[Objective] To summarize Professor WEI Yuegang's experience in treating Yangyu Hanning acne.[Methods]Through collecting medical record from outpatient clinics, Prof. WEI Yuegang's understanding of Yangyu Hanning acne and experience of Yangyu Hanning acne syndrome differentiation and treatment were analyzed and summarized.[Results]Prof. WEI Yuegang believes that the pathogenesis of Yangyu Hanning acne is Yang deficienay and Yang depression, Yang is deficient in the body, and the cold dampness blocks meridians, dysfunction of Shaoyang, Yang deficiency and Yang depression influence each other, Yang cannot supply and distribute, Yin cannot moisten, affter a long time it leads to heat in the upper and cold in the lower, or cold heat complex. In the treatment, we should give priority to warming yang and give consideration to the solution of depression, Prof. WEI Yuegang added and subtract on the basis of the Shenqi Pill and Xiaochaihu Decoction, and formulated Wenyang Jieyu Xiaocuo Decoction for treating the disease. Wenyang Jieyu Xiaocuo Decoction can both warm Yang and dispel cold and resolve Qi stagnation in the provided medical record, so the case achieved good results. [Conclusion]Prof. WEI Yuegang's treatment experience of Yangyu Hanning acne has satisfactory clinical efficacy and is worth to use for reference and promotion.

OBJECTIVETo investigate the effects of a recombinant adenovirus-mediated triple mutant hypoxia-inducible factor-1α (HIF-1α) on the proliferation and vascular endothelial growth factor (VEGF) expression in human microvascular endothelial cells (hMVECs).

METHODSThe adenovirus vector of the triple mutant HIF-1α (Ad-HIF-1α(564/402/803)), adenovirus vector of wild-type HIF-1α (Ad-HIF-1α(nature)), Ad-lacZ and Ad-Null were amplified in HEK293A cells, and the adenoviruses were purified and titrated. Dual luciferase reporter assay system was employed to detect the transcriptional activities of wild-type and triple mutant HIF-1α. After infection of the hMVECs with the adenoviruses, the cellular protein expressions of HIF-1α and VEGF were detected using Western blotting, and the cell proliferation was assessed by MTS assay.

RESULTSThe transcriptional activity of the triple mutant HIF-1α was significantly higher than that of wildtype HIF-1α in the infected hMVECs (P<0.001). The protein levels of HIF-1α and VEGF in cells infected with Ad-HIF-1α(564/402/803) were significantly higher than those in cells infected with other adenoviruses, and HIF-1α dose-dependently up-regulated VEGF protein expression. The absorbance was significantly higher in Ad-HIF-1α(564/402/803) group than in the other groups (P<0.01) on the third and fifth days after infection.

CONCLUSIONThe recombinant adenovirus-mediated triple mutant HIF-1α expression is stable under normoxic condition. The triple mutant HIF-1α can up-regulate the expression of VEGF protein in hMVECs to promote the cell proliferation.

Adenoviridae ; genetics ; Cell Proliferation ; Endothelial Cells ; cytology ; metabolism ; Endothelium, Vascular ; cytology ; Genetic Vectors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; pharmacology ; Microvessels ; cytology ; Recombinant Proteins ; genetics ; Transfection ; Vascular Endothelial Growth Factor A ; metabolism

Objective:To investigate protective effect of Pinus massoniana needle extract (PMNE) against oxidative stress in human dermal papilla cells (HDPC) , and to explore its mechanisms. Methods:As research objects, some cultured HDPC were treated with H 2O 2 at different concentrations of 0 (control group) , 0.1, 0.2, 0.4, 0.8 and 1.0 mmol/L, in order to establish the optimal condition for in vitro oxidative stress in HDPC; some other HDPC were transfected with nuclear factor-erythroid 2-related factor 2 (Nrf2) specific small interfering RNAs (siRNA1, siRNA2, siRNA3) or a Nrf2-overexpressing plasmid (pCMV6-XL5-Nrf2) , the HDPC transfected with a scrambled-siRNA and an empty plasmid pCMV6-XL5 served as the control siRNA group and control plasmid group respectively, and HDPC subjected to conventional culture served as the blank group; after the above treatment, real-time fluorescence-based quantitative PCR and Western blot analysis were performed to determine Nrf2 mRNA and protein expression, respectively; cell viability and apoptosis were detected in the above transfected cells after the treatment with H 2O 2 at an optimal concentration. In the subsequent experiment, some HDPC were divided into several groups: control group subjected to conventional culture, dihydrotestosterone group treated with 0.03 μg/ml dihydrotestosterone, proanthocyanidin group treated with 0.03 μg/ml dihydrotestosterone and 6.00 μg/ml proanthocyanidin B2, PMNE groups treated with 0.03 μg/ml dihydrotestosterone and PMNE at different concentrations of 1, 5, 25 and 100 μg/ml; after the above treatment, cell viability and apoptosis were detected, relative fluorescence intensity of intracellular reactive oxygen species (ROS) , malondialdehyde (MDA) content, mRNA and protein expression of Nrf2, quinone oxidoreductase 1 (NQO1) , heme oxygenase 1 (HO-1) , Kelch-like ECH-related protein 1 (Keap1) , transforming growth factor (TGF) -β1, Sma- and Mad-related protein 2/3 (Smad2/3) , phosphorylated Smad2/3 (p-Smad2/3) were determined in HDPC. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference- t test for multiple comparisons. Results:The viability of HDPC ranged from 75% to 85% after the treatment with 0.4 mmol/L H 2O 2, which was selected as the optimal condition for in vitro oxidative stress in HDPC. Compared with the blank group and control siRNA group, the Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups showed significantly decreased Nrf2 mRNA and protein expression (all P < 0.05) , but significantly increased apoptosis rate (Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups, blank group and control group: 12.50% ± 0.05%, 26.07% ± 0.05%, 58.44% ± 1.03%, 10.38% ± 0.64%, 13.05% ± 0.12%, respectively; all P < 0.05) . Nrf2 protein expression was the lowest in the Nrf2-siRNA2 group, so Nrf2-siRNA2 was selected as the optimal interfering fragment for subsequent experiments. Compared with the blank group and control plasmid group, the Nrf2 overexpression group showed significantly increased Nrf2 mRNA and protein expression (both P < 0.05) , but a significantly decreased apoptosis rate (all P < 0.05) . After the treatment with 0.4 mmol/L H 2O 2, the Nrf2 overexpression group showed a significantly decreased apoptosis rate, but significantly increased cell viability compared with the empty vector group ( t = 3.66, 40.40, respectively, both P < 0.001) ; the Nrf2-siRNA2 group showed a significantly increased apoptosis rate, but significantly decreased cell viability compared with the control group ( t = 13.13, 67.37, respectively, both P < 0.001) . In the PMNE treatment experiment, the proanthocyanidin group and PMNE groups showed significantly increased cell viability, but significantly decreased apoptosis rates compared with the dihydrotestosterone group (all P < 0.01) ; proanthocyanidin and PMNE at different concentrations could significantly inhibit dihydrotestosterone-induced overexpression of ROS and MDA in HDPC (all P < 0.01) ; the protein expression of Nrf2, NQO1 and HO-1 was significantly higher in the proanthocyanidin group, 5-, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) , while the protein expression of Keap1 and TGF-β1, and the Smad2/3 phosphorylation level were significantly lower in the proanthocyanidin group, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) . Conclusion:Nrf2 plays an important role in protecting against oxidative damage in HDPC, and PMNE may exert marked protective effect on HDPC by activating the Nrf2-antioxidant responsive element signaling pathway.

Objective·To investigate the causal relationship between atrial fibrillation(AF)and cognitive impairment.Methods·A two-sample Mendelian randomization(TSMR)analysis was used to assess the potential causality of AF on cognitive dysfunction.Single nucleotide polymorphisms(SNPs)strongly associated with AF were extracted as instrumental variables by using a dataset of a large-scale genome-wide association study(GWAS)on AF.The associations of SNPs with Alzheimer's disease dementia,Parkinson's disease dementia,vascular dementia,Lewy body dementia,frontotemporal dementia,undefined dementia,and overall cognitive function assessment were extracted separately from publicly available GWAS data on cognitive dysfunction.The inverse variance-weighted(IVW)method was used for the main analysis,and sensitivity analyses were conducted by using Cochran's Q test,MR-Egger regression,and leave-one-out method.To verify the robustness of the results,replicate analyses and meta-analyses were performed by using different GWAS data.Results·In the initial analysis,101 SNPs were extracted as instrumental variables from a meta-analysis of a genome-wide association study involving up to 1 030 836 individuals.The IVW analysis showed no evidence for causal associations between AF and dementia[dementia(OR=1.032;95％CI 0.973-1.094;P=0.290),Parkinson's disease dementia(OR=1.004;95％CI 0.780-1.291;P=0.977),vascular dementia(OR=1.123;95％CI 0.969-1.301;P=0.125),or unspecified dementia(OR=1.013;95％CI 0.910-1.129;P=0.807)].In the replication analysis,27 SNPs were extracted as instrumental variables from the FinnGen AF GWAS data,and the 1VW analysis were consistent with the initial analysis[cognitive function(OR=0.999;95％CI 0.982-1.016;P=0.874),Alzheimer's disease dementia(OR=0.977;95％CI 0.943-1.012;P=0.193),Lewy body dementia(OR=1.014;95％CI 0.898-1.145;P=0.826),or frontotemporal dementia(OR=0.996;95％CI 0.745-1.333;P=0.980)].Both Mendelian randomization analyses and meta-analyses showed no evidence of an association between genetically predicted AF and different types of dementia or overall cognitive function assessment.MR-Egger regression suggested no horizontal pleiotropy and leave-one-out analysis showed stable results after individually removing each SNP.Conclusion·No evidence of a causal relationship between AF and cognitive impairment was found.The associations observed in observational studies can be partially attributed to confounding factors such as shared biology or co-morbidities.