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.

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.

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.

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.