Objective: To predict and screen potential biomarkers of systemic lupus eythematosus(SLE) based on machine learning algorithms and structural biology, and to reveal their mechanisms of action and to provide new targets for disease diagnosis and treatment. Methods: Four machine learning algorithms, random forest(RF), eXtreme gradient boosting(XGBoost), support vector machine(SVM), least absolute shrinkage and selection operator(LASSO), were used to analyze the gene expression data of SLE patients in GEO(datasets: GSE121239 and GSE11907) to analyze the gene expression data of SLE patients and screen key markers. Peripheral blood single nucleated cells(PBMCs) from SLE patients were collected and RT-qPCR was used to detect differential gene expression levels. Subsequently, GSEA enrichment analysis was used to identify biomarker-related pathways. CIBERSORT immune infiltration analysis and protein interactions network were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Interaction relationships in combination with AlphaFold3(AF3) were predicted. Results: Multiple algorithms were screened together to identify the unique marker gene HERC5 , and expression analysis of multiple datasets showed that HERC5 was highly expressed in SLE compared to the normal group (P < 0. 05) , and RT⁃qPCR verified the same trend (P = 0. 006 2) . Functional enrichment analysis identified the major pathway promoted by HERC5 in SLE as the interferon receptor signalling pathway (P < 0. 05) . Immune infiltration analysis showed that HERC5 was closely associated with immune cells (Neutrophils : r = 0. 39 , P < 0. 05 ; Memory B cells : r = 0. 33 , P < 0. 05 ; Activated dendritic cell : r = 0. 52 , P < 0. 05) . Most HERC5 ⁃related interacting proteins were associated with SLE ,and potential transcription factors of HERC5 and its related genes were also significantly associated with immune responses. Conclusion The HERC5 gene is an important biomarker for SLE , which upregulates the interferon pathway to promote SLE progression and provides a new target for SLE diagnosis and treatment.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

Objective To investigate the expression of adenosine A3 receptor(ADORA3)in human glioma and its effects on prognosis and epithelial-mesenchymal transition.Methods The mRNA expression data and corresponding clinical information of ADORA3 were obtained from TCGA,CGGA,Rembrandt,Gravendeel and Gill databases,and the effects of ADORA3 expression on the prognosis of glioma patients and the process of epithelial-mesenchymal transition were analyzed.The surgically resected glioma samples of 35 cases,along with non-tumor brain tissues of 7 cases obtained from decompression surgery for severe craniocerebral injury were collected in the Department of Neurosurgery at Renmin Hospital of Wuhan University from July 2023 to April 2024,and the ADORA3 expression was detected by immunohistochemical staining.Glioblastoma multiforme(GBM)cells of U87 and U251 were transfected with NcRNA and SiRNA,respectively,as the control group and the knockdown group,and the effects of ADORA3 on cell invasion ability and epithelial-mesenchymal transition related proteins were analyzed by Transwell and Western blot.Results Bioinformatics analysis and immunohistochemical staining showed that the expression level of ADORA3 in human glioma tissues was significantly higher than that in non-tumor brain tissues(P<0.05),and the expression of ADORA3 was associated with glioma WHO grading(P<0.05).Kaplan-Meier survival curve analysis in TCGA,CGGA,Rembrandt and Gravendeel databases showed that the overall survival rate of patients with high ADORA3 expression was significantly lower than that of patients with low ADORA3 expression(P<0.001);and Cox regression analysis showed that high expression of ADORA3 was an independent risk factor for poor prognosis in patients with glioma(P<0.05);the expression level of ADORA3 in the mesenchymal type of GBM patients was significantly higher than that of the classical type and the proneural type;furthermore,ADORA3 showed significant correlations with epithelial-mesenchymal transition related markers of Vimentin,SNAI1,SNAI2,TWIST1,TWIST2,MMP2,CD44,and FN1.The knockdown of ADORA3 in vitro reduced the cell invasive ability,decreased the expression levels of MMP2,Vimentin,and SNAI1 proteins,and increased the expression of E-cadherin,with statistically significant differences(P<0.05).Conclusion ADORA3 is highly expressed in glioma,which can promote the process of epithelial-mesenchymal transition in patients,and serve as an independent risk factor for poor prognosis.

Objective:Analyse the factors affecting whether the first two batches of centralized volume-based purchase of Proprietary Chinese Medicine were selected,the price difference and the rate of reduction,so as to provide a basis for improving the policy of centralized volume-based purchase of Proprietary Chinese Medicine.Methods:The first two batches of centralized volume-based purchase of Proprietary Chinese Medicine were selected for the study.Logistic regression was used to analyse the influencing factors of whether the selection was won or not.Multiple linear regression was used to analyse the influencing factors of price difference/reduction after being selected.Results:Proprietary Chinese Medicine with a high degree of acceptance by medical institutions and belonging to the category of essential medicines have a higher probability of being selected.The probability of selected products in the first batch of centralised purchase is greater for enterprises with a market share of more than 50%.In the first batch of centralized volume-based purchase of Proprietary Chinese Medicine,the price difference of injections and medicines belonging to the catalogue of essential medicines is greater.Price reductions were greater for those with low market share,low recognition by medical institutions,and a large number of enterprises in the A-competition unit and the same competition unit.In the second batch of centralised volume-based purchase of Proprietary Chinese Medicine,the price difference is greater for injections,and those with qualifications for the production of Chinese herbal medicines.the price reduction is greater in the B competitive unit.Conclusion:The centralized volume-based purchase of Proprietary Chinese Medicine has been both'quality-assured'and'price-reduced'.The centralized volume-based purchase of Proprietary Chinese Medicine has been gradually improved,and the tilt towards large enterprises has been reduced,so that the centralized volume-based purchase of Proprietary Chinese Medicine can achieve a'bottom price'.However,it is still necessary to start from the quality of identification,fair competition,and so on,and the centralized volume-based purchase of Proprietary Chinese Medicine fully linked to promote the centralized purchase of Traditional Chinese Medicine Decoction Pieces to a stable and far-reaching.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To investigate the expression of adenosine A3 receptor(ADORA3)in human glioma and its effects on prognosis and epithelial-mesenchymal transition.Methods The mRNA expression data and corresponding clinical information of ADORA3 were obtained from TCGA,CGGA,Rembrandt,Gravendeel and Gill databases,and the effects of ADORA3 expression on the prognosis of glioma patients and the process of epithelial-mesenchymal transition were analyzed.The surgically resected glioma samples of 35 cases,along with non-tumor brain tissues of 7 cases obtained from decompression surgery for severe craniocerebral injury were collected in the Department of Neurosurgery at Renmin Hospital of Wuhan University from July 2023 to April 2024,and the ADORA3 expression was detected by immunohistochemical staining.Glioblastoma multiforme(GBM)cells of U87 and U251 were transfected with NcRNA and SiRNA,respectively,as the control group and the knockdown group,and the effects of ADORA3 on cell invasion ability and epithelial-mesenchymal transition related proteins were analyzed by Transwell and Western blot.Results Bioinformatics analysis and immunohistochemical staining showed that the expression level of ADORA3 in human glioma tissues was significantly higher than that in non-tumor brain tissues(P<0.05),and the expression of ADORA3 was associated with glioma WHO grading(P<0.05).Kaplan-Meier survival curve analysis in TCGA,CGGA,Rembrandt and Gravendeel databases showed that the overall survival rate of patients with high ADORA3 expression was significantly lower than that of patients with low ADORA3 expression(P<0.001);and Cox regression analysis showed that high expression of ADORA3 was an independent risk factor for poor prognosis in patients with glioma(P<0.05);the expression level of ADORA3 in the mesenchymal type of GBM patients was significantly higher than that of the classical type and the proneural type;furthermore,ADORA3 showed significant correlations with epithelial-mesenchymal transition related markers of Vimentin,SNAI1,SNAI2,TWIST1,TWIST2,MMP2,CD44,and FN1.The knockdown of ADORA3 in vitro reduced the cell invasive ability,decreased the expression levels of MMP2,Vimentin,and SNAI1 proteins,and increased the expression of E-cadherin,with statistically significant differences(P<0.05).Conclusion ADORA3 is highly expressed in glioma,which can promote the process of epithelial-mesenchymal transition in patients,and serve as an independent risk factor for poor prognosis.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.