Insomnia Burden among Informal Caregivers of Hospitalized Lung Cancer Patients and Its Influencing Factors / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer.@*METHODS@#A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors.@*RESULTS@#Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia.@*CONCLUSION@#Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.

Design, synthesis, and activity of 5-cyano-2-thiacetyl aromatic pyrimidinone as DENV NS5 RdRp inhibitors / 药学学报

To screen novel anti-dengue virus (DENV) NS5 RdRp enzyme inhibitors, a series of 5-cyano-2-thiacetoaryl pyrimidinone compounds were designed and synthesized by molecular hybridization method with HCV NS5B RdRp inhibitor 3jc and ZIKV NS5 RdRp inhibitor 4w as lead compounds. The anti-DENV activity of these compounds was evaluated by MTT assay and plaque assay and five compounds showed anti-DENV activity. The most active compound 7a'k showed better anti-DENV activity than that of the positive control ribavirin (EC50 = 7.86 μmol·L-1 vs EC50 = 18.07 μmol·L-1), and the other four compounds showed almost the same anti-DENV activity as ribavirin. Finally, the prediction and simulation of the binding mode through molecular provided new ideas for the further development of this new DENV NS5 RdRp inhibitor.

Anatomy and imaging of abdominal aorta and its branches in Southwestern China population / 解剖学报

Objective To investigate the normal reference values of abdominal aorta and its branches in Southwest China, so as to provide basis for clinical diagnosis and treatment of abdominal aortic aneurysm. Methods The length, diameter and angle of the abdominal aorta and its branches were measured in 20 cadavers. At the same time, 300 cases without obvious pathological changes in four urban populations were selected for abdominal CT angiography (CTA) to measure the length, diameter and angle of abdominal aorta and its branches. Results Display rate of abdominal aorta was 100%,the average length of abdominal aorta was (12.96±0.81) cm, the diameter of abdominal aorta was (1.93±0.28) cm, (1.55±0.23) cm, (1.61±0.19) cm in renal artery plane (Ⅰ), inferior mesenteric artery plane (Ⅱ) and lower edge plane of lumbar vertebrae (Ⅲ), and the average value on image was (2.17 ± 0.42) cm, (1.81 ± 0.40) cm, (1.99 ± 0.53) cm; Display rate of common iliac artery was 100%, the angle between left and right common iliac artery was (59.80± 4.66) ° and the diameter of the end was (1.16±0.33) cm and (1.12±0.11) cm; Display rate of celiac trunk on cadaver was 100%, the average length was (1.61±0.27) cm, the average diameter on cadaver was (0.78±0.71) cm, the image was (0.88± 0.31) cm; Display rate of renal artery was 100%, the average length of the left renal artery was (2.58 ± 0.50) cm, that of the right was (4.26±0.65) cm, the initial average diameter of the left renal artery was (0.55±0.24) cm, and the right renal artery was (0.62±0.20) cm; Display rate of the superior mesenteric artery was (100%), that of the on cadaver was (4.56 ± 0.29) cm, that of the image was (4.93 ± 0.84) cm, and that of the angle between the abdominal aorta was (38.05±5.99)°; Display rate of the inferior mesenteric artery was (100%),the average length of the inferior mesenteric artery was (6.57±0.79) cm on the cadaver, the image was (6.70±0.76) cm, and that of the angle between the abdominal aorta was (73.79 ± 9.62) ° and the initial diameter was (0.48 ± 0.29) cm. Conclusion The normal reference values of abdominal aorta and its visceral branches in Southwest China population were measured. CTA has a special advantage in showing the lesions of abdominal aorta and its branches in lumen, extraluminal and vascular wall, which can provide anatomical data of patients before operation.

Research progress on excitotoxicity of glutamate and its modulators / 中国药理学通报

Excitotoxicity mainly refers to the toxic effect of the excitatory neurotransmitter glutamate.Long-term activation of glutamate receptors will cause a series of neurotoxicity, eventually leading to the loss of neuronal function and cell death.Triggering excitotoxicity may involve changes in glutamate and calcium metabolism, dysfunction of glutamate transporter, N-methyl-D-aspartate receptor(NMDAR)and mitochondria, and production of ROS.Therefore, we here review the occurrence of these mechanisms and introduce the pathological mechanism of glutamate excitotoxicity in Alzheimer's disease(AD), Parkinson's disease(PD), depression and epilepsy.Finally, this review briefly describes the regulatory effects of broad-spectrum glutamic satellite modulators, marine compounds and Chinese herbal medicines on the glutamatergic system.

Baihe Dihuangtang Improves Hippocampal Neuron Damage in Anxious Depression Model Rats by Inhibiting NLRP3 Inflammasome Activation / 中国实验方剂学杂志

Objective:To investigate the anti-anxious depression mechanism of Baihe Dihuangtang from the NOD-like receptor thermal protein domain 3 （NLRP3） inflammasome. Method:Fifty SD rats were randomly divided into normal group， model group， venlafaxine group （13.5 mg·kg^-1）， Baihe Dihuangtang high and low dose group （16，4 g·kg^-1）， with 10 rats in each group. Chronic restraint stress for 28 days （6 h） combined with subcutaneous injection of corticosterone （30 mg·kg^-1） was used to establish induce an anxious depression model. From the 8th day of modeling， the rats in the normal group and the model group received distilled water， and those in groups with drug intervention were treated with corresponding drugs by gavage for 21 days. Elevated plus maze and open field test were used to evaluate the behavioral changes of rats. Enzyme- linked immunosorbent assay （ELISA） was used to detect serum and hippocampal interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-6 （IL-6） and interleukin-18 （IL-18） levels. Western blot were used to detect the relative expression of hippocampal NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， and Caspase-1. The pathological changes of the hippocampus were observed by hematoxylin-eosin（HE） staining， the average fluorescence intensity of NLRP3， ASC， and Caspase-1 was detected by immunofluorescence. The ultrastructure of neurons was observed under electron microscopy. Result:Compared with the normal group， the model group showed reduced total entries （TE）， the ratio of open-arm entries （OE%）， the ratio of open-arm times （OT%）， and the autonomous activity score （<italic>P</italic><0.01）， significant anxiety and depression-like behaviors， increased levels of IL-1<italic>β</italic>， IL-6， and IL-18 in the serum and hippocampus （<italic>P</italic><0.01）， elevated protein expression of NLRP3， ASC， and Caspase-1 （<italic>P</italic><0.01）， activated NLRP3 inflammasomes， and injured hippocampal neurons. Compared with the model group， the high-dose Baihe Dihuangtang group showed improved anxiety and depression-like behaviors （<italic>P</italic><0.01）， and decreased levels of IL-1<italic>β</italic>， IL-6， and IL-18 in the serum and hippocampus （<italic>P</italic><0.05，<italic>P</italic><0.01）， reduced protein expression of NLRP3， ASC， and Caspase-1 （<italic>P</italic><0.01）， and alleviated hippocampal neuron damage. Conclusion:Baihe Dihuangtang can improve neuronal damage in anxious depression by inhibiting the excessive activation of NLRP3 inflammasomes.

Effects of depression and insomnia on HPA axis and amino acid and monoamine neurotransmitters in hypothalamus of rats / 中国药理学通报

Aim To explore the effects of chronic unpredictable mild stress combined with sleep deprivation on the hypothalamic-pituitary-adrenal axis (HPA) and the amino acid and monoamine transmitters in hypothalamus of rats. Methods Chronic unpredictable mild stress combined with modified multi-platform water environment sleep deprivation was used to replicate depression and insomnia rat models. ELISA was used to measure the content of HPA axis related molecules in serum and hypothalamus, the content of amino acid transmitter glutamate (Glu) and GABA in hypothalamus; HPLC-ECD was applied to measure the content of monoamine transmitter NE, 5-HT, DA in hypothalamus; WB and RT-qPCR were employed to measure the expression of GABA related molecules GAD67, GABA

Effects of compound Chaijin Jieyu tablets on expression of GABA receptor in brain regions of depressive insomnia rats / 中国药理学通报

Aim To explore compound Chaijin Jieyu tablets on expression of GABA receptor in brain regions of depressive insomnia rats. Methods Seventy-two male SD rats were randomly divided into control, model, positive drug (venlafaxine hydrochloridel3. 5 mg · kg

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China / 生物医学与环境科学（英文）

Objective@#Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.@*Methods@#A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( @*Results@#Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.@*Conclusion@#Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Biotransformation of Natural Saponins / 中国实验方剂学杂志

Saponin is a kind of complex compounds with triterpenoid or spiral aglycones.Natural saponins are used as substrates,and many novel compounds are obtained by biotransformation technology. Especially, converted products of saponins with strong activities provide valuable lead compounds for the research and development of new drugs. Saponins can be divided into triterpenoid saponin and steroidal saponin according to the structure of the mother nucleus. There are about 89 reported saponin components,including 56 triterpenoid saponins and 33 steroidal saponins. Biological enzyme catalysis,microbial transformation and intestinal microflora transformation are the main bioconversion technologies and key development directions of saponins. The research and optimization technology of biological enzyme and microbial transformation of saponins are the effective methods to prepare active secondary saponins. The biotransformation reaction of saponins mainly includes hydrolysis,redox and rearrangement,resulting in the formation of aglycones,secondary glycosides and their derivatives. The hydrolysis of saponin sugar chains was the main biological transformation pathway, and could generate a number of secondary saponins with less glycosyl groups. The secondary saponins could be absorbed into blood and become real active ingredients in body. Preparation of rare secondary saponins,discovery of lead compounds and development of new drugs are the main directions of biotransformation of saponins. The studies on the metabolism and mechanism of natural saponins by microbial and intestinal microbial biotransformation will also become hotspots. According to relevant papers at home and abroad,the researches on transformation technique,transformation approach and transformation reaction of saponins from natural products in the past thirty years were summarized, and the prospects of research and development were also analyzed to provide scientific basis for further study and comprehensive utilization of these conversion products.

Cell autophagy attenuates PM2.5-induced apoptosis of human lung adenocarcinoma cell line H441 / 基础医学与临床

Objective To investigate the function of autophagy in the process of PM2.5-induced apoptosis. Methods PM2.5 was obtained from Zhanjiang in 2016. Human lung adenocarcinoma cells H441 were treated with PM2.5 at different concentrations for different times. Cell proliferation was analyzed by MTT assay; Cell apoptosis was assessed by PI and Annexin V double staining and TUNEL assay. The expression of autophagy marker LC3Ⅱ, AKT and P-AKT protein was examined by Western blot ( WB). H441 cells were treated with PM2.5 following treatment with rapamycin or 3-MA. Cell viability was evaluated by trypan blue staining. Results Compared with the control group, cell proliferation was significantly inhibited by PM2.5 at concentration of 100 μg/mL or more for 24 and 48 h. With the increase of PM2.5 concentration, the cells apoptotic rate significantly increased, the protein ex-pression of LC3Ⅱwas increased as well as the P-AKT was decreased; and the protein expression of LC3Ⅱwas in-creased significantly after AKT inhibitor treatment. Moreover, rapamycin decreased PM2.5-induced cell apoptosis, and 3-MA can promote PM2.5-induced cell apoptosis. Conclusions In H441 cells, PM2.5 activates autophagy by inhibiting activation of AKT pathway, and cell autophagy can mitigate PM2.5-induced apoptosis.

A colorimetric method for vascular endothelial growth factor detection based on aptamer and magnetic beads / 南方医科大学学报

<p><b>OBJECTIVE</b>To develop a novel colorimetric method for detecting the tumor biomarker vascular endothelial growth factor (VEGF) based on aptamer and magnetic beads.</p><p><b>METHODS</b>The capture aptamer was hybridized to urease functionalized single-stranded DNA (ssDNA) and immobilize on the surface of magnetic beads by specific biotin-avidin binding. In the presence of VEGF, aptamers bound to VEGF to form a specific stem-loop structure to release the urease functionalized ssDNA. After separation, the supernatant was transferred to a tube and urea and phenol red were added. Urease hydrolyzed urea to produce ammonia to cause an increase of the pH value and a color change of phenol red. The results were inspected with either the naked eyes or by a UV spectrophotometer.</p><p><b>RESULTS</b>Under optimized conditions, the detection system showed a good linear relationship for VEGF detection in the range of 0.1 to 10 pmol/L with a detection limit as low as 0.06 pmol/L. The results of VEGF detection in the serum of patients with lung cancer were consistent with those using an ELISA Kit. The results of examination of 10 serum samples with this aptamer-based method and ELISA kit showed that the accuracy of this method was 90%.</p><p><b>CONCLUSION</b>This aptamer-based system provides an simple and convenient method for VEGF detection with a high sensitivity and selectivity.</p>

Reverse effect of Yinchenhao decoction in dimethyl nitrosamine-induced hepatic fibrosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the reverse effect of Yinchenhao decoction(YCHD) in dimethyl nitrosamine (DMN)-induced hepatic fibrosis in rats.</p><p><b>METHOD</b>The rat hepatic fibrosis model was established through the intraperitoneal injection with 1% dimethyl nitrosamine (DMN) with a dose of 1.0 mL x kg(-1) x d(-1) for consecutively three weeks, once for the first three days of each. The rats were randomly divided into six groups: the silymarin positive control group (50.0 mg x kg(-1) x d(-1), YCHD high (20.0 g x kg(-1) d(-1)), middle (8.0 g x kg(-1) x d(-1)) and low (3.2 g x kg(-1) x d(-1)) dose groups, the model group and the normal control group. The model group and the normal control group were orally administered with normal saline for consecutively five weeks. The pathologic changes in liver tissues were observed by HE staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), g-glutamyltransferase (g-GGT), hyaluronic acid (HA), laminin (LN), collagen type IV (CIV) and type III procollagen amino terminal peptide (PIIINP) in serum were determined. The metabolite profiling of amino acid and the content of hydroxyproline in liver tissues were also measured.</p><p><b>RESULT</b>Compared with the model group, YCHD high and middle dose groups could significantly reverse the pathologic changes in liver tissues of rats. YCHD could reduce the levels of ALT, AST, gamma-GGT, HA, LN, CIV, PIIINP in serum and the content of hydroxyproline in liver tissues in a dose-dependent manner, and altered the metabolite profiling of amino acid in rat liver tissues.</p><p><b>CONCLUSION</b>YCHD has the effect in reversing dimethyl nitrosamine induced hepatic fibrosis in rats.</p>

Relevance between writing characteristic and therapeutic effect in schizophrenia / 法医学杂志

OBJECTIVE@#To explore the relevance between writing characteristic and therapeutic effect in schizophrenia and to discuss the influence of aggressive behavior on writing characteristic.@*METHODS@#Recoding the casual and fixed writing in admission, one week, two weeks, four weeks, eight weeks after treatment and rating Positive and Negative Syndrome Scale (PANSS) and Modified Overt Aggression Scale (MOAS). Choosing two characteristics, "relationship between font and grid lines" and "having big strokes or not", and comparing before and after treatment.@*RESULTS@#Eight weeks after treatment, the score of PANSS decreased. The condition of patients and the writing characteristic improved as well. The differences of writing characteristics were statistically significant in patients with aggressive behavior before and after treatment (P < 0.05).@*CONCLUSION@#The writing characteristic has relation with therapeutic effects and improved with therapeutic effects in aggressive patients.

Impact of NF-kappaB inhibitor on STAT3 translocation in PC-3 prostate cancer cell line / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the changes in the expressions of STAT3 and NF-KB in PC-3 cells after IL-6 stimulation and to verify the effects of the NF-KB inhibitor caffeic acid phenethyl ester (CAPE) on the expressions of p-STAT3 and IL-6 in the PC-3 prostate cancer cell line.</p><p><b>METHODS</b>PC-3 prostate cancer cells were treated with IL-6 at 20 ng/ml for 5, 10, 20, 30 and 45 min. The protein and mRNA expressions of STAT3 and NF-kappaB were measured by Western blot and real time PCR, respectively, and the cell cycle was detected by flow cytometry. The PC-3 cells were exposed to TNF-alpha or TNF-alpha + CAPE, followed by determination of the IL-6 expression in the supernatant of the cells by ELISA and the expression of p-STAT3 by Western blot.</p><p><b>RESULTS</b>After IL-6 stimulation, both the expression of p-STAT3 protein and the proliferation index of the PC-3 cells were significantly increased, and so were the expressions of IL-6 and p-STAT3 protein in the supernatant after TNF-alpha treatment (P < 0.05). TNF-alpha + CAPE induced statistically lower expressions of IL-6 and p-STAT3 than TNF-alpha alone (P < 0.05).</p><p><b>CONCLUSION</b>CAPE can inhibit IL-6 secretion induced by TNF-alpha in PC-3 cells and thus suppress STAT3 translocation. Therefore, by inhibiting the expression of NF-kappaB and affecting STAT3 and other related cell signaling pathways, CAPE may become a new therapeutic option for prostate cancer.</p>

Effects of SIPL1 screened by suppression subtractive hybridization (SSH) on biological function and drug resistance of renal cell carcinoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To screen the differentially expressed genes in human renal clear-cell carcinoma (RCC) cells using suppression subtractive hybridization (SSH), and to explore their biological function and underlying mechanism in RCC cells.</p><p><b>METHODS</b>Total RNAs were extracted from human renal clear-cell carcinoma cell line RLC-310 and human normal renal cell line HK-2 cells, and SSH technology was used to construct a RCC cell library of differential expression genes and to screen the most differentially expressed genes. RNA interference vector was constructed to silence the expression of the differentially expressed gene SIPL1 in human renal cell lines RLC-310 and GRC-1. Proliferation index was estimated by cell counting, MTT and tumor xenograft assay. Cell cycle analysis was performed using fluorescence activated cell sorting. Drug resistance potential to adriamycin was assessed by MTT.</p><p><b>RESULTS</b>A subtractive cDNA library of highly expressed genes in the RCC cells was constructed and 12 differentially expressed genes were screened from the subtractive library, in which SIPL1 was the most differently expressed gene in the RCC cell line. SIPL1 overexpression in the RCC cells and clinical samples was confirmed by RT-PCR and Western blot analyses. The shRNA expression plasmid targeting to SIPL1 gene was constructed and transfected into RLC-310 and GRC-1 cells, resulting in downregulation of SIPL1. SIPL1 knockdown inhibited the cell proliferation (P < 0.05) and tumorgenesis. The tumor weights formed by RLC-310 cells transfected with SIPL1 shRNA was (0.22 ± 0.07)g and that of negative control vector was (0.85 ± 0.06)g. The tumor weight formed by GRC-1 cells was (0.32 ± 0.07)g and that of control vectors was (1.21 ± 0.11)g (P < 0.05). SIPL1 shRNA-transfected RLC-310 cells showed that more cells were arrested at G0/G1 phase [(71.13 ± 4.58)%] than that in the negative control RLC-310 cells [(53.27 ± 3.34)%, P < 0.05]. The proportion of G0/G1 phase in the SIPL1 shRNA transfected GRC-1 cells was (73.83 ± 3.97)%, significantly higher than that of (59.33 ± 3.03)% in the negative control GRC-1 cells (P < 0.05), and enhanced their sensitivity to adriamycin (P < 0.05). Silence of SIPL1 caused inactivation of AKT signaling and up-regulated expression of P27(Kip1) and P21(Cip1) proteins.</p><p><b>CONCLUSIONS</b>A differentially expressed gene SIPL1 in the renal clear-cell carcinoma is successfully screened using SSH technology. SIPL1 functions as an oncogene in RCC, and may become a novel molecular target for RCC diagnosis and therapy.</p>

Clinicopathological features and prognosis of triple-negative breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This study was conducted to analyze the clinicopathological characteristics and patient survival factors in triple-negative breast cancer (TNBC).</p><p><b>METHODS</b>A retrospective analysis was performed on 14 506 breast cancer patients admitted to the Departmrnt of Breast Surgery, Tianjin Medical University Cancer Hospital from January 2004 to June 2010. The correlation of pathological characteristics, recurrence time and patterns, and prognosis with TNBC was analyzed.</p><p><b>RESULTS</b>Among the 14 506 cases, there were 1886 (13.0%) cases of triple-negative breast cancer, 7282 (50.2%) cases of luminal A breast caner, 3380 (23.3%) cases of luminal B breast caner, and 1958 (13.5%) cases of HER-2 overexpressing breast cancer. Compared with the other groups, the triple-negative breast cancer patients had significantly higher histological grade, lower percentage of invasive breast ductal carcinoma and higher pathological stage (P < 0.001) . The 5-year disease-free survival rate of the triple negative breast cancer was 79.5%, significantly lower than that of the other subtype breast cancer (P < 0.001), but the difference in 5-year overall survival rate was not significant (P = 0.113). The independent factors of DFS in TNBC including: age, tumor size, clinical stage, surgery and chemotherapy (P < 0.05).</p><p><b>CONCLUSION</b>Compared with the other subtype breast cancers, the patients with triple-negative breast cancer have higher histological grade, lower percentage of invasive breast ductal carcinoma and higher pathological stage, and they also have a poor prognosis.</p>

Decreased skin function may be a risk factor for metabolic syndrome / 生理学报

The metabolic syndrome, a cluster of risk factors for cardiovascular disease, is closely related to environmental and lifestyle risk factors. Increasing evidence suggests that environmental risk factors may involve an increase in xenobiotic exposure, for example due to environmental toxins, medications, high meat intake, food additives and supplements; while lifestyle risk factors, such as sedentary lifestyles, may involve a decrease in the detoxification and elimination of xenobiotics. The skin, the body's largest organ, plays a distinct role in the detoxification and elimination of xenobiotics and the body lipid homeostasis, which is affected by sedentary lifestyle and physical activity, as well as by ambient temperature. Thus, it seems that decreased skin biotransformation and excretion, for example due to low ambient temperature and sedentary lifestyle, may be an important risk factor for metabolic syndrome. This review aims to provide insight into the role of the skin in the development of metabolic syndrome.

Effects of bone morphogenetic protein-7 therapy on E3 ubiquitin ligase expression in mouse liver with experimentally induced fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>This study explored the dynamic expression of the E3 ubiquitin-protein ligase gene, Arkadia, in response to carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model and investigated the differential expression that occurs following treatment with the anti-fibrotic bone morphogenetic protein-7 (BMP-7).</p><p><b>METHODS</b>Thirty healthy male imprinting control region (ICR) mice were randomly assigned to three groups: normal (control; n = 6), CCl4-induced model group (model; n = 18), and CCl4-induced model with BMP-7 treatment group (treatment; n = 6). The model group was further divided into three subgroups (n = 6 each) for analysis at 4, 8 and 12 weeks after fibrosis induction. Liver fibrosis was induced by hypodermic injections of 60% CCl4 /peanut oil (5 mL/kg) to the hind legs of mice two-times per week in alternating legs for a period of 12 weeks. At week 9, the treatment group of CCl4-induced mice were given an intraperitoneal injection of BMP-7 (300 pg/g) simultaneously with that day's hypodermic injection of 60% CCl4 /peanut oil, and then every other day for a period of four weeks. The pathological changes in liver tissues were observed after staining with hematoxylin-eosin (HE) and Masson's trichrome. Messenger RNA (mRNA) and protein expression of Arkadia in liver were evaluated using reverse transcription-polymerase chain reaction and immunohistochemistry and Western blotting, respectively.</p><p><b>RESULTS</b>Mouse models of liver fibrosis were successfully established by CCl4 exposure. Arkadia, Smad7 and TGF-beta1 mRNA levels were up-regulated in the model group in a time-dependent manner (vs. control group), and BMP-7 treatment led to significant down-regulation of the CCl4-induced expression of the three genes (vs. control group: F = 812.80, 451.46, and 998.96, respectively; P less than 0.01). At week 12, the mRNA levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the BMP-7 treatment group than in the model group (t = 12.108, 18.737, and 16.364, respectively; P less than 0.01). Arkadia, Smad7, and TGF-b1 protein staining was weak in the portal area of control liver tissue. In contrast, the model group showed significantly stronger staining for all three proteins in the portal area and in the cytoplasm of liver cells. The staining of Arkadia, Smad7, and TGF-b1 proteins was significantly lower in the treatment group (vs. control group: F = 8.399, 609.690, and 900.561, respectively; P < 0.01). At week 12, the protein levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the treatment group than in the model group (t = 23.438, 11.667, and 42.889, respectively; P < 0.01).</p><p><b>CONCLUSION</b>Arkadia expression gradually increased along with the development of liver fibrosis but was suppressed by treatment with the anti-fibrotic factor, BMP-7.</p>

A preliminary study on the influence of human plasma exosomes-like vesicles on macrophage Wnt5A-Ca²+ pathway / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the influence of human plasma exosomes-like vesicles on the regulatory function of macrophages.</p><p><b>METHODS</b>The exosomes-like vesicles were purified from healthy donors plasma with a series of high-speed centrifugation and ultrafiltration. Macrophages were derived from cultured human blood monocytes. The molecular markers of macrophages were assayed by FACS. After cultured with exosomes-like vesicles, the changes of macrophages cytoplasma Ca(2+), and related genes and proteins were assayed by FACS, RT-PCR and Western Blot, respectively.</p><p><b>RESULTS</b>After cultured with exosomes-like vesicles, mean fluorescent intensity (MFI) of macrophages cytoplasma Ca(2+) was increased. The vesicles enhanced macrophages to express cytokines genes, the expression of IL-1β and TNF-α genes being increased by 0.85 and 1.69 times respectively at 2 h, and that of IL-6 gene 3.7 times compared with the control at 8 h. However, the vesicles inhibited the expression of macrophages IL-10 gene, had no influence on the Frizzled5 receptor expression and could induce CaMKII phosphorylation.</p><p><b>CONCLUSIONS</b>Exosomes-like vesicles can up-regulat macrophages expression of inflammatory cytokines genes, and increase the secretion of inflammatory cytokines by activating the Wnt5A-Ca(2+) signaling pathway.</p>

Effect of alendronate sodium on torque-out testing on implant-bone interfaces in estrogen-deficient rabbits with alendronate systemic administration / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the influence of systemic application of Alendronate sodium, a bone resorption inhibitor, on the osseointegration of implant-bone interface in estrogen-deficient rabbits through mechanical assessment.</p><p><b>METHODS</b>27 five-month-old Japanese white female rabbits were randomly divided into three groups (9 rabbits each group). An ovariectomy group (OVX), an ovariectomy and Alendronate sodium group (ALN) and a shamed-operated group (S). 12 weeks after operation, implants were installed into bilateral distal femurs and proximal tibias in each group. Alendronate sodium was administrated by intraperitoneal injection in ALN group; meanwhile equivalent of normal saline was administrated by intraperitoneal injection in OVX group and S group. Bone mineral density was measured right after the implant operation and also in 4, 8, 12 weeks. Torque-out values were measured in 4, 8, 12 weeks after animal sacrifice.</p><p><b>RESULTS</b>Bone mineral density of tibias in ALN group was closed to S group and was significantly different from OVX group (P < 0.05) after 8 weeks. While after 12 weeks, the bone mineral density of tibias and femurs in ALN group was both closed to S group and was significantly different from OVX group (P < 0.05). The torque-out values of tibias in ALN group were closed to S group and were significantly different from OVX group (P < 0.05) after 8 weeks. After 12 weeks, the torque-out values of tibias and femurs in ALN group were both closed to S group and were significantly different from OVX group (P < 0.05).</p><p><b>CONCLUSION</b>Systemic application of Alendronate sodium in osteoporosis rabbits can improve the bone-implant osseointegration significantly.</p>