Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.

Thyroid cancer can be classified into three different types based on the degree of differentiation: well-differentiated, poorly differentiated, and anaplastic thyroid carcinoma. Well-differentiated thyroid cancer refers to cancer cells that closely resemble normal thyroid cells, while poorly differentiated and anaplastic thyroid carcinoma are characterized by cells that have lost their resemblance to normal thyroid cells. Advanced thyroid carcinoma, regardless of its degree of differentiation, is known to have a higher likelihood of disease progression and is generally associated with a poor prognosis. However, the process through which well-differentiated thyroid carcinoma transforms into anaplastic thyroid carcinoma, also known as "dedifferentiation", has been a subject of intensive research. In recent years, there have been significant breakthroughs in the treatment of refractory advanced thyroid cancer. Clinical studies have been conducted to evaluate the efficacy and safety of molecular targeted drugs and immune checkpoint inhibitors in the treatment of dedifferentiated thyroid cancer. These drugs work by targeting specific molecules or proteins in cancer cells to inhibit their growth or by enhancing the body's immune response against the cancer cells. This article aims to explore some of the possible mechanisms behind the dedifferentiation process in well-differentiated thyroid carcinoma. It also discusses the clinical effects of molecular targeted drugs and immune checkpoint inhibitors in thyroid cancer patients with different degrees of differentiation. Furthermore, it offers insights into the future trends in the treatment of advanced thyroid cancer, highlighting the potential for improved outcomes and better patient care.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

Screening for functional circular RNAs using the CRISPR-Cas13 system.

Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood owing to the lack of adequate methods for distinguishing circRNAs from cognate messenger RNAs with overlapping exons. Here, we report that CRISPR-RfxCas13d can effectively discriminate circRNAs from mRNAs by using guide RNAs targeting sequences spanning back-splicing junction (BSJ) sites featured in RNA circles. Using a lentiviral library that targets sequences across BSJ sites of highly expressed human circRNAs, we show that a group of circRNAs are important for cell growth mostly in a cell-type-specific manner and that a common oncogenic circRNA, circFAM120A, promotes cell proliferation by preventing the mRNA for family with sequence similarity 120A (FAM120A) from binding the translation inhibitor IGF2BP2. Further application of RfxCas13d-BSJ-gRNA screening has uncovered circMan1a2, which has regulatory potential in mouse embryo preimplantation development. Together, these results establish CRISPR-RfxCas13d as a useful tool for the discovery and functional study of circRNAs at both individual and large-scale levels.

A network pharmacology strategy to investigate the anti-inflammatory mechanism of luteolin combined with in vitro transcriptomics and proteomics.

Luteolin, a natural flavonoid exists in various medicinal plants, has strong anti-inflammatory effect. However, anti-inflammatory mechanism of luteolin has not been fully explored. Hence, we systematically investigated druggability and anti-inflammatory mechanism of luteolin based on network pharmacology and in vitro experiments. The absorption, distribution, metabolism and excretion of luteolin were evaluated by TCMSP server. Targets associated with luteolin and inflammation were collected from public databases, and the overlapping targets between luteolin and inflammation were analyzed by Draw Venn diagram. Then the protein-protein interaction network of luteolin against inflammation was constructed. Further, gene function and pathway enrichment analysis were performed. Finally, in vitro experiments were carried out to estimate the accuracy of predicted target genes. ADME results indicated that luteolin has great potential to be developed into a drug. 226 overlapping targets were screened by matching 280 targets of luteolin with 9015 targets of inflammation. 9 core targets of luteolin against inflammation were identified, including MMP9, MAPK1, HSP90AA1, CASP3, ALB, EGFR, SRC, HRAS and ESR1. Gene function were mainly involved in metabolism, energy pathways and signal transduction. Metabolic pathways, pathways in cancer, PI3K-AKT signaling pathway, Ras signaling pathway and so on might be the critical pathways of luteolin against inflammation. RT-qPCR and ELISA results indicated that luteolin decreased the expression of most of core genes at protein and mRNA levels (MMP9, MAPK1, HSP90AA1, EGFR, SRC and HRAS). Luteolin is expounded to have great potential to be developed into a drug and target various genes and pathways to perform anti-inflammatory effect.

Extraction, purification, characterization, anticoagulant activity, and anticoagulant mechanism of polysaccharides from the heads of Hypomesus olidus.

The aim of this work was to extract, isolate, and purify polysaccharides from the heads of Hypomesus olidus and to evaluate their anticoagulant activities and anticoagulant mechanisms. Response surface methodology was used to optimize the extraction conditions for ultrasonic-assisted extraction of polysaccharides from the heads of Hypomesus olidus. The optimal extraction conditions consisted of ultrasonic power of 275 W, ultrasonic time of 50 min, and solid-liquid ratio of 5 ml/g, giving the yield of crude polysaccharides (GYT) of 7.73 ± 0.042%. Three polysaccharide fractions, GYT-1, GYT-2, and GYT-3 were purified from GYT by using DEAE-cellulose-52 column and Sephadex G-100 column for anticoagulant activities. The results showed that two doses (2 and 4 mg/ml) of GYT-1 and GYT-3 could significantly prolong (p < .01) in partial thromboplastin time (APTT) (2.19 and 2.37 times, 2.22 and 2.44 times, respectively) and thrombin time (TT) (2.39 and 2.46 times, 2.44 and 2.80 times, respectively) compared with normal control. In particular, GYT-3 had stronger anticoagulant activity than GYT-1, and it was composed of arabinose, fructose, glucose, and lactose with molar ratios of 0.595:1: 2.026:0.273. However, GYT-2 had no anticoagulant activity (p > .05). In addition, anticoagulation mechanism of polysaccharides from the heads of Hypomesus olidus (GYT-3) was evaluated. The results showed that the anticoagulant activity of GYT-3 was based on their binding with antithrombin AT-III. And the inhibitory effects of GYT-3 on factor IIa and Xa were related to the concentration of AT-III in plasma. This study may provide a new and promising anticoagulant drug.

Single-incision robotic cholecystectomy versus single-incision laparoscopic cholecystectomy: A systematic review and meta-analysis.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is the result of the ongoing trend to minimally invasive of laparoscopy, but some surgeons thought that the SILC can increase the risk of bile duct injure or bile spillage, and the single-incision robotic cholecystectomy (SIRC) can overcome the drawbacks of SILC. Some articles described that the SIRC had longer operative time and more cost than SILC. The advantages and disadvantages of SIRC have still not been extensively studied. We aimed to investigate the outcomes of SIRC compared to SILC and evaluate the safety and feasibility of SIRC. METHODS: To find relevant studies, the electronic databases PubMed, MEDLINE, The Cochrane Library, and EMBASE were searched to seek information in English literature from 2011 to 2017. Studies comparing SIRC to SILC, for any indication, were included in the analysis. This systematic review and meta-analysis were performed with RevMan Version 5.3. RESULTS: Six comparative studies (n = 633 patients) were included in our analysis. The data showed that the SIRC and SILC had equivalent outcomes for operative time [mean difference (MD) = 17.32, 95% confidence interval (CI): -8.93-43.57, P = .20], intraoperative complications [odd ratio (OR) = 0.48, 95% CI: 0.17-1.39, P = .18], postoperative complications (OR = 0.62, 95% CI: 0.21-1.86, P = .39), hospital stay (MD = -0.01, 95% CI: -0.21-0.19, P = .90), readmissions rate (OR = 0.70, 95% CI: 0.09-5.63, P = .74), and conversion rate (OR = 0.52, 95% CI: 0.14-1.96, P = .33), but total cost was statistically significant (MD = 3.7, 95% CI: 3.61-3.79, P < .00001). CONCLUSION: SIRC is a safe and feasible procedure for cholecystectomy, and the operative time is same as SILC, but the total cost of SIRC is significantly higher than SILC.

Geniposide attenuates Aß25-35-induced neurotoxicity via the TLR4/NF-κB pathway in HT22 cells.

Alzheimer's disease (AD), a neurodegenerative disorder, is marked by the accumulation of amyloid-ß (Aß) and neuroinflammation which promote the development of AD. Geniposide, the main ingredient isolated from Chinese herbal medicine Gardenia jasminoides Ellis, has a variety of pharmacological functions such as anti-apoptosis and anti-inflammatory activity. Hence, we estimated the inflammatory cytotoxicity caused by Aß25-35 and the neuroprotective effects of geniposide in HT22 cells. In this research, following incubation with Aß25-35 (40 µM, 24 h) in HT22 cells, the methylthiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) release assays showed that the cell survival rate was significantly decreased. In contrast, the reactive oxygen species (ROS) assay indicated that Aß25-35 enhanced ROS accumulation and apoptosis showed in both hoechst 33342 staining and annexin V-FITC/PI double staining. And then, immunofluorescence test revealed that Aß25-35 promoted p65 to transfer into the nucleus indicating p65 was activated by Aß25-35. Moreover, western blot analysis proved that Aß25-35 increased the expression of nitric oxide species (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-1ß (IL-1ß). Simultaneously, Aß25-35 also promoted the expression of toll-like receptor 4 (TLR4), p-p65 and p-IκB-α accompanied with the increase in the level of beta-secretase 1 (BACE1) and caspase-3 which further supported Aß25-35 induced apoptosis and inflammation. Fortunately, this up-regulation was reversed by geniposide. In conclusion, our data suggest that geniposide can alleviate Aß25-35-induced inflammatory response to protect neurons, which is possibly involved with the inhibition of the TLR4/NF-κB pathway in HT22 cells. Geniposide may be the latent treatment for AD induced by neuroinflammation and apoptosis.

Basiliximab application on liver recipients: a meta-analysis of randomized controlled trials.

BACKGROUND: The benefits of the application of basiliximab induction therapy in liver transplantation are not clear. The present meta-analysis was to evaluate the pros and cons of basiliximab use in liver transplantation. DATA SOURCES: We searched the associated publications in English from July 1998 to December 2015 in the following databases: MEDLINE, PubMed, Ovid, EMBASE, Web of Science and Cochrane Library. RESULTS: Basiliximab significantly decreased the incidence of de novo diabetes mellitus after liver transplantation (RR=0.56; 95% CI: 0.34-0.91; P=0.02). Subgroup analysis showed that basiliximab in combination with steroids-free immunosuppressant significantly decreased the incidence of biopsy-proven acute rejection (RR=0.62; 95% CI: 0.39-0.97; P=0.04) and new-onset hypertension (RR=0.62; 95% CI: 0.42-0.93; P=0.02). CONCLUSIONS: Basiliximab may be effective in reducing de novo diabetes mellitus. What is more, basiliximab in combination with steroids-free immunosuppressant shows statistical benefit to reduce biopsy-proven acute rejection and de novo hypertension.

The Biogenesis of Nascent Circular RNAs.

Steady-state circular RNAs (circRNAs) have been mapped to thousands of genomic loci in mammals. We studied circRNA processing using metabolic tagging of nascent RNAs with 4-thiouridine (4sU). Strikingly, the efficiency of circRNA processing from pre-mRNA is extremely low endogenously. Additional studies revealed that back-splicing outcomes correlate with fast RNA Polymerase II elongation rate and are tightly controlled by cis-elements in vivo. Additionally, prolonged 4sU labeling in cells shows that circRNAs are largely processed post-transcriptionally and that circRNAs are stable. Circular RNAs that are abundant at a steady-state level tend to accumulate. This is particularly true in cells, such as neurons, that have slow division rates. This study uncovers features of circRNA biogenesis by investigating the link between nascent circRNA processing and transcription.

[Chemical constituents from ripe fruit of Cornus officinalis].

To investigate the chemical compounds from the fruit of Cornus officinalis, six compounds were isolated and determined by extensive spectroscopic analysis as 6'-O-acetyl-7α-O-ethyl morroniside (1), (-)-isolariciresinol 3α-O-ß-D-glucopyranoside(2), apigenin (3), cirsiumaldehyde(4), p-coumaric acid (5), caffeic acid (6). Compound 1 was a new iridoid glucoside,and compounds 2-4 were obtained from the Cornus genus for the first time. Compounds 2-6 were evaluated for the viability of PC12 cells when exposed in conditions of oxygen and glucose deprivation. The MTT results showed that compound 4 increased cell viability moderately in OGD/R treated PC12 cells at the concentration of 1.0 µmol•L⁻¹.

Is radiofrequency ablation equal to surgical re-resection for recurrent hepatocellular carcinoma meeting the Milan criteria? A meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of radiofrequency ablation (RFA) with surgical re-resection (SRR) in patients with postoperative recurrent hepatocellular carcinoma (RHCC) meeting the Milan criteria. METHODS: A literature search was performed to identify comparative studies addressing outcomes of both RFA and SRR for RHCC meeting the Milan criteria. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or the random effects model. RESULTS: Five nonrandomized controlled trials were included in the analysis. These studies included a total of 543 patients: 243 treated with RFA and 300 treated with SRR. The SRR group had a better 3-year recurrence-free survival rate compared with RFA group (OR 0.44, 95%CI 0.25-0.77, p=0.004). However, there were no obvious differences between RFA and SRR group in overall survival (OS) rates, re-recurrence rate and OS rates with tumors ≤ 3cm. What's more, the RFA group had a safety advantage with less complications of Clavien classification grade II or higher compared with SRR group (OR 0.21, 95%CI 0.05-0.94, p=0.04). CONCLUSIONS: RFA seemed to be superior to SRR in the treatment of patients with RHCC meeting the Milan criteria on account of clinical safety. However, these findings have to be carefully interpreted due to the lower level of evidence.

Self-assembled two-dimensional nanoporous molecular arrays and photoinduced polymerization of 4-bromo-4'-hydroxybiphenyl on Ag(111).

Self-assembled two-dimensional molecular arrays and photoinduced polymerization of 4-bromo-4'-hydroxybiphenyl on Ag(111) were studied using low-temperature scanning tunneling microscopy combined with density functional theory calculations. Square-like self-assembled structures of 4-bromo-4'-hydroxybiphenyl stabilized by intermolecular hydrogen and halogen bonds were transformed into hexagonal nanopores of biphenyl biradicals by 266 nm UV laser irradiation at 80 K. The biradicals further coupled to each other and formed covalently linked polyphenylene polymer chains at room temperature.

Tumor cells forming sinusoids connected to vasculature are involved in hemorrhage of pineal choriocarcinoma.

Intratumor hemorrhage is a poor prognostic factor in pineal choriocarcinoma (PCCC). The aim of this study was to understand the relationship of tumor cells to the blood vessels to gain insights into the formation of intratumor hemorrhage in PCCC. The clinical data indicated that total tumor removal by surgical procedures followed immediately by radiotherapy and chemotherapy improved the prognosis in PCCC. The PCCC tissues removed from the patients were examined by histology and immunohistochemistry. Hematoxylin and eosin staining showed that the tumor stroma mainly consists of hemorrhagic tissues with tumor cells scattered inside. The pattern of distribution suggests that the tumor cells were possibly flushed and compressed by the bleeding. The tumor cells tended to form sinusoids that lacked CD34, but laminin expression provided evidence of vasculogenic mimicry. Interestingly, CD34-positive blood vessels were found connected to these sinusoids, suggesting that blood may flow from the tumor vasculature to the sinusoids. This may subsequently cause the enlargement of the sinusoids, blood clotting, the widening of the blood lakes, and eventually extensive hemorrhagic necrosis. Our study identified the key features of the PCCC vasculature. The findings add to the previous understanding of the formation of vascular channels, blood lakes, and extensive hemorrhagic necrosis. The intimate connections between the tumor-formed sinusoids and the blood vessels might be a major cause of severe hemorrhage in PCCC. The new information may be useful for the development of treatment strategies for managing PCCC.

Hepatobiliary cystadenoma and cystadenocarcinoma: a single center experience.

AIMS AND BACKGROUND: Hepatobiliary cystadenoma and cystadenocarcinoma are rare cystic lesions of the liver. The aim of the study was to discuss the clinical features, diagnostic methods and surgical treatment of hepatobiliary cystadenoma and cystadenocarcinoma in our hospital. METHODS: Six patients with hepatobiliary cystadenomas and four with hepatobiliary cystadenocarcinomas were evaluated. We collected detailed clinical data, and all patients were followed. RESULTS: Three patients of the 6 with cystadenomas and 2 patients of the 4 with cystadenocarcinomas had marked elevation of CA19-9 (average, 707.0 U/ml and 1078.5 U/ml, respectively). CT scan with contrast revealed typical lesions in all 10 cases, i.e., cyst-occupying lesions with separations in the liver. All patients with hepatobiliary cystadenoma were treated by partial hepatectomy. None of them recurred at a mean follow-up of 40 months. Three patients with hepatobiliary cystadenocarcinoma underwent hepatectomy, without recurrence or metastasis at a mean follow-up of 32 months. CONCLUSIONS: Tumor markers (CA19-9) and imaging findings may be helpful for an early diagnosis. Complete resection is still the best choice. Even for hepatobiliary cystadenocarcinoma, considering the low malignant grade, we suggest that for the best prognosis radical excision should be attempted.

Colorectal liver metastases rarely occur in patients with chronic hepatitis virus infection.

BACKGROUND/AIMS: There are studies that report that liver metastases rarely occur in patients with cirrhosis. This study evaluates the relationship between the incidence of liver metastases from colorectal cancer (CRC) and chronic hepatitis virus infection in patients. METHODOLOGY: Three hundred and fifty-four cases of advanced CRC from our hospital were evaluated. The patients were divided into a chronic hepatitis virus infection group and a non-hepatitis virus infection group. The two groups were compared regarding the incidence of colorectal liver metastases and survival. The criterion of colorectal liver metastases was based on liver CT examination and intraoperative exploration results. RESULTS: There were two cases with colorectal liver metastases among the seventy cases of the chronic hepatitis virus infection group. The rate of liver metastases was 2.86%. There were 48 cases with colorectal liver metastases among 284 cases of the non-hepatitis virus infection. The rate of liver metastases was 16.9%. The incidence of colorectal liver metastases between the two groups was significantly different (p<0.01). Five-year survival rates were 60% and 40.8% in the chronic hepatitis virus infection group and the non-hepatitis virus infection group, respectively (p<0.05). The degree of progress in the two groups of patients showed no significant difference. CONCLUSIONS: Colorectal liver metastases occur rarely with chronic hepatitis virus infection and the patients in our study had good prognoses.

Propranolol regulates cardiac transient outward potassium channel in rat myocardium via cAMP/PKA after short-term but not after long-term ischemia.

It was recently suggested that the antiarrhythmic effect of propranolol, a ss-adrenoceptor antagonist, on ischemic myocardium includes restoration of I(K1) current and Cx43 conductance; however, little is known whether effects on the transient outward current I(to) contribute. A model of myocardial infarction (MI) by ligating the left anterior descending coronary artery was established. Propranolol was given 1 h or daily for 3 months, whole-cell patch-clamp techniques were used to measure I(to). Kv4.2 and PKA levels were analyzed by Western blot and cAMP level was determined by radioimmunoassay. The results showed that propranolol decreased the incidence of arrhythmias induced by acute ischemia and mortality in 3 month MI rats. Propranolol restored the diminished I(to) density and Kv4.2 protein in MI hearts. In addition, neonatal cardiomyocyte pretreatment with propranolol or administrated after hypoxia can resume I(to) density. cAMP/PKA was enhanced in acute MI, the reason of decreased Kv4.2 expression. Treatment with propranolol prevented the increased cAMP/PKA in 1 h MI, whereas propranolol had little effect on decreased cAMP/PKA in 3 months MI. This study demonstrated that both short- and long-term propranolol administrations protect cardiomyocytes against arrhythmias and mortality caused by cardiac ischemia; the involvement of cAMP/PKA signal pathway in the regulation of propranolol on I(to) acted differently along with the ischemic progression.

[Effect of inducible nitric oxide synthase on pancreas islet apoptosis in rats].

AIM: To investigate the effect and mechanism of cytokine and inducible nitric oxide synthase on apoptosis and function of rat pancreas islets cultured in vitro. METHODS: Islets from Wistar rats were cultured in vitro and divided randomly into four groups: blank control group, cytokine group of islets cultured with TNF-alpha+IL-1beta, aminoguanidine (AG) group of islets cultured with aminoguanidine, and AG + cytokine group of islets cultured with TNF-alpha+IL-1beta and aminoguanidine. The nutrient fluid nitric oxide level and islets cNOS/iNOS activity were detected by test kit and the expressions of iNOS mRNA and apoptosis related gene (Bax, Bcl-2) were evaluated by RT-PCR. The viability of the islets was examined by AO/EB staining and the function of the islets was detected by insulin secretion index assay. RESULTS: After co-cultured with cytokines IL-1beta and TNF-alpha, the expression and activity of iNOS in islet tissues enhanced (38.93+/-4.72) U/mL and the concentration of NO in medium increased remarkably(313.0+/-35.4) mol/L.The survival rate of cells and the insulin secretion index decreased with the up-regulation of proapoptosis gene and down-regulation of anti-apoptosis gene. But the activity of cNOS remained unchanged. Aminoguanidine reduced the cell apoptosis and increased the survival rate and insulin secretion index, and the activity of iNOS was inhibited. CONCLUSION: iNOS plays an important role in the apoptosis of islets cultured by cytokines TNF-alpha and IL1-beta. Aminoguanidine prevents the islets from the damage of iNOS, alleviates the impairment of cytokines to islets, lessens the cell apoptosis and ameliorates the survival and function of islets.

Localization of small sized insulinoma by means of combining arteriography with CT: a case report and review of the literature.

BACKGROUND: The majority of pancreatic insulinomas are of small size and conventional imaging examinations such as percutaneous ultrasonography (US), Computerized Tomography (CT) and MRI usually fail to reveal the lesion. In this article we describe the potential role of combining arteriography with CT, which is superior to single arteriography or CT. METHODOLOGY: A 45-year-old man who suffered from significant catecholaminergic and neuroglycopenic symptoms, such as hypodynamia, sweating, impaired memory and confusion, was diagnosed with insulinoma by biochemical tests. The serum level of glucose of fast in the morning was as low as 1.2 mmol/L, coincident with the low serum level of glucose; the serum level of insulin was 28.77 mIU/L. The fasting insulin-to-glucose ratio was higher than 0.4. The C-peptide of 1097.62 pmol/L was higher than normal. The lesion was not identified on US, CT scan or arteriography. However the combination of arteriography with CT revealed the small insulinoma located at junction of the body and the tail of the pancreas, about 1.0 x 0.8 cm. RESULTS: Intraoperative ultrasound (IOUS) verified the lesion which located in the posterior and superior aspect of the pancreas and spleen-preserving distal pancreatectomy was performed. Histopathology confirmed the diagnosis. After the surgery the patient underwent a good recovery and was discharged two weeks later. He has developed no further episodes of hypoglycemia two years after the surgery. CONCLUSION: Combining arteriography with CT is a valuable examination for insulinoma, and IOUS is helpful to verify the lesion. Entire excision of the lesion is the best way of treatment.

[Liver transplantation in end-stage liver disease with portal vein thrombosis].

OBJECTIVE: To summarize the experience in the managements of portal vein thrombosis (PVT) and to evaluate the impact of PVT on intraoperative course and postoperative outcome in liver transplantation. METHODS: Between May 1995 and September 2007, 194 orthotopic liver transplantations were performed, of which 24 cases presented portal vein thrombosis. There were 12 patients with grade I, 9 with grade II, 2 with grade III and 1 with grade IV. The management of PVT depended mainly on its extent. Ligation of the collateral circulation, especially spontaneous or surgical splenorenal shunt, was made as approaches to improve portal flow.Heparin or low-molecule-weight heparin as a prophylactic anticoagulation therapy was maintained during and after operation if prothrombin time is less than eighteen seconds. Follow-up Doppler ultrasonography was used daily in the early postoperative period. Risk factors and variables associated with the transplant and the post-transplant period were analyzed and compared with 170 patients transplanted without PVT. RESULTS: Surgical techniques were eversion thromboendovenectomy in 21 patients with PVT grades I and II, extra-anatomic mesenteric graft in 2 with grade III, and anastomosis to a collateral vein in 1 with grade IV. The study demonstrated more RBC transfusions [(15.2 +/- 11.8) U vs. (8.6 +/- 6.6) U, P = 0.006], longer surgery procedures [(492 +/- 89) min vs. (403 +/- 105) min, P = 0.001] and hospital stay [(32.4 +/- 13.5) d vs. (22.1 +/- 9.1) d, P = 0.001] in the PVT group. However, there were no differences in overall morbidity (58.3% vs. 50.6%, P = 0.478), hospital mortality (8.3% vs.6.5%, P = 0.73) and 1-year survival (87.5% vs. 89.4%, P = 0.778). The incidence of rethrombosis was higher in the PVT group (8.3% vs.1.2%, P = 0.021). Two cases rethrombosis were successfully cured by percutaneous thrombolysis, balloon angioplasty, and stent placement. CONCLUSION: Portal thrombosis is associated with greater operative complexity and rethrombosis, but has no influence on overall morbidity and mortality in liver transplantation.

[The effect of iNOS gene expression inhibited by RNA inference on the pancreas islet apoptosis and function in rats].

OBJECTIVE: To investigate the effect of iNOS gene on cell apoptosis and insulin secretion of pancreas islet in rats by RNA inference (RNAi). METHODS: Islets obtained from thirty Wistar rats were randomly divided into five groups, and siRNA oligo was purchased from Genepharma in Shanghai. The cultured islets were transfected with iNOS siRNA, and then were divided into five groups. Islet cultured only was taken as blank control group, and cultured with TNF-alpha + IL-1 beta as cytokine group. Islet transfected with negative or iNOS siRNA were taken as negative transfection control group or RNAi group, while that transfected with iNOS siRNA and cultured with TNF-alpha + IL-1 beta as RNAi + cytokine group. Expression of iNOS mRNA was evaluated by RT-PCR and iNOS protein was evaluated by Western blot to detect the effect of RNAi. The expression of apoptosis correlated gene, Bax, Fas were analyzed, and the apoptotic cells were identified by TUNEL method meanwhile. Insulin secretion index assay the function of the islets. RESULTS: 500 - 600 IEQ islets could be extracted from every rat. RNAi attenuated the expression of iNOS and restrained the synthesis of iNOS protein.With treatment of cytokines IL-1 beta and TNF-alpha, the level of iNOS increased remarkably, the expression of Bax and Fas ascended distinctly, and insulin secretion index decreased strikingly. While, the expression of apoptosis gene and amount of apoptotic cells descended in group of RNAi + cytokine, and insulin secretion index were satisfying. CONCLUSION: The apoptosis from cytokines to islets mediated by iNOS could be suppressed by RNAi, which leaded to favorable function and survival of islets.