Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China.

The aim of this study was to investigate the frequency distribution of the cytochrome P450 (CYP450) enzymes, CYP2D6 and CYP2C19, and the form of tamoxifen metabolisation in premenopausal patients with breast cancer in the Han and Uygur ethnic groups of Xinjiang to guide rational clinical drug use. A total of 125 Han patients and 121 Uygur patients with premenopausal hormone-receptor-positive breast cancer treated at the Xinjiang Uygur Autonomous Region Cancer Hospital between 1 June 2011 and 1 December 2013 were selected. The common mutation sites in CYP450 were analysed using TaqMan® minor groove binder technology. Genetic testing was performed to determine other metabolic types of tamoxifen, and the genotypes and metabolic types were compared using a Chi-squared test. Between the Han and Uygur groups, there were significant differences in the frequencies of the CYP2D6 (*10/*10) and CYP2C19 (*1/*1) genotypes, with P-values of 0.002 and 0.015, respectively. Genotypes of CYP2D6 (*1/*1), CYP2D6 (*1/*5), CYP2D6 (*5/*5), CYP2D6 (*5/*10) and CYP2C19 (*3/*3) were expressed in the two patient groups, and the difference was not statistically significant (P > 0.05). In the Han patients, the proportions of extensive, intermediate and poor metabolisers of tamoxifen were 72, 24 and 4%, respectively, whereas those in the Uygur patients were 76.9, 17.4 and 5.7%, respectively, with no significant difference (P > 0.05). In conclusion, There were partial differences in the CYP2D6 and CYP2C19 gene polymorphisms of CYP450 between the Han and Uygur patients with premenopausal breast cancer, but there was no significant difference between the CYP2D6 and CYP2C19 phenotypes. Further research is needed to determine the relationship between the enzyme genetic differences of CYP450 and the pharmacokinetics and efficacy of tamoxifen. Although there were some differences in genotypes, these did not result in differences in the predicted tamoxifen metabolisation phenotype between the Han and Uygur patients with breast cancer. Therefore, the doses should be adjusted according to the individual genotype data.

Molecular mechanisms of cellular metabolic homeostasis in stem cells / 国际口腔科学杂志·英文版

Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.

Efficacy and safety of microwave ablation combined with systemic chemotherapy in treatment of recurrent intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Objective To investigate the efficacy and safety of microwave ablation (MWA) combined with chemotherapy versus MWA alone in the treatment of recurrent intrahepatic cholangiocarcinoma (RICC). Methods A retrospective cohort study was conducted among the patients with RICC who received MWA+chemotherapy or MWA in The Second People's Hospital of Neijiang and The Affiliated Hospital of Southwest Medical University from January 2014 to March 2021, and their clinicopathological data were collected. The independent samples t -test was used for comparison of continuous data, and the chi-square test and the Fisher's exact test were used for comparison of categorical data. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used for comparison of survival differences. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the risk factors for survival and prognosis. Results A total of 106 patients with RIC were enrolled, among whom there were 55 patients in the MWA+chemotherapy group and 51 in the MWA group. By the end of follow-up, the MWA+chemotherapy group had a median PFS of 15.0 months (95% confidence interval [ CI ]: 14.5-15.5), and the MWA group had a median PFS of 13.4 months (95% CI : 11.6-15.2), with a significant difference between the two groups ( χ 2 =9.624, P =0.002). The MWA+chemotherapy group had a median OS of 21.0 months (95% CI : 20.0-21.8), and the MWA group had a median OS of 18.0 months (95% CI : 16.3-19.7), with a significant difference between the two groups ( χ 2 =12.784, P 5 cm, time to recurrence < 1 year, and absence of systemic chemotherapy tend to have a poor prognosis.

Clinical effect of transcatheter arterial chemoembolization combined with microwave ablation versus repeat resection in treatment of recurrent hepatocellular carcinoma / 临床肝胆病杂志

Objective To investigate the clinical effect of transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) (TACE-MWA) versus repeat resection (RR) in the treatment of recurrent hepatocellular carcinoma (RHCC). Methods A total of 178 patients with RHCC who were admitted to The Second People's Hospital of Neijiang from June 2015 to September 2020 were enrolled, and according to the treatment modality, they were divided into RR group with 64 patients and TACE-MWA group with 114 patients. Baseline demographic data, liver function, and tumor conditions before treatment were recorded, and the patients were followed up to October 2021 to compare postoperative overall survival (OS) time and recurrence-free survival (RFS) time between the two groups. Subgroup analysis based on recurrence pattern (recurrence time and tumor size) was performed, and the influencing factors for prognosis were analyzed. The independent samples t -test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data; the Kaplan-Meier method was used for postoperative survival rate, the Log-rank test was used for survival difference analysis, and a multivariate Cox regression analysis was used to investigate independent risk factors for survival. Results The multivariate analysis showed that tumor diameter, alpha-fetoprotein (AFP) level, alanine aminotransferase, albumin, and time to recurrence were independent prognostic factors for OS (all P 2 years), there were significant differences between the two groups in median OS (54.0 months vs 36.0 months, χ 2 =6.171, P =0.013) and median RFS (28.0 months vs 21.0 months, χ 2 = 5.211, P =0.022). For RHCC with a tumor diameter of ≤5 cm, there was a significant difference in median OS between the two groups (33.0 months vs 27.0 months, χ 2 =6.447, P =0.011). Conclusion RR has a similar clinical effect to TACE-MWA in RHCC with early recurrence or a tumor diameter of > 5 cm, but RR should be the first choice for RHCC with late recurrence or a tumor diameter of ≤5 cm.

[Risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants].

OBJECTIVE: To explore the risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants. METHODS: A retrospective analysis was performed for 455 very preterm infants who were admitted to the neonatal intensive care unit from January 2017 to December 2019. They were divided into an intubation group (n=79) and a non-intubation group (n=376) according to whether endotracheal intubation was performed during resuscitation. The risk factors for endotracheal intubation during resuscitation were evaluated by multivariate logistic regression analysis. RESULTS: The intubation rate was 17.4% (79/455). Compared with the intubation group, the non-intubation group had significantly higher gestational age, birth weight, and rates of caesarean birth, delayed cord clamping (DCC), resuscitation quality improvement, regular use of antenatal glucocorticoids in mothers and premature rupture of membranes > 18 hours (P < 0.05), but significantly lower rates of maternal gestational diabetes mellitus, placental abruption, placenta previa or placenta previa status, and maternal thyroid dysfunction (P < 0.05). Regular use of antenatal glucocorticoids in mothers (OR=0.368, P < 0.05) and DCC (OR=0.222, P < 0.05) were protective factors against intubation during resuscitation, while younger gestational age, birth weight < 750 g, maternal gestational diabetes mellitus, and placenta previa or placenta previa status were risk factors for intubation during resuscitation (P < 0.05). CONCLUSIONS: Very preterm infants with younger gestational age, birth weight < 750 g, maternal diabetes mellitus, placenta previa or placenta previa status may have a higher risk for endotracheal intubation after birth. The regular use of antenatal glucocorticoids and DCC can reduce the risk of intubation during resuscitation in very preterm infants.

Degradation, adsorption and leaching of phenazine-1-carboxamide in agricultural soils.

Phenazines, a large group of nitrogen-containing heterocycles with promising bioactivities, can be widely used as medicines and pesticides. But phenazines also generate toxicity risks due to their non-selective DNA binding. The environmental fate of phenazines in soils is the key to assess their risks; however, hitherto, there have been very few related studies. Therefore in the present study, the degradation, adsorption and leaching behaviors of a typical natural phenazine-phenazine-1-carboxamide (PCN) in agricultural soils from three representative places in China with different physicochemical properties were, for the first time, systematically studied in laboratory simulation experiments. Our results indicated that the degradation of PCN in all the tested soils followed the first order kinetics, with half-lives ranging from 14.4 to 57.8 d under different conditions. Soil anaerobic microorganisms, organic matter content and pH conditions are important factors that regulating PCN degradation. The adsorption data of PCN were found to be well fitted using the Freundlich model, with the r2 values above 0.978. Freundlich adsorption coefficient Kf of PCN ranged from 5.75 to 12.8 [(mg/kg)/(mg/L)1/n] in soils. The retention factor Rf values ranged from 0.0833 to 0.354, which means that the mobility of PCN in the three types of soil is between immobile to moderately mobile. Our results demonstrate that PCN is easily degraded, has high adsorption affinity and low mobility in high organic matter content and clay soils, thus resulting in lower risks of contamination to groundwater systems. In contrast, it degraded slowly, has low adsorption affinity and moderately mobile in soils with low organic matter and clay content, therefore it has higher polluting potential to groundwater systems. Overall, these findings provide useful insights into the future evaluation of environmental as well as health risks of PCN.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Analysis of Chemical Constituents and Activity on Zanthoxylum nitidum Husk / 中国实验方剂学杂志

Objective:To analyze and identify the non-medicinal parts in Zanthoxylum nitidum husk by HPLC-LTQ/Orbitrap-MS, and study the antioxidant activity, in order to provide the scientific basis for further research and development of Z. nitidum. Method:Data is collected by HPLC-LTQ/Orbitrap-MS,and high-resolution MS and MS2 spectra of mass spectrogram of chromatographic peaks were analyzed and compared with the literature database. The structure of each chromatographic peak was calculated and confirmed. The anti-oxidative activity of the Z. nitidum husk was studied by DPPH scavenging free radical ability and ABTS free radical scavenging ability. Result:Twenty-five alkaloids were identified from Z. nitidum husk. The main constituents were isoquinoline alkaloids (nitidine,liriodenine,magnocurarine),pyrrolidine alkaloid (allocryptopine,oxymatrine,oxysophocarpine),quinoline alkaloid (magnoflorine,nitidine chloride),and organic amine alkaloids (γ-sanshool). Antioxygenic activity was studied by DPPH scavenging free radical ability and ABTS free radical scavenging ability. The results showed that they were within the measured concentration range, the antioxidant activity increased with the rise of the sample concentration, a good dose dependence was presented. Conclusion:In this paper,the chemical constituents and the activity Z. nitidum husk were studied. Studies have shown a variety of alkaloids, with a good antioxidant activity. This study provides a reference for further research and development of Z. nitidum.

[Association of blood lipids with childhood asthma].

OBJECTIVE: To study the association of blood lipids with the development, clinical stage, allergic condition, and pulmonary function of asthma. METHODS: A total of 56 children with asthma who attended the hospital between October 2016 and March 2017 were enrolled as the asthma group, and 46 children who underwent physical examination as the healthy control group. According to the clinical manifestations, the children with asthma were divided into acute exacerbation group (n=24) and chronic persistent group (n=32). According to the results of skin prick test (SPT) and serum IgE measurement, the children with asthma were divided into non-allergic asthma group (n=16) and allergic asthma group (n=38). Fasting blood lipid levels were measured in both asthma and control groups. Pulmonary function tests were performed for asthmatic children. RESULTS: There were no significant differences in blood lipid levels between the asthma and control groups (P>0.05). The acute exacerbation group had significantly lower serum levels of high-density lipoprotein (HDL) and total cholesterol compared with the control group and the chronic persistent group (P<0.05). The allergic asthma group had a significantly lower serum HDL level than the non-allergic asthma group (P<0.05). In asthmatic children aged 6-13 years, the ratios of the measured values to the predicted values for forced vital capacity, peak expiratory flow, and maximal expiratory flow at 50% of vital capacity had a linear regression relationship with HDL and were positively correlated with HDL (P<0.05). Forced expiratory volume in one second and maximal mid-expiratory flow had a linear regression relationship with both HDL and LDL and were positively correlated with them (P<0.05). CONCLUSIONS: Blood lipids are associated with the clinical stage, allergic condition, and lung function of childhood asthma. This indicates that blood lipids may be involved in several aspects of the pathogenesis of childhood asthma.

Clinicopathologic Factors Related to the Histological Tumor Grade of Breast Cancer in Western China: An Epidemiological Multicenter Study of 8619 Female Patients.

BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2 cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti-HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.

Ligation of the Left Hepatic Duct and Proper Hepatic Artery Following a Traffic Accident Injury.

A 32-year-old man was admitted to our hospital due to a traffic accident. Intraoperative observations revealed hemoperitoneum, splenic transection, pancreatic tail contusion, comminuted injury in the porta hepatis, rupture in the left hepatic duct, an irregular crevasse in the ductus hepaticus communis, the caudate lobe was transversely broken on the left, and under the gap, there was a fracture in retrohepatic inferior vena cava with huge retroperitoneal hematoma. We carried out a ligation of the left hepatic duct and the proper hepatic artery. Postoperation, the man recovered smoothly. At 5 years and 5 months postoperation, MRI showed that the left liver had atrophied partly. So, we consider that the ligation of the left hepatic duct is a safe procedure for patients without cirrhosis under the conditions of ligation of the proper hepatic artery.

Relationship between mammographic calcifications and the clinicopathologic characteristics of breast cancer in Western China: a retrospective multi-center study of 7317 female patients.

BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.

Anatomic hepatectomy and lithotomy of liver parenchyma for regional hepatolithiasis / 中华普通外科杂志

Objective To evaluate anatomic hepatectomy (AH) vs lithotomy of liver parenchyma (LLP) for regional hepatolithiasis.Methods From January 2012 to June 2015,fifty-nine cases underwent LLP and 47 received AH.Clinical end-points included residual stones,infection of the raw surface of liver remnant,time to restoration of liver function,bile leakage,recurrent stones,morbidity and mortality.Results The time of liver function restoration was not statistically different between the two groups (2.96 d vs.2.82 d,P ＞0.05).Patients in AH group suffered from less residual stones (2 cases vs.13 cases,P ＜0.01),lower infection rate of the raw surface of liver remnant (1 case vs.21 cases,P ＜ 0.01),and less bile leakage rate (0 case vs.7 cases,P ＜ 0.05).With a median follow-up of 31 months (range 3-48 mon).AH group suffered from less recurrent hepatolithiasis (0 case vs.12 cases,P ＜ 0.01).There was no mortality in both groups.Conclusions Anatomic hepatectomy is a safe and effective treatment for hepatolithiasis,with a high stone clearance rate and low surgical complications.

Elevated survivin mediated multidrug resistance and reduced apoptosis in breast cancer stem cells.

PURPOSE: Overexpression of survivin in breast cancer cells is associated with aberrant inhibition of apoptosis which leads to massive proliferation of cancer cells. Downregulation of survivin by the anticancer agent prodigiosin can efficiently induce apoptosis in cancer cells. METHODS: The levels of survivin expression in breast cancer stem like side population (SP) cells were assessed. Analyzed were also the rate of apoptosis, drug resistance and the efficiency of clone formation of breast cancer SP cells after treatment with progiosin. RESULTS: Breast cancer samples contained about 2.7% of cancer stem like SP cells which possessed elevated mRNA expression of stem cell proteins Oct-4, EpCAM and ABC transporter ABCG2, essential for the maintenance of SP cells. Furthermore, the SP cells displayed overexpression of survivin in conjunction with reduced apoptosis and increased multidrug resistance. After treatment with prodigiosin, the SP cells became more sensitive to apoptosis and to several chemotherapeutic agents. CONCLUSION: These data suggest that increased expression of survivin in SP cells is one of the major factors involved in apoptosis and resistance to chemotherapy.

PALB2 mutations in breast cancer patients from a multi-ethnic region in northwest China.

BACKGROUND: Germline mutations in PALB2 gene make a small contribution to heritable breast cancer susceptibility. A recent report has revealed that women with mutations in the PALB2 gene were more than nine times as likely to develop breast cancer compared to those without. The aim of this study is to understand the status of PALB2 mutations among Chinese high-risk breast cancer patients in a multi-ethnic region in China. METHODS: 152 patients with hereditary predisposition to breast cancer from the Xinjing region of China were enrolled in the study, and 100 control samples from healthy women were collected in the same locality. We sequenced the coding sequences and flanking intronic regions of PALB2 gene from DNA samples obtained from all subjects by direct sequencing. RESULTS: A total of 4 deleterious PALB2 mutations were identified in 152 breast cancer patients with a prevalence of about 2.6 % (4/152). The PALB2 mutation prevalence was 3.2 % (3/95) in cases with family history of breast cancer. In addition to the four deleterious mutations, we identified nine missense variants in 12 patients, using the prediction Softwares SIFT and PolyPhen, four of which might be disease associated (in 5 patients). Two of the 4 patients with deleterious mutations and 2 of the 5 patients presenting putative deleterious missense mutations had triple-negative breast cancer. No PALB2 mutation carriers were identified in 100 healthy controls. CONCLUSION: PALB2 mutations account for a small, but not negligible, proportion of patients with hereditary predisposition to breast cancer in the Xinjing region of China.

[Serum procalcitonin in cirrhotic patients with sepsis].

OBJECTIVE: To assess the clinical value ofprocalcitonin in cirrhotic patients with severe infection by comparing the serum procalcitonin levels in those patients with and without liver cirrhosis when suffering from sepsis. METHODS: A total of 225 septic patients were included in the study,including 91 patients without hepatopathy, 80 patients with cirrhosis, and 54 patients with chronic liver disease. The serum procalcitonin level was measured in all patients and statistically assessed for correlation with relevant clinical biochemistry indicators. The t-test, ANOVA test, Mann-Whitney U test, chi-square test and Spearman's correlation analysis were used for statistical analyses. RESULTS: The patients with cirrhosis showed significantly lower serum procalcitonin levels (0.84 (0.32-3.44) ng/ml) than the patients with no hepatopathy (2.17 (0.70-9.18) ng/ml) or the patients with chronic liver disease (2.12 (0.33-13.61) ng/ml) (both P less than 0.05); the patients in the no hepatopathy group and the chronic liver disease group showed statistically similar levels of serum procalcitonin (P=0.616). The patients with cirrhosis of Child-Pugh grade C showed significantly higher level of serum procalcitonin (1.25 (0.54-4.61) ng/ml) than those patients with Child-Pugh grade B (0.33 (0.14-1.31) ng/ml; P=0.026), suggesting that patients with Child-Pugh C stage cirrhosis may be more susceptible to gram-negative bacterial infection. In the cirrhosis group,serum procalcitonin level was positively correlated with white blood cell (WBC) count (r=0.312) and percentage of neutrophils (N%) (r=0.228) (both P less than 0.05). Correlation analysis of the no hepatopathy group and the chronic liver disease group showed no correlation between serum procalcitonin level and either WBC or N%. CONCLUSION: Under the sepsis condition, cirrhotic patients have lower serum procalcitonin level than patients without cirrhosis, and the serum procalcitonin level is positively correlated with WBC count and N%.

Clinical Significance of Spleen-Remnant Liver Volume Ratio in Hepatocellular Carcinoma Surgery.

The objective of this study was to explore the value of spleen-remnant liver volume ratio for hepatocellular carcinoma surgery and liver reserve assessment. Spleen-remnant liver volume ratio postoperation was measured with imageological methods and water displacement, and the liver function postoperation and hospital stay of patients with different spleen-remnant liver volume ratios were compared. Spleen-remnant liver volume ratio was closely related to liver function assessment postoperation. The higher the ratio, the higher the assessment score of liver function postoperation would be. When spleen-remnant liver volume ratio was ≤0.9, the patients had a fast recovery and short hospital stay. Spleen-remnant liver volume ratio can effectively predict the recovery and liver reserve of patients with hepatocellular carcinoma postoperation. When postoperative spleen-remnant liver volume ratio is predicted to be ≤0.9, the operation can be performed; and when the ratio is predicted to be ≥1.2, the operation is not suggested.

Heat shock protein 90 in Alzheimer's disease.

Alzheimer's disease (AD) is the first most common neurodegenerative disease. Despite a large amount of research, the pathogenetic mechanism of AD has not yet been clarified. The two hallmarks of the pathology of AD are the extracellular senile plaques (SPs) of aggregated amyloid-beta (Aß) peptide and the accumulation of the intracellular microtubule-associated protein tau into fibrillar aggregates. Heat shock proteins (HSPs) play a key role in preventing protein misfolding and aggregation, and Hsp90 can be viewed as a ubiquitous molecular chaperone potentially involved in AD pathogenesis. A role of Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response. In AD, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70. Therefore, we review here to further discuss the recent advances and challenges in targeting Hsp90 for AD therapy.

The prevalence of BRCA1/2 mutations of triple-negative breast cancer patients in Xinjiang multiple ethnic region of China.

BACKGROUND: The screening of BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer, early-onset breast cancer and bilateral breast cancer patients. There is still some controversy about whether this screening should be done in triple-negative breast cancers. Therefore, we evaluated the BRCA mutation prevalence in patients with triple-negative breast cancer in a multi-ethnic region of China. METHODS: A total 96 women who were diagnosed with triple-negative breast cancer in the Xinjiang region of China were enrolled in this study. BRCA1 and BRCA2 screening was performed by polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) sequencing analysis. All mutations were confirmed with direct sequencing. RESULTS: The prevalence of a BRCA1/2 germline mutation was about 25% (24/96) in the Xinjiang region of China. Among 35 selected cases with a family history and/or bilateral breast cancers, the BRCA1/2 mutation prevalence was 25.7% (9/35). Of the remaining 61 patients with unselected triple-negative breast cancer, the BRCA1/2 mutation prevalence was 24.6% (15/61), and all 15 individuals with these mutations were premenopausal patients. CONCLUSIONS: These results suggest that premenopausal women with triple-negative breast cancer may be candidates for genetic testing for BRCA1/2 in the Xinjiang region of China, even in the absence of a family history or bilateral breast cancer.

Single nucleotide polymorphism rs7294919 on chromosome 12q24.22 is associated with late-onset Alzheimer's disease in Han Chinese.

Recently, two large genome-wide association studies (GWASs) have identified several variants at 12q14 and 12q24 which are associated with hippocampal volume, one of the most important biological markers of Alzheimer's disease (AD). The strongest association was reported for the rs7294919 polymorphism on chromosome 12q24.22. In order to explore whether rs7294919 polymorphism was also associated with late-onset AD (LOAD) risk, we recruited 1132 LOAD patients and 1159 sex- and age-matched healthy controls in the study. The results showed that rs7294919 polymorphism was significantly associated with LOAD (genotype P<0.01, allele P=0.02). After stratification by APOE, significant difference was only observed in non-APOE ɛ4 carriers (P=0.01). Logistic regression demonstrated that the C allele at rs7294919 was a risk factor for LOAD in dominant and recessive models after adjusting for age, gender and the APOE ɛ4 carrier status. In conclusion, our study demonstrates an association of rs7294919 polymorphism locus on chromosome 12q24.22 with risk for LOAD in Han Chinese.