Research progress of circadian rhythm and circadian rhythm sleep-wake disorders / 中华神经科杂志

Circadian rhythm is driven by the suprachiasmatic nucleus biological clock, and many life activities and physiological functions are regulated by circadian rhythm, such as central nervous system activity, autonomic nervous system activity, endocrine function, metabolism and immune function. At the molecular level, circadian rhythm is regulated by molecular mechanisms generated by clock genes′ oscillations. Endogenous circadian rhythm is one of the main processes controlling sleep. Circadian rhythm disorder is the most common cause of abnormal sleep-wake cycle, and can also lead to a series of diseases and adverse consequences such as other sleep disorders, abnormal cognitive function, hypertension, diabetes and tumors. Recently, the relationship between circadian rhythm and sleeping awakening has become a hot topic for researchers. In this paper, the research progress of circadian rhythm and circadian rhythm sleep-wake disorders was reviewed.

LPS stimulating neutrophils firmly adhered to ICAM-1 to form extracellular traps depends on integrin Mac-1 and cytoskeletal proteins / 生物医学工程学杂志

Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.

Effect of high-fat diet and exercise on asprosin and CTRP6 expression in subcutaneous and retroperitoneal adipose tissues in rats during mid-gestation / 南方医科大学学报

OBJECTIVE@#To study the effects of high-fat (HF) diet and exercise on the expressions of asprosin and CTRP6 in adipose tissues in different regions of rats during mid-gestation.@*METHODS@#Pregnant SD rats were fed on a standard chow diet or a high-fat (60% fat content) diet for 14 days starting on gestation day (GD) 1. Starting from GD3, the rats fed either on normal or high-fat diet in the exercise groups (CH-RW and HF-RW groups) were allowed access to the running wheels for voluntary running, and those in sedentary groups (CH-SD and HF-SD groups) remained sedentary. At the end of the 14 days, adipose tissues were sampled from different regions of the rats for detecting the mRNA and protein expressions of asprosin and CTRP6 using RT-qPCR and Western blotting.@*RESULTS@#The mRNA expression of asprosin in retroperitoneal adipose tissues was significantly higher in HF-RW group than in the other 3 groups (@*CONCLUSIONS@#High-fat diet and exercise during mid-gedtation can affect the expression levels of asprosin and CTRP6 in adipose tissues of rats in a site-specific manner.

Analysis of risk factors for acute kidney injury after radical nephrectomy / 中华泌尿外科杂志

Objective:To explore the risk factors of acute kidney injury(AKI) in patients after radical nephrectomy.Methods:We retrospectively collected clinical information of 920 patients with renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University from February 2013 to September 2017. There were 612 male and 308 female patients included in this study, with a median age of 60 (range from 20-75 years). 313 patients (34.0%) had hypertension, 132 patients (14.3%) had diabetes, and 111 patients (12.1%) had smoking history. 829 cases (90.1%) were in stage 1-2 for preoperative renal function staging, and 91 cases (9.9%) were in stage 3-5. Preoperative hemoglobin was lower than the lower limit of normal in 391 cases (42.5%), white blood cell count increased in 66 cases (7.2%), and platelet increased in 72 cases (7.8%). Albumin was lower than the lower limit of normal in 65 cases (7.1%), lactate dehydrogenase increased in 73 cases (7.9%). blood urea nitrogen increased in 48 cases (5.2%), uric acid increased in 123 cases (13.4%), and urinary protein was positive in 88 cases (9.7%). 496 cases (53.9%) underwent open surgery and 424 (46.1%) underwent laparoscopic surgery. The changes in serum creatinine were followed up within 48 hours after surgery. AKI was defined according to the KDIGO standard. Logistic regression was used to analyze the risk factors for postoperative stage 2-3 AKI in patients.Results:Stage 1-3 AKI occurred on 627, 42 and 10 patients during hospitalization, respectively. Univariate analysis showed that diabetes ( OR=2.34, P=0.01), positive urine protein ( OR=2.22, P=0.04), and elevated white blood cell count ( OR=2.54, P=0.02) were significantly associated with postoperative stage 2-3 AKI. Multivariate logistic regression analysis showed that diabetes ( OR=2.51, P=0.01) and elevated white blood cell count ( OR=2.69, P=0.02) were independent risk factors for postoperative stage 2-3 AKI. Conclusion:Renal cell carcinoma patients with diabetes or preoperative elevated white blood cell count are more likely to develop stage 2-3 AKI after radical nephrectomy.

Time-sequential expression of lnc AK079912 during adipose tissue development and browning in mice / 南方医科大学学报

OBJECTIVE@#To investigate the time-sequential expression of a novel long non-coding RNA, lnc AK079912, in metabolically related tissues and during adipose tissue development and browning in mice.@*METHODS@#The interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue (sWAT), epididymal white adipose tissue (eWAT), liver tissues and muscular tissues were collected from 8-week-old C57BL/6J mice. The iBAT, sWAT and eWAT were also collected from the mice during development (0 day, 21 days, 8 weeks and 6 months after birth) and from 8- to 10-week- mice with cold exposure (4 ℃) and intraperitoneal injections of CL316, 243 (1 μg/g body weight) for 1 to 5 days. Trizol was used to extract the total RNA from the tissues, and RT-qPCR was performed to detect the expressions of lnc AK079912. Isolated mouse preadipocytes in primary culture were induced for adipogenic differentiation for 9 days and then treated with CL316, 243 (2 μmol/L) for different durations (no longer than 24 h); the expression of lnc AK079912 in the cells was detected using RT-qPCR at different time points of the treatment.@*RESULTS@#Lnc AK079912 was highly expressed in mouse adipose tissues, the highest in iBAT, followed by the muscular tissue, but was hardly detected in the liver tissue. The expression level of lnc AK079912 increased progressively in iBAT and sWAT during development of the mice, while its expression in eWAT showed an initial increase followed by a reduction at 8 weeks ( 0.05). The expression of lnc AK079912 was significantly decreased in iBAT and eWAT ( < 0.05) but increased in eWAT from mice with intraperitoneal injection of CL316, 243 for 1 to 5 days ( < 0.05). The expression level in the adipocytes in primary culture was significantly increased in response to treatment with CL316, 243 ( < 0.05).@*CONCLUSIONS@#Lnc AK079912 is highly expressed in mouse adipose tissue, and its expression gradually increases with the development of adipose tissue but with a depot-specific difference. Lnc AK079912 is significantly elevated in the early stage of adipose tissue browning, indicating its important role in the development and browning of adipose tissue.

Progress on PD-1/PD-L1 Checkpoint Inhibitors in Lung Cancer / 中国肺癌杂志

In recent years, research on immunotherapy has made great progress. Currently, immunotherapy has made significant breakthrough, especially programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors (e.g, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab and Avelumab, etc.) have brought clinical benefits to patients with various pathological types of lung cancer, including squamous cell carcinoma, adenocarcinoma and small cell lung cancer. In this paper, the application value and current status of PD-1/PD-L1 checkpoint inhibitors in lung cancer were comprehensively analyzed by reviewing and interpreting representative clinical studies. Based on the results of various large-scale clinical trials results, the indications of immunotherapy in lung cancer have been continuously broadened, and the details of immunotherapy have also been constantly optimized. However, immunotherapy still faces many challenges, such as the selection of immune combination strategies, the exploration of biomarkers, the management of adverse events, the feasibility of application of driver gene mutation population and so on. In this article, we made a systematic review about the latest progress of PD-1/PD-L1 checkpoint inhibitors in lung cancer, in order to provide cutting-edge reference for the clinical workers.
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Timeliness of β3 adrenergic receptor agonist-induced browning of white adipose tissues in mice / 中南大学学报(医学版)

To characterize the timeliness of β3 adrenergic receptor agonist CL316,243-induced browning of white adipose tissues in mice.
 Methods: Male C57BL/6J mice at 10 weeks of age were housed in conventional cages and given sterile saline for the control group or CL316,243 (1 μg/g) for the experimental group via intraperitoneal injection for 1, 3, and 5 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous white adipose (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological and gene expression analysis.
 Results: Compared with the control group, intraperitoneal injection of CL316,243 reduced the weight of eWAT on the first day. Meanwhile, CL316,243 continuously promoted the mRNA and protein expression of uncoupling protein-1 (UCP-1) in sWAT and eWAT. Furthermore, CL316,243 injection significantly decreased the food intake and weight gain of the mice, and reduced the diameter of adipocyte and accumulation of small lipid droplets in adipose tissues.
 Conclusion: CL316,243 can induce the brown-like remodeling in adipose tissues of mice in vivo, which show different time-dependent manners in different adipose tissues.

The changes of beta-adrenergic receptor on circulating intact lymphocytes in hypertensive-diabetic rats / 中国病理生理杂志

Some kinetic characteristics of beta-adrenoceptor on circulating intact lymphocytes (CIL) in the combined renovasoeular hypertensive and diabetic (HD) rats were studied and the relation of betareceptos between CIL and cardium as well as the morphologic changes in the processe of dilated cardiomypathy (DCM) were observed. The results show that: the density of beta-adrenoceptor on CIL (Bmax) was going up 41.28%(P0.05), but the Kd was still 50.01%(P