Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

Impact of Thyroid Function on the Prevalence and Mortality of Metabolic Dysfunction-Associated Fatty Liver Disease.

CONTEXT: Thyroid function variation within the thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed definition. OBJECTIVE: We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD. METHODS: Data of 10 666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within the thyroxine reference range was defined based on thyroid-stimulating hormone (TSH) levels: subclinical hyperthyroidism, <0.39 mIU/L; strict-normal thyroid function, 0.39-2.5 mIU/L; and low thyroid function, >2.5 mIU/L, which comprised low-normal thyroid function (2.5-4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and Cox regression were used in multivariate analysis. RESULTS: Low thyroid function is independently associated with MAFLD (odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in the total population (hazard ratio [HR] for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99); meanwhile, in the low-normal thyroid function group, an increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in the total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality. CONCLUSIONS: Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in the MAFLD population. Reevaluation of TSH reference range should be considered.

Population-specific cut-off points of fatty liver index: a study based on the National Health and Nutrition Examination Survey data.

BACKGROUND: Fatty liver index (FLI) is the most recognized blood biomarker for diagnosis of hepatic steatosis (HS), but lacks the reliable specific cut-off points (COPs). Therefore, we aim to investigate the population-specific COPs of FLI based on the results of liver ultrasound transient elastography (LUTE) and conventional ultrasonography in the National Health and Nutrition Examination Survey (NHANES). METHODS: 5948 participants who underwent LUTE from the NHANES 2017-2018 and 14,797 participants who underwent conventional ultrasonography from the Third NHANES (NHANES III) were recruited. FLI was calculated by using body mass index (BMI), waist circumference (WC), triglyceride, and gamma-glutamyl transferase, and its optimal COPs in a specific population (stratified by sex, BMI, and WC) were obtained from receiver operator characteristics (ROC) curve with ultrasonic-diagnosed HS as the reference standard. RESULTS: Based on LUTE in NHANES 2017-2018, the prevalence of HS and metabolic dysfunction-associated fatty liver disease (MAFLD) were 58.7% and 56.2%, respectively, and the optimal COP of FLI for HS diagnosis in the overall population was 45.60, with an area under ROC curve (AUROC) of 0.833 (0.822-0.844). Based on conventional ultrasonography in NHANES III, the prevalence of HS and MAFLD were 34.4% and 27. 9%, respectively, and the optimal COP of FLI for HS was 59.5, with an AUROC of 0.681 (0.671-0.691). With the increase of BMI and WC, the COPs increased gradually with significant differences between different groups. Compared with conventional ultrasonography, the COPs of FLI based on LUTE were much more precise, with higher diagnostic ability. The population-specific COPs of FLI stratified by gender, WC, and BMI were tabulated. CONCLUSION: In the United States, the incidences of HS and MAFLD were high, especially when assessed by LUTE. The FLI based on LUTE is well capable of predicting HS when stratified by gender, WC, and BMI.

[Results of micro-TESE and outcomes of ICSI in patients with different etiological types of non-obstructive azoospermia].

OBJECTIVE: To compare the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (micro-TESE) and the outcomes of intracytoplasmic sperm injection (ICSI) among different etiological types of non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data on 155 cases of NOA undergoing micro-TESE in our hospital from September 2016 to December 2017, which were classified into three types according to etiological factors: congenital NOA (n = 49), acquired NOA (n = 15) and idiopathic NOA (n = 91). We compared the age, testis volume, levels of reproductive hormones, ultrasonographic manifestations, and SRR of micro-TESE among the three groups of patients. We also recorded and analyzed the rates of fertilization, available embryos and clinical pregnancy in the spouses of the patients included for successful sperm retrieval in micro-TESE. RESULTS: The testis volume was significantly lower in the congenital than in the acquired and idiopathic NOA groups (ï¼»6.4 ± 5.0ï¼½ vs ï¼»10.2 ± 2.0ï¼½ and ï¼»9.9 ± 3.2ï¼½ ml, P < 0.05), while the LH level was markedly higher in the former group than in the latter two (ï¼»15.2 ± 10.1ï¼½ vs ï¼»9.1 ± 6.5ï¼½ and ï¼»7.8 ± 3.5ï¼½ mIU/ml, P < 0.05), and so was the T level in the idiopathic than in the congenital NOA group (ï¼»11.8 ± 4.8ï¼½ vs ï¼»8.9 ± 4.5ï¼½ nmol /L, P < 0.05). The SRRs of micro-TESE in the congenital, acquired and idiopathic NOA patients were 73.5% (36/49), 100% (15/15), and 24.2% (22/91) respectively, with statistically significant differences among the three groups (P < 0.05). The fertilization rate after ICSI was remarkably higher in the acquired than in the congenital and idiopathic NOA groups (ï¼»73.1±23.3ï¼½% vs ï¼»48.9±21.7ï¼½% and ï¼»52.6±22.7ï¼½%, P < 0.05). There were no statistically significant differences among the three groups in the rates of embryo utilization and clinical pregnancy. CONCLUSIONS: The sperm retrieval rate of micro-TESE and the rates of fertilization, embryo utilization and clinical pregnancy after ICSI were the highest in the acquired NOA but the lowest in the idiopathic NOA patients.

Activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat.

The polycystic kidney (PCK) rat is an animal model of Caroli's disease as well as autosomal recessive polycystic kidney disease (ARPKD). The signaling pathways involving the mammalian target of rapamycin (mTOR) are aberrantly activated in ARPKD. This study investigated the effects of inhibitors for the cell signaling pathways including mTOR on cholangiocyte proliferation of the PCK rat. Cultured PCK cholangiocytes were treated with rapamycin and everolimus [inhibitors of mTOR complex 1 (mTOC1)], LY294002 [an inhibitor of phosphatidylinositol 3-kinase (PI3K)] and NVP-BEZ235 (an inhibitor of PI3K and mTORC1/2), and the cell proliferative activity was determined in relation to autophagy and apoptosis. The expression of phosphorylated (p)-mTOR, p-Akt, and PI3K was increased in PCK cholangiocytes compared to normal cholangiocytes. All inhibitors significantly inhibited the cell proliferative activity of PCK cholangiocytes, where NVP-BEZ235 had the most prominent effect. NVP-BEZ235, but not rapamycin and everolimus, further inhibited biliary cyst formation in the three-dimensional cell culture system. Rapamycin and everolimus induced apoptosis in PCK cholangiocytes, whereas NVP-BEZ235 inhibited cholangiocyte apoptosis. Notably, the autophagic response was significantly induced following the treatment with NVP-BEZ235, but not rapamycin and everolimus. Inhibition of autophagy using siRNA against protein-light chain3 and 3-methyladenine significantly increased the cell proliferative activity of PCK cholangiocytes treated with NVP-BEZ235. In vivo, treatment of the PCK rat with NVP-BEZ235 attenuated cystic dilatation of the intrahepatic bile ducts, whereas renal cyst development was unaffected. These results suggest that the aberrant activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat, and inhibition of the pathway can reduce cholangiocyte proliferation via the mechanism involving apoptosis and/or autophagy.