Association between ultrasound BI-RADS signs and molecular typing of invasive breast cancer.

Objective: To explore the correlation between ultrasound images and molecular typing of invasive breast cancer, so as to analyze the predictive value of preoperative ultrasound for invasive breast cancer. Methods: 302 invasive breast cancer patients were enrolled in Heping Hospital affiliated to Changzhi Medical College in Shanxi, China during 2020 to 2022. All patients accepted ultrasonic and pathological examination, and all pathological tissues received molecular typing with immunohistochemical (IHC) staining. The relevance between different molecular typings and ultrasonic image, pathology were evaluated. Results: Univariate analysis: among the four molecular typings, there were significant differences in tumor size, shape, margin, lymph node and histological grade (P<0.05). 1. Size: Luminal A tumor was smaller (69.4%), Basal -like type tumors are mostly larger (60.9%); 2. Shape: Basal-like type is more likely to show regular shape (45.7%); 3. Margin: Luminal A and Luminal B mostly are not circumscribed (79.6%, 74.8%), Basal -like type shows circumscribed(52.2%); 4. Lymph nodes: Luminal A type tends to be normal (87.8%), Luminal B type,Her-2+ type and Basal-like type tend to be abnormal (35.6%,36.4% and 39.1%). There was no significant difference in mass orientation, echo pattern, rear echo and calcification (P>0.05). Multivariate analysis: Basal-like breast cancer mostly showed regular shape, circumscribed margin and abnormal lymph nodes (P<0.05). Conclusion: There are differences in the ultrasound manifestations of different molecular typings of breast cancer, and ultrasound features can be used as a potential imaging index to provide important information for the precise diagnosis and treatment of breast cancer.

Glucose 6 phosphatase dehydrogenase (G6PD): a novel diagnosis marker related to gastrointestinal cancers.

BACKGROUND: Glucose 6 phosphatase dehydrogenase (G6PD) is a key regulator of the pentose phosphate pathway (PPP). However, the exact role of G6PD in gastrointestinal cancers remains unclear. The purpose of this study is to explore the correlation of G6PD with clinical features, pathological stages, diagnosis and prognosis of gastrointestinal cancers, as well as uncover possible mechanisms of G6PD on mutations, immunity and signaling pathways. METHODS: G6PD mRNA expression data were downloaded from TCGA and GEO databases. Protein expression was examined by the HPA database. The correlation of G6PD expression with clinical and pathological characteristics was explored. The pROC package in R language was used to evaluate the diagnostic value of G6PD expression in gastrointestinal cancers. We accessed the correlation of disease-free survival (DFS) with G6PD online by Kaplan-Meier plotter. Univariate Cox regression and stepwise multiple Cox regression analysis were performed to determine the association between G6PD and patient's overall survival. In addition, genomic alterations, mutation profiles, immune infiltration, drug sensitivity and enrichment analysis related with G6PD were visualized. RESULTS: After a pan-cancerous genomic analysis, we found that G6PD expression was the highest in African American esophageal carcinoma (ESCA) patients (P<0.05). G6PD was correlated with age, weight, disease stage, lymph node metastasis and pathological grade. Notably, G6PD showed an excellent predictive diagnosis ability for liver hepatocellular carcinoma (LIHC) (AUC=0.949, 95% CI=0.925-0.973, P<0.001). G6PD can improve the DFS of esophageal adenocarcinoma (EAC) and pancreatic adenocarcinoma (PAAD) patients (P<0.05). Both Univariate Cox regression and stepwise multiple Cox regression analysis in R language determined that G6PD expression was closely related with LIHC (P<0.001). G6PD was found to have a high mutation rate in colon adenocarcinoma and ESCA and gene amplification in ESCA, Cholangiocarcinoma, PAAD and LIHC. Copy number of G6PD was missing in LIHC. G6PD was also related to mutation of TP53 (P<0.05). Particularly, it was positively correlated with CD276 in all gastrointestinal cancers and negatively with HERV-H LTR-associating 2 in ESCA and stomach adenocarcinoma. The abnormal expression of G6PD was related to the increase of CD4+ Th2 subsets and the decrease of CD4+ (non-regulatory) of T cells. G6PD was sensitive to FK866, Phenformin, AICAR etc., while resistant to RO-3306, CGP-082996, TGX221 etc. G6PD was found to closely interact with TALDO1, GAPDH and TP53. G6PD related biological processes included aging, nutritional response and daunorubicin metabolism, and related pathways included PPP, cytochrome P450 metabolism of exogenous substances and glutathione metabolism. CONCLUSION: G6PD is highly expressed in gastrointestinal cancers. It is a carcinogenic indicator related to prognosis and can be used as a potential diagnostic marker of gastrointestinal cancers, so as to provide new strategy for cancer treatment.

Anti-Aging Effect of Chitosan Oligosaccharide on d-Galactose-Induced Subacute Aging in Mice.

Chitosan oligosaccharide (COS), a natural polysaccharide with good antioxidant and anti-inflammatory properties, is the depolymerized product of chitosan possessing various biological activities. The present study was designed to investigate the possible anti-aging effect of COS on the aging model mouse induced by d-galactose (d-gal) and explore the underlying mechanism. In the experiment, 48 male Kunming mice (KM mice) were randomly divided into the normal group, model group, positive group, and low-medium-high dose polysaccharide groups (300, 600, 1200 mg/kg/day). The results showed that COS, by intragastric gavage after subcutaneous injection of d-gal (250 mg/kg/day) into the neck of mice consecutively for eight weeks, gradually recovered the body weight, the activity of daily living, and organ indices of mice, as well as effectively ameliorated the histological deterioration of the liver and kidney in mice triggered by d-gal. To be specific, COS obviously improved the activities of antioxidant enzymes in liver and kidney of KM mice, including catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as decreased malondialdehyde (MDA) levels when compared with those in model group mice. Furthermore, COS not only elevated the diminished levels of serum immunoglobulin G (IgG) and IgM induced by d-gal, but also significantly inhibited the d-gal-caused upregulation of serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA) and creatinine (CREA) levels as compared with those of mice in the model group. These results demonstrate that COS has an obvious anti-aging activity in d-gal-induced subacute aging mice, the mechanism of which, to some extent, is associated with enhancing the antioxidant defenses, reducing oxidative stress, and improving the immune function of aging model mice.

Pharmacokinetics and tissue distribution of docetaxel liposome mediated by a novel galactosylated cholesterol derivatives synthesized by lipase-catalyzed esterification in non-aqueous phase.

The purpose of this study is to synthesize a novel galactosylated cholesterol derivative, cholesterol-diethenyl decanedioate-lactitol (CHS-DD-LA) through lipase-catalyzed esterification in non-aqueous and to evaluate the preparation, pharmacokinetics and biodistribution of docetaxel (DOC) liposomes modified with CHS-DD-LA (G-DOC-L), which may actively gather at the liver compared with the conventional DOC liposomes (DOC-L) and commercial dosage form of DOC injection (DOC-i). A rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of the DOC concentration in plasma and tissues with Taxol as the internal standard (IS). To measure the liver-targeting effect of the G-DOC-L, relative uptake rate (Re), peak concentration ratio (Ce), targeting efficiency (Te) and relative targeting efficiency (RTe) were reduced as the evaluation parameters. The results showed that the entrapment efficiency, particle size and Zeta potential of G-DOC-L was 76.8 ± 3.5%, 95.6 nm and 27.19 mV, respectively. After i.v. administration at the dose of 2.5 mg/kg in rats, a decrease in the AUC, MRT and an increase in CL (p < 0.05) were observed in the G-DOC-L group compared with DOC-L. All these results suggested that galactose-anchored liposomes could rapidly be removed from the circulation in vivo. The tissue distribution of G-DOC-L was widely different from that of DOC-L. The Re of G-DOC-L, DOC-L on liver was 4.011, 0.102; Ce was 3.391, 0.111; Te was 55.01, 3.08, respectively, demonstrating that G-DOC-L had an excellent effect on liver-targeting, which may help to improve the therapeutic effect of hepatic diseases.

Factors associated with support for smoke-free policies among government workers in Six Chinese cities: a cross-sectional study.

BACKGROUND: A certain level of public support for smoke-free environments is a prerequisite for adoption and enforcement of policies and can be used as an indicator of readiness for legislative action. This study assessed support for comprehensive smoke-free policies in a range of settings such as hotels and colleges among government workers in China and identified factors associated with support for smoke-free policies. Understanding the extent to which government workers, a large segment of the working population in China, report a smoke-free workplace and support for smoke-free policies may be important indicators of readiness for strengthened policies given their role in formulating, implementing and enforcing regulations. METHODS: Data were from an evaluation of the Tobacco Free Cities initiative of Emory University's Global Health Institute-China Tobacco Control Partnership. Self-administered surveys were completed by 6,646 workers in 160 government agencies in six Chinese cities. Multivariate logistic regression was used to identify factors associated with support for smoke-free worksites, bars, hotels, and colleges. RESULTS: Over half (54.6%) of participants were male. A large percentage of the male workers smoked (45.9%,) whereas very few women did (1.9%). Fewer than 50% of government workers reported smoke-free policies at work, with 19.0% reporting that smoking is allowed anywhere. Support for smoke-free policies was generally very high, with the lowest levels of support for smoke-free bars (79.0%) and hotels (82.3%), higher levels of support for restaurants (90.0%) and worksites (93.0%), and above 95% support for hospitals, schools, colleges, public transportation and religious settings. Knowledge of the harmfulness of secondhand smoke was positively associated with support for smoke-free policies. Stricter worksite smoking policies were associated with support for smoke-free workplaces and bars, but not hotels and colleges. Women and nonsmokers were more supportive of smoke-free policies in general. CONCLUSION: Government workers play important roles in formulating, implementing and enforcing regulations; results suggest support for a more comprehensive approach to smoke-free environments in China among workers across a broad range of agencies.

Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in Qidong, China.

BACKGROUND/AIM: To investigate the roles of mutations in pre-S and S regions of hepatitis B virus (HBV) on the progression of hepatocellular carcinoma (HCC) in Qidong, China. METHODS: We conducted an age matched case-control study within a cohort of 2387 male HBV carriers who were recruited from August, 1996. The HBV DNA sequence in pre-S/S regions was successfully determined in 96 HCC cases and 97 control subjects. In addition, a consecutive series of samples from 11 HCC cases were employed to evaluate the pre-S deletion patterns before and after the occurrence of HCC. RESULTS: After adjustment for age, history of cigarette smoking and alcohol consumption, HBeAg positivity, pre-S deletions, pre-S2 start codon mutations, and T53C mutation were significantly associated with HCC, showing adjusted odds ratios (ORs) from 1.914 to 3.199. HCC patients also had a lower frequency of T31C mutation in pre-S2 gene, compared with control subjects (0.524; 95% CI 0.280-0.982). HBV pre-S deletions were clustered mainly in the 5' end of pre-S2 region. Multivariate analysis showed that pre-S deletions and pre-S2 start codon mutations were independent risk factors for HCC. The OR (95% CI) were 2.434 (1.063-5.573) and 3.065 (1.099-8.547), respectively. The longitudinal observation indicated that the pre-S deletion mutations were not acquired at the beginning of HBV infection, but that the mutations occurred during the long course of liver disease. CONCLUSION: Pre-S deletions and pre-S2 start codon mutations were independently associated with the development of HCC. The results also provided direct evidence that pre-S deletion mutations were not acquired from the beginning of infection but arose de novo during the progression of liver disease.

Transforming growth factor-ß signaling participates in the maintenance of the primordial follicle pool in the mouse ovary.

Physiologically, only a few primordial follicles are activated to enter the growing follicle pool each wave. Recent studies in knock-out mice show that early follicular activation depends on signaling from the tuberous sclerosis complex, the mammalian target of rapamycin complex 1 (mTORC1), phosphatase and tensin homolog deleted on chromosome 10, and phosphatidylinositol 3-kinase (PI3K) pathways. However, the manner in which these pathways are normally regulated, and whether or not TGF-ß acts on them are poorly understood. So, this study aims to identify whether or not TGF-ß acts on the process. Ovary organ culture experiments showed that the culture of 18.5 days post-coitus (dpc) ovaries with TGF-ß1 reduced the total population of oocytes and activated follicles, accelerated oocyte growth was observed in ovaries treated with TGF-ßR1 inhibitor 2-(5-chloro-2-fluorophenyl)pteridin-4-yl]pyridin-4-yl-amine (SD208) compared with control ovaries, the down-regulation of TGF-ßR1 gene expression also activated early primordial follicle oocyte growth. We further showed that there was dramatically more proliferation of granulosa cells in SD208-treated ovaries and less proliferation in TGF-ß1-treated ovaries. Western blot and morphological analyses indicated that TGF-ß signaling manipulated primordial follicle growth through tuberous sclerosis complex/mTORC1 signaling in oocytes, and the mTORC1-specific inhibitor rapamycin could partially reverse the stimulated effect of SD208 on the oocyte growth and decreased the numbers of growing follicles. In conclusion, our results suggest that TGF-ß signaling plays an important physiological role in the maintenance of the dormant pool of primordial follicles, which functions through activation of p70 S6 kinase 1 (S6K1)/ribosomal protein S6 (rpS6) signaling in mouse ovaries.

Effect of combined mutations in the enhancer II and basal core promoter of hepatitis B virus on development of hepatocellular carcinoma in Qidong, China.

AIM: To investigate the roles of mutations in enhancer II (Enh II), basal core promoter (BCP) and precore (PC) regions of hepatitis B virus (HBV) in the progression of hepatocellular carcinoma (HCC) in Qidong, China. METHODS: We conducted a case-control study within a cohort of 2387 male HBV carriers who were recruited between August and September 1996. The HBV DNA sequence was determined in 152 HCC and 131 chronic hepatitis patients. Mutation exchanges during follow up in 115 cases were compared with 108 controls with serum samples taken during a similar length of follow up. In addition, a longitudinal study was conducted in 22 cases in which serial serum samples were available before HCC. RESULTS: After adjustment for age, history of cigarette smoking and alcohol consumption, hepatitis B e-antigen positivity, T1653, V1753 and T1762/A1764 double mutations were associated with risk of HCC. Multivariate analysis showed that T1653, V1753 and T1762/A1764 double mutations were independent risk factors of HCC. Moreover, a significant biological gradient of HCC risk by number of mutations in Enh II/BCP regions was observed. Paired samples analysis indicated that the increased HCC risk for at-risk sequence mutations were attributable to the persistence of these mutations, but not a single time point mutation. The longitudinal observation demonstrated a gradual combination of mutations in Enh II/BCP regions accumulated during the development of HCC. CONCLUSION: T1653, V1753 and T1762/A1764 double mutations were independent risk factors of HCC. The effect of combined mutations in Enh II/BCP regions increased the risk and persistence of at-risk sequence mutations and was critical for HCC development.

[Detection of FasL mRNA, sFasL and their regulatory effect on T lymphocyte subsets in patients with severe acute pancreatitis].

OBJECTIVE: To investigate the levels of FasL mRNA in peripheral blood mononualear cells (PBMCs), serum soluble Fas ligand (sFasL) and their regulatory effect on T lymphocyte subsets in patients with severe acute pancreatitis (SAP). METHODS: Forty-eight patients with pancreatitis were randomly divided into two groups: 20 cases with SAP and 28 cases with mild acute pancreatitis (MAP). Twenty-eight healthy volunteers were selected as control group. The expression of FasL mRNA in PBMCs was detected by real-time quantitative PCR(qRT-PCR), and serum sFasL was measured by ELISA. T lymphocyte subsets in peripheral blood were detected by flow cytometry. RESULTS: Compared with control group and MAP group, FasL mRNA of PBMCs and serum sFasL increased significantly in SAP group (P<0.05), a little increase in MAP group, and there was no significant difference between MAP group and control group (P>0.05). The CD4(+) T cell ratio, CD4(+)/CD8(+) ratio decreased significantly in SAP group (P<0.05) vs control group and MAP group), and they were found negatively related to FasL mRNA, serum sFasL level. CONCLUSION: The SAP patients showed the significantly increased FasL mRNA of PBMCs and serum sFasL and decreased CD4(+) T-cell ratio, CD4(+)/CD8(+) ratio. FasL may mediate the apoptosis of T lymphocytes.

Combined pre-S deletion and core promoter mutations related to hepatocellular carcinoma: A nested case-control study in China.

AIM: To investigate the roles of biomedical factors, hepatitis B virus (HBV) DNA levels, genotypes, and specific viral mutation patterns on the progression of hepatocellular carcinoma (HCC) in Qidong, China. METHODS: A total of 2387 males (aged 20-65 years) who were seropositive for the hepatitis B surface antigen (HBsAg), but had not been diagnosed with HCC, were recruited to a community-based HCC screening study from August, 1996. Evaluation of virological parameters at recruitment was determined for 196 HCC patients during 10 years of follow-up and 323 controls. RESULTS: After adjustment for age at recruitment, history of cigarette smoking and alcohol consumption, alanine aminotransferase (ALT) elevation, alpha-fetoprotein (AFP) levels >20 ng/mL, hepatitis B e antigen positive, HBV DNA levels ≥4.00 log(10) copies/mL, pre-S deletion, T1653 mutation, T1762/A1764 double mutations, and T1766 and/or A1768 mutations were associated with subsequent risk of HCC. A significant biological gradient of HCC risk by HBV DNA levels from less than 2.69 log(10) copies/mL to 6.00 log(10) copies/mL or greater was observed. HBV with a complex mutation combination pattern (pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations) rather than a single mutation was associated with the development of HCC. The longitudinal observation demonstrated a gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations during the development of HCC. CONCLUSIONS: AFP levels >20 ng/mL, high HBV DNA levels, pre-S deletion, and T1762/A1764 double mutations at recruitment were independent risk factors of HCC. Combination of pre-S deletion and core promoter mutations increased the risk of HCC.

A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong, China.

AIM: To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS: One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS: In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels > or = 10(4) to < 10(5); > or = 10(5) to < 10(6); > or = 10(6) to < 10(7); > or = 10(7) copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly. CONCLUSION: The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 10(4)-10(7) range.

[Smoking prevention and control among students of middle schools in Shanghai].

OBJECTIVE: To appraise the effectiveness of a school-based smoking control program and explore the effective smoking prevention and control intervention model in middle schools. METHODS: Through two phase cluster sampling, students in grade 1 and grade 2 of two schools were assigned to intervention group and control group. Comprehensive smoking intervention was implemented in the intervention group for one year. The assessment was carried out through three phases: baseline, after intervention, and 6-month after intervention. RESULTS: After intervention, the proportion of attempt smoking rate in the recent one year decreased from 9.7% to 4.2% and the heavy passive smoking rate declined from 15.5% to 12.2%. In addition, some knowledge, attitudes and skills related to tobacco prevention among the students in the intervention group were significantly improved and most effects can be sustained at 6-month follow up survey. CONCLUSION: It is concluded that tobacco control in middle school was effective and feasible and it should be closely integrated with tobacco control in the community.

[Smoking prevention and control among elementary school students in Xuhui district, Shanghai].

OBJECTIVE: To evaluate the effectiveness of a school-based smoking prevention and control intervention program among elementary school students. METHODS: Through two phase cluster sampling, 566 pupils in grade 4 and grade 5 of two schools were assigned to intervention group and control group. One year comprehensive smoking intervention was conducted in the intervention group. The assessment was carried out through three questionnaires: pre- and post-intervention, 6-month after intervention. RESULTS: After one year intervention, pupils in the intervention group significantly improved their knowledge and attitudes related to tobacco use. The rate of attempting smoking decreased form 7.8% to 2.6% and the rate of passive smoking from 53.6% to 41.8%. The difference between the intervention and control groups was statistically significant. However, several index started to decline at 6-month follow up survey. CONCLUSION: The result demonstrated the effectiveness and feasibility of tobacco control in elementary school and the positive effect must be developed.