Objective To evaluate the efficacy and safety of Jiawei Dihuang Decoction in the treatment of vascular dementia(VD);To explore its mechanism and the VD susceptibility genesby using whole exome sequencing.Methods A total of 75 patients with VD who were hospitalized or received outpatient treatment at The Second Affiliated Hospital of Shaanxi University of Chinese Medicine were included.They were divided into the control group(37 cases,treated with conventional Western medicine)and the experimental group(38 cases,treated with conventional Western medicine+Jiawei Dihuang Decoction)using random number table method.The treatment course was 3 months.The general data,TCM syndrome scores,MMSE scores,ADL scores,Blessed scores and adverse reactions of the two groups were compared.Peripheral blood samples from 36 patients with kidney-yin deficiency type VD were selected for whole exome sequencing.Susceptible genes were screened,and the targets of Jiawei Dihuang Decoction were analyzed by network pharmacology.A"drug-gene"network was constructed,and key pathways were enriched.Results There was no statistical significance in the baseline data between the two groups(P>0.05),and they were comparable.Compared with before treatment,the MMSE scores of patients in both groups significantly increased after treatment,while TCM syndrome scores and ADL scores significantly decreased(P<0.05).Compared with the control group,the TCM syndrome scores,MMSE scores,ADL scores and clinical efficacy of the experimental group were significantly better than those of the control group(P<0.05).Moreover,the Blessed score showed that the experimental group had more advantages in improving the patients'living ability and daily habits(P<0.05).No adverse reactions were observed in both groups during the treatment period.A total of 1 250 744 single nucleotide polymorphism(SNP)loci and 37 314 insertion and deletion(InDel)loci were detected by whole exome sequencing.After screening,3 041 VD susceptibility genes were obtained.It was found that they were involved in biological processes such as the response to nutrient levels,positive regulation of the MAPK cascade,vascular processes in the circulatory system,the response to nutrients,etc.And enriched in PI3K-Akt,cholinergic/glutamatergic synapses,lipid metabolism and atherosclerosis pathways.The potential targets of 854 of Jiawei Dihuang Decoction were intersected with the susceptibility genes to obtain 353 common targets.The top 10 key genes were analyzed and found to be involved in positive regulation of cytosine-serine phosphorylation,miRNA-mediated gene silencing regulation,and the response of cells to decreased oxygen levels,etc.They were enriched in PI3K-Akt,lipid and atherosclerosis signaling pathways.Conclusion Jiawei Dihuang Decoction can alleviate the symptoms of patients with VD,protect cognitive function,enhance their ability of daily living,and has good safety profile.Its mechanism may involve regulating susceptibility genes through PI3K-Akt signaling pathway and lipid atherosclerosis signaling pathway,and improving lipid metabolism,inflammatory response and oxidative stress.

Objective To evaluate the efficacy and safety of Jiawei Dihuang Decoction in the treatment of vascular dementia(VD);To explore its mechanism and the VD susceptibility genesby using whole exome sequencing.Methods A total of 75 patients with VD who were hospitalized or received outpatient treatment at The Second Affiliated Hospital of Shaanxi University of Chinese Medicine were included.They were divided into the control group(37 cases,treated with conventional Western medicine)and the experimental group(38 cases,treated with conventional Western medicine+Jiawei Dihuang Decoction)using random number table method.The treatment course was 3 months.The general data,TCM syndrome scores,MMSE scores,ADL scores,Blessed scores and adverse reactions of the two groups were compared.Peripheral blood samples from 36 patients with kidney-yin deficiency type VD were selected for whole exome sequencing.Susceptible genes were screened,and the targets of Jiawei Dihuang Decoction were analyzed by network pharmacology.A"drug-gene"network was constructed,and key pathways were enriched.Results There was no statistical significance in the baseline data between the two groups(P>0.05),and they were comparable.Compared with before treatment,the MMSE scores of patients in both groups significantly increased after treatment,while TCM syndrome scores and ADL scores significantly decreased(P<0.05).Compared with the control group,the TCM syndrome scores,MMSE scores,ADL scores and clinical efficacy of the experimental group were significantly better than those of the control group(P<0.05).Moreover,the Blessed score showed that the experimental group had more advantages in improving the patients'living ability and daily habits(P<0.05).No adverse reactions were observed in both groups during the treatment period.A total of 1 250 744 single nucleotide polymorphism(SNP)loci and 37 314 insertion and deletion(InDel)loci were detected by whole exome sequencing.After screening,3 041 VD susceptibility genes were obtained.It was found that they were involved in biological processes such as the response to nutrient levels,positive regulation of the MAPK cascade,vascular processes in the circulatory system,the response to nutrients,etc.And enriched in PI3K-Akt,cholinergic/glutamatergic synapses,lipid metabolism and atherosclerosis pathways.The potential targets of 854 of Jiawei Dihuang Decoction were intersected with the susceptibility genes to obtain 353 common targets.The top 10 key genes were analyzed and found to be involved in positive regulation of cytosine-serine phosphorylation,miRNA-mediated gene silencing regulation,and the response of cells to decreased oxygen levels,etc.They were enriched in PI3K-Akt,lipid and atherosclerosis signaling pathways.Conclusion Jiawei Dihuang Decoction can alleviate the symptoms of patients with VD,protect cognitive function,enhance their ability of daily living,and has good safety profile.Its mechanism may involve regulating susceptibility genes through PI3K-Akt signaling pathway and lipid atherosclerosis signaling pathway,and improving lipid metabolism,inflammatory response and oxidative stress.

BACKGROUND: Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. METHODS: Mice with scleroderma received a single 50 lg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. RESULTS: HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages. CONCLUSION We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycininduced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.

Objective:To observe the clinical effect of Buyang huanwu decoction combined with hyperbaric oxygen therapy on acute cerebral infarction (ACI) of qi deficiency and blood stasis type.Methods:A total of 78 patients with acute cerebral infarction of qi deficiency and blood stasis type admitted to the 901 Hospital of CPLA from June 2016 to May 2019 were selected as study objects and randomly divided into 3 groups according to random number table method: Traditional Chinese medicine (TCM) group, HBO group, and combination group ( n=26). The TCM group was treated with traditional Chinese medicine decoction on the basis of the conventional treatment of ACI; the HBO group was treated with HBO on the basis of conventional treatment of ACI; the combination group was treated with traditional Chinese medicine decoction and HBO on the basis of the conventional treatment of ACI. After 20 days of treatment, the National Institute of Health stroke scale (NIHSS) scores and TCM syndrome scores of the 3 groups were statistically analyzed according to their basic clinical characteristics. Results:There were no significantly statistical differences in terms of NIHSS score or TCM syndrome score before treatment among the 3 groups ( H=0.304, P=0.859; H=0.379, P=0.827). After treatment, the NIHSS score of the combination group was lower than those of the TCM group and the HBO group ( P’=0.033, P’=0.011). The difference of NIHSS score after treatment in the combination group was higher than those in the TCM group and the HBO group ( P’=0.025, P’=0.003). After treatment, the TCM syndrome score of the combination group was lower than those of the TCM group and the HBO group ( P’=0.016, P’=0.046). After treatment, the difference of TCM syndrome score in the combination group was higher than those in the TCM group and the HBO group ( P’=0.005, P’=0.023). The overall clinical efficacy of the combination group was better than those of the TCM group and the HBO group ( P’=0.045, P’=0.010)). Conclusion:Buyang Huanwu decoction combined with hyperbaric oxygen therapy has a synergistic effect in the treatment of ACI, which is worthy of clinical application.

Objective:To observe the clinical effect of Buyang huanwu decoction combined with hyperbaric oxygen therapy on acute cerebral infarction (ACI) of qi deficiency and blood stasis type.Methods:A total of 78 patients with acute cerebral infarction of qi deficiency and blood stasis type admitted to the 901 Hospital of CPLA from June 2016 to May 2019 were selected as study objects and randomly divided into 3 groups according to random number table method: Traditional Chinese medicine (TCM) group, HBO group, and combination group ( n=26). The TCM group was treated with traditional Chinese medicine decoction on the basis of the conventional treatment of ACI; the HBO group was treated with HBO on the basis of conventional treatment of ACI; the combination group was treated with traditional Chinese medicine decoction and HBO on the basis of the conventional treatment of ACI. After 20 days of treatment, the National Institute of Health stroke scale (NIHSS) scores and TCM syndrome scores of the 3 groups were statistically analyzed according to their basic clinical characteristics. Results:There were no significantly statistical differences in terms of NIHSS score or TCM syndrome score before treatment among the 3 groups ( H=0.304, P=0.859; H=0.379, P=0.827). After treatment, the NIHSS score of the combination group was lower than those of the TCM group and the HBO group ( P’=0.033, P’=0.011). The difference of NIHSS score after treatment in the combination group was higher than those in the TCM group and the HBO group ( P’=0.025, P’=0.003). After treatment, the TCM syndrome score of the combination group was lower than those of the TCM group and the HBO group ( P’=0.016, P’=0.046). After treatment, the difference of TCM syndrome score in the combination group was higher than those in the TCM group and the HBO group ( P’=0.005, P’=0.023). The overall clinical efficacy of the combination group was better than those of the TCM group and the HBO group ( P’=0.045, P’=0.010)). Conclusion:Buyang Huanwu decoction combined with hyperbaric oxygen therapy has a synergistic effect in the treatment of ACI, which is worthy of clinical application.

To investigate the clinical efficacy, feasibility and safety of new "three tubes" method in the treatment of spontaneous esophageal rupture. A total of 22 patients with spontaneous esophageal rupture were retrospectively analyzed. Through the new "three tubes" method of treatment, patients achieved leak cured with reduced hospital stay, less medical expenses and early resumption of oral diet. The new "three tubes" method for spontaneous esophageal rupture has the advantages of easy handling, minimal invasion, few complication and exact curative effect.

This study aimed at investigating the inhibitory effects and the anti-tumor mechanisms of co-adminis-tration of fusion proteins mGM-CSF/βhCG ( GC ) and hVEGF121/βhCG ( VC ) on RM-1 prostatic cancer and B16 F10 melanoma in the C57 BL/6 J mouse model. Two recombinant stains containing pET-28 a-mGM-CSF-X10-βhCGCTP37 and pET-28 a-VEGF-M2-X10-βhCG-CTP37 were induced by lactose to express fusion proteins. The fusion proteins were separated and purified to prepare the anti-tumor protein vaccines ( VC protein vaccine and GC protein vaccine) , which were then mixed to prepare a combined protein vaccine named VGC protein vac-cine. The prostatic cancer and melanoma tumor-bearing mice C57 BL/6 J were immunized with described vac-cines, then the growth of each tumor was measured;splenocyte proliferation of immunized mice was detected;and the cytotoxic effects of the vaccine on tumor cells were tested. After that, the in vivo concentrations of IFN-γ and anti-hVEGF antibodies were investigated by ELISA. The difference between each experimental group and normal saline group ( NS) was statistically significant in both tumor-bearing mouse models ( P <0. 05) respectively. Besides, VGC group exhibited significantly better anti-tumor effect compared with the GC and VC groups with the anti-tumor rate ( 41. 7 ± 0. 83)% and ( 46. 4 ± 1. 27)% for prostatic cancer and melanoma tumor, respectively. The co-administration of the two proteins, VC and GC, could inhibit the growth of RM-1 prostatic tumor and B16F10 melanoma effectively via anti-tumor immunity and anti-tumor angiogenesis.

The ability of clinical teachers plays a key role in residents standardized training. The teachers should fully understand the relevant policies and improve the awareness of resident standardized training. The construction of clinical teaching ability is the essential ability for clinical teachers and is the focus of the teacher training, which can guarantee to guide the improvement of residents' clinical thinking ability and the training of their clinical skills. Establishing teacher training system, making a suitable train-ing plan, selecting applicable training content and participating in various types of teacher training should effectively improve the comprehensive teaching ability of clinical teachers for resident standardized training.

Objective To describe the CSP genotypic profile in clinical isolates of Aspergillus fumigates from different regions of China,and to investigate if there is a difference in antifungal susceptibility among A.fumigates of different CSP genotypes and from different regions.Methods Totally,112 A.fumigates strains clinically isolated from Fujian,Shanghai,Hebei and Beijing were included in this study,and identified according to macro-and micro-morphological characters,growth temperature and β-tubulin sequence.Classic A.fumigatus strains were typed according to CSP gene sequence.The minimal inhibitory concentrations (MICs) of voriconazole,itraconazole and amphotericin B to A.fumigates were determined in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) M38-A protocol.Results All the strains were identified as classic A.fumigates,and fall into 11 CSP genotypes.The most common genotypes were t04A (n =32),t03 (n =17) and t01 (n =24) in all the strains,tl0,t04A and t01 in Fujian,t04A and t01 in Shanghai,t01,t03 and t04A in Hebei,t02,t04A,t01and t03 in Beijing.One A.fumigatus strain was identified as a new CSP type t25 in Fujian,which showed no obvious difference in morphology,growth rate or appropriate growth temperature from the other CSP genotypes of A.fumigatus strains.No statistical difference was found in the susceptibility to amphotericin B,itraconazole or fluconazole among different genotypes of A.fumigates,whereas the MICs of itraconazole were significantly lower in A.fumigates isolates from Fujian than in those from the other three regions.Conclusions The CSP genotypic profile of A.fumigates varies in clinical isolates from different regions.No significant difference is observed in the susceptibility to amphotericin B,itraconazole or fluconazole among different CSP genotypes of A.fumigates,but the susceptibility to itraconazole is somewhat different between A.fumigates strains from different regions.

Retinoic acid-inducible gene I (RIG-I) is an important pattern recognition receptor that detects viral RNA and triggers the production of type-I interferons through the downstream adaptor MAVS (also called IPS-1, CARDIF, or VISA). A series of structural studies have elaborated some of the mechanisms of dsRNA recognition and activation of RIG-I. Recent studies have proposed that K63-linked ubiquitination of, or unanchored K63-linked polyubiquitin binding to RIG-I positively regulates MAVS-mediated antiviral signaling. Conversely phosphorylation of RIG-I appears to play an inhibitory role in controlling RIG-I antiviral signal transduction. Here we performed a combined structural and biochemical study to further define the regulatory features of RIG-I signaling. ATP and dsRNA binding triggered dimerization of RIG-I with conformational rearrangements of the tandem CARD domains. Full length RIG-I appeared to form a complex with dsRNA in a 2:2 molar ratio. Compared with the previously reported crystal structures of RIG-I in inactive state, our electron microscopic structure of full length RIG-I in complex with blunt-ended dsRNA, for the first time, revealed an exposed active conformation of the CARD domains. Moreover, we found that purified recombinant RIG-I proteins could bind to the CARD domain of MAVS independently of dsRNA, while S8E and T170E phosphorylation-mimicking mutants of RIG-I were defective in binding E3 ligase TRIM25, unanchored K63-linked polyubiquitin, and MAVS regardless of dsRNA. These findings suggested that phosphorylation of RIG inhibited downstream signaling by impairing RIG-I binding with polyubiquitin and its interaction with MAVS.
Adaptor Proteins, Signal Transducing ; metabolism ; Adenosine Triphosphate ; metabolism ; DEAD Box Protein 58 ; DEAD-box RNA Helicases ; chemistry ; genetics ; metabolism ; Dimerization ; Humans ; Mutagenesis, Site-Directed ; Phosphorylation ; Polyubiquitin ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; RNA, Double-Stranded ; metabolism ; Recombinant Proteins ; biosynthesis ; chemistry ; genetics ; Signal Transduction ; Transcription Factors ; metabolism ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination