[Analysis of pregnancy outcomes in 66 patients with systemic lupus erythematosus].

OBJECTIVE: To analyze the outcomes of pregnancies in women with systemic lupus erythematosus (SLE) and the risk factors affecting the outcomes. METHODS: The data of SLE patients with pregnancy admitted from October, 2006 and September, 2015 were analyzed for assessing the maternal and fetal outcomes and complications. Their risk factors affecting the outcomes of the pregnancies were analyzed. RESULTS: The 66 SLE patients (69 pregnancies) had a mean age at SLE diagnosis of 22.9 ∓ 5.1 years with a mean duration of SLE of 4.1∓3.6 years before pregnancy. Forty-five (65.2%) of the patients received oral medication for SLE treatment during pregnancy, and 44 (63.8%) were treated with prednisone and 19 (27.5%) were treated with hydroxychloroquine. The highest SLEDAI score was 6.8∓7.4 during pregnancy. The patients with moderate-to-severe disease activity had a higher rate of fetal loss (12 [54.5%] vs 12 [25.5%]) with a significantly lower birth weight of the newborns than those with remittent or mild disease (2073.0∓ 778.7 vs 2817.8∓533.7 g, P<0.05). The patients with moderate-to-severe disease activity also had higher rates of new-onset SLE (9 [40.9%] vs 6 [12.8%]), hypertension (12 [54.5%] vs 3 [6.4%]), active lupus nephritis (22 [100%] vs 4 [8.5%]), pneumonia (5 [22.7%] vs 2 [4.3%]), and renal insufficiency (8 [36.4%] vs 2 [4.3%]) compared with patients with remittent and mild disease (P<0.05). Active lupus nephritis (OR=6.10,95%CI: 1.43-25.96) was a significant predictor of adverse outcomes of the pregnancies. CONCLUSION: Fetal loss and maternal complications are common in patients with SLE in relation with the disease activity. Active lupus nephritis is a predictor for poor outcomes of pregnancies in SLE patients.

Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC), and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of these pathways. Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer.

[The study on correlativity between HLA-DQ gene polymorphism and primary Sjogren's syndrome of the Han nationality in Shanxi province].

AIM: To explore the correlativity between HLA-DQ allele and primary Sjogren's syndrome(pSS) of the Han nationality in Shanxi province and to understand the pathogenesis of pSS at the gene level. METHODS: Polymerase chain reaction sequence specific primers (PCR-SSP) technique was used to determine the alleles of HLA-DQA1 and HLA-DQB1 of pSS patients and healthy populations, and the difference in their HLA-DQA1 and HLA-DQB1 allelic frequencies were analyzed by using chi-square test and Fisher's exact test. RESULTS: (1) The gene frequency of HLA-DQA1*0501 in pSS patients was significantly higher than that in healthy controls(22.0% vs 12.0%, x(2);=7.087, P<0.05, RR=2.068). (2)The gene frequency of HLA-DQA1*0301/2 in pSS patients was significantly lower than that in controls(13.0% vs 24.5%, x(2);=8.681, P<0.05, RR=0.460). (3) The gene frequency of HLA-DQB1*0201 in pSS patients was significantly higher than that in controls(28.5% vs 18.5%, x(2);=5.563, P<0.05, RR=1.756). CONCLUSION: In Han nationality of Shanxi province, HLA-DQA1*0501 and HLA-DQB1*0201 alleles probably are susceptible genes of pSS, while HLA-DQA1*0301/2 allele probably is a protective gene of pSS.

Amyloid-ß neurotoxicity restricts glucose window for neuronal survival in rat hippocampal slice cultures.

Diabetes may increase the risk of Alzheimer's disease (AD). However, a preventive strategy to combat cognitive decline in diabetic elderly with preexisting AD has remained unknown. The aim of this study was to determine the effects of metabolic perturbation on amyloid-ß (Aß) neurotoxicity and the optimal glucose range for improved neuronal survival, which is referred to as the "glucose window". Organotypic hippocampal slice cultures were incubated in either normoglycemic or hyperglycemic medium for 48 h, and subsequently treated in experimental media containing 0-30 mM glucose, with and without Aß(25-35). Neuronal survival was evaluated by the propidium iodide method. Aß neurotoxicity was exacerbated during hypoglycemia/hyperglycemia (≦2 mM/≧30 mM) without Aß and ≦3 mM/≧20 mM with Aß. ROS elevated in the respective glucose ranges and supplementation of ROS scavengers effectively improved neuronal survival. Interestingly, a sharp and sudden drop in glucose levels from preceding hyperglycemia further increased Aß neurotoxicity. Supplementation of pyruvate protected exacerbated Aß neurotoxicity. These results indicate that increased oxidative stress during severe hypoglycemia, hyperglycemia and fluctuation of blood glucose enhances neuronal cell death, resulting in the extremely limited glucose window, and therefore suggest that careful management of glucose avoiding hypoglycemia is needed to prevent brain degeneration in diabetic patients with AD.

Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice.

In this study, we investigated the role of acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by reducing its expression in liver and fat with an optimized antisense oligonucleotide (ASO). High-fat diet-induced obese (DIO) C57BL/6J mice and ob/ob mice were treated with DGAT2 ASO, control ASO, or saline. DGAT2 ASO treatment reduced DGAT2 messenger RNA (mRNA) levels by more than 75% in both liver and fat but did not change DGAT1 mRNA levels in either of these tissues, which resulted in decreased DGAT activity in liver but not in fat. DGAT2 ASO treatment did not cause significant changes in body weight, adiposity, metabolic rate, insulin sensitivity, or skin microstructure. However, DGAT2 ASO treatment caused a marked reduction in hepatic triglyceride content and improved hepatic steatosis in both models, which was consistent with a dramatic decrease in triglyceride synthesis and an increase in fatty acid oxidation observed in primary mouse hepatocytes treated with DGAT2 ASO. In addition, the treatment lowered hepatic triglyceride secretion rate and plasma triglyceride levels, and improved plasma lipoprotein profile in DIO mice. The positive effects of the DGAT2 ASO were accompanied by a reduction in the mRNA levels of several hepatic lipogenic genes, including SCD1, FAS, ACC1, ACC2, ATP-citrate lyase, glycerol kinase, and HMG-CoA reductase. In conclusion, reduction of DGAT2 expression in obese animals can reduce hepatic lipogenesis and hepatic steatosis as well as attenuate hyperlipidemia, thereby leading to an improvement in metabolic syndrome.

Neuroprotective effect of D-fructose-1,6-bisphosphate against beta-amyloid induced neurotoxicity in rat hippocampal organotypic slice culture: involvement of PLC and MEK/ERK signaling pathways.

D-fructose-1,6-bisphosphate (FBP) is an endogenous intermediate of glycolytic pathway which has potent neuroprotective effect against various neurotoxic insults. This study examined whether FBP could antagonize the neurotoxicity induced by amyloid beta-peptide (Abeta) in rat hippocampal organotypic slice cultures, and the possible mechanism was also explored. Treatment with FBP (concentration ranges from 1.7 mM to 10 mM) significantly decreased the cell death in hippocampal slices in the presence of Abeta at 24h, 48 h and 72 h, and this neuroprotective effect of FBP against Abeta was not in a dose-dependent manner, FBP 3.5 mM has better neuroprotective effect than that of other FBP concentration groups. Treatment with FBP slightly but significantly increases the ATP levels in hippocampal slices in the presence of Abeta. However, the increment of ATP levels was similar among various FBP concentration groups. Neuroprotective effect of FBP 3.5 mM against Abeta induced neurotoxicity in hippocampal slices was attenuated by addition of phospholipase C (PLC) inhibitor, U73122, mitogen activated extracellular signal protein kinase (MEK) inhibitor, U0126, or extracellular signal activated protein kinase (ERK) inhibitor, PD98059 at 24 h, 48 h and 72 h. However, co-treatment with these three kinds of inhibitors did not change the FBP's effect on ATP levels. Our results suggested FBP has neuroprotective effect against Abeta induced neurotoxicity in hippocampal slice cultures, and FBP plays role not only as an alternative energy source, but also a modulator of PLC and MEK/ERK pathways to regulate the cellular response and survival.

[Geriatric medicine and long-term care insurance].

Long-term care insurance (LCI) started from April 2000 in Japan. LCI now occupies a central position in the health care of the aged. We reviewed all original papers and reports on LCI published in 1996-2002. At the end of 2002, we searched for papers on LCI in a computer database using the keyword of LCI, and found 3,606 papers. Authors and contents of each paper were categorized using 54 kinds of keywords. Frequent authors were government agencies, care managers, physical therapists, and physicians. When we analyzed these papers according to the places where LCI was used, more than 50% of reports concerned LCI at home. Most frequent keywords were Government/LCI system. Regional health, Physician' assessment and grades for care. Care management, Care manager, and Rehabilitation. Care manager was less observed after the start of LCI. In contrast, the use of keywords including Care service. Dementia, Geriatric syndrome, Nurse, Institutional medicine, Hospital care, Medicine for the aged, Terminal care, Dialysis therapy, Abuse of the aged, and Caregiver burden were increased after LCI. At the beginning of LCI, main concerns are on the new LCI system. However, more individual issues in the care of the aged are now discussed. New issues such as Abuse of the aged and Caregiver burden have been recently raised. From these observations, the role of geriatric medicine seems also to be changing after the induction of LCI. We would now contribute actively to crucial aspects of LCI, such as comprehensive assessment of the aged, functional medical network with care staffs, and new therapeutic approaches to each geriatric syndrome.