IL-23R antibodies 0.1 microg/mL, 0.5 microg/mL, 1.0 microg/mL. Cells were harvested for Acridine orange (AO)/propidium iodide (PD) fluorescence staining, insulin and glucagon staining and glucose-stimulated insulin secretion test. The in vivo experiments (the purified islet to be transplanted under the left kidney capsule of the mice) were divided into four groups: Control group, BABL/c mice were transplanted with islets of SD rats with no treatments, IL-23R antibody (200 microg) treatment alone, anti-CD154mAb (200 microg) treatment alone and a combination of both. The blood glucose of the transplanted mice were monitored. The kidney of islet grafts were sliced for HE staining and insulin and glucagon immunohistochemical detection. RESULTS: Three days after mixed cultivation, the glucose stimulation index was 3.66 +/- 0.10 in blank control group, which was higher than that of other groups. Stimulation index of D group was 1.95 +/- 0.75, which was significantly higher than that of other groups. The functional graft survival of all experimental groups were significantly better than that of control group as demonstrated by immunohistochemical staining of insulin and glucagon, as well as in vitro and in vivo experiments. After three days of islet transplantation, the blood glucose of control group was higher than that of experimental groups, but no significant difference was observed among experimental groups. CONCLUSION: Th17 cells were involved in the islet transplant rejection. The expression of IL-17 could be considerably reduced through the block of the IL-23R, the effect of the block had a positive correlation in a dose-dependent manner. The combination of Anti-CD154 mAb and IL-23R antibody could prevent the acute rejection to some extent. However, there's no significant difference compared with the Anti-CD154mAb alone.

The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer.

Interleukin (IL)-16, a multifunctional cytokine, plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in the DNA sequence of the IL-16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individual's susceptibility to both colorectal cancer (CRC) and gastric cancer (GC). To test this hypothesis, we investigated the association of IL-16 gene polymorphisms with serum levels of IL-16 and the risk of CRC and GC in a Chinese population. We analyzed single-nucleotide polymorphisms of the IL-16 gene in 596 cancer patients (376 patients with CRC and 220 patients with GC), and also in 480 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. Serum IL-16 levels were measured by enzyme-linked immunosorbent assay. The rs11556218 T/G polymorphism of the IL-16 gene was significantly associated with the susceptibility to CRC and GC patients. Both male and female patients carrying the G allele had a significantly higher risk for developing CRC and GC compared with individuals carrying the T allele. Alternatively, women carrying the T allele (rs4072111 C/T) showed a decreased risk for CRC and GC compared with individuals carrying the C allele. In patients with CRC or GC, IL-16 serum levels were significantly higher than those in the healthy controls, although no significant association between IL-16 polymorphisms and serum levels of IL-16 was observed. Our data indicate that IL-16 polymorphisms may contribute to CRC and GC susceptibility.

Advances in mechanisms of postsurgical gastroparesis syndrome and its diagnosis and treatment.

Postsurgical gastroparesis syndrome (PGS) is a complex disorder characterized by post-prandial nausea and vomiting, and gastric atony in the absence of mechanical gastric outlet obstruction, and is often caused by operation at the upper abdomen, especially by gastric or pancreatic resection, and sometimes also by operation at the lower abdomen, such as gynecological or obstetrical procedures. PGS occurs easily with oral intake of food or change in the form of food after operation. These symptoms can be disabling and often fail to be alleviated by drug therapy, and gastric reoperations usually prove unsuccessful. The cause of PGS has not been identified, nor has its mechanism quite been clarified. PGS after gastrectomy has been reported in many previous studies, with an incidence of approximately 0.4-5.0%. PGS is also a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD), and the complication occurs in the early postoperative period in 20-50% of patients. PGS caused by pancreatic cancer cryoablation (PCC) has been reported about in 50-70% of patients. Therefore, PGS has a complex etiology and might be caused by multiple factors and mechanisms. The frequency of this complication varies directly with the type and number of gastric operations performed. The loss of gastric parasympathetic control resulting from vagotomy contributes to PGS via several mechanisms. It has been reported that the interstitial cells of Cajal (ICC) may play a role in the pathogenesis of PGS. Recent studies in animal models of diabetes suggest specific molecular changes in the enteric nervous system may result in delayed gastric emptying. The absence of the duodenum, and hence gastric phase III, may be a cause of gastric stasis. It was thought that PGS after PPPD might be attributable, at least in part, to delayed recovery of gastric phase III, due to lowered concentrations of plasma motilin after resection of the duodenum. The damage to ICC might play a role in the pathogenesis of PGS after PCC, for which multiple factors are possibly responsible, including ischemic and neural injury to the antropyloric muscle and the duodenum after freezing of the pancreatoduodenal regions or reduction of circulating levels of motilin. As the treatment of gastroparesis is far from ideal, non-conventional approaches and non-standard medications might be of use. Multiple treatments are better than single treatment. This article reviews almost all the papers related to PGS from various journals published in English and Chinese in recent years in order to facilitate a better understanding of PGS.