ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Apoptosis is a process of programmed cell death,which has the function of maintaining skin balance.In psoriasis,the disturbance of apoptosis is characterized by abnormal prolif-eration of keratinocytes.Traditional Chinese medicine(TCM)has a regulatory effect on keratinocyte apoptosis,which can in-hibit the excessive proliferation of psoriasis epidermis,promote normal epidermal differentiation,and maintain epidermal homeo-stasis.It has the advantages of fewer adverse reactions and multi-targets.Therefore,this article summarizes and analyzes the specific mechanism of various active ingredients of TCM to in-duce the apoptosis of psoriasis keratinocytes by interfering with related factors and signaling pathways,hoping to provide a refer-ence for the treatment of psoriasis with TCM.

Objective To investigate the involvement of calmodulin(CaM)in the pathogenesis of Alzheimer disease(AD)and the mechanism by which CaM binds to amyloid-β(Aβ).Methods The hub genes expressed in AD and predicted to be the target proteins for AD prevention and treatment were obtained using bioinformatics methods.The GST-Aβ1-42 recombinant plasmid was constructed through genetic recombination and was then sequenced.The recombinant plasmids were identified using agarose gel electrophoresis,while the extracted and purified GST-Aβ1-42 fusion protein was confirmed using SDS-PAGE gel electrophoresis.GST pull-down assay was used to detect the interaction between GST-Aβ1-42 protein and CaM,expressed in the plasmid.Results The top 20 hub genes in degree ranking were obtained.The DNA sequencing results of the plasmid proved that the recombinant plasmid was successfully constructed.The agarose gel electrophoresis results indicated that the fragment digested by the enzyme was similar to the molecular weight of the Aβ1-42 gene seg-ments,further proving the successful construction of the recombinant plasmid.Binding of GST-Aβ1-42 protein to CaM in a concentration dependent manner was revealed through the GST pull down experiment.Conclusion The GST-Aβ1-42 recombinant plasmid is success-fully constructed and is shown to bind to CaM.

Objective To comprehensively explore the Chinese literature on medical insurance drug list,to sort out the research lineage of medical insurance drug list,and to summarize and discuss the future trends of relevant research development.Methods The research literature related to the list of medical insurance drug list in China from 2003 to 2023 were retrieved from databases including CNKI,Wanfang Database and VIP Chinese Journal Database.CiteSpace 6.2.R4 was used to draw a vis-ual graph,and text analysis was carried out according to the release time of relevant important policies.Results A total of 413 articles were included,and the authors of the published articles were relatively independent from each other,and no large aca-demic community has been formed in this field yet;Topics such as adjustment of medical insurance drug list,use of medical in-surance funds,and expert negotiations on medical insurance drugs are hot topics.Conclusions The number of papers pub-lished in this field is generally increasing,and cooperative research,diversified research and empirical research in this field should be strengthened.Focusing on hot topics and improving the quantity and quality of papers are the key factors to develop the literature in this field.

Alzheimer's disease(AD)is a common neurodegenerative disease with the main manifesta-tions of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an impor-tant role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory stor-age,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major path-ological factor in the occurrence and development of AD.This article reviews the role and research progress in in-tracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloidβ,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling path-ways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflamma-tion.

Objective To analyze the correlation between the expression of soluble glycoprotein A(GPA)in plasma of healthy blood donors and anti-M and anti-"Mia"antibodies.Methods Plasma from healthy donors from February 9,2022 to February 15,2023 was collected:irregular antibody-negative NN type(group Ⅰ,n=118)and MM type(group Ⅱ,n=51),anti-M antibody positive NN type(group Ⅲ,n=145)and anti-"Mia"antibody positive companion type(group Ⅳ,n= 87),the GPA content in plasma of different individuals in 4 groups was detected,and the difference in GPA expression was analyzed by t-test.Results The average plasma GPA contents in groupsⅠ,Ⅱ,Ⅲ and Ⅳ were 9.941±0.252,10.97±0.256,5.139±0.129 and 4.28±0.139ng/ml,respectively.The average GPA content of groups Ⅰ and Ⅱ was higher,and the average GPA content of groups Ⅲ and Ⅳ was lower,and the differences were statistically significant(all P＜0.01).Conclusion The GPA content in plasma of healthy donors with anti-M and anti-"Mia"antibodies was significantly lower than that of the antibody-negative group.The results of this study lay a foundation for further investigation of whether GPA in plasma has the ability to neutralize anti-M and anti-"Mia"antibodies,improve disease diagnosis and safe blood transfusion.

BACKGROUND:The specific mechanism of Gushukang,as a Chinese traditional patent medicine for the treatment of postmenopausal osteoporosis of kidney deficiency and blood stasis,needs further studies. OBJECTIVE:To investigate the effect of Gushukang on serum sex hormones,bone microstructure and estrogen receptor in postmenopausal osteoporosis. METHODS:Firstly,network pharmacological analysis was performed.The active ingredients and action targets of Gushukang and the targets of postmenopausal osteoporosis were obtained respectively.Cytoscape was used to construct the active ingredient-target network.STRING database and Cytoscape were used for protein-protein interaction analysis and screening of core targets.DAVID database was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of intersection targets.Then the ovariectomized Sprague-Dawley rats were used in the animal experiment.Gushukang was administered by gavage for 3 months.The serum estrogen level was detected by ELISA,the bone microstructure was detected by microCT,and the protein expression of estrogen receptor α and estrogen receptor β in bone tiusse was detected by western blot. RESULTS AND CONCLUSION:The network pharmacological research results identified 132 active ingredients and 150 targets of Gushukang and 1155 targets of postmenopausal osteoporosis.After intersections with 1155 postmenopausal osteoporosis targets,87 targets of active ingredients of Gushukang against postmenopausal osteoporosis were obtained.By constructing the active ingredient-target network,it was found that the active ingredients at the core were quercetin,kaempferol,luteolin,naringin and isorhamnetin,and the targets at the core were NCOA2,ESR2,AR,F2,ESR1 and PTGS1.The final targets obtained after the protein-protein interaction analysis and screening included MAPK8,ESR1,JUN,R3C1,RELA and FOS,of which ESR1 was the common core target obtained from the two analyses.KEGG enrichment analysis showed estrogen,tumor necrosis factor,apoptosis and other signaling pathways.Therefore,animal experiments focused on the effect of Gushukang on different subtypes of estrogen receptors in the estrogen signaling pathway.The results showed that in the Gushukang group,bone microstructure was significantly improved,serum estrogen level had no significant change,but the protein expression of estrogen receptor α and β in bone tissue was significantly increased.All the findings indicate that the mechanism of Gushukang in the treatment of postmenopausal osteoporosis may be related to its hormone-like effect and the enhancement of estrogen receptor expression.