Impact of CD44 genetic variants on clinicopathological characteristics of uterine cervical cancer patients.

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.

HER2 mutations in advanced cervical neuroendocrine carcinoma: implications for trastuzumab deruxtecan therapy.

Recent clinical evidence shows that the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) can successfully treat patients with advanced HER2-mutant non-small cell lung cancer (NSCLC). We aimed to characterize HER2 mutations in cervical neuroendocrine carcinoma (NEC) among Taiwanese women to provide the rationale for exploring T-DXd as a tumor-agnostic targeted therapy option. We analyzed 12 archived primary cervical NEC samples from Taiwanese patients. Tumor-rich areas were marked for microdissection on 10 µm unstained sections. DNA was extracted, and HER2 hotspots were sequenced using a targeted panel on the Illumina MiSeq. HER2 missense mutations were identified in 5 of 12 cases (41.7%). Of the 5 cases with mutations, 2 patients (40%) had a single mutation, while 3 patients (60%) had double mutations. We detected 4 substitutions outside the tyrosine kinase domain (non-TKD), which were p.P1170A, p.S305C, p.I655V, and a novel T328K alteration. No mutations were found within the tyrosine kinase domain (TKD). The 41.7% HER2 mutation rate warrants expanded screening and future clinical investigation of the T-DXd targeting HER2 mutations in cervical NEC patients. Overall, this study contributes to the molecular understanding of cervical NEC and lays the groundwork for developing more effective treatment strategies.

Short-Term Outcome of Robotic versus Laparoscopic Hysterectomy for Endometrial Cancer in Women with Diabetes: Analysis of the US Nationwide Inpatient Sample.

This study investigated short-term outcomes of robotic versus laparoscopic hysterectomy for endometrial cancer (EC) in women with diabetes. We extracted the data of hospitalized females aged ≥18 years who were diagnosed with EC and diabetes and underwent robotic or laparoscopic hysterectomy from the US Nationwide Inpatient Sample (NIS) 2005-2018. Associations between study variables and in-hospital outcomes, including complications, unfavorable discharge, length of stay (LOS), and hospital costs, were examined using logistic regression. A total of 5745 women (representing 28,176 women in the US) were included. Multivariable analysis revealed that robotic surgery was significantly associated with a decreased risk of unfavorable discharge (adjusted odds ratio [aOR] = 0.63, 95% confidence interval [CI]: 0.46, 0.85) than pure laparoscopic surgery. Women who underwent robotic surgery had a significantly shorter LOS (0.46 fewer days, 95% CI: -0.57, -0.35) but higher total hospital costs (6129.93 greater USD; 95% CI: 4448.74, 7811.12). Compared with pure laparoscopic surgery, robotic hysterectomy was associated with less unfavorable discharge among women aged ≥60 years (aOR = 0.60, 95% CI: 0.44, 0.80). For US women with EC and diabetes, robotic hysterectomy is associated with shorter LOS, decreased risk of unfavorable discharge, especially among older patients, and higher total costs than laparoscopic surgery.

ß-catenin inhibitor ICG-001 suppress cell cycle progression and induce autophagy in endometrial cancer cells.

The incidence of endometrial cancer has been rising in recent years. Gene mutation and high protein expression of ß-catenin are commonly detected in endometrioid endometrial cancer. ICG-001 is a ß-catenin inhibitor via blocking the complex formation of ß-catenin and cAMP response element-binding protein (CREB)-binding protein (CBP). This study aims to investigate the effect of ICG-001 on endometrial cancer inhibition. First, endometrial carcinoma patient-derived xenograft (PDX)-derived organoids and primary cells were used to verify the inhibiting ability of ICG-001 on endometrial cancer. Furthermore, endometrial cancer cell lines were used to investigate the anticancer mechanism of ICG-001. Using MTT assay and tumor spheroid formation assay, ICG-001 significantly reduced the cell viability of HEC-59 and HEC-1A cells. ICG-001 enhanced cisplatin-mediated cytotoxicity. ICG-001 decreased cancer stem cell sphere formation. ICG-001 decreased the protein expressions of CD44, hexokinase 2 (HK2), and cyclin A. ICG-001 lowered the cell cycle progression by flow cytometer analysis. Autophagy, but no apoptosis, was activated by ICG-001 in endometrial cancer cells. Autophagy inhibition by ATG5 silencing enhanced ICG-001-mediated suppression of cell viability, tumor spheroid formation, and protein expression of cyclin A and CD44. This study clarified the mechanism and revealed the clinical potential of ICG-001 against endometrial cancer.

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway.

AIM: To construct an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion (I/R) injury in 661W cells and the protective effect of ginsenoside Rg1. METHODS: The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro. Apoptosis, intracellular reactive oxygen species (ROS) levels and superoxide dismutase (SOD) levels were measured at different time points during the reperfusion injury process. The injury model was pretreated with graded concentrations of ginsenoside Rg1. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of cytochrome C (cyt C)/B-cell lymphoma-2 (Bcl2)/Bcl2 associated protein X (Bax), heme oxygenase-1 (HO-1), caspase9, nuclear factor erythroid 2-related factor 2 (nrf2), kelch-like ECH-associated protein 1 (keap1) and other genes. Western blot was used to detect the expression of nrf2, phosphorylated nrf2 (pnrf2) and keap1 protein levels. RESULTS: Compared to the untreated group, the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased (P<0.01). Additionally, the ROS content increased and SOD levels decreased significantly (P<0.01). In contrast, treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na2S2O4 treated group (P<0.01). Moreover, Rg1 reduced the levels of caspase3, caspase9, and cytC, while increasing the Bcl2/Bax level. These differences were all statistically significant (P<0.05). Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment, however, Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na2S2O4 treated group (P<0.001). CONCLUSION: The OGD/R process is induced in 661W cells using Na2S2O4. Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway. These results suggest a potential protective effect of Rg1 against retinal I/R injury.

Effect of Sea Cucumber Enzymolysis Fermentation Liquid on immunosuppressed mice based on metabonomics / 中国药理学通报

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4

Mechanism of isovitexin in alcoholic fatty liver based on metabolomics combined with molecular docking analysis / 中国药理学通报

Aim To explore the effects of isovitexin (IVT) on alcoholic fatty liver disease (AFLD) and its mechanism based on metabolomics and in vivo methods and combined molecular docking. Methods 8-week-old male C57BL/6J mice were randomly divided into control, model and IVT groups, with 6 mice in each group. The control group was fed with alcoholic liquid feed control feed, the model group and IVT group were fed with alcoholic liquid feed model feed, and the IVT group was fed daily gastric IVT (100 mg • kg

Research Status and Prospects of Non-Traumatic Fat Embolism in Forensic Medicine / 法医学杂志

In the practice of forensic pathology, fat embolism is one of the common causes of death, which can be divided into two categories: traumatic and non-traumatic. Non-traumatic fat embolism refers to the blockage of small blood vessels by fat droplets in the circulatory blood flow caused by non-traumatic factors such as underlying diseases, stress, poisoning and lipid metabolism disorders. At present, it is believed that the production of non-traumatic fat embolism is related to the disturbance of lipid metabolism, C-reactive protein-related cascade reaction, the agglutination of chylomicron and very low-density lipoprotein. The forensic identification of the cause of death of non-traumatic fat embolism is mainly based on the case, systematic autopsy, HE staining and fat staining, but it is often missed or misdiagnosed by forensic examiners because of its unknown risk factors, hidden onset, the difficulty of HE staining observation and irregular implementation of fat staining. In view of the lack of attention to non-traumatic fat embolism in forensic identification, this paper reviews the concepts, pathophysiological mechanism, research progress, existing problems and countermeasures of non-traumatic fat embolism, providing reference for forensic scholars.

Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 Positive Feedback Loop Induces Cell Cycle Arrest by Dual PI3K/mTOR Inhibitor PQR309 in Endometrial Cancer Cell Lines.

Gene mutations in PIK3CA, PIK3R1, KRAS, PTEN, and PPP2R1A commonly detected in type I endometrial cancer lead to PI3K/Akt/mTOR pathway activation. Bimiralisib (PQR309), an orally bioavailable selective dual inhibitor of PI3K and mTOR, has been studied in preclinical models and clinical trials. The aim of this study is to evaluate the anticancer effect of PQR309 on endometrial cancer cells. PQR309 decreased cell viability in two-dimensional and three-dimensional cell culture models. PQR309 induced G1 cell cycle arrest and little cell death in endometrial cancer cell lines. It decreased CDK6 expression and increased p27 expression. Using the Proteome Profiler Human XL Oncology Array and Western blot assay, the dual inhibitor could inhibit the expressions of c-Myc and mtp53. KJ-Pyr-9, a c-Myc inhibitor, was used to prove the role of c-Myc in endometrial cancer survival and regulating the expression of mtp53. Knockdown of mtp53 lowered cell proliferation, Akt/mTOR pathway activity, and the expressions of c-Myc. mtp53 silence enhanced PQR309-inhibited cell viability, spheroid formation, and the expressions of p-Akt, c-Myc, and CDK6. This is the first study to reveal the novel finding of the PI3K/mTOR dual inhibitor in lowering cell viability by abolishing the PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop in endometrial cancer cell lines.

Study of standardizing nomenclatures for organs at risk of nasopharyngeal carcinoma via the contouring content-based image retrieval method / 中华放射肿瘤学杂志

Objective:Based on the AAPM TG-263, a Content-Based Standardizing Nomenclatures (CBSN) was proposed to explore the feasibility of its standardization verification for organs at risk (OAR) of nasopharyngeal carcinoma (NPC).Methods:The radiotherapy structure files of 855 patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT) from 2017 to 2019(15 of whom showed clinical anomalous structures) were retrospectively collected and processed. The Matlab self-developed software was used to obtain the image position, geometric features, first-order gray histogram, and the Gray-level Co-occurrence Matrix′s texture features of the OAR contour outlined by the doctor to establish the CBSN Location Verification model and CBSN Knowledge Library. Fisher discriminant analysis was employed to establish a CBSN OAR classification model, which was evaluated using self-validation, cross-validation, and external validation, respectively.Results:99%(69/70) of the simulated anomalous structures were outside the 90% reference range of the CBSN Knowledge Library and the characteristic parameters significantly differed among different OARs (all P<0.001). The accuracy rates of self-validation, cross-validation and external verification of the CBSN OAR classification model were 92.1%, 92.0% and 91.8%, respectively. Fourteen cases of clinical abnormal structures were successfully detected by CBSN with an accuracy rate of 93%(14/15). In the simulation test, the accuracy of the left and right location verification reached 100%, such as detecting the right eye lens named Len_L. Conclusion:CBSN can be used for OAR verification of NPC, providing reference for multi-center cooperation and standardized radiotherapy of NPC patients.

Investigation of metastasis-associated in colon cancer-1 genetic variants in the development and clinicopathologcial characteristics of uterine cervical cancer in Taiwanese women.

The objectives of this study were to define the associations among single nucleotide polymorphisms (SNPs) of metastasis-associated in colon cancer-1 (MACC1) gene, development and clinicopathological characteristics of uterine cervical cancer, and patient survival in Taiwan. Genotypic frequencies of 5 MACC1 SNPs rs975263, rs3095007, rs4721888, rs3735615 and rs1990172 were identified for 132 patients with invasive cancer, 99 with high-grade cervical intraepithelial neoplasia and 338 normal controls using real-time polymerase chain reaction. It revealed that there were no associations of these MACC1 SNPs with cervical carcinogenesis. In the meantime, cervical cancer patients with genotype GG in MACC1 SNP rs975263 tended to display more risk to have vaginal invasion than those with AA/AG (p=0.042, OR: 8.70, 95% CI: 0.81-433.22). In multivariate analysis, positive pelvic lymph node metastasis could significantly predict worse 5 years survival rate (p=0.001; HR=9.98, 95% CI=2.64-37.77) for cervical cancer patients. In conclusion, pelvic lymph node status rather than MACC1 SNPs was the only independent parameter that could significantly predict 5 years survival rate in Taiwanese women with cervical cancer.

Human Body Mixed Motion Pattern Recognition Method Based on Multi-Source Feature Parameter Fusion.

Aiming at the requirement of rapid recognition of the wearer's gait stage in the process of intelligent hybrid control of an exoskeleton, this paper studies the human body mixed motion pattern recognition technology based on multi-source feature parameters. We obtain information on human lower extremity acceleration and plantar analyze the relationship between these parameters and gait cycle studying the motion state recognition method based on feature evaluation and neural network. Based on the actual requirements of exoskeleton per use, 15 common gait patterns were determined. Using this, the studies were carried out on the time domain, frequency domain, and energy feature extraction of multi-source lower extremity motion information. The distance-based feature screening method was used to extract the optimal features. Finally, based on the multi-layer BP (back propagation) neural network, a nonlinear mapping model between feature quantity and motion state was established. The experimental results showed that the recognition accuracy in single motion mode can reach up to 98.28%, while the recognition accuracy of the two groups of experiments in mixed motion mode was found to be 92.7% and 97.4%, respectively. The feasibility and effectiveness of the model were verified.

Main nutrients and functional ingredients in flowers of Polygonatum cyrtonema and P. filipes / 中国中药杂志

To reveal the main nutrients and functional ingredients in the flowers of Polygonatum cyrtonema and P. filipes, the content of the polysaccharides, saponins, amino acids, total phenols, mineral elements, and the DPPH free radical scavenging rates were determined. The flowers and rhizomes of P. cyrtonema were collected from Qingyang in Anhui and Qingyuan in Zhejiang, while the flowers and rhizomes of P. filipes were collected from Longyou in Zhejiang, respectively. The results showed that the polysaccharides content in flowers varied from 60.88 to 97.00 mg·g~(-1), about half of that in rhizomes. The saponins content in flowers varied from 32.55 to 40.93 mg·g~(-1), which was close to the content in rhizomes. The content of total phenols ranged from 40.79 to 50.95 mg·g~(-1), approximately 4.5 times of that in rhizomes. The total amino acids content in flowers was 111.85 to 131.03 mg·g~(-1), about 2.3 times of the content in rhizomes. The essential trace element content was abundant in flowers. The contents of heavy metal elements were all within the limits set by the standards. The DPPH free radical scavenging rate IC_(50) varied from 1.77 to 3.25 mg·mL~(-1), less than one-fifth of that in rhizomes, showing a significant superiority of antioxidant activity compared to rhizomes. The results initially revealed the fundamental of "the flowers exceed the rhizomes in effect", the common saying about the traditional Chinese medicinal herbs over the years, indicating a great developing potential of the flowers. Besides, as polysaccharides, saponins, amino acids, total phenols and other nutritive substances in flowers differ widely among species and provenances, it's important to develop variety breeding to improve the quality and yield of flowers.

Main nutrients and functional ingredients in shoots of Polygonatum cyrtonema / 中国中药杂志

In order to reveal the main nutrients and functional ingredients in the shoots of Polygonatum cyrtonema, the polysaccharides, proteins, amino acids, and total phenols were determined. The tested samples cultured in Ma'nijiaonong, Hengtang village, Tianmushan town, Lin'an, Zhejiang, which were collected from three provenances(Pan'an and Longquan in Zhejiang and Qingyang in Anhui). The results showed that the polysaccharide content of the shoots varied from 2.34% to 12.73%, roughly one-third of rhizomes. The protein content varied from 107.75 to 192.49 mg·g~(-1), nearly 5.50 times more than rhizomes. Moreover, the average of total amino acid content was 193.13-248.74 mg·g~(-1), approximately 4.16 times of rhizomes. And the essential amino acids account for 35.57%-39.44% of the total amino acids content, which was close to the standard of the ideal protein proposed by FAO/WHO(the essential amino acid/total amino acid is about 40%). In addition, the taste amino acids(TaAA) changed from 160.12 to 208.29 mg·g~(-1), revealing the material basis of "shoots were extremely delicious" in Chinese ancient herbal medicine. Additionally, the total phenols varied from 51.21-58.76 mg·g~(-1), about 2.96 times of rhizomes. The DPPH free radical scavenging rate of tested shoots was over 95%, which obviously superior to rhizomes. Therefore, the shoots of P. cyrtonema is a very high-quality vegetable and functional food with good development potential. Furthermore, the main nutrients and functional substances in P. cyrtonema shoots are closely related to the provenances and harvesting seasons. It is important to improve the quality and yield of the shoots by strengthening the variety of breeding and cultivation techniques.

Combined treatment for big submucosal myoma with High Intensity Focused Ultrasound and hysteroscopic resection.

OBJECTIVE: Big submucosal myoma often causes heavy menstrual bleeding and are complicated in hysterscopic surgery. High Intensity Focused Ultrasound (HIFU), is a method for myoma ablation therapy, which may benefit on size reduction, and assist following hysterscopic myomectomy. CASE REPORT: Two cases, case one,. 44-year-old female with 3.8 cm submucosal myoma, STEPW (Size, Topography, Extension, Penetration and Wall) score 6 and case 2. 48-year-old female, with 6.0 cm submucosal myoma, STEPW score 8, both received HIFU treatment before hysterscopic myomectomy was done. The myomas reduced after 5 months with improvement of anemia. The following hysterscopic myomectomy shows less operative time and fewer blood loss. CONCLUSION: HIFU reduce size of submucosal myoma and may improve anemia after months. Less operating time and blood loss were demonstrated in the following hysterscopic myomectomy. For well selected patients, combined treatment with HIFU and hysteroscopic resection may decrease complication rate.

The clinicopathological characteristic associations of long non-coding RNA gene H19 polymorphisms with uterine cervical cancer.

The purposes of the current study were conducted to explore the relationships among long non-coding RNA gene H19 (LncRNA H19) polymorphisms and clinicopathological characteristics of uterine cervical cancer, and patient prognosis in Taiwan. Five genetic variants of LncRNA H19 rs3024270, rs2839698, rs3741219, rs2107425 and rs217727 were recruited from one hundred and thirty-four patients with invasive cancer, 101 with high-grade cervical intraepithelial neoplasia (CIN) of uterine cervix and 325 controls and their genetic distributions were determined. It indicated no associations of these LncRNA H19 genetic variants with development of cervical cancer. CC/CT in LncRNA H19 rs2839698 exhibited less risk to have pelvic lymph node metastasis [Odds ratio (OR): 0.19, 95% Confidence interval (CI):0.04-0.82, p=0.028)], as compared with TT. Meanwhile, cervical cancer patients with AA/AG in rs3741219 also had less risk to develop pelvic lymph node metastasis (OR: 0.17, 95% CI: 0.05-0.63, p=0.008), large tumor (OR: 0.17, 95% CI: 0.04-0.82, p=0.014) as well as parametrium (OR: 0.26, 95% CI: 0.07-0.95, p=0.045) and vagina invasion (OR: 0.25, 95% CI: 0.07-0.91, p=0.041, as compared to those with GG. However, only positive pelvic lymph node metastasis was related to worse recurrence-free survival and poor overall survival. Conclusively, it indicated no association of LncRNA H19 SNPs with cervical carcinogensis in Taiwanese women. Although genotypes TT in LncRNA H19 rs2839698 and GG in rs3741219 are related to some poor clinicopathological parameters of cervical cancer, only pelvic lymph node status could predict 5 year patient survival significantly.

Effects of ABT-737 combined with irradiation treatment on uterine cervical cancer cells.

The aim of the present study was to examine the role of ABT-737, an inhibitor of B-cell lymphoma 2 (Bcl-2), in enhancing the effect of irradiation on uterine cervical cancer. Based on The Cancer Genomic Atlas (TCGA), Bcl-2 mRNA expression was associated with the Tumor-Node-Metastasis stage of cervical cancer. Therefore, it was hypothesized that Bcl-2 inhibition may decrease the progression of cervical cancer. ABT-737 was added to irradiation treatment to evaluate its effectiveness in inhibiting cancer cell progression. SiHa and CaSki cervical cancer cells were selected for in vitro assays. Patients with advanced stage III uterine cancer had slightly increased mRNA expression levels of Bcl-2 compared with patients with stage I cancer, although the difference was not significant. ABT-737 and radiation administration induced a synergistic cytotoxic effect based on the MTT assay and flow cytometry results, where an increase in apoptosis was observed. The apoptotic percentages were significantly increased in the cells treated with a combination of ABT-737 and irradiation. Loss of mitochondrial membrane potential and gain of reactive oxygen species (ROS) were detected by flow cytometry in CaSki and SiHa cells treated with ABT-737 and radiation. Additionally, the protein expression levels of the cleaved forms of poly ADP ribose polymerase and caspase-7 were increased following the combined treatment. In conclusion, ABT-737 and irradiation may induce apoptosis via loss of mitochondrial membrane potential and a ROS-dependent apoptotic pathway in CaSki and SiHa cells. The present study indicates that ABT-737 may be a potential irradiation adjuvant when treating cervical cancer.

Impact of matrix metalloproteinase-11 gene polymorphisms on development and clinicopathologcial variables of uterine cervical cancer in Taiwanese women.

The purposes of this study were to examine whether there were associations among matrix metalloproteinase-11 (MMP-11) gene polymorphisms, development and clinicopathological characteristics of uterine cervical cancer as well as patient survival or not. Five single-nucleotide polymorphisms (SNPs) of the MMP-11 gene rs738791, rs738792, rs2267029, rs28382575, and rs131451 from one hundred and thirty patients with invasive cancer, 99 patients with high-grade cervical intraepithelial neoplasia (CIN) of uterine and 335 normal controls were analyzed using real-time polymerase chain reaction. Our results revealed that genotypic frequencies of CT/TT in MMP-11 SNP rs738791, with CC as a reference, tended to exhibit significantly different distributions (p=0.044, AOR: 0.63, 95% CI: 0.41-0.99) between patients with cervical invasive cancer and normal control women when controlling age. After multiple significance adjustment, the tendency becomes insignificant (Holm's adjusted p 0.176). Although CT/TT genotype of MMP-11 gene rs738791 tended to increase the risk of developing stage II disease at least (p=0.035; OR: 2.16, 95% CI: 1.05-4.44) and deep stromal invasion more than 10 mm (p=0.043; OR: 2.08, 95% CI: 1.02-4.26) with CC as a reference in patients with uterine cervical cancer. They became insignificant after multiple significance adjustment and the Holm's adjusted p values would become as 0.245 and 0.258, respectively. However, lymph node metastasis exhibited significant worse recurrence-free survival (p=0.033; HR: 2.83, 95% CI: 1.09-7.35), and overall survival (p=0.001; HR: 4.80, 95% CI: 1.82-12.62) compared to those without pelvic lymph node metastasis. In conclusion, it indicates no impact of the MMP-11 SNPs on uterine cervical cancer in Taiwanese women.

Involvement of endothelial nitric oxide synthase gene variants in the aggressiveness of uterine cervical cancer.

To date, few studies explore the involvement of endothelial nitric oxide synthase (eNOS) gene variants in uterine cervical cancer. Therefore, we conducted this study to assess the clinical implication of eNOS in cervical carcinogenesis, clinicopathological characteristics and patient survival. One hundred and seventeen patients with cervical invasive cancer and 95 with preinvasive lesions and 330 control women were consecutively enrolled. Real time polymerase chain reaction was used to examine the genotypic distributions of eNOS single nucleotide polymorphisms (SNPs) rs1799983 (894G>T) at the exon 7 region and rs2070744 (-786T>C) at the promoter region. Our results indicated no significant associations among genotypic distributions of eNOS SNPs and patients with cervical invasive cancer and those with preinvasive lesions as well as normal controls. However, cervical cancer patients with genotypes TC/CC in eNOS SNP rs2070744 carried less risk of advanced stage [odds ratios (OR) = 0.30, 95% confidence interval (CI)=0.09-0.97, p=0.036], parametrium invasion (OR=0.16, 95% CI=0.02-0.75, p=0.009) and pelvic lymph node metastasis (OR=0.12, 95% CI=0.01-0.89, p=0.016). In conclusion, although eNOS SNPs rs2070744 and rs1799983 do not display significant associations with cervical carcinogenesis and patient survival, cervical cancer patients with genotypes TC/CC in rs2070744 carry less risk of advanced stage, parametrium invasion and pelvic lymph node metastasis in Taiwan.

Mechanism of action of protein phosphatase 2A in the promotion and inhibition of hepatocellular carcinoma / 临床肝胆病杂志

Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase involved in many signaling pathways associated with cell growth and proliferation, and it also regulates many cellular processes. With an in-depth exploration of PP2A in the process of cell activity, especially malignant tumors, the association between PP2A and hepatocellular carcinoma (HCC) has attracted more and more attention in recent years; however, there is still a controversy over whether PP2A can promote or inhibit HCC. This article reviews the research advances in the mechanism of action of PP2A as a tumor factor in the regulation of HCC and target therapy.