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.

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.

Objective To investigate the medication and blood glucose control of type 2 diabetes patients under chronic diseases management in Xi'an chain pharmacies,and provides reference for improving the management policy of diabetes at grassroots level.Methods A number of chain pharmacies in the sixth district of Xi'an were selected by random sampling method,and on-site interviews were conducted by questionnaire survey to patients with type 2 diabetes under the management of chronic diseases.The basic information of patients,medication status(medication plan,drug adherence,etc.),diabetes-related conditions(blood glucose status,family history,course and complications,etc.)were collected.Multivariate logistic regression was used to analyze the relevant factors of blood glucose control in patients.Results A total of 403 patients were surveyed,the largest number of patients use oral hypoglycemic drugs alone(53.4％),followed by insulin medication(including insulin only and insulin in combination with oral hypoglycemic drugs)(35.7％),and the differences between disease course and glycemic control among patients with different drug regimens were statistically significant(P＜0.05).Only 43.7％of patients had good medication compliance.In addition,the patient's fast plasma glucose compliance rate was only 39.2％.The results of multivariate logistic regression analysis showed that good medication compliance(OR=1.744,95％CI 1.104 to 2.754,P=0.017)were independent influencing factors for achieving glycemic control.Conclusion The medication compliance of type 2 diabetes patients with poor blood glucose control in chronic disease management of chain pharmacies in Xi'an needs to be strengthened.Pharmacies should emphasize and give full play to the professional and service advantages of pharmacists to realize the functional role of pharmacies and strengthen diabetes management.

Objective:To develop a genotyping method for the Junior blood type and report on a rare blood type with Jr(a-).Methods:Healthy O-type RhD+ volunteer donors of the Shenzhen Blood Center from January to May 2021 ( n=1 568) and a pedigree with difficult cross-matching ( n=3) were selected as the study subjects. Serological methods were used for proband′s blood type identification, unexpected antibody identification, and antibody titer determination. Polymerase chain reaction-sequence specific primer (PCR-SSP) method was used for typing the proband′s RHD gene. ABCG2 gene coding region sequencing and a PCR-SSP genotyping method were established for determining the genotypes of the proband and his family members and screening of Jra antigen-negative rare blood type among the 1 568 blood donors. Results:The proband′s ABO and RhD blood types were respectively determined as B and partial D (RHDDVI.3/RHD01N.01), Junior blood type Jra antigen was negative, and plasma had contained anti-D and anti-Jra. Sequencing of the ABCG2 gene revealed that the proband′s genotype was ABGG201N.01/ABGG201N.01 [homozygous c. 376C>T (p.Gln126X) variants], which is the most common Jr(a-) blood type allele in the Asian population. Screening of the voluntary blood donors has detected no Jr(a-) rare blood type. Statistical analysis of the heterozygotes suggested that the allelic frequency for ABCG2*01N.01 (c.376T) was 0.45%, and the frequency of Jr(a-) rare blood type with this molecular background was about 0.2‰. Conclusion:A very rare case of partial DVI.3 type and Jr(a-) rare blood type has been identified. And a method for identifying the Junior blood type through sequencing the coding regions of the ABCG2 gene and PCR-SSP has been established.

AIM To explore the mechanism of Yiqi Wenyang Huwei Decoction on airway inflammation improvement of rats with bronchial asthma based on IL-25/NF-κB signaling pathway.METHODS 60 rats were randomly divided into the control group,the model group,the dexamethasone group(0.2 mg/mL),the low-dose,medium-dose and high-dose Yiqi Wenyang Huwei Decoction groups(1,2,4 g/mL),with 10 rats in each group.Intraperitoneal injection of ovalbumin(OVA)and aluminum hydroxide suspension was applied to establish the rat asthma model,followed by 2-week corresponding dosing of the drugs.The rats of each group had their daily diet,mental status,hair growth and respiration observed;their differential count of inflammatory cells in bronchoalveolar lavage fluid(BALF)detected by automatic hematology analyzer;their pathological changes of lung tissue observed by HE staining;their pulmonary IL-25 protein expression detected by immunohistochemistry(IHC);their levels of IL-4,IL-5 and IL-13 in BALF measured by ELISA;their pulmonary expression of IL-25 and TRAF6 mRNA detected by RT-qPCR;and their pulmonary protein expressions of IL-25,TRAF6,IκBα,p-IκBα,NF-κB p65 and p-NF-κB p65 detected by Western blot.RESULTS Compared with the control group,the model group displayed severe damage of the lung tissue and infiltration of a large number of inflammatory cells;increased number of inflammatory cells and levels of IL-4,IL-5 and IL-13 in BALF(P<0.01);increased mRNA expressions of IL-25 and TRAF6,and pulmonary protein expressions of IL-25,TRAF6,p-IκBα/IκBα and p-NF-κB p65/NF-κB p65(P<0.01).Compared with the model group,all of the Yiqi Wenyang Huwei Decoction groups shared improved pulmonary infiltration of inflammatory cells;decreased number of inflammatory cells and levels of IL-4,IL-5 and IL-13 in BALF(P<0.05,P<0.01);and decreased mRNA expressions of IL-25 and TRAF6,and pulmonary protein expressions of IL-25,TRAF6,p-IκBα/IκBα and p-NF-κB p65/NF-κB p65(P<0.01).CONCLUSION Yiqi Wenyang Huwei Decoction can inhibit the airway inflammation in the rat model of bronchial asthma,which may be related to the inhibited activation of IL-25/NF-κB signaling pathway and the reduced expression of inflammatory factors.

Objective To study the inhibitory effect of Huidu Yinhua powder from the Orthodox Manual of External Medicine on methicillin-resistant Staphylococcus aureus(MRSA),virulence factor α-hemolysin(Hla)activity,and biofilm formation,and to explore the optimal ratios of Huidu Yinhua powder and provide experimental support for its use.Methods The inhibitory effects of Huidu Yinhua powder and the herbs in the formula on USA300 were analyzed by the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),and disk diffusion assay(K-B method).Hemolysis,neutralization,oligomerization,and Western blot assays were used to verify in which form the drug inhibits the activity of virulence factor α-hemolysin(Hla).A biofilm assay was performed to evaluate the inhibitory effect of Huidu Yinhua powder on biofilm.Orthogonal experiments were performed to explore the optimal ratio of Huidu Yinhua powder.Results Huidu Yinhua powder inhibited the MRSA strain with a MIC90 of 64 mg/mL and an MBC of 256 mg/mL with antibacterial circle diameter of(7.50±0.50)mm.Huidu Yinhua powder inhibited Hla activity by inhibiting Hla secretion.The minimum effective concentration(MEC)was 16 mg/mL,and the MEC of biofilm was 8 mg/mL.In Huidu Yinhua powder,honeysuckle and astragalus only affected the hemolytic activity of MRSA and biofilm formation without inhibiting bacterial growth.The hemolytic activity and biofilm of MEC were both 32 mg/mL.Glycyrrhiza had a strong bacterial inhibitory capacity with a MIC90 of 8 mg/mL and biofilm MEC of 1 mg/mL without showing inhibitory hemolytic activity at subinhibitory concentrations.The orthogonal experiment showed that,at a ratio of honeysuckle,astragalus,and glycyrrhiza in Huidu Yinhua powder of 1∶2∶4,the MIC90 was 16 mg/mL,MEC of hemolytic activity was 8 mg/mL and that of biofilm was 4 mg/mL,both of which were the lowest among the nine groups.Conclusions Huidu Yinhua powder affects the hemolytic activity and biofilm formation of MRSA at subinhibitory concentrations with the optimal ratio of honeysuckle,astragalus,and glycyrrhiza being 1∶2∶4.

Objective:To analyze the whole genome sequence and key site mutations of hepatitis B virus (HBV) in patients with different stages of disease progression, and to understand the relationship between HBV genetic characteristics and disease progression.Methods:Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier, chronic hepatitis B patients, cirrhosis patients and primary hepatocellular carcinoma patients were collected. Nested PCR was used to amplify the samples to obtain HBV whole gene sequences. Phylogenetic trees were constructed to determine the genotype of the samples, and gene mutations of the samples were analyzed combined with reference sequences of each type.Results:A total of 256 samples were successfully amplified, including 68 asymptomatic HBV carrier patients, 118 CHB patients, 15 LC patients and 55 HCC patients, and five genotypes (B, C, D, I and C/D) were detected. The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups ( P<0.05). In addition to the discovery of C105T, A1762T/G1764A and G1899A and other previously reported key site mutations, the mutation rates of T53A, C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups, and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups. A total of 26 sequences were deleted, mainly distributed in the pre-C and pre-S regions. The deletion mutation rate in the HCC group was significantly higher than that in the other groups. Conclusions:The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases, and HCC patients are more likely to have gene mutations than non-HCC patients. These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.

AIM: To investigate the diagnostic value of the axial length/corneal radius of curvature(AL/CR)for myopia in children and adolescents.METHODS: PubMed, Embase, The Cochrane Library, CNKI, CBM, WanFang Data and VIP databases were searched to collect clinical research on the value of AL/CR in diagnosing myopia in children and adolescents, and the retrieval time was from establishment to September 30, 2023. The QUADAS-2 tool was used to evaluate the quality of the extracted literature. A random-effects model was used to pool diagnostic test data, Meta-regression and subgroup analysis were performed to explore sources of heterogeneity.RESULTS: A total of 10 articles involving 19 872 study participants were included, and Meta-analysis showed that the pooled sensitivity of the AL/CR for the diagnosis of myopia in children and adolescents was 0.91[95%CI(0.90-0.91)], the pooled specificity was 0.84 [95%CI(0.84-0.85)], and area under the SROC curve of 0.95 [95%CI(0.93-0.96)].CONCLUSION: The AL/CR is a good indicator of myopia in children and adolescents.