Relevance and mechanism of STAT3/miR-221-3p/Fascin-1 axis in EGFR TKI resistance of triple-negative breast cancer.

The epidermal growth factor receptor 1 (EGFR) plays a crucial role in the progression of various malignant tumors and is considered a potential target for treating triple-negative breast cancer (TNBC). However, the effectiveness of representative tyrosine kinase inhibitors (TKIs) used in EGFR-targeted therapy is limited in TNBC patients. In our study, we observed that the TNBC cell lines MDA-MB-231 and MDA-MB-468 exhibited resistance to Gefitinib. Treatment with Gefitinib caused an upregulation of Fascin-1 (FSCN1) protein expression and a downregulation of miR-221-3p in these cell lines. However, sensitivity to Gefitinib was significantly improved in both cell lines with either inhibition of FSCN1 expression or overexpression of miR-221-3p. Our luciferase reporter assay confirmed that FSCN1 is a target of miR-221-3p. Moreover, Gefitinib treatment resulted in an upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in MDA-MB-231 cells. Using Stattic, a small-molecule inhibitor of STAT3, we observed a significant enhancement in the inhibitory effect of Gefitinib on the growth, migration, and invasion of MDA-MB-231 cells. Additionally, Stattic treatment upregulated miR-221-3p expression and downregulated FSCN1 mRNA and protein expression. A strong positive correlation was noted between the expression of STAT3 and FSCN1 in breast cancer tissues. Furthermore, patients with high expression levels of both STAT3 and FSCN1 had a worse prognosis. Our findings suggest that elevated FSCN1 expression is linked to primary resistance to EGFR TKIs in TNBC. Moreover, we propose that STAT3 regulates the expression of miR-221-3p/FSCN1 and therefore modulates resistance to EGFR TKI therapy in TNBC. Combining EGFR TKI therapy with inhibition of FSCN1 or STAT3 may offer a promising new therapeutic option for TNBC.

Characteristics and risk factors for colorectal polyps among children in an urban area of Wenzhou, China: a retrospective case control study.

BACKGROUND: Scarce evidence exists on pediatric colorectal polyp risk factors. This study explored the clinical manifestations, morphological and pathological characteristics of, and risk factors for pediatric colorectal polyps. METHODS: This retrospective case-control study included children who received colonoscopy, divided into a colorectal polyp group and a normal control group based on colonoscopy results. The risk factors for colorectal polyps in children were analyzed through logistic regression analysis. RESULTS: The mean age of children with polyps was 6.77 ± 3.44 years. Polyps were detected predominantly in males (72.9%); hematochezia was the primary clinical manifestation (80.25%). Most polyps were juvenile (88.9%) and solitary (87.7%); 50.6% were located in the rectosigmoid area. Univariate analysis showed that gender (P = 0.037), age (P < 0.001), family aggregation (P < 0.001), specific immunoglobulin E (sIgE) (P < 0.001), platelet count (P = 0.001), aspartate aminotransferase (AST) (P = 0.016), meat intake (P = 0.010), and vegetable intake (P < 0.001) were significantly associated with colorectal polyps. Age ≤ 6 years (3-6 years: OR: 26.601, 95% CI: 3.761-160.910; < 3 years: OR: 22.678, 95% CI: 1.873-274.535), positive family aggregation (OR: 3.540, 95% CI: 1.177-10.643), positive sIgE (OR:2.263, 95% CI: 1.076-4.761), and higher meat intake (OR:1.046, 95% CI: 1.029-1.063) were risk factors for pediatric colorectal polyps in logistic regression analysis. Higher vegetable intake (OR: 0.993, 95% CI: 0.986-1.000) was a protective factor against pediatric colorectal polyps. The area under the curve (AUC) of meat intake in the receiver operating characteristic (ROC) curve analysis for predicting colorectal polyps was 0.607; the best cut-off value was 92.14 g/d (P = 0.010, 95% CI: 0.527-0.687). The meat and vegetable intake combination AUC in predicting pediatric colorectal polyps was 0.781 (P < 0.001, 95% CI: 0.718-0.845). CONCLUSIONS: Juvenile, solitary, and located in the rectosigmoid region polyps are most common in children. Hematochezia is the main clinical manifestation. Most polyps were, but multiple and proximally located polyps were also detected. Age ≤ 6 years, especially 3-6 years, positive family aggregation, positive sIgE, and higher meat intake are risk factors for pediatric colorectal polyps. A higher vegetable intake is a protective factor.

Circ_0078710 promotes the development of liver cancer by upregulating TXNDC5 via miR-431-5p.

INTRODUCTION AND OBJECTIVES: Liver cancer, with high recurrence and metastasis rate, is a common malignant tumor. Circular RNA_0078710 (circ_0078710) has been shown to be take part in the advance of hepatocellular carcinoma. However, the interaction between circ_0091579 and microRNA-431-5p (miR-431-5p) in liver cancer has not been studied. MATERIALS AND METHODS: The expressions of circ_0078710, miR-431-5p and Thioredoxin domain-containing 5 (TXNDC5) in liver cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of cric_0078710 in liver cancer cells was assessed by Cell Counting Kit-8 (CCK-8) assay, Transwell, flow cytometry and Dual-luciferase reporter assay. Glycolysis metabolism was examined by lactate production, glucose uptake and ATP level. The protein levels of ki-67, bax and TXNEC5 were tested by western blot. The role of circ_0078710 in vivo was determined by animal study. RESULTS: Circ_0078710 and TXNDC5 were notably expressed in liver cancer tissues and cells. Circ_0078710 knockdown diminished proliferation, migration, invasion and glycolytic metabolism of huh7 and Hep3B cells, and accelerated cell apoptosis. MiR-431-5p is the target of circ_0078710, and silence circ_0078710 can inhibit the malignant behavior and glycolysis of hepatocellular carcinoma (HCC) cells by releasing miR-431-5p. In addition, TXNDC5 was a target of miR-431-5p, and overexpression of TXNDC5 restored cell proliferation and glycolysis inhibition due to miR-431-5p. Animal experiments made clear the anti-tumor effect of circ_0078710 knockdown. CONCLUSION: Circ_0078710 promotes the progression of liver cancer by regulating TXNDC5 expression by targeting miR-431-5p. These results demonstrate that circ_0078710 could be a remedy target for liver cancer.

1H NMR-based metabolomics analyses in children with Helicobacter pylori infection and the alteration of serum metabolites after treatment.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) infection can occur in early childhood, without eradication therapies such infection can persist throughout life and cause many different diseases. This study investigated the metabolic characteristics and explored the underlying mechanism of children with H. pylori infection, and identified potential biomarkers for evaluating the efficacy of H. pylori eradication therapies. METHODS: We performed 1H NMR-based metabonomics coupled with multivariate analysis to investigate the metabolic profiling of serum samples between Children with and without H. pylori infection. In the same manner, we compared the alternations of metabolites in H. pylori-infected children before and after H. pylori eradication therapies. RESULTS: 21 metabolites from serum in H. pylori-infected and H. pylori-uninfected children were identified, which were mainly involved in energy, amino acid, lipid and microbial metabolism. We found that the serum levels of trimethylamine N-oxide and alanine were significantly higher in H. pylori-infected children compared to uninfected sera, whereas lactate was significantly lower. We also found that the levels of trimethylamine N-oxide and creatine in H. pylori-infected children was significantly decreased after H. pylori eradication therapies, whereas lactate and low-density lipoprotein/very low-density lipoprotein was significantly increased. CONCLUSIONS: This is the first study using 1H NMR-based metabolomics approach to explore the effects of H. pylori infection in children. Our results demonstrated that the disturbances of metabolism in energy, amino acids, lipids and microbiota could play an important role in the pathogenesis of gastrointestinal and extragastric diseases caused by H. pylori infection. Trimethylamine N-oxide and lactate might serve as potential serum biomarkers for evaluating the efficacy of H. pylori eradication therapies.

4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable stearoyl-CoA desaturase-1 (SCD1) inhibitors: part 2. Pyridazine-based analogs.

Design, synthesis, and biological evaluation of pyridazine-based, 4-bicyclic heteroaryl-piperidine derivatives as potent stearoyl-CoA desaturase-1 (SCD1) inhibitors are described. In a chronic study of selected analog (3e) in Zucker fa/fa (ZF) rat, dose-dependent decrease of body weight gain and plasma fatty acid desaturation index (DI) in both C16 and C18 are also demonstrated. The results indicate that the plasma fatty acid DI may serve as an indicator for direct target engagement and biomarker for SCD1 inhibition.

Driving among patients with epilepsy in West China.

PURPOSE: This study was conducted to survey the driving status of PWE in West China and to explore the sociodemographic and clinical factors associated with driving. METHODS: Between October 2012 and October 2013, all adult patients who came to our epilepsy clinic in the West China Hospital were invited to participate. Logistic regression was used to detect the patient factors associated with driving. RESULTS: A total of 657 patients completed this study. We found that 128 (19.5%) of these patients had driven recently (during the past year); among them, 80 (62.5%) experienced at least one seizure in the previous year. A logistic regression suggested that age, being male, being married, having a higher personal income, experiencing no seizure while awake, and taking fewer antiepileptic drugs were independently associated with recent driving. CONCLUSION: This study showed that a considerable proportion of patients continue driving despite uncontrolled seizures. More detailed and operational driving restrictions may be needed for patients in China in order to strike a better balance between patients' quality of life and public safety.

4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs.

A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.

Synthesis and biopharmaceutical studies of JLTN as potential dasatinib prodrug.

Dasatinib was identified as a potent orally administered Src/Abl kinase inhibitor with excellent antiproliferative activity against Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. The low bioavailability of Dasatinib may be due to both incomplete oral absorption and first-pass metabolism. A prodrug, JLTN, was synthesized to minimize the first-pass effect of Dasatinib and improve the oral bioavailability following oral administration via targeting intestinal peptide transporter and enhancing chemical stability. Biological evaluation data indicated that there was a 150%-fold increase in oral bioavailability of this prodrug compared to the parent drug Dasatinib in monkeys.

Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation.

Few reports exist regarding the expression and function of Wilms' tumor 1-associated protein (WTAP) in colorectal cancer (CRC), and the evidence is controversial. Our analysis explored the expression of WTAP in CRC tissue, and analyzed its clinical and prognostic significance. WTAP expression was significantly higher in CRC tissue than in colorectal adenoma and normal colorectal tissue. WTAP was highest in left colon tumor samples and negatively associated with tumor differentiation, as well as depth of tumor invasion. In multiple logistic regression analysis, independent predictors of WTAP expression in CRC included tumor in the left colon (odds ratio = 2.634; 95% confidence interval: 1.129-6.142; P = 0.025) and poorly differentiated tissue (0.072; 0.014-0.367; P = 0.002). No clear relationship was observed between CRC patient prognosis and WTAP expression. We suggest that WTAP expression is upregulated in CRC, highly expressed in left colon cancer and negatively correlated with tumor differentiation.

[Detection of epidermal growth factor receptor gene mutations in non-small cell lung cancer using bi-loop probe specific primer quantitative PCR].

OBJECTIVE: To investigate the sensitivity of bi-loop probe and specific primer quantitative PCR (BPSP-qPCR) in the detection of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). METHODS: BPSP-qPCR was employed to examine the presence of mutations of EFGR exon 19 through 21. Correlation of the mutations with clinicopathological characteristics and types of tumor samples were performed. RESULTS: In the cohort of 265 specimens, 30.2% (80/265) mutations were found to be 19-del and/or L858R. Females (39.7%, 31/78), non-smokers (41.0%, 43/105) and adenocarcinoma patients (37.8%, 51/135) had a higher mutation rate (P<0.05) among 184 patients whose profiles were available. T790M combined with 19-del and/or L858R accounted for 3.3% (6/184) of the mutations. Male metastatic tumors (29.6%, 8/27), pleural fluids of females (42.9%, 9/21) and non-smokers (40.7%, 11/27) were found to have higher percentage of 19-del and/or L858R mutations, in contrast, no mutations were found in the metastatic lesions of non-adenocarcinoma patients (P>0.05). CONCLUSIONS: BPSP-qPCR is a robust method in detection of EGFR mutations with high consistency and sensitivity. The difference of EGFR mutations in primary tumors, metastatic lesions and pleural fluids suggests that EGFR tyrosine kinase inhibitors (EGFR-TKI) treatment may have variable treatment effects depending on the tumor sites.

Combined High Resistin and EGFR Expression Predicts a Poor Prognosis in Breast Cancer.

Elevated levels of resistin and epidermal growth factor receptor (EGFR) facilitate the development of breast cancer, although there are no reports of any correlation between these proteins. This study analyzed 392 human breast cancer tissue specimens and 42 samples of adjacent normal tissue. Rates of positive and strongly positive resistin expression were significantly higher in breast cancer tissue than in the adjacent nontumor tissue (83.2% vs. 23.8% and 20.9% vs. 0.0%, respectively; P < 0.001 for both comparisons). Positive resistin expression was significantly associated with tumor size, grade, stage, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and molecular classification; strongly positive resistin expression was associated with tumor grade, ER, PR, HER2 status, and molecular classification. Significantly positive correlations were observed between positive and strongly positive resistin expression and corresponding levels of EGFR expression. Relapse-free and overall survival was worse for patients with high levels of both proteins than for those with high levels of only one protein or normal levels of both proteins. Our evidence suggests that combined high levels of resistin and EGFR expression correlate with survival in patients with breast cancer.

Human Mitotic Centromere-Associated Kinesin Is Targeted by MicroRNA 485-5p/181c and Prognosticates Poor Survivability of Breast Cancer.

PURPOSE: This study aims to evaluate the prognostic value of human Mitotic Centromere-Associated Kinesin (MCAK), a microtubule-dependent molecular motor, in breast cancers. The posttranscriptional regulation of MCAK by microRNAs will also be explored. METHODS: The large-scale gene expression datasets of breast cancer (total n=4,677) were obtained from GEO, NKI, and TCGA database. Kaplan-Meier and Cox analyses were used for survival analysis. MicroRNAs targeting MCAK were predicted by bioinformatic analysis and validated by a dual-luciferase reporter assay. RESULTS: The expression of MCAK was significantly associated with aggressive features of breast cancer, including tumor stage, Elston grade, and molecular subtypes, for global gene expression datasets of breast cancer (p<0.05). Overexpression of MCAK was significantly associated with poor outcome in a dose-dependent manner for either ER-positive or ER-negative breast cancer. Evidence from bioinformatic prediction, coexpression assays, and gene set enrichment analyses suggested that miR-485-5p and miR-181c might target MCAK and suppress its expression. A 3'UTR dual-luciferase target reporter assay demonstrated that miR-485-5p and miR-181c mimics specifically inhibited relative Firefly/Renilla luciferase activity by about 50% in corresponding reporter plasmids. Further survival analysis also revealed that miR-485-5p (HR=0.59, 95% CI 0.37-0.92) and miR-181c (HR=0.54, 95% CI 0.34-0.84) played opposite roles of MCAK (HR=2.80, 95% CI 1.77-4.57) and were significantly associated with better outcome in breast cancers. CONCLUSION: MCAK could serve as a prognostic biomarker for breast cancers. miR-485-5p and miR-181c could specifically target and suppress the MCAK gene expression in breast cancer cells.

Highly Sensitive and Transparent Strain Sensors with an Ordered Array Structure of AgNWs for Wearable Motion and Health Monitoring.

Sensitivity and transparency are critical properties for flexible and wearable electronic devices, and how to engineer both these properties simultaneously is dramatically essential. Here, for the first time, we report the assembly of ordered array structures of silver nanowires (AgNWs) via a simple water-bath pulling method to align the AgNWs embedded on polydimethylsiloxane (PDMS). Compared with sensors prepared by direct drop-casting or transfer-printing methods, our developed sensor represents a considerable breakthrough in both sensitivity and transparency. The maximum transmittance was 86.3% at a wavelength of 550 nm, and the maximum gauge factor was as high as 84.6 at a strain of 30%. This remarkably sensitive and transparent flexible sensor has strictly stable and reliable responses to motion capture and human body signals; it is also expected to be able to help monitor disabled physical conditions or assist medical therapy while ensuring privacy protection.

Ultra-low temperature sintering of Cu@Ag core-shell nanoparticle paste by ultrasonic in air for high-temperature power device packaging.

Sintering of low-cost Cu nanoparticles (NPs) for interconnection of chips to substrate at low temperature and in atmosphere conditions is difficult because they are prone to oxidation, but dramatically required in semiconductor industry. In the present work, we successfully synthesized Cu@Ag NPs paste, and they were successfully applied for joining Cu/Cu@Ag NPs paste/Cu firstly in air by the ultrasonic-assisted sintering (UAS) at a temperature of as low as 160 °C. Their sintered microstructures featuring with dense and crystallized cells are completely different from the traditional thermo-compression sintering (TCS). The optimized shear strength of the joints reached to 54.27 MPa, exhibiting one order of magnitude higher than TCS at the same temperature (180 °C) under the UAS. This ultra-low sintering temperature and high performance of the sintered joints were ascribed to ultrasonic effects. The ultrasonic vibrations have distinct effects on the metallurgical reactions of the joints, resulting in the contact and growth of Cu core and the stripping and connection of Ag shell, which contributes to the high shear strength. Thus, the UAS of Cu@Ag NPs paste has a great potential to be applied for high-temperature power device packaging.

Protective effect of baicalin on the small intestine in rats with food allergy.

AIMS: The therapeutic effect of baicalin and its mechanism were explored. MATERIALS AND METHODS: A total of 30 Sprague Dawley (SD) rats were randomly divided into 3 groups of 10: ovalbumin group (OVA group), baicalin intervention group (HQ group), and saline-group (NC group). Serum OVA-IgE antibody levels were detected by enzyme-linked immunosorbent assay (ELISA); and diarrhea in rats was observed. Animals were sacrificed at week seven. Then, a 5-cm long duodenum beneath the Treitz ligament was collected from each rat, and was fixed, embedded, sliced and stained with toluidine blue to evaluate the integrity of mast cells. Next, pathological changes of the intestine were observed by hematoxylin and eosin (H&E) staining, and the ultrastructure of the intestinal mucosa was observed under a transmission electron microscope. KEY FINDINGS: Serum OVA-sIgE level were significantly lower (at sixth week, OVA group: 12.86±1.35, HQ group: 3.47±0.51, F=117.05, P<0.01), the number of eosinophils significantly decreased (HQ group: 2.73±1.02, OVA group: 16.48±2.32, P<0.01), mast cell integrated rate was significantly increased (HQ group: 89.90±4.43, OVA group: 35.30±9.78, P<0.01) uniform small intestinal villi were observed, the organelles were basically normal, and lesions were significantly fewer in the HQ group, compared with the OVA group. SIGNIFICANCE: Baicalin can effectively reduce serum OVA-sIgE in rats with food allergy, increase mast cell integrated rate and alleviate intestinal pathological changes. Hence, baicalin has a good therapeutic effect on food allergy.

[Prognostic value of E-cadherin, CD34 in the patients with hepatocellular carcinoma].

OBJECTIVE: To study the expression of E-cadherin and CD34 in the tissues of hepatocellular carcinoma (HCC), to discuss the relationship between them and the clinical pathology and evaluate the prognosis of HCC patients. METHODS: The expression of E-cadherin and CD34 in HCC tissues of 41 patients were examined by two-step methods of PV-6000 of immunohistochemistry. Clinical-pathological data, tumor recurrent rate and survival rate after hepatectomy were recorded and analyzed. RESULTS: The positive expression rate was observed in 48.78% for E-cadherin and 100% for CD34. The decreased E-cadherin expression were significantly associated with larger tumor, the high-dangerous group with invasion and poor differentiation of HCC tissues (chi(2) = 4.1881, 4.8118, 6.2695, P < 0.05). In the group with negative-expression of E-cadherin, the percent of tumor recurrence within 2 years after hepatectomy was higher and the rate of 5 years survival was significantly lower than the positive-expressed group. A significant negative-correlation between the expression of CD34 and the patients' age and the invasion of tumor (t = 1.9371, 1.9010, P < 0.05) were found. There was no relationship between the expression of E-cadherin and CD34 in HCC tissues. CONCLUSIONS: The patient with a negative-expression of E-cadherin in HCC tissues has a poor prognosis. No relationship between the expression of CD34 and tumor recurrence and patients' survival and no relationship between the expression of E-cadherin and CD34 was found.

[A study of lymphocyte apoptosis and endoplasmic reticulum stress in the development of sepsis and their association with outcome in septic patients].

OBJECTIVE: To investigate the role of lymphocyte apoptosis and endoplasmic reticulum stress (ERS) on the development of sepsis and their association with the prognosis of sepsis patients. METHODS: A prospective cohort study was conducted. Seventy septic patients admitted to intensive care unit (ICU) of Shanghai East Hospital of Tongji University were enrolled. Blood samples were collected on days 1, 3 and 7 to measure percentage of circulating apoptotic lymphocyte with flow cytometry analysis. The relative expressions of endoplasmic reticulum specific glucose regulated protein 78 (GRP78) mRNA and transcription factor CHOP mRNA were measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). The correlation between CHOP mRNA expression and percentage of circulating apoptotic lymphocyte was analyzed by Spearman relative analysis. The patients were divided into death (n = 23) and survival subgroups (n = 47). Twenty healthy volunteers during the same period were selected as the healthy control group. RESULTS: (1) Rate of lymphocyte apoptosis: compared with healthy control group [(2.86±0.66)%], septic patients, either survival or death subgroup, exhibited higher rate of lymphocyte apoptosis on days 1, 3 and 7 [survival subgroup: (12.44±4.43)%, (8.57±3.38)%, (6.78±3.35)%; death subgroup: (14.42±2.01)%, (11.32±2.53)%, (8.87±3.62)%, all P < 0.01], and it was obvious on day 1, and the phenomenon became less marked gradually. The rate of circulating apoptotic lymphocytes did not differ between the death and survival subgroups on day 1, but there was a significant difference in the rate on day 3 and day 7 (both P < 0.05). (2) The expression of CHOP mRNA (2(-ΔΔCt)): compared with that in healthy controls [(2.56±1.09)×10-3], CHOP mRNA expression was increased on days 1, 3 and 7 in septic patients [survival subgroup: (5.83±1.96)×10(-3), (4.24±1.60)×10(-3), (4.15±1.64)×10(-3), death subgroup: (37.20±20.70)×10(-3), (18.80±13.90)×10(-3), (9.28±7.78)×10(-3), all P < 0.01], and it was more obvious in the death subgroup, as it was increased by 6.38, 4.43, and 2.24 folds (P values was 0.000, 0.000, and 0.001), but it decreased rapidly in death subgroup. (3) The expression of GRP78 mRNA (2(-ΔΔCt)): compared with healthy controls [(3.31±2.04)×10(-3)], the expression of GRP78 mRNA in both survival and death subgroups increased in septic patients on day 1 [(5.83±2.00)×10-3, (11.30±6.48)×10(-3), both P < 0.01], and they decreased subsequently. The expression of GRP78 mRNA in the survival subgroup declined to the levels of the healthy control group on day 3 and day 7 [3 days: (3.99±1.60)×10(-3), 7 days: (3.30±1.35)×10(-3), both P > 0.05], and GRP78 mRNA expression in the death subgroup was gradually lowered, but it was still higher than that in the healthy control group [3 days: (7.27±3.64)×10(-3), 7 days: (5.23±1.94)×10(-3), both P < 0.01]. (4) Spearman relative analysis showed that the expression of CHOP mRNA was positively correlated with the rate of lymphocyte apoptosis (r = 0.414, P = 0.000). CONCLUSIONS: The increase in the rate of lymphocyte apoptosis and activation of ERS play an important role in the development of sepsis, and it is associated with worse outcome in the septic patients.

Efficacy of intra-tumor injection of Kang-Lai-Te in treating transplanted hepatoma in rats.

BACKGROUND: Non-operative therapy takes an important position in comprehensive therapy of liver cancer. Despite some effects by using ethanol, acetic acid and heat saline for intra-tumor injection in the treatment of liver cancer, it is difficult to attain a complete cure but bring about injury to the liver to some extent. Hence, searching for other drugs for the local treatment of liver tumor is an important option. This study was designed to set up rat models of transplanted liver cancer, intra-tumor injection of Kang-Lai-Te (KLT), and negative control (saline) and positive control (ethanol). The effect of intra-tumor injection of KLT in treating transplanted hepatoma in rats and its advantages and disadvantages were assessed and the possibility of its use in treating patients with liver cancer was evaluated. METHODS: Forty rats were divided into 4 groups (G1, G2, G3 and G4, 10 rats in each group). Different drugs were injected into their implanted hepatoma (G1 with 0.2 ml saline as control, G2 with 10 mg KLT, G3 with 20 mg KLT, G4 with 0.2 ml ethanol). After 3 and 8 days, the hepatoma volume (HV), the serum levels of albumin, alanine aminotransferase(ALT), aspartate aminotransferase alkaline phosphatase(ALP) and creatinine, as well as the expression of proliferation cell nuclear antigen(PCNA) in hepatoma were detected. RESULTS: After 3 days, the HVs were smaller in G3 and G4 than in G1 (P<0.05), the serum levels of albumin were higher in G2 and G3 than in G1 and G4 (P<0.05), the serum levels of ALT and AST were lower in G2 and G3 than in G4 (P<0.05), the serum levels of ALP was lower in G2 and G3 than in G1 and G4 (P<0.05),the PCNA labeling indexes (PCNA LI) were lower in G2 and G3 than in G1 and G4 (P<0.05). After 8 days, the HVs were smaller in G2, G3 and G4 than in G1 (P<0.05), and the differences of HVs among G2, G3 and G4 were not significant. The serum levels of ALP were lower in G1, G2 and G3 than in G4 (P<0.05), and the PCNA LI were lower in G3 than in G1 and G4 (P<0.05). CONCLUSION: Intra-tumor injection of KLT into implanted hepatoma is evidently effective, but it is less effective than ethanol. The effect of KLT on liver function is markedly lower than that of ethanol.

[Study on the distribution of vitamin D receptor gene start codon polymorphism in the Achangs and Hans].

OBJECTIVE: To detect the difference between the Chinese Achang and Han ethnic groups in Yunnan province in the distribution of vitamin D receptor (VDR) gene start codon polymorphism. METHODS: Polymerase chain reaction-restriction fragment length polymorphism, gene sequencing and genetic analysis methods were used. A restriction fragment length polymorphism in the start codon of VDR (Fok I) gene was tested in the Achangs (n=68) and the Hans (n=92). RESULTS: The frequencies of FF, Ff and ff genotypes were found to be 18%, 35% and 47% in the Achangs, and 22%, 52% and 26% in the Hans, respectively. A significant difference was seen in the frequency distribution of VDR genotype between the Achangs and the Hans(Chi2=7.716, P=0.021). CONCLUSION: The Achang and Han ethnic groups differ in the frequency distribution of VDR gene start codon polymorphism.