ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma， and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography（HPLC） was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces， and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside， chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics， the contents and quantity ratio relationships of the glycosides， aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed， and the partial least squares-discriminant analysis（PLS-DA） and cluster analysis of the main components in different steaming times were conducted， the statistically significant differential markers were selected with the variable importance in the projection（VIP） value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma， there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times， the anthraquinone glycosides and aglycones could be roughly divided into three stages， including rapid change stage， fluctuation change stage and stable stage， and the total amount of tannins showed a decreasing trend. However， the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes， while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening， it was found that chrysophanol， emodin， chrysophanol-8-O-β-D-glucoside， rhein， physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb， which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective: To understand the current situation and differences in physical activity among children and adolescents in different regions of China, so as to provide a scientific reference for promoting the level of overall physical activity promotion among children and adolescents in China. Methods: From June to December 2023, the student satisfaction assessment questionnaire for the national children and adolescents theme fitness activity "Run, Youth!" was conducted, which was administered via a combined online and offline questionnaire survey to explore 397 013 students participation in the "Run, Youth!" activity in 2023. Descriptive statistics, Logistic regression, and other approaches were utilized for data analysis. Results: There were notable disparities in the rates of children and adolescents meeting the physical activity standards among northeast China, northwest China, north China, east China, central China and southwest China (10.27%, 11.79%, 9.32%, 8.48%, 8.81%, 7.30%) ( χ 2=33.48, P <0.05). The results of multivariate Logistic regression analysis showed that rate of recommended level of physical activity among children in northwest China, boys, children aged 16-18, children in urban areas were relatively high ( OR =1.12, 1.68, 0.60, 1.88, P < 0.05 ). After adjusting for confounding factors, the results of binary Logistic regression analysis showed that there was an interactive effect relationship between the interaction of region, age, gender, and urban-rural distribution and physical activity among children and adolescents ( OR=0.51, P <0.01). Based on gender analysis, weekly physical activity duration of boys in each region surpassed that of girls; based on age analysis, except for the central and southwestern regions, weekly physical activity duration of children and adolescents gradually increased with age in other regions; based on the proportion of urban and rural areas, weekly physical activity duration of children and adolescents in urban areas across all regions exceeded that in rural areas. Conclusions The attainment rate of sufficient physical activity among children and adolescents in northwest China is the highest, and the differences between regions are not significant. The participation and level of physical activity of male students in each region surpass those of females and the attainment rate of physical activity of physical activity of urban children and adolescents is higher than that of those in rural areas.

Objective To explore the core drugs and antidepressant molecular mechanisms of Chinese herbal compound in the clinical treatment of depression.Methods Relevant literature was searched through CNKI,Wanfang and VIP to screen and sort out the Chinese Herbal compounds used in clinical practice.By analyzing the frequency of medication and the association rules of Chinese medicines,Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix were determined as the core Chinese medicinals for the treatment of depression.The active components and target proteins of these drugs were screened by TCMSP database,and depression-related targets were obtained from TTD,OMIM,DrugBank and GeneCards.Protein-protein interaction(PPI)network and'core drug-active ingredient-intersection target'network were constructed by STRING and Cytoscape.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by Metascape.Molecular docking analysis used RCSB database,AutoDockTools and PyMOL to verify the binding activity of key active components with core targets.Results The drugs for the treatment of depression in clinical Chinese herbal compound prescriptions were mainly cold,sweet,bitter and pungent,and the liver meridian was the first.Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix had the highest frequency of medication,and the combination of"Paeoniae Radix Alba-Bupleuri Radix"and"Curcumae Radix-Paeoniae Radix Alba-Bupleuri Radix"had the highest support.In the PPI network,SLC6A4,AKT1 and CHRNA4 were the key targets.GO enrichment analysis results showed that core drugs play a role in synaptic membranes and other parts through biological processes such as chemical synaptic transmission,as well as molecular functions such as G protein-coupled receptor activity.KEGG pathway enrichment analysis results showed that core drugs may treat depression through neuroactive ligand-receptor interaction,calcium signaling pathway and other pathways.Molecular docking confirmed that there was a strong binding activity between the key active ingredients and the core target.Conclusion Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix are the core drugs for clinical treatment of depression,which can treat depression through multi-component,multi-target and multi-pathway.

OBJECTIVE To study the mechanism of Qingre huashi decoction in the treatment of gastric cancer by intervening in miRNA-155 and inhibiting Wnt/β-catenin signaling pathway. METHODS Thirty nude mice were randomly divided into model group， control group （0.004 g/kg cisplatin+0.02 g/kg fluorouracil）， overexpression group， Qingre huashi prescription low-dose， medium-dose and high-dose groups （2.71， 5.43， 10.86 g/kg）， with 5 mice in each group. The overexpression group was inoculated with miRNA-155 AGS cell line， and the other groups were inoculated with AGS cells to induce tumor-bearing gastric cancer model. The control group was given relevant medicine intraperitoneally， and other groups were given relevant medicine or normal saline intragastrically， once a day， for 3 consecutive weeks. The weight of tumor tissue in nude mice was determined； the pathological morphology of tumor tissue was observed； the miRNA-155 expression， mRNA and protein expressions of Wnt7， β-catenin and T- cell factor-4（TCF-4） in tumor tissue were detected. RESULTS Compared with the model group， the tumor weights of nude mice in the control group， the overexpression group and Qingre huashi decoction high-dose group were significantly reduced （P＜0.05）； mRNA and protein expressions of Wnt7， β -catenin and TCF-4 were significantly decreased （P＜0.05）， while miRNA-155 expression was increased significantly （P＜0.05）. Tumor cells exhibited varying degrees of loose arrangement， shallow nuclear staining， and necrotic foci. CONCLUSIONS Qingre huashi decoction can inhibit the protein and mRNA expressions of Wnt7， β-catenin and TCF-4 in Wnt/β-catenin signaling pathway by up-regulating miRNA-155， thus inhibiting the tumor growth of tumor-bearing nude mice.

Humans ; Hearing Loss/etiology* ; Lupus Erythematosus, Systemic/complications* ; Prognosis

Osteoporosis （OP） and osteoarthritis （OA） are common bone diseases in clinic. OP is a systemic skeletal disease， and OA is a chronic degenerative joint disease with high prevalence and disability rates. With the advent of the aging population， the incidence rate of OA and OP is increasing year by year， and they have become common diseases of the elderly. The quality of life and physical and mental health of patients are severely affected by the above two bone diseases. Chinese medicine has a long history of treating bone diseases， with a good clinical effect on preventing and treating OP， OA， and other bone diseases with few side effects. It is one of the commonly used methods to treat bone diseases. Polysaccharides， as one of the active substances of Chinese medicine， have various pharmacological activities and a wide range of sources with low toxicity， and their effect cannot be ignored. The role of polysaccharides in the treatment of bone diseases has been deeply studied. It has been found that the mechanism of Chinese medicine polysaccharides in treating OP and OA involves multiple levels， targets， and pathways. Through the analysis and summary of the relevant literature on the mechanism of Chinese medicine polysaccharides in treating OP and OA， it was found that Chinese medicine polysaccharides mainly treated OP by regulating the bone dynamic balance between osteoblasts and osteoclasts and affecting bone marrow mesenchymal stem cells and bone microstructure. The mechanism of Chinese medicine polysaccharides in the treatment of OA is related to the regulation of chondrocyte growth， the increase in the proteoglycan and collagen content in the cartilage matrix， and the reduction of oxygen free radical content and inflammatory mediator level. This study aimed to further explore the internal relationship among mechanisms of Chinese medicine polysaccharides in the treatment of bone diseases， to provide relevant ideas for the study of Chinese medicine polysaccharides in the treatment of bone diseases.

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.
Lycium/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Structure-Activity Relationship ; Antioxidants/pharmacology* ; Antineoplastic Agents ; Polysaccharides/chemistry*

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen of coronavirus disease 2019. Diagnostic methods based on the clustered regularly interspaced short palindromic repeats (CRISPR) have been developed to detect SARSCoV-2 rapidly. Therefore, a systematic review and meta-analysis were performed to assess the diagnostic accuracy of CRISPR for detecting SARS-CoV-2 infection. Materials and Methods: Studies published before August 2021 were retrieved from four databases, using the keywords “SARS-CoV-2” and “CRISPR.” Data were collected from these publications, and the sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic curve was plotted for analysis with MetaDiSc 1.4. The Stata 15.0 software was used to draw Deeks’ funnel plots to evaluate publication bias. Results: We performed a pooled analysis of 38 independent studies shown in 30 publications. The reference standard was reverse transcription-quantitative PCR. The results indicated that the sensitivity of CRISPR-based methods for diagnosis was 0.94 (95% CI 0.93–0.95), the specificity was 0.98 (95% CI 0.97–0.99), the PLR was 34.03 (95% CI 20.81–55.66), the NLR was 0.08 (95% CI 0.06– 0.10), and the DOR was 575.74 (95% CI 382.36–866.95). The area under the curve was 0.9894. Conclusion Studies indicate that a diagnostic method based on CRISPR has high sensitivity and specificity. Therefore, this would be a potential diagnostic tool to improve the accuracy of SARS-CoV-2 detection.