OBJECTIVES: To explore the therapeutic mechanism of Flos Sophorae (FS) for treatment of psoriasis. METHODS: The active ingredients, targets and psoriasis-related disease targets of FS were obtained from TCMSP, GeneCards, OMIM, DisGeNET and String databases, and Cytoscape 3.8.0 software was used to construct the "FS -active ingredient-key target-signaling pathway-psoriasis" network. GO and KEGG enrichment analyses of the key targets were conducted, and molecular docking was performed using Discovery Studio 2019. In a BALB/c mouse model of imiquimod-induced psoriasis, the effects of vaseline, FS at high, medium and low doses (3.00, 1.50 and 0.75 g/kg, respectively) and a positive drug, given 1 week before and during modeling, were evaluated on body weight changes, spleen coefficient, psoriasis area and severity index (PASI) score and skin pathological changes. Phosphorylation levels of PI3K and AKT proteins were detected using immunohistochemistry and Western blotting. RESULTS: A total of 10 active components and 110 key targets were screened. GO and KEGG pathway enrichment analysis suggested that FS improved psoriasis primarily through the PI3K/AKT, TNF, and IL-17 signaling pathways. Molecular docking showed that both quercetin and kaempferol could spontaneously bind to AKT1, TNF and other sites. In the mouse model of psoriasis, treatment with low-dose FS significantly improved epidermal thickening, increased body weight, lowered PASI score, and reduced phosphorylation levels of PI3K and AKT proteins. CONCLUSIONS The therapeutic mechanism of FS for psoriasis involves multiple components, targets, and pathways that mediate the inhibition of the phosphorylation levels of PI3K and AKT proteins to suppress the activation of the PI3K/AKT signaling pathway.
Animals ; Psoriasis/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Signal Transduction/drug effects* ; Mice, Inbred BALB C ; Phosphatidylinositol 3-Kinases/metabolism* ; Molecular Docking Simulation ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Imiquimod ; Phosphorylation

Objective To investigate the effect of Yigong San(YGS)on learning and memory abilities of rats with lipopolysaccharide(LPS)-induced cognitive decline and explore its possible mechanism in light of intestinal microbiota.Methods Forty SD rats were randomly divided into control group,model group,donepezil(1.3 mg/kg)group,and high-dose(5.25 g/kg)and low-dose(2.63 g/kg)YGS treatment groups.After 24 days of treatment with the corresponding drugs or water by gavage,the rats in the latter 4 groups received an intraperitoneal injection of LPS(0.5 mg/kg)to establish models of Alzheimer's disease(AD).Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus.The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing,and the levels of IL-6,TNF-α,and IL-1β in the brain tissue and serum were detected using ELISA.Results Compared with the AD model group,the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling,reduced neuronal degeneration and necrosis in the hippocampus,lowered pathological score of cell damage,and decreased levels IL-6,TNF-α and IL-1β in the brain tissue and serum.The YGS-treated rats showed also obvious reduction of Alpha diversity indicators(ACE and Chao1)of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae,which were involved in such metabolic signaling pathways as cell community prokaryotes,membrane transport,and energy metabolism.Conclusion YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction,cofactors,and vitamin metabolism.

Objective To explore the mechanism by which Yigong San(YGS)improves learning and memory abilities of APP/PS1 transgenic mice in light of cerebral fluid metabolism regulation.Methods Three-month-old male APP/PS1 transgenic mice and wild-type C57BL/6 mice were both randomized into control group,model group,donepezil(1.67 mg/kg)group,and YGS(7.5 g/kg)group and received the corresponding treatments via gavage once daily for one month.After the treatments,the mice were assessed for learning and memory functions using Morris water maze test and examined for hippocampal and cortical pathologies and amyloid plaques using HE,immunohistochemical and thioflavin S staining;ELISA and Evans blue method were used for detecting Aβ1-40 and Aβ1-42 levels in the brain tissue and serum and assessing blood-brain barrier(BBB)integrity.Immunofluorescence colocalization was used to investigate AQP4 polarization on astrocytes.Western blotting was performed to detect the expressions of VE-cadherin,ZO-1,occludin,β-amyloid precursor protein(APP),BACE1,insulin-degrading enzyme(IDE),LRP1,RAGE,and AQP4 proteins.Results Compared with the control mice,APP/PS1 mice showed significant impairment of learning and memory abilities,increased degeneration or necrosis of hippocampal and cortical neurons,pathological scores,Aβ-positive plaques,elevated Aβ1-40 and Aβ1-42 levels in the brain tissue and serum,increased BBB permeability,upregulated RAGE expression,lowered expressions of VE-cadherin,LRP1,ZO-1,occludin,and AQP4 proteins,and reduced AQP4-expressing GFAP-positive cells.YGS treatment significantly improved the performance of the transgenic mice in Morris water maze test,reduced hippocampal and cortical pathologies and Aβ-positive plaques,and ameliorated the abnormal changes in Aβ1-40 and Aβ1-42 levels,BBB permeability,protein expressions of RAGE,VE-cadherin,LRP1,ZO-1,occludin and AQP4,and the number of AQP4-expressing GFAP-positive cells.Conclusion YGS improves learning and memory changes in APP/PS1 mice by ameliorating neuronal damage and Aβ pathology in the brain and regulating brain fluid metabolism.

Objective To investigate the effect of Yigong San(YGS)on learning and memory abilities of rats with lipopolysaccharide(LPS)-induced cognitive decline and explore its possible mechanism in light of intestinal microbiota.Methods Forty SD rats were randomly divided into control group,model group,donepezil(1.3 mg/kg)group,and high-dose(5.25 g/kg)and low-dose(2.63 g/kg)YGS treatment groups.After 24 days of treatment with the corresponding drugs or water by gavage,the rats in the latter 4 groups received an intraperitoneal injection of LPS(0.5 mg/kg)to establish models of Alzheimer's disease(AD).Water maze test and HE staining were used to evaluate the changes in learning and memory abilities and pathomorphology of the hippocampus.The changes in gut microbial species of the rats were analyzed with 16S rRNA sequencing,and the levels of IL-6,TNF-α,and IL-1β in the brain tissue and serum were detected using ELISA.Results Compared with the AD model group,the YGS-treated rats showed significantly shortened escape latency on day 5 after modeling,reduced neuronal degeneration and necrosis in the hippocampus,lowered pathological score of cell damage,and decreased levels IL-6,TNF-α and IL-1β in the brain tissue and serum.The YGS-treated rats showed also obvious reduction of Alpha diversity indicators(ACE and Chao1)of intestinal microbiota with significantly increased abundance of Prevotellaceae species at the family level and decreased abundance of Desulfovibrionaceae,which were involved in such metabolic signaling pathways as cell community prokaryotes,membrane transport,and energy metabolism.Conclusion YGS improves learning and memory abilities and hippocampal pathomorphology in AD rat models possibly by regulating the abundance of intestinal microbial species such as Prevotellaceae to affect the metabolic pathways for signal transduction,cofactors,and vitamin metabolism.

Objective To explore the mechanism by which Yigong San(YGS)improves learning and memory abilities of APP/PS1 transgenic mice in light of cerebral fluid metabolism regulation.Methods Three-month-old male APP/PS1 transgenic mice and wild-type C57BL/6 mice were both randomized into control group,model group,donepezil(1.67 mg/kg)group,and YGS(7.5 g/kg)group and received the corresponding treatments via gavage once daily for one month.After the treatments,the mice were assessed for learning and memory functions using Morris water maze test and examined for hippocampal and cortical pathologies and amyloid plaques using HE,immunohistochemical and thioflavin S staining;ELISA and Evans blue method were used for detecting Aβ1-40 and Aβ1-42 levels in the brain tissue and serum and assessing blood-brain barrier(BBB)integrity.Immunofluorescence colocalization was used to investigate AQP4 polarization on astrocytes.Western blotting was performed to detect the expressions of VE-cadherin,ZO-1,occludin,β-amyloid precursor protein(APP),BACE1,insulin-degrading enzyme(IDE),LRP1,RAGE,and AQP4 proteins.Results Compared with the control mice,APP/PS1 mice showed significant impairment of learning and memory abilities,increased degeneration or necrosis of hippocampal and cortical neurons,pathological scores,Aβ-positive plaques,elevated Aβ1-40 and Aβ1-42 levels in the brain tissue and serum,increased BBB permeability,upregulated RAGE expression,lowered expressions of VE-cadherin,LRP1,ZO-1,occludin,and AQP4 proteins,and reduced AQP4-expressing GFAP-positive cells.YGS treatment significantly improved the performance of the transgenic mice in Morris water maze test,reduced hippocampal and cortical pathologies and Aβ-positive plaques,and ameliorated the abnormal changes in Aβ1-40 and Aβ1-42 levels,BBB permeability,protein expressions of RAGE,VE-cadherin,LRP1,ZO-1,occludin and AQP4,and the number of AQP4-expressing GFAP-positive cells.Conclusion YGS improves learning and memory changes in APP/PS1 mice by ameliorating neuronal damage and Aβ pathology in the brain and regulating brain fluid metabolism.

Body fluid refers to all normal fluids in the human body,which are the basic substances that constitute human tissues and organs.It is also an essential foundation for maintaining normal life activities of the body.Its abnormal evolution in the human body is highly consistent with the pathological changes of dementia.This paper combs the internal relationship between normal body fluid metabolism and healthy human cognitive function,analyzes the corresponding relationship between the viscera related to regulating body fluid metabolism and the evolution of body fluid pathological changes and the degenerative pathological evolution of dementia from the natural aging time axis,emphasizes that the body fluid metabolism disorder is the core pathogenesis of dementia.We believe that in the early stages,preventive and conditioning methods such as a balanced diet and regular living habits should be implemented;In the mid-term stage,the focus is on regulating the Pi circulation and dialectical medication;In the later stage,on the basis of strengthening Pi circulation,it is necessary to support the diseased organs and treat them according to relevant syndromes.

Objective:To assess the susceptibility of gonococcal clinical isolates to gentamicin in Guangxi region, China, and to analyze the correlation between the minimum inhibitory concentration (MIC) of gentamicin and MICs of 7 other antibiotics.Methods:From December 2020 to December 2021, 584 gonococcal clinical isolates were collected from 37 medical institutions in 14 prefecture-level cities in Guangxi region. The susceptibility of gonococcal clinical isolates to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, tetracycline, ciprofloxacin and gentamicin was determined by using an agar dilution method. The MIC values of antibiotics were logarithmically transformed with base 2, and Spearman correlation analysis was carried out to evaluate the correlation between the MIC of gentamicin and MICs of the other 7 antibiotics.Results:The MIC of gentamicin ranged from 1 to 16 mg/L, and the MIC50 and MIC90 values were 4 and 8 mg/L, respectively; 361 strains (61.8%) were fully sensitive to gentamicin with the MIC ≤ 4 mg/L, 223 strains (38.2%) moderately sensitive with the MIC ranging from 8 to 16 mg/L, and no gentamicin-resistant strains were found. The number of strains resistant to azithromycin, penicillin, tetracycline and ciprofloxacin was 136 (23.3%), 415 (71.1%), 339 (58.0%) and 574 (98.3%) respectively, the number of lowly sensitive strains to ceftriaxone and cefixime was 17 (2.9%) and 6 (1.0%) respectively, and no spectinomycin-resistant strains were found. Spearman correlation analysis showed that the MIC of gentamicin was weakly correlated with the MICs of azithromycin, spectinomycin, penicillin, tetracycline, and ciprofloxacin (all P < 0.05), but was uncorrelated with the MICs of ceftriaxone and cefixime (both P > 0.05) . Conclusion:All gonococcal clinical isolates tested in this study showed a certain degree of susceptibility to gentamicin, and cross-resistance between gentamicin and other antibiotics was less likely to occur.

The contents of general practice discipline construction comprise of orientation, team development, personnel training, scientific research, teaching base establishment and management of the discipline, etc. At present, the weakness in above aspects of general practice discipline construction is still the major challenges in most of the primary healthcare institutions. Our experiences in last 10 years shows that the application of Leicester Assessment Package can effectively promote the general practice discipline development for primary care institutions.

Three-amino acid loop extension (TALE) transcription factors play important roles in plant growth and cell differentiation. There are plenty of studies on TALE transcription factors in several model plants, but not in radish (Raphanus sativas). A genome-wide bioinformatics analysis identified 33 TALE family genes in the Xiang-Ya-Bai (XYB) radish, These genes, are distributed on nine chromosomes and all contain 4-6 exons. The 33 TALE genes in radish showed a co-linearity relationship with the 17 homologous genes in Arabidopsis thaliana. Moreover, a large number of stress response cis-elements were found in the promoter regions of these genes. Expression analysis showed that four genes in the BELL subfamily were highly expressed in roots, and two genes in the KNOX subfamily were highly expressed in shoots of bolting plants and callus. All radish TALE genes contain sequences encoding the conserved HOX domain, except for the gene RSA10037940, which is homologous to Arabidopsis KNATM. The deduced 3D structures of the TALE proteins irrespective of subtypes are highly similar. All the encoded proteins were weakly acidic and hydrophilic. The radish TALE gene family is relatively evolutionarily conserved, which was consistent with results from Arabidopsis, but quite different from that of rice. This study provides important clues for studying the biological functions of TALE transcription factors in radish.
Amino Acids ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Raphanus/metabolism* ; Transcription Factors/metabolism*

Objective:To compare the dosimetric difference between 3D-printed multi-channel applicator and conventional vaginal single-channel applicator for brachytherapy, aiming to provide guidance for patients receiving brachytherapy after cervical cancer surgery.Methods:From January 2019 to November 2020, 25 cervical cancer patients complicated with VAIN Ⅲ receiving 192Ir high-dose-rate brachytherapy after cervical cancer surgery were selected. Each patient was located by CT scanning with 3D-printed multi-channel applicator and conventional vaginal single-channel applicator, and corresponding plan and evaluation were carried out. The dose volume histogram (DVH) was obtained by inverse dose optimization algorithm. The dosimetric differences of high-risk clinical target volume (HRCTV), bladder and rectum during brachytherapy were compared with those of source applicators. The optimal treatment plan was selected. Results:D 90%, D 100%, V 100% and V 150% of the plans designed by 3D-printed individual multi-channel applicator had no significant differences compared with those designed by conventional single-channel applicator (all P>0.05). The bladder and rectal D 2cm 3 designed by 3D-printed multi-channel applicator were significantly lower than those using conventional single-channel applicator, and the differences were statistically significant (both P<0.05). Conclusion:The multi-channel individual applicator target made by 3D-printing technology has good conformal property, properly protects the bladder and rectum and possesses treatment advantages over conventional single-channel applicator.