Preoperative Clinical and Ultrasonographic Predictors for Aggressive Behaviors in Sporadic Medullary Thyroid Carcinomas.

Objective: To explore the clinical and ultrasonographic predictors for aggressive behaviors preoperatively in sporadic medullary thyroid carcinomas (MTCs). Materials and Methods: The preoperative clinical and ultrasonographic characteristics of patients diagnosed with MTCs between January 2009 and May 2022 were retrospectively reviewed. MTCs were described and categorized according to the American College of Radiology (ACR) thyroid imaging reporting and data system classification by 2 radiologists. Interobserver agreement was evaluated by kappa test. Univariate and multivariate analyses were performed to identify predictors of aggressive behaviors in MTCs. The log-rank test was utilized to compare differences in Kaplan-Meier (K-M) curves for postoperative disease-free survival (PDFS). Results: A total of 120 patients were enrolled in the final study. Male sex was significant risk factor for metastasis, perithyroidal invasion, and lateral cervical lymph node (LCLN) metastasis [odds ratio (OR): 3.109, P = .019; OR: 5.316, P = .018; OR: 5.154 P = .012, respectively]. The kappa values for all ultrasonic characteristics were high (ranged from 0.811 to 0.941). Size, focality, and margin of the nodule were independent risk factors for metastasis, as well as for LCLN metastasis. Whereas margin (P < .001) and a subcapsular location (P = .021) were risk factors for perithyroidal invasion. According to K-M analysis, PDFS of patients differed significantly between groups with/without metastasis (P < .001), groups with/without perithyroidal extension (P < .001) and groups with/without LCLN metastasis (P < .001). Conclusions: Male sex is an independent risk factor for metastasis, perithyroidal invasion, and LCLN metastasis. The large size (≥2.55 cm for metastasis, ≥2.15 cm for LCLN metastasis, respectively), multifocality, and irregular margin of nodules were independent risk factors for both metastasis and LCLN metastasis. Extrathyroidal extension and a subcapsular location were risk factors for perithyroidal invasion. Moreover, patients with metastasis/perithyroidal extension/LCLN metastasis exhibited worse PDFS.

ACSS2 controls PPARγ activity homeostasis to potentiate adipose-tissue plasticity.

The appropriate transcriptional activity of PPARγ is indispensable for controlling inflammation, tumor and obesity. Therefore, the identification of key switch that couples PPARγ activation with degradation to sustain its activity homeostasis is extremely important. Unexpectedly, we here show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) critically controls PPARγ activity homeostasis via SIRT1 to enhance adipose plasticity via promoting white adipose tissues beiging and brown adipose tissues thermogenesis. Mechanistically, ACSS2 binds directly acetylated PPARγ in the presence of ligand and recruits SIRT1 and PRDM16 to activate UCP1 expression. In turn, SIRT1 triggers ACSS2 translocation from deacetylated PPARγ to P300 and thereafter induces PPARγ polyubiquitination and degradation. Interestingly, D-mannose rapidly activates ACSS2-PPARγ-UCP1 axis to resist high fat diet induced obesity in mice. We thus reveal a novel ACSS2 function in coupling PPARγ activation with degradation via SIRT1 and suggest D-mannose as a novel adipose plasticity regulator via ACSS2 to prevent obesity.

Associations between maternal stressful life events experiences and risk of neural tube defects in offspring: a systematic review and meta-analysis.

OBJECTIVES: Multiple factors associated with neural tube defects (NTDs) risk have been identified, yet there is little evidence on the possible effects of maternal stressful life events. In this study, we aimed to investigate the association between stressful life events during the periconceptional period and risk of NTDs in offspring. METHODS: Relevant literature was searched in PubMed, Springer Link, ScienceDirect, and Cochrane Library up to July 2023. The pooled odds ratio (OR) and 95% confidence interval (CI) of NTDs risk with maternal stressful life events were estimated using a random effects model. Publication bias was assessed using Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. RESULTS: Analysis results showed that mothers who experienced stressful life events during the periconceptional period were at greater risk of having NTDs offspring (OR: 1.37, 95% CI: 1.08-1.73) than those who did not. In subgroup analysis, the pooled OR was 1.37 (1.13-1.67) and 1.73 (0.36-8.32) for with and without adjusting for folic acid supplementation in each included study, while was 1.37 (1.13-1.67) and 1.64 (0.39-6.88) for exposure time of three months preconception until three months post conception and one year preconception until three months post conception, respectively. CONCLUSIONS: This study suggests that maternal stressful life events during the periconceptional period are significantly associated with higher NTDs risk in offspring. Tailored approaches for evaluating the risk and policy of NTDs among women of childbearing age should emphasize individual stressful experiences before and during early pregnancy.

D-mannose acts as a V-ATPase inhibitor to suppress inflammatory cytokines generation and bacterial killing in macrophage.

Vacuolar-type H+-ATPase (V-ATPase) critically controls phagosome acidification to promote pathogen digestion and clearance in macrophage. However, the specific subunits of V-ATPase have been evidenced to play contradictory functions in inflammatory cytokines generation and secretion exposure to external bacterial or LPS stimulation. Therefore, identifying the unique function of the separate subunit of V-ATPase is extremely important to regulate macrophage function. Here, we found that D-mannose, a C-2 epimer of glucose, suppressed ATP6V1B2 lysosomal translocation to inhibit V-ATPase activity in macrophages, thereby causing the scaffold protein axis inhibitor protein (AXIN) recruitment to lysosomal membrane and AMPK activation. Correspondingly, LPS-stimulated macrophage M1 polarization was significantly suppressed by D-mannose via down-regulating NF-κB signaling pathway in response to AMPK activation, while IL-4 induced macrophage M2 polarization were not affected. Furthermore, the failure of lysosomal localization of ATP6V1B2 caused by D-mannose also led to the acidification defects of lysosome. Therefore, D-mannose displayed a remarkable function in inhibiting macrophage phagocytosis and bacterial killing. Taken together, D-mannose acts a novel V-ATPase suppressor to attenuate macrophage inflammatory production but simultaneously prevent macrophage phagocytosis and bacterial killing.

IL-37 isoform D acts as an inhibitor of soluble ST2 to boost type 2 immune homeostasis in white adipose tissue.

White adipose tissue (WAT) homeostasis substantiated by type 2 immunity is indispensable to counteract obesity and metabolic disorders. IL-33/suppression of tumorigenicity (ST) 2 signaling promotes type 2 response in WAT, while potential regulators remain to be discovered. We identified human IL-37 isoform D (IL-37D) as an effective trigger for ST2-mediated type 2 immune homeostasis in WAT. IL-37D transgene amplified ST2+ immune cells, promoted M2 macrophage polarization and type 2 cytokine secretion in WAT that mediate beiging and inflammation resolution, thereby increasing energy expenditure, reducing obesity and insulin resistance in high-fat diet (HFD)-fed mice. Mechanistically, either endogenous or exogenous IL-37D inhibited soluble ST2 (sST2) production from WAT challenged with HFD or TNF-α. Recombinant sST2 impaired the beneficial effects of IL-37D transgene in HFD-fed mice, characterized by damaged weight loss, insulin action, and type 2 cytokine secretion from WAT. In adipose-derived stem cells, IL-37D inhibited TNF-α-stimulated sST2 expression through IL-1 receptor 8 (IL-1R8)-dependent NF-κB inactivation. Collectively, human IL-37D suppresses sST2 to boost type 2 immune homeostasis in WAT, which may be a promising therapy target for obesity and metabolic disorders.

USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis.

BACKGROUND: Colorectal cancer (CRC) is a familiar malignancy accompanied by higher morbidity and mortality. The deubiquitination enzyme USP20 has been discovered to be one key factor in several cancers progression. SOX4 is a critical transcription factor to regulate the expression of various genes, and participates into the occurrence and progression of cancers. In this study, it was aimed to illustrate the role of USP20 and the regulatory relationship between USP20 and SOX4 in CRC. METHODS: The protein expressions of USP20, SOX4, E-cadherin, N-cadherin, Snail and slug were tested through western blot. The cell proliferation ability was verified through CCK-8 assay. The migration and invasion abilities were detected through Transwell assay. The mRNA expression of SOX4 was confirmed through RT-qPCR. The interaction between USP20 and SOX4 was notarized through Co-IP assay. RESULT: Our study demonstrated that USP20 displayed higher expression, and facilitated CRC progression through regulating cell proliferation, migration, invasion and EMT process markers. USP20 was found to modulate SOX4 protein expression. Next, it was verified that USP20 regulated SOX4 degradation through deubiquitination. Finally, through rescue assays, we revealed that USP20 mediated SOX4 expression to accelerate CRC progression. CONCLUSIONS: In this study, USP20 regulated the stability of EMT transcription factor SOX4 and aggravated colorectal cancer metastasis. This finding might highlight the function of USP20 in the treatment of CRC.

Serum-derived exosomes from SD rats induce inflammation in macrophages through the mTOR pathway.

Inhalation of beryllium and its compounds can cause lung injuries, resulting from inflammation and oxidative stress. Multivesicular bodies (MVB), such as exosomes, are membrane vesicles produced by early and late endosomes that mediate intercellular communications. However, the role of exosomes in beryllium toxicity has not been elucidated. This current study aimed to investigate the functional role of exosomes in lung injury resulting from beryllium sulfate (BeSO4 ). Here, Sprague-Dawley (SD) rats were exposed to 4, 8, and 12 mg/kg BeSO4 by nonexposed intratracheal instillation. Murine macrophage (RAW 264.7) cells were pretreated with 50 nmol/L rapamycin (an mTOR signaling pathway inhibitor) for 30 min and then cultured for 24 h with 100 µg/mL exosomes, which had been previously isolated from the serum of 12 mg/kg BeSO4 -treated SD rats. Compared with those of the controls, exposure to BeSO4 in vivo increased LDH activity, elevated levels of inflammatory cytokines (IL-10, TNF-α, and IFN-γ) alongside inflammation-related proteins expression (COX-2 and iNOS), and enhanced secretion of exosomes from the SD rat's serum. Moreover, the BeSO4 -Exos-induced upregulation of LDH activity and inflammatory responses in RAW 264.7 cells can be alleviated following pretreatment with rapamycin. Collectively, these results suggest that serum exosomes play an important role in pulmonary inflammation induced by BeSO4 in RAW 264.7 cells via the mTOR pathway.

Hydrogen sulfide alleviates apoptosis and autophagy induced by beryllium sulfate in 16HBE cells.

Beryllium and its compounds are systemic toxicants that are widely applied in many industries. Hydrogen sulfide has been found to protect cells. The present study aimed to determine the protective mechanisms involved in hydrogen sulfide treatment of 16HBE cells following beryllium sulfate-induced injury. 16HBE cells were treated with beryllium sulfate doses ranging between 0 and 300 µM BeSO4 . Additionally, 16HBE cells were subjected to pretreatment with either a 300 µM dose of sodium hydrosulfide (a hydrogen sulfide donor) or 10 mM DL-propargylglycine (a cystathionine-γ-lyase inhibitor) for 6 hr before then being treated with 150 µM beryllium sulfate for 48 hr. This study illustrates that beryllium sulfate induces a reduction in cell viability, increases lactate dehydrogenase (LDH) release, and increases cellular apoptosis and autophagy in 16HBE cells. Interestingly, pretreating 16HBE cells with sodium hydrosulfide significantly reduced the beryllium sulfate-induced apoptosis and autophagy. Moreover, it increased the mitochondrial membrane potential and alleviated the G2/M-phase cell cycle arrest. However, pretreatment with 10 mM DL-propargylglycine promoted the opposite effects. PI3K/Akt/mTOR and Nrf2/ARE signaling pathways are also activated following pretreatment with sodium hydrosulfide. These results indicate the protection provided by hydrogen sulfide in 16HBE cells against beryllium sulfate-induced injury is associated with the inhibition of apoptosis and autophagy through the activation of the PI3K/Akt/mTOR and Nrf2/ARE signaling pathways. Therefore, hydrogen sulfide has the potential to be a promising candidate in the treatment against beryllium disease.

Identification of an Immune-Related LncRNA Prognostic Signature in Uterine Corpus Endometrial Carcinoma Patients.

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is the third most prevalent female reproductive system malignant tumor with poor prognosis, particularly at advanced stage. On the other hand, recent studies have reported the prognostic role of long non-coding RNAs (lncRNAs) in UCEC. The aim of this study was to determine the immune-related lncRNA signature for predicting overall survival (OS) in UCEC patients. METHODS: The genomic data and clinical information of UCEC patients were extracted from the Cancer Genome Atlas. Pearson's correlation analysis was carried out to identify the immune-related lncRNAs. Univariate and multivariate Cox regression analyses were conducted to obtain the prognostic lncRNAs from the immune-related lncRNAs for the construction of the prognostic signature. Afterwards, the UCEC patients were divided into high-risk and low-risk groups. The prognostic value of the signature was assessed by survival, receiver operating characteristic (ROC), and nomogram analyses. Finally, the immune status for high-risk and low-risk groups was evaluated by the ESTIMATE algorithm. RESULTS: A total of 13 immune-related lncRNAs (AC108860.2, AC015849.5, AL592494.3, LINC01234, U91319.1, AC092969.1, AL356133.2, AC103563.2, AL138962.1, AC138965.1, LINC01687, AC091987.1, and MIR7-3HG) were finally identified for the construction of the prognostic signature. Patients in the high-risk group had worse prognosis than those in the low-risk group. The prognostic signature was confirmed as an independent prognostic factor through the multivariate Cox regression analysis. The nomogram based on the prognostic signature and clinicopathologic features was constructed with a superior overall predictive power to evaluate the survival outcomes in UCEC patients. Finally, according to the ESTIMATE algorithm results, we discovered different immune statuses in the low-risk and high-risk groups. CONCLUSIONS: The immune-related lncRNA signature for the assessment of the OS of UCEC patients had a good practical value.

[Relationship between BCR-ABLIS and Prognosis and Affecting Factors for Prognosis in CML Patients Treated with TKI for 12 Months].

OBJECTIVE: To evaluate the long-term prognosis of CML patients whose BCR-ABL transcript level was warning and best response at 12 months of treatment with tyrosine kinase inhititor (TKI), and to investigate the factors affecting therapeutic efficacy and prognosis. METHODS: The clinical data of patients with newly diagnosed CML were analyzed retrospectively. According to BCR-ABL transcript level, the 80 patients were divided into group A and group B, the patients with BCR-ABLIS >0.1% and ≤ 1% (warning response) were entolled in group A, and the patients with BCR-ABLIS ≤ 0.1% (best response) were enrolled in group B as control. The ratio of patients with main molecular response (MMR) and deep molecular response (DMR), as well as aquistation rate and cummulative rate of MR4 (DMR) at specified fine points in 2 groups were compared, the independent risk factors affecting the therapeutic efficacy and prognosis were analyzed. RESULTS: The MMR and MR4 of the B group at 15, 18 and 24 months after TKI treatment were significantly higher than those of the A group, and the patients in the B group reached MR4 faster. In the 3 months, 6 months and 12 months after the demarcation point (TKI 12 months), the A group was much less easy to obtain MR4 (P<0.05) than the B group. Through survival analysis, there were more patients in the B group than the A group at different time points to reach MR4, and the difference was statistically significant (P<0.01). The single factor analysis showed that the splenomegaly (below rib edge)> 10cm (P<0.01) and lactate dehydrogenase > 400 U/L (P<0.05) were the long-term warning factors for patients. Multivariate analysis showed that the size of the spleen was an independent factor (P<0.01) to affect the prognosis of the patients who had been warned for 12 months. CONCLUSION: Patients at 12 months warning effect are slower and less easier to get DMR, which has a poor long-term prognosis. The size of the spleen in the patient at warning for 12 months of treatment effect can predict the relatively poor long-term prognosis. For a patient with a 12 months response to the warning, an early replacement therapy is available on the basis of combining other factors..

New Evidence on the Effect of Medical Insurance on the Obesity Risk of Rural Residents: Findings from the China Health and Nutrition Survey (CHNS, 2004-2011).

The obesity rate in China has risen significantly in the past few decades. While a number of causes for the rise in obesity have been explored, little attention has been paid to the role of health insurance per se. This study aims to investigate the impact of health insurance on the risk of obesity in rural China using longitudinal data from the China Health and Nutrition Survey (CHNS). We employed pooled ordinary least squares (OLS), probit estimation, and pooled two-stage least squares (2SLS) for an instrumental variable (IV). The IV model revealed that New rural cooperative medical insurance (NRCMS) participation had a significant positive impact on people's tendency towards unhealthy lifestyles, for instances, high-fat food (8.01% for female and 7.35% for male), cigarette smoking (25% for male), heavy drinking (25% for female), sedentary activity (6.48 h/w for female and 6.48 h/w for male), waist circumference (1.97 cm for female and 1.80 cm for male), body mass index (0.58 kg/m² for female), which in turn leads to an elevated probability of general obesity (51% for female) and abdominal obesity (24% for female and 20% for male). An "ex ante moral hazard" is prevalent in rural China, which should not be ignored by policymakers so as to minimize the related low efficiency in the process of promoting the universal coverage of insurance.

Digit ratio (2D:4D) in Chinese women with gastric cancer.

OBJECTIVES: Digit ratio, especially the second-to-fourth digit ratio (2D:4D), is a proxy indicator for prenatal exposure and sensitivity to sexual hormones which may influence the susceptibility to certain cancers. The aim of the present study was to investigate whether there is a possible association between 2D:4D and gastric cancer (GCA) in north Chinese women. METHODS: Photographs of the left and right hands of 167 women (controls: 113; patients: 54) were collected. Left hand, right hand, and right minus left hand (Dr-l) 2D:4D were analyzed and compared. RESULTS: The GCA group presented significantly lower 2D:4D than controls (left: P < .01; right: P < .05). No significant difference was observed in Dr-l between the two groups. In patients, there were no correlations between 2D:4D and age at GCA or tumor staging. CONCLUSIONS: Decreased 2D:4D (especially of the left hand) may suggest a higher prenatal testosterone (lower prenatal estrogen) exposure in north Chinese women with GCA.

Histone deacetylase inhibitors regulate P-gp expression in colorectal cancer via transcriptional activation and mRNA stabilization.

Histone deacetylase inhibitors (HDACIs) are emerging as a novel class of anti-tumor drugs. But the effect of HDACIs in tumors treatment has been disappointing, which mainly due to the acquisition of resistance to HDACIs. However, the underlying mechanisms have not been clearly understood. In this study, it was found that HDACIs SAHA and TSA increased P-gp expression in CRC cells, which has been well known to contribute to drug resistant. The mechanisms underlying these effects were investigated. We showed that HDACIs enhanced transcriptional activity of P-gp protein encoding gene ABCB1. HDACIs treatment also increased the protein and mRNA expression of STAT3, but not PXR, CAR, Foxo3a or ß-catenin, which are known to be involved in ABCB transcription regulation. Interestingly, knockdown of STAT3 significantly attenuated HDACIs-induced P-gp up-regulation in colorectal cancer cells, suggesting that STAT3 plays a crucial role in HDACIs-up-regulated P-gp. Furthermore, this study revealed for the first time that HDACIs enhanced the stability of ABCB1 at post-transcriptional level. Taken together, these results proved that HDACIs induced P-gp expression by two distinct ways, transcriptional activation and mRNA stabilization. Our results suggested that more attention should be paid to the cancer treatment using HDACIs since they will induce multidrug resistance in cancer cells.

Up-regulation of microRNA-302a inhibited the proliferation and invasion of colorectal cancer cells by regulation of the MAPK and PI3K/Akt signaling pathways.

Aberrant expression of microRNA-302a (miR-302a) has been frequently reported in some cancers excluding colorectal cancer (CRC). However, the role of miR-302a in CRC has not been reported. In this paper, we examined the effect of miR-302a overexpression on proliferation and invasion in CRC cells. The mRNA level of miR-302a in CRC cell lines was determined by real-time PCR. The miR-302a mimic was transiently transfected into CRC cells using Lipofectamine™ 2000 reagent. Subsequently, cell proliferation and invasion were assessed by MTT and Transwell assays. Western blot and ELISA assay were used to detect the expressions and secretions of matrix metalloproteinases (MMPs). Moreover, the expressions of epithelial marker, mesenchymal markers and transcription factors were also determined by Western blot. In addition, the effects of miR-302a overexpression on the MAPK and PI3K/Akt signaling pathways were investigated by Western blot. Our results showed that the mRNA level of miR-302a was remarkably decreased in CRC cell lines compared with normal colon epithelium cells. Up-regulation of miR-302a inhibited the proliferation and invasion of CRC cells. The expressions and secretions of MMP-9 and -2 were evidently reduced by increasing miR-302a. Besides, we found a decrease of ß-catenin, fibronection, vimentin, Snail, Slug, ZEB1 and ZEB2 expressions and an increase of E-cadherin expression. We also found that miR-302a overexpression might decrease the phosphorylation of Erk1/2 and Akt. Altogether, our results indicated that miR-302a overexpression was shown to inhibit proliferation and invasion of CRC cells by reducing the expressions of related proteins through suppressing the MAPK and PI3K/Akt signaling pathways.

Digit ratio (2D:4D) in Chinese women with breast cancer.

OBJECTIVES: Digit ratio, especially second-to-fourth digit ratio (2D:4D) is established in utero and is positively correlated with oestrogen in men and women. It is a putative biomarker for prenatal hormone exposure and may represent an individual predisposition to certain diseases (e.g., breast cancer). The aim of the present study is to investigate whether there is a link between digit ratio (2D:4D) and breast cancer in Chinese populations. METHODS: The controls we chose were healthy subjects-age and -sex matched to the patients diagnosed with breast cancer. Photocopies of the two hands of 218 women (controls: 109; patients: 109) were collected. Left hand, right hand, mean hand, and right minus left 2D:4D (Dr-l ) were analyzed. RESULTS: The patients with breast cancer presented significantly higher 2D:4D than controls (left: P < 0.01; right: P < 0.05; mean: P < 0.05). The mean values of 2D:4D on the left hand were significantly higher than those on the right hand in the two groups, respectively (controls: P < 0.05; patients: P ≤ 0.01). In patients, there was a significantly negative correlation between 2D:4D (left hand: P < 0.01; right hand, mean: P < 0.05) and the presented age with breast cancer, but no association between Dr-l and age of presented disease. CONCLUSIONS: Digit ratio (2D:4D) may correlate with the increased risk of breast cancer.

[Surgical complications after pancreatoduodenectomy: risk factors and treatments].

OBJECTIVE: To explore the impact factors and treatment of post pancreatoduodenectomy complications. METHODS: The clinical data of 412 cases between January 1995 and April 2010 underwent pancreatoduodenectomy were analyzed retrospectively. There were 232 male, 180 female. Univariate and multivariate logistic regression model were used to identify the risk factors related to occurrence of postoperative complications. RESULTS: The overall postoperative morbidity rate was 37.1% (153/412), and mortality rate was 4.6% (19/412). Total uncinate process resection, type of pancreatic-enteric anastomosis, duct diameter and pancreatic texture had effects on postoperative pancreatic fistula statistically. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. Delayed gastric empting occurrence in the patients with pylorus-preserving pancreaticoduodenectomy was higher than those with standard pancreaticoduodenectomy significantly. The multivariate Logistic regression analysis revealed that duct diameter and pancreatic texture were the independent risk factors of pancreatic fistula. Total uncinate process resection, the amount of intra-operative blood loss ≥ 600 ml and pancreatic fistula were independent risk factors of bleeding. There were no statistically significant differences between the radical group and the standard group when postoperative complication rates were analyzed (P < 0.05). CONCLUSIONS: Pancreaticojejunal anastomoses by means of duct-to-mucosa is fit for the patients with dilated pancreatic duct and end-to-end invaginated pancreaticojejunostomy is fit for the patients with undilated pancreatic duct. The prevention of postoperative bleeding depends on total uncinate process resection and meticulous hemostatic technique during operation. The pancreatic fistula is one of the most important factors which can result in postoperative bleeding. Pancreaticoduodenectomy combines with SMV/PV resection and extended lymphadenectomy do not significantly increase the morbidity rates.

Small interference RNA targeting Krüppel-like factor 8 inhibits the renal carcinoma 786-0 cells growth in vitro and in vivo.

PURPOSE: Krüppel-like factor 8 (KLF8) plays an important role in oncogenic transformation and is highly overexpressed in several types of human cancer. We investigated the expression of KLF8 in renal cell carcinoma (RCC) tissues and the role of small interference RNA targeting KLF8 on growth, cell cycle, and apoptosis of human renal carcinoma cell line 786-0 in vitro and in vivo. METHODS: The expression of KLF8 protein and mRNA in human renal carcinoma samples was detected by immunochemistry and reverse transcription polymerase chain reaction (RT-PCR). The effects of small interference RNA (siRNA) targeting KLF8 on growth, invasiveness, cell cycle, and apoptosis of 786-0 cells were evaluated by MTT assay, Matrigel Invasion Assay, and flow cytometry in vitro. We also investigated effect of siRNA targeting KLF8 on growth of 786-0 cells in nude mice in vivo. RESULTS: Immunohistochemistry and RT-PCR results showed the expression of KLF8 protein and mRNA in RCC specimens was significantly higher than that in the adjacent non-tumorous renal tissues (P < 0.001). KLF8-siRNA depressed the cellular growth and invasion of 786-0 cells in vitro. The flow cytometry results revealed that KLF8-siRNA could induce an increase in G0/G1 phase cells and induce cell apoptosis. Intratumor injection of siRNA targeting KLF8 inhibited the growth of 786-0 cells in vivo in nude mice tumor model. CONCLUSIONS: KLF8 possibly involved in regulating the cell growth, invasion, apoptosis, and proliferation of renal carcinoma cancer cells. Blocking the KLF8 channel might be a potential therapeutic strategy for RCC.

[Reconstruction of rabbit urethra using urethral extracellular matrix].

OBJECTIVE: To evaluate the feasibility of reconstruction of rabbit urethra using urethral extracellular matrix. METHODS: Extracellular matrix was obtained from the urethra of 20 donor New Zealand rabbits. In experimental group, 20 rabbits underwent segmental urethral resection (about 1.0 to 1.5 cm in length) and the defects were replaced by a tube of extracellular matrix. The serum TNFalpha was detected by ELISA to assess the immunity response preoperatively and 12, 24, 48 h postoperatively. The regenerated urethral segments were taken for histologic and pathologic study 10 days, 3 weeks, 6 weeks and 24 weeks after operation. The urodynamics, urethroscopy and urethrography were also performed. RESULTS: The serum TNFalpha in experiment group slightly rised, with no significant difference when compared with that in control group. 10 days after operation, epithelial cell migrated into the extracellular matrix from two ends, and small vessels were also found. 3 weeks later, several layers of urothelium covered the whole surface of the matrix tube. 6 weeks later, the irregularly arranged smooth muscle fibers were fist observed by Van Gieson staining. 24 weeks after operation, the smooth muscle cells increased, the appearance of the regenerated urethra segments were very similar to normal urethral wall components. The urethrography and urodynamic evaluation revealed no difference between the normal and the regenerated urethral tube. CONCLUSIONS: The urethral extracellular matrix might be an ideal replacement material for urethral defect.

[Clinical analysis of post pancreatoduodenectomy hemorrhage].

OBJECTIVE: To explore the factors of post pancreatoduodenectomy hemorrhage. METHODS: The clinical data of 263 cases between January 1998 and April 2008 underwent pancreatoduodenectomy were analyzed prospectively. RESULTS: The overall mortality rate was 4.94% (13/263). Postoperative bleeding occurred in 23 patients (8.75%), with 8 episodes ending fatally (34.8%). The tumor size, Child classification, caput total resection and pancreatic leakage were identified as significant risk factors for post pancreatoduodenectomy hemorrhage by means of univariate analysis. The multivariate Logistic regression analysis revealed that all of the five factors turned out to be the independent risk factors. CONCLUSIONS: The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. The pancreatic leakage is also one of the most important factors due to postoperative bleeding. The prophylactic use of somatostatin is not necessary.

[The Predictive Role of Vascular Endothelial Growth Factor and Estradiol in Infertile Patients with Ovarian Hyperstimulation Syndrome].

OBJECTIVE: To determine the predictive values of vascular endothelial growth factor (VEGF) and estradiol (E2) in patients with ovarian hyperstimulation syndrome (OHSS) and to go further into the relevant pathogenisis. METHODS: Blood samples were collected from 51 high risk patients and 30 control patients undergoing superovulation on the day of hCG administration and follicular fluid at the time of egg retrieval. The high risk patients were divided into two groups[OHSS group (n=11) and non-OHSS group (n=40)] VEGF and E2 were detected and then differences between the high risk groups and control group were analyzed. RESULTS: There wa no significant difference in VEGF between high risk groups and control group on the day of hCG injection (P>0.05). After hCG administration, serum VEGF concentrations rose significantly in OHSS group (P<0.01). The serum and follicular fluid VEGF levels were obviously higher than those of the control group. The follicular fluid concentrations of VEGF were significantly higher than that of serum in every group (P<0.001). E2 concentrations of OHSS group rose obviously after hCG injection (P<0.01) and were significantly higher than those of the control group (P<0.01), but there no statistically significant change in E2 concentrations in non-OHSS groups (P>0.05). CONCLUSION: The results from this study show that the serum and follicular fluid VEGF concentrations are significantly higher than those of control group on the day of ovum retrieval, indicating that VEGF may play an important role in the pathogenesis of OHSS. It cannot predict the risk of OHSS on the day hCG administration, but it may be considered as a predictive marker for the development of OHSS after hCG administration. Serum VEGF concentrations in combination with consective E2 measurements can assist in predicting OHSS.