1.Mechanism of total flavonoids of Dracocephalum moldavica L . in treatment of vascular cognitive impairment based on network pharmacology and animal experimental verification
Shangjia Ma ; Lu Wang ; Hua Li ; Jiayu Lv ; Dewang Gao ; Shuaiqiang Zhang ; Zi Guo ; Li' ; e Wu ; Xia Guo
Acta Universitatis Medicinalis Anhui 2025;60(4):675-684
Objective:
To investigate the molecular mechanisms and pathways of action of total flavonoids of Dracocephalum moldavica L.(TFDM) in treating vascular cognitive impairment(VCI) based on network pharmacology and in vivo animal experiments.
Methods :
The swiss target prediction database, literature, and PubChem were used to screen the active components and action targets of TFDM. The online mendelian inheritance in man(OMIM) and GeneCards databases were utilized to screen for possible VCI targets. Venny software was used to obtain the intersection target of TFDM and VCI. The search tool for recurring instances of neighbouring genes(String) database and Cytoscape software was used to construct the PPI network. The database for annotation, visualization and integrated discovery(DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI. 24 rats were divided into Sham, Model, Donepezil, and TFDM groups. Except for the Sham group, the VCI model was created using modified bilateral common carotid artery ligation. After continuous gavage for 21 days, the Morris water maze test was used to evaluate the spatial learning and memory ability of rats. Hematoxy-lineosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats. Western blot was used to detect nuclear factor kappa-B p65(NF-κB p65) and tumor necrosis factor-α(TNF-α) in rat brains.
Results :
A total of 39 active ingredients of TFDM were screened, 209 corresponding targets, 10 417 gene targets of VCI, and 193 intersecting targets. According to the results of the GO enrichment of function analysis, TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species, etc. KEGG pathway enrichment analysis suggested that TFDM might regulate TNF, IL-17 signing pathway, etc. The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats. In addition, TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-α and NF-κB p65(P<0.05).
Conclusion
TFDM can improve the cognitive function of VCI through multi-components and multi-targets, and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway,reducing neuroinflammation,and improvement of blood-brain barrier permeability.
2.Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer
Yinfei CHEN ; Shiyu ZHU ; Jiayu FU ; Jianguo LIN ; Yan SUN ; Gaochao LV ; Minhao XIE ; Tao XU ; Ling QIU
Journal of Pharmaceutical Analysis 2022;12(6):869-878
Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
3.Distribution and haplotype polymorphism of HLA-A、-B、-C、-DRB1、-DQB1 alleles in Anhui Han population
Chao WANG ; Xiaoyu HU ; Yang ZHAO ; Juan YU ; Huixin JIN ; Jiayu WEI ; Feifei JIANG ; Nana ZHAO ; Chaoqun GU ; Rong LV
Chinese Journal of Blood Transfusion 2021;34(3):240-244
【Objective】 To study the distribution and haplotype polymorphism of HLA-A, -B, -C, -DRB1, -DQB1 alleles in Anhui Han population. 【Methods】 The HLA-A, -B, -C, -DRB1 and -DQB1 genotyping of 3 169 random unrelated stem cell donors was performed by PCR-SBT. The allele frequency, haplotype frequency and linkage imbalance parameters were calculated by counting method, maximum expectation algorithm and PyPop software. 【Results】 A total of 411 HLA alleles were detected in the population, of which 67, 143, 65, 75 and 64 alleles were detected for HLA-A, -B, -C, -DRB1 and -DQB1, respectively. The alleles with frequency >0.1 were HLA-A*11∶01, A*11∶01, A*24∶02, A*02∶01, C*01∶02, C*07∶02, C*06∶02, DRB1*09∶01, DRB1*15∶01, DRB1*07∶01, DQB1* 03∶01, DQB1* 03∶03, and DQB1*02∶01. 1426 HLA-A~HLA-B, 1 772 HLA-B~HLA-DRB1, 798 HLA-B~HLA-C, and 446 HLA-DRB1~HLA-DQB1 haplotypes were detected. The haplotypes showed linkage imbalance, and 19 of them showed strong linkage imbalance (RLD>0.80). 【Conclusion】 The frequency and haplotype distribution of HLA-A, -B, -C, -DRB1 and -DQB1 alleles in Anhui Han population were obtained. The distribution of those alleles and haplotypes have their own characteristics.
4.Observations on the Therapeutic Effect of Abdominal Acupuncture on Rheumatoid Arthritis
Shanghai Journal of Acupuncture and Moxibustion 2016;35(9):1106-1108
Objective To investigate the clinical therapeutic effect of abdominal acupuncture on rheumatoid arthritis.Methods Sixty patients with rheumatoid arthritis were randomly allocated to treatment and control groups, 30 cases. The treatment group received abdominal acupuncture and the control group, conventional acupuncture. Pre-/post-treatment changes in erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and C-reactive protein (CRP) were observed after three courses of treatment. The clinical therapeutic effects were compared between the two groups.Results There were statistically significant pre-/post-treatment differences in ESR, RF and CRP in the two groups (P<0.01). There were statistically significant post-treatment differences in ESR, RF and CRP between the treatment and control groups (P<0.01). The total efficacy rate was 86.7% in the treatment group and 56.7% in the control group; there was a statistically significant difference between the two groups (P<0.05).Conclusion Abdominal acupuncture is an effective way to treat rheumatoid arthritis.
5.Surgical site infection in five patients
Qian XIANG ; Jiayu WU ; Daoqiong WEI ; Zhonghua ZHOU ; Min DAI ; Yu LV
Chinese Journal of Infection Control 2014;(7):415-417
Objective To investigate the possible causes of surgical site infection(SSI)in neurosurgical patients in a hospital during a short period of time.Methods Medical data of 135 neurosurgical operative patients from February 1 to March 15,2013 were reviewed,the possible risk factors for SSI were analyzed retrospectively with case-control study.Results Of 135 operative neurosurgical patients,5 (3.70%)developed SSI.Case-control study showed that the ratio of the run of the fifth operating room and undergoing of secondary operation was 4.07 (95%CI :0.52 -36.65)and 18.00(95%CI :2.00 -180.00)respectively.The difference between each surgeon special SSI rate and the average SSI rate in 2012 (2.54%[17/669])was not significantly different (P >0.05).Bacterial detection of en-vironmental specimens of the fifth operating room showed that except anesthetic cuff exceeded standard,the others were met the national requirements,and the isolated bacteria from anesthetic cuff was coagulase negative Staphylo-coccus ,which was not related with pathogens in infection.Conclusion “The secondary surgery”is the key risk fac-tor for SSI of neurosurgical patients.


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