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With the increasing incidence of type 2 diabetes, it is imperative to identify how to effectively prevent or treat this disease. Studies have shown that some lactic acid bacteria can improve type 2 diabetes with almost no side effects. Therefore, in this experimental study, we explored the preventive and therapeutic effects of Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) on streptozotocin-induced type 2 diabetes in rats. The results showed that L. fermentum TKSN041 could reduce the amount of water intake, reduce weight loss, and control the increase in the fasting blood glucose level of diabetic rats. The organ index and tissue section results showed that L. fermentum TKSN041 could reduce the damage caused by diabetes to the liver, kidney, spleen, pancreatic, and brain tissue. Furthermore, L. fermentum TKSN041 decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), aminotransferase (AST), alanine aminotransferase (ALT), glycated serum proteins (GSP), malondialdehyde (MDA), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and endothelin 1 (ET-1) in serum and increased the serum levels of high-density lipoprotein cholesterol (HDL) and interleukin 10 (IL-10). Finally, L. fermentum TKSN041 up-regulated the mRNA and protein expressions of NF-kappa-B inhibitor-α (IκB-α), AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), liver kinase B1 (LKB1), and glucose transporter 4 (GLUT4) and down-regulated those of nuclear factor-κBp65 (NFκB-p65) and tumor necrosis factor alpha (TNF-α). Furthermore, LF-TKSN041 up-regulated the mRNA expressions of peroxisome proliferator-activated receptor γ (PPAR-γ) and down-regulated neuropeptide Y (NPY), sterol regulatory element-binding protein-1 (SREBF-1), and vascular endothelial growth factor (VEGF). These results suggest that L. fermentum TKSN041 may be a useful intervention factor for the prevention or treatment of type 2 diabetes induced by STZ. Clinical trials are needed to further demonstrate its effectiveness.

There has been considerable research on oxidative stress and inflammation, and their relationship with degenerative diseases. This study investigated the effect of Lactobacillus fermentum HFY06 on aging mice induced by D-galactose. The results showed that L. fermentum HFY06 inhibited the atrophy of the brain, kidneys, liver, and spleen, increased serum SOD, GSH, CAT, and MDA, and decreased IL-6, IL-1β, TNF-α, and IFN-γ. Quantitative PCR showed that L. fermentum HFY06 upregulated the expression of Nrf2, γ-GCS, NOS1, NOS3, SOD1, SOD2, and CAT in the liver and brain tissues, but decreased the expression of NOS2. Western blot analysis showed that L. fermentum HFY06 effectively upregulated the protein expression of SOD1, SOD2, and CAT in the livers and brains of mice. These results suggest that L. fermentum HFY06 can effectively alleviate D-galactose-induced aging in mice, and may activate the Nrf2 signaling pathway and increase the levels of downstream regulatory inflammatory factors and antioxidant enzymes. In conclusion, consumption of L. fermentum HFY06 may prevent aging or reduce oxidative stress.

Selenium (Se), an essential micronutrient for humans, is also a beneficial nutrient for growth and development of many plants. The aim of the present study was to determine whether low-dose Se application could increase plum growth and serotonin synthesis, as well as upregulate the glutathione redox cycle. Two-year-old plum trees were treated with Se6+ (Na2SeO4) and Se2− (SeMet). Growth parameters, levels of serotonin synthesis precursors, compounds and enzymes of the glutathione (GSH) redox cycle, and the antioxidant capacity were analyzed. Results showed that plant height and stem diameter were increased by Se treatment. The leaf Se content was significantly increased; tryptophan was not affected by Se treatment, while the 5-hydroxytryptophan content was significantly higher than control. Although serotonin levels were also increased, the effect was not significant, and no tryptamine was detected in our study. On the 30th day, the MDA content in Se2− was highest followed by the control and Se6+ treatment, and the activities of T-AOT and CAT were increased, while GST was reduced by Se treatment. The two forms of Se treatments increased the activity of GPX and GR, and the total content of GSH + glutathione disulfide (GSSG) at the end of treatment. Furthermore, the level of GSH and GSH/GSSG was instable changed. GSSG content was similar during the treatment time except on the 20 days. Conclusively, the pathway of plum serotonin was clear, both Se6+ and Se2− could influence the serotonin synthesis. Additionally, the GSH redox cycle was sensitive to the Se application. Moreover, Se6+ performed better than Se2− on leaf Se content, plant growth parameters, and antioxidant capacity.

Prostate cancer (PCa) is one of the most common types of malignant tumor, which places a major burden on the health of men, worldwide. A prerequisite to ensure good treatment outcomes for patients with PCa is an accurate diagnosis. The present study aimed to investigate the diagnostic value of prostate-specific antigen (PSA) and α-methylacyl-CoA racemase (P504S) in PCa, using the tumor-associated immunolabels. In total, clinical data was collected from 125 patients undergoing prostate biopsy or surgery between January 2015 and September 2019, and stratified into: PCa (45), benign prostatic hyperplasia (BPH) (60) and unconfirmed diagnosis (20). Immunohistochemistry analysis was performed to assess PSA and P504S expression levels in each group compared with that in the controls (the normal tissue in each group was the internal control). The results demonstrated that the expression level of P504S was significantly higher in the PCa group compared with that in the BPH group. Furthermore, no significant association was observed in the PCa group between PSA and P504S expression levels, and the Gleason grading groups. A total of 20 unconfirmed diagnoses was verified via PSA/P504S. Taken together, the results suggest that combination PSA and P504S have a positive effect in identifying prostate cancer. However, PSA and P504S still have limitations in their diagnosis and the final results need to be carefully and comprehensively analyzed, thus further studies are required to determine their diagnostic values.

Herein, we used a HFD/F to induce NAFLD in mice and intervened with CQPC06 to determine the preventive effect of CQPC06 on NAFLD and its potential regulatory mechanism. C57BL/6J mice were fed with LFD, HFD/F, HFD/F supplemented with CQPC06, and HFD/F supplemented with LDBS for 8 weeks to test the properties of the probiotic. Biochemical and molecular biology methods were used to determine the levels of related indexes in mouse serum, liver tissue, epididymal fat, small intestine tissue, and feces. The results showed that CQPC06 exhibited satisfactory probiotic properties, significantly inhibited mouse weight gain, and decreased the liver index and serum lipid levels, including ALT, AKP, AST, TC, TG, LDL-C, LPS, and HDL-C levels. The HOMA-IR index calculated based on the blood glucose levels and serum insulin levels showed that the HOMA-IR index of NAFLD mice treated with CQPC06 significantly decreased. From the molecular biology level, CQPC06 significantly increased the mRNA and protein expression of PPAR-α, CYP7A1, CPT1, and LPL in NAFLD mouse livers, and decreased the expression of PPAR-γ and C/EBP-α. Furthermore, CQPC06 enhanced the expression of ZO-1, occludin, and claudin-1 in the small intestine of NAFLD mice, and decreased the expression of CD36. CQPC06 decreased the level of Firmicutes and increased the levels of Bacteroides and Akkermansia in the feces of NAFLD mice, and the ratio of Firmicutes/Bacteroides was significantly decreased. CQPC06 is highly resistant in vitro and survived in the gastrointestinal tract and exerted its probiotic effect, altered the intestinal microecology of NAFLD mice, and played an important role in NAFLD prevention through the unique anatomical advantages of the gut-liver axis. There was a clear preventive effect with high concentrations of CQPC06 and it was stronger than that of l-carnitine.

In this study, lactic acid bacterium, Lactobacillus plantarum KFY04, was isolated from Xinjiang yogurt, and it was used to intervene in obese mice maintained on a 45% fat diet, and we compared its effects to those of a commercial strain, LDSB, and l-carnitine. The results showed that the LP-KFY04 intervention mice gained weight more slowly and had lower liver, epididymal adipose, and perirenal adipose tissue indices when compared to the other high-fat groups. Moreover, the LP-KFY04 can reduce the formation of fat vacuoles in the liver, while also reducing adipocyte differentiation and volume, and LP-KFY04 groups had the lowest liver and serum AST, ALT, TG, and TC levels and lowest serum LDL-C and highest HDL-C levels among the groups maintained on a high-fat diet. LP-KFY04 was also shown to mitigate obesity-associated oxidative damage and inflammatory responses. Additionally, quantitative real-time PCR and western blot analysis examining liver and adipose tissue expression of PPAR-α, CYP7A1, CPT1, and LPL showed an increased expression in the LP-KFY04 groups while decreased expression levels of PPAR-γ and C/EBPα relative to the other high-fat diet groups. These results show that of the different interventions, LP-KFY04 was the most effective at mitigating the effects of obesity than LDSB and l-carnitine. The results confirmed that LP-KEY04 has better anti-obesity, anti-oxidative, and anti-inflammatory effects than current fermentation strains. It indicates LP-KFY04 is a fermentation strain with potential practical value and high functionality, and it shows that a fermentation strain should not only have good fermentation performance, but, more importantly, it must provide more functionality on the basis of fermentation.

Xylooligosaccharide (XOS) is a source of prebiotics with multiple biological activities. The present study aimed to investigate the effects of XOS on mice fed a high-fat diet. Mice were fed either a normal diet or a high-fat diet supplemented without or with XOS (250 and 500 mg/kg), respectively, for 12 weeks. The results showed that the XOS inhibited mouse weight gain, decreased the epididymal adipose index, and improved the blood lipid levels, including triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. Moreover, XOS reduced the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated the damage to the liver caused by the high-fat diet. XOS also reduced hyperlipidemia-associated inflammatory responses. Additionally, quantitative real-time polymerase chain reaction results showed that XOS intervention activated the AMP-activated protein kinase (AMPK) pathway to regulate the fat synthesis, decomposition, and β oxidation; upregulated the mRNA expression levels of carnitine palmitoyl transferase 1 (CPT-1), peroxisome proliferator–activated receptors α (PPAR-α), and cholesterol 7-alpha hydroxylase (CYP7A1); and downregulated the mRNA expression levels of acetyl-CoA carboxylase (ACC), CCAAT/enhancer-binding protein alpha (C/EBPα), and lipoprotein lipase (LPL). On the other hand, XOS enhanced the mRNA expression levels of zonula occludens-1 (ZO-1), occludin, and claudin-1 in the small intestine; increased the strength of the intestinal barrier; and optimized the composition of the intestinal microbiota. Therefore, it was concluded that XOS regulated the intestinal barrier, changed the intestinal microecology, and played an important role in preventing hyperlipidemia through the unique anatomical advantages of the gut–liver axis.

BACKGROUND The objective of this study was to examine the prevalence of human papillomavirus 16/18 (HPV-16/18) genotypes and immediate histopathologic correlations in a Chinese population with negative cytology and positive high-risk human papillomavirus (hrHPV) testing. METHODS Patients who had documented negative cytology with immediate follow-up (within the 6 months after negative for intraepithelial lesion or malignancy Papanicolaou [Pap] testing), including a histopathologic examination and/or hrHPV testing, between 2011 and 2018 were included, and the data were analyzed. RESULTS Among 1,424,182 Pap tests, 1,333,453 (93.6%) were interpreted as negative cytology. Although conventional Pap smears had the highest reporting rate, cervical intraepithelial neoplasia 2 and higher (CIN-2+) lesions were detected significantly more with liquid-based cytology preparations (2.1%) than the conventional method (1.4%; P

Summary Plant proteins exert effects of reducing cardio-cerebrovascular disease-related mortality partly via cholesterol-lowering, which was associated with gut microbiota. Here, we verify that there are significant differences in cholesterol levels among hamsters consuming different proteins. The decisive roles of gut microbiota in regulating host cholesterol are illustrated by the fact that the difference in serum cholesterol levels between hamsters feeding with pea protein and pork protein disappeared when treated with antibiotics. The results of cross-over intervention of pea and pork protein show that serum cholesterol levels are reversed with dietary exchange. The corresponding changes in microbiota suggest that Muribaculaceae are responsible for the inhibitory effect of pea protein on serum cholesterol level, whereas the opposite effect of pork protein is due to Erysipelotrichaceae. Moreover, pea protein supplement alters cecal metabolites including arginine/histidine pathway, primary bile acid biosynthesis, short-chain fatty acids, and other lipid-like molecules involved in cholesterol metabolism., Graphical abstract, Highlights • Gut microbiota play a decisive role in modulating cholesterol levels • Serum cholesterols are reversed by protein exchange correlating with gut bacteria change • Pea protein alters cecal metabolites involved in amino acids and cholesterol metabolism, Biological science; Endocrinology; Microbiology

Introduction We investigated the prevalence and carcinogenic risks of individual high-risk human papillomavirus (HR-HPV) in all types of cervical cytology specimens in the Shanghai population. Methods A total of 124,251 cases with cotesting of cytology and HPV genotyping between October 2017 and February 2020 were included. Results The overall HPV positive rate was 24.3%, with 22.9% for HR-HPV and 6.1% for low-risk HPV. The top five most common HR-HPV subtypes were HPV 52/16/58/53/39 in the entire studied population, and HPV 16/53/56/51/39 in women with abnormal cytology. The most prevalent subtypes in negative/LSIL, HSIL, and glandular lesions were HPV 52, 16, and 18, respectively. HPV 16, 33, 26, 18, 58, and 82 were the most common subtypes significantly associated with an increased risk for HSIL + cytology. HPV 16/18 were present in 53.6% and 66.7%, and HPV 16/18/31/33/45/52/58 were identified in 90.3% and 80.1% of HSIL and squamous cell carcinoma cytology, respectively. HPV 16/18 and HPV 16/18/31/33/45/52/58 were detected in 37.0% and 44.4% of women with cytologic interpretation of in situ and invasive adenocarcinoma. Conclusions This large-scale study identified the most common HPV subtypes in each cytology category, and the carcinogenic risks of individual HR-HPV in the studied Shanghai population. The results would provide valuable information for the development of next-generation HPV vaccines and cervical cancer screening programs for the Chinese population, and, more specifically, the Shanghai metropolitan population.

Background Obesity is an epidemic disease in the world, the treatment and prevention of obesity methods have gained great attention. Lactobacillus is the main member of probiotics, and the physiological activity of it is specific to different strains. This study systematically explored the anti-obesity effect and possible mechanism of Lactobacillus fermentum CQPC07 (LF-CQPC07), which was isolated from pickled vegetables. Results LF-CQPC07 effectively controlled the weight gain of mice caused by a high-fat diet. The results of pathological sections indicated that LF-CQPC07 alleviated hepatocyte damage and fat accumulation in adipocytes. The detection of biochemical indictors revealed that LF-CQPC07 decreased the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and increased the level of high-density lipoprotein cholesterol (HDL-C). Additionally, LF-CQPC07 caused the decrease in the amounts of inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ), and the increase in the amounts of the anti-inflammatory cytokines IL-10 and IL-4. LF-CQPC07 also decreased the amounts of alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Confirmed by qPCR, LF-CQPC07 enhanced the mRNA expression of catalase (CAT), gamma glutamylcysteine synthetase 1 (GSH1), copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and glutathione peroxidase (GSH-Px). It also increased the mRNA expression levels of carnitine palmitoyltransferase 1 (CPT1), peroxisome proliferator-activated receptor alpha (PPAR-α), lipoprotein lipase (LPL), and cholesterol 7 alpha hydroxylase (CYP7A1), and decreased that of PPAR-γ and CCAAT/enhancer binding protein alpha (C/EBP-α) in the liver of mice. Conclusion This research confirmed that LF-CQPC07 is capable of ameliorating obesity, improving hyperlipemia, and alleviating chronic low-grade inflammation and liver injury accompanied with obesity. Its mechanism may be the regulation of antioxidant capacity and lipid metabolism. Therefore, LF-CQPC07 has enormous potential to serve as a potential probiotic for the prevention or treatment of obesity.

Lactic acid bacteria (LAB) are an important group of microorganisms in the food industry. LAB with health benefits are considered natural elements promoting consumer health. The study investigated the anti-obesity effects of Lactobacillus plantarum CQPC01 (LP-CQPC01) on high-fat diet-induced mice. Liver morphology, liver function indexes, lipid indexes, and inflammatory factors in the serum and liver were determined. Expressions of lipid metabolism-related gene were also detected by qPCR. LP-CQPC01 slowed the HFD-induced increase in body weight, decreased the organ indexes, alleviated hepatic lipid accumulation, and inhibited the increased adipose cell volume. LP-CQPC01 decreased lipid levels of serum and liver, and the contents of pro-inflammatory factors, and increased the IL-4 and IL-10 contents. LP-CQPC01 downregulated the expressions of the C/EBP-α and PPARγ mRNA and upregulated CYP7A1, CPT1, LPL, CAT, SOD1, and SOD2 mRNA. Our results indicated that LP-CQPC01 is a potential probiotic for preventing or alleviating high-energy intake-related lipid conditions. PRACTICAL APPLICATIONS: Obesity is a factor of a variety of cardiovascular diseases. Therefore, it is necessary to suppress the occurrence of fat accumulation in time. This study investigated the effect of LP-CQPC01 on lipid regulation in mice fed a high-fat diet (HFD) and clarified the mechanism of strain to alleviate obesity by enhancing the decomposition of cholesterol and detoxification of fat. LP-CQPC01 reduced fat accumulation without oxidative damage, and was confirmed by the attenuated pathological changes of liver. This research can serve as a significant reference for future research, prevention, and treatment of high-energy intake-related lipid conditions, and the development of functional foods with anti-obesity activity.

Probiotics are regard as safety approaches for preventing and treating some chronic diseases. This study investigated the regulating effect of Lactobacillus plantarum CQPC03 (LP-CQPC03) on lipid metabolism in high-fat diet (HFD)-induced obesity in mice. The results showed that administration of LP-CQPC03 at a concentration of 1.0 × 109 CFU/kg body weight inhibits HFD-induced obesity and improves lipid metabolism in the liver and serum. LP-CQPC03 intervention attenuated obesity-induced hepatic tissue damage, led decreases in hepatic triglyceride (42.02 mmol/gprot), total cholesterol (3.85 mmol/gprot), and LDL-C (1.03 mmol/gprot), and an increase in HDL-C (1.07 mmol/gprot). The same tendencies were observed in serum of HFD-fed mice. LP-CQPC03 intervention led a decrease in serum levels of aspartic transaminase, alanine transaminase, and alkaline phosphatase. LP-CQPC03 alleviated inflammation by increasing the level of interleukin (IL)-4 and IL-10, and decreasing the levels of pro-inflammatory factors, including IL-6, IL-1β, tumor necrosis factor-α, and interferon-γ. LP-CQPC03 also increased activities of SOD and GSH-Px in liver significantly and dropped the hepatic malondialdehyde (MDA) level from 3.39 nmol/gprot to 1.90 nmol/gprot. RT-qPCR results showed that the lipid metabolism-improving effect of LP-CQPC03 was performed by upregulating the expression of carnitine palmitoyltransferase 1, lipoprotein lipase, catalase, and superoxide dismutase 1. This study indicates that L. plantarum CQPC03 might be a potential probiotic that can help mitigate the adverse effects of excessive lipids on the liver, and prevent or alleviate high-energy intake-related obesity. PRACTICAL APPLICATIONS: Intaking high-energy foods is a potential risk of lipid metabolic disorder. Therefore, it is necessary to seek an effective and safe approach for preventing the obesity-related disease. This study found that LP-CQPC03 limited the rate of increase in body weight of mice fed on HFD, maintained normal hepatic tissue morphology, and exhibited a strong regulating effect on lipid metabolism. And the threshold concentration of LP-CQPC03 for the lipid-lowering effect was 1.0 × 109 CFU/kg body weight. Therefore, LP-CQPC03 is a potential probiotic for preventing or alleviating high-energy intake-related obesity.

Probiotics are functional foods that can effectively regulate lipid reduction and maintain body health. In this study, a strain of Lactobacillus fermentum CQPC04 (LF-CQPC04) isolated from traditional naturally fermented vegetables (Sichuan pickles) was studied, and its effects on lipid reduction in mice, as well as its mechanism of action, were observed. The results of this experiment show that LF-CQPC04 can reduce the abnormal weight gain and abnormal visceral index of mice caused by a high-fat diet. LF-CQPC04 can decrease TG (triglycerides), TC (total cholesterol), LDL-c (low-density lipoprotein cholesterol), AST (aspartate transaminase), ALT (alanine aminotransferase), and AKP (alkaline phosphatase) levels and increase HDL-c (high-density lipoprotein cholesterol) levels in the serum of high-fat mice. LF-CQPC04 can also decrease the levels of inflammatory cytokines, such as IL-6 (interleukin-6), IL-1β (interleukin-1 beta), TNF-α (tumor necrosis factor alpha), and IFN-γ (interferon gamma), and increase IL-4 and IL-10 levels in the serum of high-fat mice. The results of RT-qPCR (real-time quantitative polymerase chain reaction) and western blot experiments show that LF-CQPC04 can also down-regulate the expression of PPAR-γ (peroxisome proliferator-activated receptor gamma), C/EBP-α (CCAAT/enhances binding protein alpha) mRNA, and protein in the liver tissue of high-fat mice, while up-regulating the expression of Cu/Zn-SOD (copper/zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), CAT (catalase), CYP7A1 (cholesterol 7 alpha hydroxylase), PPAR-α (peroxisome proliferator-activated receptor alpha), CPT1 (carnitine palmitoyl transferase 1), LPL (lipoprotein lipase), and ABCA1 (ATP-binding cassette transporter A1). Moreover, LF-CQPC04 shows stronger effects in regulating lipid reduction in mice than L-carnitine and commercial LB (Lactobacillus delbrueckii subsp. Bulgaricus) bacteria. LF-CQPC04 is beneficial for lipid reduction in animals and has good probiotic potential.

Background The US American Society of Colposcopy and Cervical Pathology guidelines for cervical cancer screening have been largely adopted worldwide. Pooled high-risk human papillomavirus (hrHPV) testing has been routinely used to risk-stratify women who have atypical squamous cells of undetermined significance (ASC-US) cytology. However, it has been reported that there are distinguished differences in the distribution of hrHPV genotypes between the Chinese and American populations. Methods The objective of this study was to analyze the age-stratified reporting rates, hrHPV-positive rates, and genotyping by different cytology preparation methods and hrHPV testing assays, along with the immediate histopathologic correlation of ASC-US cytology, in the Chinese population. Results The ASC-US reporting rate of 1,597,136 Papanicolaou (Pap) tests was 4.2%, and the overall hrHPV-positive rate was 48.7% in the ASC-US cases. In total, 25,338 women with ASC-US Pap tests had immediate histologic follow-up, and the detection rate for cervical intraepithelial neoplasia 2 and higher lesions (CIN2+) was 7.1%, including 0.6% carcinomas. Among the women who underwent hrHPV testing, CIN2+ lesions were identified in 657 of 6154 (10.7%) who had hrHPV-positive results and in only 1.5% those who had hrHPV-negative results. Further genotyping analysis revealed that HPV types 16 and/or 18 were commonly identified genotypes among the Chinese women who had ASC-US cytology. Conclusions This large-scale study demonstrated that the hrHPV-positive rate, the CIN2+ detection rate, and the distribution of hrHPV genotypes in Chinese women with ASC-US cytology were essentially consistent with those from the American population, further supporting that the current and newly released 2019 American Society of Colposcopy and Cervical Pathology guidelines should be applicable to the Chinese population.

In this study, the effect of lotus leaf flavonoids (LLF) on carbon tetrachloride (CCl4)-induced liver injury in mice was studied. CCl4 was injected intraperitoneally to induce liver injury in Kunming mice. Mice were treated with LLF by gavage, and the mRNA expression levels in serum and liver were detected. Compared with the model group, LLF significantly reduced the liver index and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) levels in mice with CCl4-induced liver injury. Pathological observation showed that LLF effectively reduced morphological incompleteness and hepatocyte necrosis in CCl4-treated liver tissue. The result of quantitative polymerase chain reaction (qPCR) indicated that LLF significantly up-regulated the mRNA expression levels of copper/zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), and catalase (CAT) and down- regulated the expression levels of tumor necrosis factor-alpha (TNF-&alpha, ), nuclear factor kappa B (NF-&kappa, B), and interleukin-1&beta, (IL-1&beta, ) (p &lt, 0.05). Thus, LLF is an active ingredient that ameliorates liver injury, and it has good application prospect.

BACKGROUND Cervical cancer screening in China is largely limited to occasional opportunistic screening in urban centers. The current study reports histopathologic follow-up and human papillomavirus (HPV) results in women with high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) tests reported at the largest academic women's hospital in China and compares these findings with those of published Western studies among frequently screened women. METHODS A retrospective cohort study documented HSIL Pap tests, patient age, HPV results, and histopathologic follow-up from 2011 through 2015 in the Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai, China. Of 886,122 Pap test results, 4269 (0.48%) reported HSIL. Histopathologic follow-up was available for 2351 cases and HPV results were available for 2092 cases. RESULTS HSIL reporting rates increased with patient age from 0.16% at age

Objectives Recently, three large Chinese cohort studies showed that 7.5% to 15.5% of patients with cervical carcinoma had negative high-risk human papillomavirus (hrHPV) test results on prior cytology specimens. These studies raise the question as to whether these negative hrHPV results represent truly hrHPV-negative carcinomas or false-negative hrHPV test results due to limitations in the testing of cytology specimens. This is increasingly an important question with increasing push to use hrHPV testing alone to screen for cervical cancer. Methods We investigated the hrHPV status on the surgical specimens from these same patients with cervical carcinoma using three polymerase chain reaction methods and a linear assay genotyping method. Results A variety of HPV genotypes were detected in 28 (45.9%) of 61 cases, all belonging to carcinogenic or possibly carcinogenic categories. HPV 16 was the most common genotype detected in positive cases (66.7%). HPV was detected in 25 (50%) of 50 squamous cell carcinomas and two (66.7%) of three adenosquamous carcinomas and only one (12.5%) of eight endocervical adenocarcinomas. Conclusions Our findings demonstrate that negative hrHPV testing on cervicovaginal cytology specimens in women later diagnosed with cervical carcinoma can be explained by the occurrence of truly HPV-negative carcinomas in more than half of patients. These results should be considered in the development of future cervical cancer screening guidelines.

Introduction Cervical cancer rates in China remain high, with only limited opportunistic screening in urban centers and large mostly unscreened rural areas. Cervical cytology practices in China have been changing over the last decade with introduction of The Bethesda System reporting terminology, liquid-based cytology (LBC), and programs for cervical cytology screening of underserved rural populations. An effort was undertaken for the first time to collect nationwide data on cervical cytology laboratory practices in China, a possible first step toward increased standardization and potential development of nationwide cytology quality benchmarks. Materials and methods Data on cervical cytology practices from 1572 laboratories operating in 26 nationwide Provisional Level Administrative Divisions was collected in an online survey approved through the Obstetrics and Gynecology Hospital of Fudan University in Shanghai. Results Over 90% of cervical cytology laboratories in China now solely use Bethesda System reporting terminology. LBC is now the most commonly utilized form of cervical cytology, with lower-cost Chinese-manufactured LBC formulations used in almost 70% of laboratories. Nationwide, significantly higher abnormal cytology rates were reported with LBC than with the conventional Papanicolaou smear (CPS); however, the CPS remains a useful low-cost alternative as China strives to extend cervical screening to large underserved rural areas. Conclusions Abnormal cytology rates were not significantly different when different levels of hospitals were compared. The survey identified nationwide opportunities for cytology quality improvement, including low rates of reporting of unsatisfactory cases and low rates for atypical glandular cells.

This study mainly investigated the influences of Lactobacillus plantarum CQPC05 (CQPC05) isolated from pickled vegetables on mouse constipation caused by activated carbon water. We used 16S rDNA technology to identify the microorganism, and activated carbon to establish a mouse constipation model. After the mice received L. plantarum (109 CFU/mL) by gavage, small intestine tissue sections were collected. The serum indices and small intestine-related mRNA expression were obtained. A strain of L. plantarum was identified, and named CQPC05. The body weight and activated carbon progradation rate in the mice of the CQPC05 treatment groups were significantly higher than those in the control group, and the excretion time of the first tarry stool was earlier than that of the control group. The results of serum indices indicated that serum gastrin (Gas), endothelin (ET), and acetylcholinesterase (AchE) levels in the CQPC05 treatment groups were significantly higher than those in the control group, while the somatostatin (SS) level was significantly lower. Compared to the constipation control group, the result of q-PCR demonstrated that CQPC05 could up-regulate the mRNA expression of c-Kit (stem cell factor receptor), SCF (stem cell factor), and GDNF (glial cell-derived neurotrophic factor) genes, and down-regulate the expression of TRPV1 (transient receptor potential cation channel subfamily V member 1) and iNOS (inducible nitric oxide synthase). In conclusion, L. plantarum CQPC05 can effectively alleviate constipation, and has good probiotic potential and application value.

Wushan Shencha (Malus doumeri leaf) is a unique tea‐like drink. Herein, the effect of flavonoids from Wushan Shencha (FWSSC) on carbon tetrachloride‐induced liver injury was studied. The serum and liver tissues of experimental mice were analyzed by kits, a slice technique, and qPCR assay. The liver index is a calculated liver‐to‐body weight ratio, and the experimental results showed that FWSSC reduced the liver index of the model group with liver injury, which was the highest. Sections stained with H&E showed that FWSSC reduced stem cell necrosis caused by liver injury. FWSSC reduced the serum levels of AST, ALT, TG, and TC, as well as the levels of IL‐6, TNF‐α, and IFN‐γ cytokines in the serum of mice with liver injury. Liver biochemical tests also showed that FWSSC increased the SOD activity and decreased TC, TG, and MPO levels in mice with liver injury. It was found that FWSSC upregulated the expression of Cu/Zn‐SOD, Mn‐SOD, CAT, and IκB‐α, and downregulated the expression of NF‐κB, COX‐2, TNF‐α, and IL‐1β in the liver tissue of mice with liver injury by detecting the expression of mRNA in liver tissue. It is concluded that FWSSC is an active substance with hepatoprotective effects. The activity of FWSSC increased with increasing concentration, and the hepatoprotective effect of FWSSC at 100 mg/kg concentration was stronger than that of silymarin.

BACKGROUND Cervical cancer remains a major health problem in China. To provide baseline data for establishing the appropriate screening strategy, the authors investigated the histopathologic follow-up and human papillomavirus (HPV) testing results of low-grade squamous intraepithelial lesion (LSIL) cytology in the Chinese Largest Women Hospital. METHODS Women with LSIL cytology, human papillomavirus (HPV) testing, and immediate histopathologic follow-up between 2011 and 2016 were analyzed. RESULTS The frequency of LSIL among 1,095,022 Papanicolaou (Pap) tests was 1.4%, and was significantly higher in cases using liquid-based cytology (LBC; 1.5%-1.6%) compared with conventional Pap smears (CPS; 0.5%). The CPS method had performance for predicting cervical intraepithelial neoplasia (CIN) that was comparable to that of LBC (75% vs 69.1% and 71.9%). Among 8079 LSIL cases with an immediate histopathologic diagnosis, CIN-2/3 or higher (CIN-2/3+) was found in 11.9% of cases and carcinoma in 0.3% of cases. A total of 158 patients (15.7%) with HPV-positive LSIL had a diagnosis of CIN-2/3 compared with 18 patients (5.5%) with HPV-negative LSIL. In postmenopausal women with LSIL cytology, the detection rate for CIN-2/3 in HPV-negative patients was significant lower than that in HPV-positive patients. Furthermore, HPV type 16 (HPV-16) was the most common genotype noted in patients with CIN-2+ lesions, whereas HPV-18 was the most common in patients with CIN-1. CONCLUSIONS Although its reporting rate is lower than that of LBC, CPS is useful due to its low cost and comparable predictive value. HPV testing is helpful for stratifying postmenopausal women with LSIL into lower and higher risk groups. HPV-16 is the most commonly identified genotype in CIN-2+ lesions diagnosed in Chinese women with LSIL cytology, whereas HPV-18 is the most commonly identified genotype in patients with CIN-1 lesions.

// Yiqin Wang 1 , Xianrong Zhou 1 , Midie Xu 2, 3, 4, 5 , Weiwei Weng 2, 3, 4, 5 , Qiongyan Zhang 2, 3, 4, 5 , Yusi Yang 2, 3, 4, 5 , Ping Wei 2, 4, 6 , Xiang Du 2, 3, 4, 5 1 Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200044, China 2 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China 3 Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China 4 Institute of Pathology, Fudan University, Shanghai 200032, China 5 Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China 6 Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China Correspondence to: Ping Wei, e-mail: ripplepz@gmail.com Xiang Du, e-mail: dx2008cn@163.com Keywords: OTUB1, FOXM1, ovarian carcinoma, ubiquitination, deubiquitination Received: August 12, 2015 Accepted: April 22, 2016 Published: May 4, 2016 ABSTRACT Ubiquitination is essential for regulation of cell physiology, protein stability, and signal transduction [ 1 ]. Its dysregulation is an important factor in many diseases, including cancer. We explored the potential OTUB1-catalyzed deubiquitination of FOXM1, a transcription factor linked to carcinogenesis, and the biological consequence of that interaction in ovarian cancer. We found that FOXM1 is ubiquitinated by multiple polyUb chains and targeted for proteosomal degradation in a reaction dependent on its ubiquitination-required KEN box. Additionally, the OTUB1 N-terminus and catalytic triad bind to FOXM1, specifically catalyzing cleavage of the K48-specific ubiquitin linkage from FOXM1. Moreover, OTUB1-FOXM1 interaction drives tumor progression and OTUB1 expression predicts a poor prognosis in ovarian cancer. Our study suggests that inhibiting OTUB1-FOXM1 interaction is a potential new avenue for ovarian cancer therapy.

Objective This study aimed to identify the prognostic factors for primary fallopian tube carcinoma. Methods A retrospective analysis was conducted of the patients treated with primary surgery and adjuvant chemotherapy at the Obstetrics and Gynecology Hospital of Fudan University from February 2003 to December 2010. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results Included in this study were 101 patients with a median follow-up of 64 months and a mean age of 57 years. Latzko triad symptom of abdominal pain, vaginal bleeding or discharge, and palpable pelvic mass was reported in 14 patients, and elevated CA 125 (≥35 U/mL) was found in 63. Four patients were classified as grade 1, 31 were grade 2, and 66 were grade 3. The distribution of International Federation of Gynecology and Obstetrics stage was 33 at stage I, 28 at stage II, 39 at stage III, and 1 at stage IV. Ninety patients underwent optimal tumor debulking in which residual tumor was no larger than 1 cm, and 67 patients received no fewer than 6 cycles of postoperative chemotherapy with paclitaxel and carboplatin (TP)–based regimen. Recurrence occurred in 44 patients after a median of 20 months (range, 1–72 months). The 5-year overall survival rate was 67.7%, and the 5-year disease-free survival was 57.4%. Multivariate analysis revealed that International Federation of Gynecology and Obstetrics stage (I–II) [hazard ratio (HR), 2.670; 95% confidence interval (CI), 1.316–5.418; P = 0.007 vs HR, 2.716; 95% CI, 1.416–5.211; P = 0.003], pelvic lymphadenectomy (HR, 0.274; 95% CI, 0.136–0.555; P Conclusions Preoperative diagnosis of fallopian tube carcinoma is difficult due to the silent course of this neoplasm. Comprehensive surgical staging including pelvic lymphadenectomy followed by adequate cycles of chemotherapy is an important strategy to improve patients’ prognosis.

Objective: The Obstetrics and Gynecology Hospital of Fudan University (OGHFU) in Shanghai is the largest academic women's hospital in China. Between 2009 and 2014, the use of liquid-based cytology (LBC) significantly increased while gradually adopting the Bethesda System (TBS), and in 2012 local regulations mandated that pathologists replace technicians to sign out Pap tests. Design: A retrospective OGHFU database search documented all Pap test reports between 2009 and 2014 by specimen type, either LBC or conventional Pap smears (CPS), and final reporting category. A total of 1,224,785 Pap reports were analyzed to document variations in Pap test reporting during a period of major change in cervical screening in China. Results: LBC gradually replaced CPS, which declined from over 65% of Pap tests in 2010 to 6.4% in 2014. Of 514,811 Pap reports using the traditional class system, class I (negative) reports accounted for 98.3% of results. With the introduction of TBS reporting, pathologist reviews and substantial replacement of CPS by LBC, the laboratory abnormal Pap test rate increased significantly to almost 5%. Conclusions: Changes in cervical cytology reporting between 2009 and 2014 in China's largest academic women's hospital reflected both increased use of LBC and the introduction of pathologist TBS reporting. Abnormality rates increased significantly and fell within CAP benchmark ranges.

The ectopic endometrial tissues lining the lumen of the fallopian tubes are currently defined as either "endometrial colonization" or "endometriosis" on the basis of their location within or beyond the isthmic portion of the fallopian tubes. The underlying etiology is unclear. The goal of this study was to define the fallopian endometrial lesions pathogenetically rather than anatomically. We investigated 39 cases of the ectopic endometrial tissues within the fallopian tubes, most of which exceeded the isthmus. Immunohistochemical analysis was performed to evaluate the expression of Cox-2, NF-κB, and VEGF, which are specifically expressed by classic endometriosis. Other clinicopathologic parameters were also recorded. The results indicated that the lesions that were confined to the mucosa might differ from those observed in the muscular or serosal layers, which showed significantly less surrounding inflammatory reaction and less concurrent salpingitis and other endometriotic lesions. The expression of Cox-2, NF-κB, and VEGF of the ectopic endometrial stromal cells tended to increase in the progression from the inner to the outer part of the tubes with significance. The expression of NF-κB and VEGF correlates with the microscopic findings of inflammation. Sterilization by tubal ligation exhibited a unique pattern of distribution. Except in those patients with tubal ligation, considering the different expression patterns observed in the tubal ectopic endometrial lesions, the mucosal type should be diagnosed as "endometrial colonization" wherever the lesion occurs. The others should be diagnosed as "endometriosis" to reveal the etiology identical to typical endometriotic lesions.

Sichuan pickle is a traditional fermented food in China which is produced by the spontaneous fermentation of Chinese cabbage. In this study, the anti-obesity effects of a new lactic acid bacterium (Lactobacillus fermentum CQPC05, LF-CQPC05) isolated from Sichuan pickles were assessed in vivo. An obese animal model was established in mice by inducing obesity with high-fat diet. Both serum and tissues were collected from the mice, and then subjected to qPCR and Western blot analyses. The results showed that LF-CQPC05 could decrease the values of hepatosomatic, epididymal fat, and perirenal fat indices that were induced by a high-fat diet in mice. Moreover, LF-CQPC05 reduced the levels of alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), and increased the level of high-density lipoprotein cholesterol (HDL-C) in both serum samples and liver tissues of obese mice fed with a high-fat diet. Pathological observations demonstrated that LF-CQPC05 could alleviate the obesity-induced pathological changes in the liver tissue of mice, and reduce the degree of adipocyte enlargement. The results of qPCR and Western blot analyses further indicated that LF-CQPC05 upregulated the mRNA and protein expression levels of lipoprotein lipase (LPL), PPAR-&alpha, peroxisome proliferator-activated receptor-alpha (PPAR-&alpha, ), (cholesterol 7 alpha-hydroxylase) CYP7A1, and carnitine palmitoyltransferase 1 (CPT1A), and downregulated the expression levels of peroxisome proliferator-activated receptor-gamma (PPAR-&gamma, ) and CCAAT enhancer-binding protein alpha (C/EBP-&alpha, ) in both liver tissue and epididymal adipose tissue. Taken altogether, this study reveals that LF-CQPC05 can effectively inhibit high-fat diet-induced obesity. Its anti-obesity effect is comparable to that of l-carnitine, and is superior to that of Lactobacillus delbrueckii subsp. bulgaricus, a common strain used in the dairy industry. Therefore, LF-CQPC05 is a high-quality microbial strain with probiotic potential.

Aims: The aim of this study was to determine the value of morphometric features in distinguishing mild and moderate atypia and predicting the recurrence of World Health Organization 2003-defined endometrial stromal sarcoma and highly malignant undifferentiated endometrial sarcoma. Methods and results: Nuclear and cytological size, shape and arrangement were morphometrically evaluated in 41 cases with consensus no/mild (n = 38) or moderate (n = 3) atypia. None of the cases showed necrosis. The prognostic value of these features in predicting recurrence was also assessed. Seven features differed. The mean and standard deviation of the nuclear volume and the distance between the nuclei were the best discriminators between the no/mild and moderate atypia, with the maximum of the nuclear volume being a practically and rapidly evaluable alternative. With the use of these features, all mild and moderate atypias were correctly classified. Seven cases recurred. The distance between the nuclei and the percentage of nuclei with one neighbour (assessed with morphometric minimum spanning tree analysis) predicted recurrence. Conclusions: In invasive endometrial stromal tumours, morphometric features are useful diagnostic support tools for distinguishing mild from moderate atypia and predicting recurrence.

ObjectiveBefore 2003, invasive endometrial stromal sarcomas (ESS) were classified into 2 categories, low-grade and high-grade ESS, according to the mitotic index. In 2003, the World Health Organization changed the definition and the diagnostic criteria. Before 2003, 20% to 35% low-grade ESS recurred, but WHO 2003–defined low-grade ESS has 10 years’ recurrence rates of less than 10%. With so few recurrences, the balance between treatment guaranteeing cure and overtreatment (“not too little” or “too much”) becomes increasingly important. However, primary treatment practices range from limited surgery only to extensive surgery combined with adjuvant chemotherapy and radiotherapy. We focused on the primary treatment of early-stage WHO 2003–defined low-grade ESS.MethodsWe evaluated the effect of different therapeutic strategies in 57 patients with International Federation of Gynecology and Obstetrics 2009 stages I to II expert-reviewed WHO 2003–defined low-grade ESS treated at a single institution between 1992 and 2007.ResultsThe patients’ median age was 43 years (range, 19–63 years). After 68 months’ median follow-up (range, 17–140 months), recurrence and mortality rates were 9% and 2%, respectively. The patients with WHO 2003–defined low-grade ESS with ovary-preserving primary surgery had a much higher recurrence rate (75%) than those without (2%; P < 0.0001). Lymphadenectomy, radical abdominal hysterectomy, and omentectomy did not influence survival. Ten patients refused chemotherapy. With univariate analysis, multiple-agent chemotherapy improved the prognosis (P = 0.02) With multivariate analysis, only ovary preservation-or-not surgery had independent prognostic value.ConclusionsIn International Federation of Gynecology and Obstetrics 2009 stage I to stage II WHO 2003–defined low-grade ESS, total abdominal hysterectomy with bilateral salpingo-oophorectomy is sufficient surgery, but ovary-preserving primary surgery increases the risk of recurrence. More extensive surgical procedures than total abdominal hysterectomy with bilateral salpingo-oophorectomy do not improve prognosis in early-stage WHO 2003–defined low-grade ESS. Chemotherapy may improve progression-free survival in early-stage low-grade ESS, but a large sample size is needed to confirm this.

Aims: Endometrial stromal sarcoma (ESS) has traditionally been divided into low and high grade, but the World Health Organization (WHO, 2003) has changed the definition. Since 2003, many studies have used the old criteria, and few have focused on WHO 2003-defined ESS low grade (ESS-LG). The aim of this study was to investigate prognosticators in ESS-LG. Methods and results: We reviewed the WHO 2003 diagnostic criteria in 91 tumours (previously classified as ESS low and high grade). There were 68 cases of ESS-LG and 23 of undifferentiated endometrial sarcoma (UES). In the ESS-LG cases, the prognostic value of clinicopathological variables was studied. With a median follow-up of 79 months (range: 20–474 months), the recurrence and death rates were 5/68 (7%) and 1/68 (1.5%) in the ESS-LG cases. Ovarian preservation or no ovarian preservation (P 3, P = 0.005, HR 8.6) had independent prognostic value. Other frequently used MAI thresholds – age, tumour diameter, and vessel invasion – were not prognostic. Among patients without ovarian preservation (n = 61), none of 53 with MAI 0–3 suffered recurrence, contrasting with two of eight (25%) of those with MAI >3 (P = 0.003); one of these two recurrence patients died (P = 0.02). Among patients with ovarian preservation (n = 7), three (43%) suffered recurrence but none died, and MAI had no additional prognostic value. Conclusions: In ESS-LG, ovarian preservation and MAI >3 are associated with increased risk of recurrence.

Aim: To compare the clinical outcomes and associated costs between laparoscopic and abdominal surgery for patients with endometrioid endometrial cancer. Methods: From 2003 to 2008, 115 patients who underwent laparoscopically-assisted surgery for endometrioid endometrial cancers were enrolled in this retrospective study. Another 123 patients who had abdominal surgery for the same histological type of endometrial cancer were included as the control group. The clinico-pathological variables, surgical outcome, costs, death and case recurrence of the two groups were compared. Results: There was no difference in the patients' age, body mass index, FIGO stage, histological grade or surgical types between the two groups. The patients in the laparoscopy group had less blood loss (P = 0.010), a shorter hospital stay (P

There is evidence to suggest that follicle-stimulating hormone (FSH) can facilitate the neovascularization of ovarian cancers by increasing vascular endothelial growth factor (VEGF) expression in cancer cells, although the underlying molecular mechanism of this process is not well known. Therefore, we investigated the effect of FSH on VEGF expression in the ovarian cancer cell lines SKOV-3 and ES-2. Treatment with FSH significantly increased VEGF expression in a dose- and time-dependent manner. In addition, FSH treatment enhanced the expression of survivin and hypoxia-inducible factor-1 (HIF-1alpha). Knockdown of survivin or HIF-1alpha suppressed VEGF expression, but only knockdown of survivin inhibited FSH-stimulated VEGF expression. Pretreatment with LY294002, a phosphoinositide 3-kinase (PI3K)/AKT inhibitor, neutralized the enhanced expression of survivin induced by FSH, but treatment with U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, had no such effect. We further showed that ovarian serous cystadenocarcinoma samples had much higher incidence of positive AKT and phosphorylated AKT (pAKT) protein staining than did benign ovarian cystadenoma samples (p < 0.01). The 5-year survival rate was only about 15% in patients with ovarian serous cystadenocarcinoma who had AKT and pAKT expression, whereas it was about 80% in those who did not have AKT or pAKT expression. Taken together, these results indicate that FSH increases the expression of VEGF by upregulating the expression of survivin, which is activated by the PI3K/AKT signaling pathway. Understanding the role of the PI3K/AKT pathway in FSH-stimulated expression of survivin and VEGF will be beneficial for evaluating the prognosis for patients with ovarian serous cystadenocarcinoma and for pursuing effective treatment against this disease.

Background In 5–20 % of patients with cervical high-grade squamous intraepithelial lesion (HSIL), a positive margin after the loop electrosurgical excision procedure (LEEP) is associated with persistence/recurrence, but the prognostic value of other clinico-pathological factors is less clear. Methods Among 4336 patients with HSIL who underwent an initial LEEP, 275 (6 %) had HSIL-positive margins, 37 of whom were lost to follow-up. We evaluated the remaining 238 patients. Persistence/recurrence was defined as histopathological HSIL during follow-up. Results The age of the patients ranged from 21 to 69 years (median: 40). The median follow-up period was 25 months (range: 6–43). Of the 238 patients, 211 (88.7 %) patients remained free of persistence/recurrence, while 27 (11.3 %) experienced persistence/recurrence. According to a univariate analysis, age (P = 0.03) and maximum specimen diameter (P = 0.043) were associated with persistence/recurrence, but number/location of involved margin sections and the pathology of the endocervical curettage were not (P > 0.10). The relative risk of the subjects (greater than or equal to 35 years ages) was 4.6 times of the subject less than 35 years, the difference was statistically significant (14 % vs. 3 %, P

The aim of the present study is to investigate the hypocholesterolemic effects of dietary hull-less barley β-glucan (HBG) on cholesterol metabolism in hamsters which were fed a hypercholesterolemic diet. The hamsters were divided into 3 groups and fed experimental diets, containing 5‰ HBG or 5‰ oat β-glucan (OG), for 30days. The HBG, as well as OG, lowered the concentration of plasma LDL-cholesterol significantly. The excretion of total lipids and cholesterol in feces were increased in HBG and OG groups compared with the control group. The activity of 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase in liver was reduced significantly in the HBG group compared with the control and OG groups. The activity of cholesterol 7-α hydroxylase (CYP7A1) in the liver, in the HBG and OG groups, was significantly increased compared with the control group. The concentrations of acetate, propionate and total short chain fatty acids (SCFAs) were not significantly different between the HBG and control groups. These results indicate that dietary HBG reduces the concentration of plasma LDL cholesterol by promoting the excretion of fecal lipids, and regulating the activities of HMG-CoA reductase and CYP7A1 in hypercholesterolemic hamsters.

The World Health Organization (WHO 2003) recognizes 3 endometrial stromal neoplasms: noninvasive endometrial stromal nodule and the 2 invasive neoplasms, endometrial stromal sarcoma (ESS), low grade and undifferentiated endometrial sarcoma (UES). It is important to note that the WHO 2003 does not define moderate atypia (an important differentiating diagnostic criterion for ESS, low grade and UES), nor does it discuss its significance. Moreover, studies on reproducibility and additional prognostic value of other diagnostic features in large are lacking. Using strict definitions, we analyzed the agreement between routine and expert-review necrosis and nuclear atypia in 91 invasive endometrial stromal neoplasias (IESN). The overall 5-year and 10-year recurrence-free survival rate estimates of the 91 IESN patients were 82% and 75%, respectively. Necrosis was well reproducible, and nuclear atypia was reasonably well reproducible. The 10-year recurrence-free survival rates for necrosis absent/inconspicuous versus prominent were 89% and 45% (P

Human homeobox gene (HOX) A10 is a homeobox allotype gene of the HOXA family in the HOX family. Human homeobox gene A10 may play an important role in cancer development. However, the role of HOXA10 in the carcinogenesis of ovarian clear cell adenocarcinoma (OCCA) has not been established. We have evaluated the prognostic significance of HOXA10 expression for human OCCA and the effects of HOXA10 on proliferation, motility, and invasion of OCCA cells. We found that HOXA10 was not expressed in normal ovarian epithelium, ovarian endometrial cysts, and ovarian serous carcinomas, but 20 (68.9%) of the 29 OCCAs were positive for the expression of HOXA10. Human homeobox gene A10 expression was negatively correlated to the 5-year survival of OCCA patients (R = -0.442, P = 0.043). When a HOXA10 expression vector was stably transfected into a human OCCA cell line, ES-2, the proliferation rate of ES-2-HOXA10 was much higher than the vector control, the motility of ES-2-HOXA10 cells was significantly increased compared with the control (P < 0.05), and the invasion of ES-2-HOXA10 cells was also much higher than the vector control (P < 0.01 at 5 hours and 12 hours after scratching). In conclusion, HOXA10 was overexpressed in OCCA and was correlated with poor survival. HOXA10 promotes proliferation, migration, and invasion of OCCA cells. Human homeobox gene A10 could be a promising prognostic marker for OCCA.

Snail, a key inducer of epithelial-mesenchymal transition (EMT), plays an important role in cancer metastasis. To better understand the role of Snail in the metastasis of ovarian carcinoma, expression of Snail was knocked down by antisense-Snail in the highly metastatic ovarian cancer cell line HO8910PM. Gene array analysis revealed that blocking Snail expression suppressed the activity of matrix metalloproteinases (MMPs) and upregulated TIMP3, an MMP inhibitor. These findings suggest that Snail interacts with MMP during tumor invasion and metastasis. In addition, we examined the role of Snail in an ovarian cancer orthotopic model by using the antisense-Snail HO8910PM cell line. We found that the size of primary ovarian cancer tumor and the number of metastatic lesions were significantly reduced when Snail was knocked down. Confirming our initial findings, the activity of MMP2 was greatly inhibited in tumors from antisense-Snail cells. Furthermore, immunohistochemical analysis on ovarian cancer progression tissue array demonstrated that the expression of Snail was significantly higher in metastatic lesions, and Snail expression correlated with the stage of ovarian cancer. Interestingly, in early-stage tumors, Snail was localized in both the cytoplasm and nucleus. In late stage and metastatic lesions, the level of Snail was elevated, and Snail was localized to the nucleus. The expression level and nuclear localization of Snail were also inversely correlated with E-cadherin expression. Overall, our study indicates that Snail plays a critical role in tumor growth and metastasis of ovarian carcinoma through regulation of MMP activity.

Estrogen and progestin are involved in ovarian carcinogenesis. Change in nm23-H1 expression and the PIK3/AKT pathway are involved in carcinogenesis, development, invasion and metastasis of ovarian cancers. Therefore, it is critical to understand the signaling pathways that regulate hormone-induced cell migration and invasion in ovarian cancer. We investigated nm23-H1, AKT and pAKT expression by using immunohistochemical staining in ovarian clear cell adenocarcinoma, ovarian benign, borderline and malignant serous tumors and analyzed their relationship with prognostic factors. Using ES-2 and SKOV-3 ovarian cancer cell lines, we studied the modulation of estrogen and progestin on cell migration and invasion as well as their effect on AKT, pAKT and nm23-H1 expression. Furthermore, the signaling pathways were examined using pharmacological inhibitors (LY294002 and PD98059) or AKT siRNA combined with estrogen or progestin in the two cell lines. Weak nm23-H1 and high AKT and pAKT expression was observed in ovarian serous adeno-carcinoma and ovarian clear cell adenocarcinoma. Our data demonstrated that the expression of nm23-H1 was negatively correlated with tumor stage and grade and lymph node metastasis, whereas the expression of AKT/pAKT was positively correlated with these clinic factors. Estrogen up-regulated pAKT expression and reduced nm23-H1 expression, which ultimately resulted in increased cell migration and invasion. In contrast, progestin reduced pAKT expression and increased nm23-H1 expression, which inhibited cell migration. PIK3 kinase inhibitor LY294002 antagonized the effect of estrogen. On the other hand, it reinforced the effect of progestin. Our data suggest that AKT and pAKT are unfavorable prognostic factors for ovarian serous adenocarcinoma and clear cell carcinomas whereas nm23-H1 expression predicates favorable patient prognosis. Estrogen down-regulates nm23-H1 expression and promotes cell migration and invasion by activating the PIK3/AKT pathway. Progestin has an opposing effect.

An estimated 1500-3000 invasive Endometrial Stromal Sarcomas (ESS) cases annually occur worldwide. Before 2003, ESS was divided as low and high grade ESS based on mitotic activity. In 2003 the WHO changed the names, excluded mitoses and made nuclear atypia and necrosis the essential diagnostic criteria to distinguish ESS, Low Grade (ESS-LG, recurrence-free survival >90%) and Undifferentiated Endometrial Sarcoma (UES, poor prognosis). We have evaluated in WHO2003 defined ESS-LG whether proliferation biomarkers predict recurrence. Using survival analysis, the prognostic value of classical mitosis counts (Mitotic Activity Index, MAI) in haematoxyllin-eosin (H&E) sections, and immunohistochemical proliferation biomarkers (Ki-67 and PhosphoHistone-3 (PPH3)) were examined in 24 invasive endometrial stromal sarcomas. Three of 24 (12.5%) ESS-LG recurred. The MAI, PPH3 and Ki-67 were all prognostic (P = 0.001, 0.002 and 0.03). MAI values were >3 in the recurrent cases, but never exceeded 10 (the classical threshold for low and high grade). Non-recurrent cases had 0 ≤ MAI ≤ 3. PPH3 and Ki67 counts can be easier to perform than MAI and therefore helpful in the diagnosis of ESS, Low Grade. In conclusion, in this small study of WHO2003 defined ESS-LG, high levels of proliferation as measured by MAI, PPH3 and Ki-67 are predictive of recurrence. Larger studies are required to confirm these results.