ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

Background/Aims: The purpose of this study was to develop a diagnostic model utilizing multimodal ultrasound parameters to aid in the detection of cervical lymph node metastasis in papillary thyroid cancer (PTC) patients. Methods: The study included 84 suspicious lymph nodes from 69 PTC patients, all of whom underwent fine needle aspiration with pathological results. Data from conventional grayscale ultrasound, shear wave elastography (SWE), and superb microvascular imaging were analyzed. Key ultrasound features were compared between benign and metastatic groups to create a diagnostic model using Fisher’s stepwise discriminant analysis. The model’s effectiveness was assessed with self-testing, cross-validation, and receiver operating characteristic curve analysis. Results: Four features, namely lymphatic hilum (X1), cortical hyperechogenicity (X2), vascular pattern (X4), and SWEmean (X7), were integral to the discriminant analysis, resulting in the equation: Y1 = -3.461 + 2.423X1 + 0.321X2 + 1.620X4 + 0.109X7, Y2 = -8.053 + 0.414X1 + 2.600X2 + 2.504X4 + 0.192X7. If Y1 < Y2, the LN would be diagnosed as metastatic lymph nodes. The model demonstrated an area under the curve of 0.833, with a sensitivity of 83.33% and specificity of 83.33%. Conclusions The multimodal ultrasound diagnostic model, established through Fisher’s stepwise discriminant analysis, proved effective in identifying metastatic lymph nodes in PTC patients.

Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.
Animals ; Drugs, Chinese Herbal/chemistry* ; Mice ; Macrophages/immunology* ; Glucose/metabolism* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics* ; Male ; Mice, Inbred C57BL ; Humans ; Colitis/drug therapy* ; Disease Models, Animal ; Colitis, Ulcerative/drug therapy* ; Metabolic Reprogramming

Objective: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. Methods: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nervesparing was performed. The surgical, functional and oncological outcomes were evaluated. Results: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. Conclusion NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

Objective By reviewing the access policies for new antimicrobial drugs internationally,this study provides a reference for the development of China's antimicrobial drug access policy.Methods The Chinese and English databases,offi-cial websites of health agencies,and health technology assessment agencies of various countries(CNKI,PubMed,NICE in the UK,HAS in France,etc.)were searched to collect and sort out the access policies of new antibacterial drugs.Taking the antibacte-rial drug ceftazidime-avibactam and the antifungal drug esaconazole sulfate as examples,the key evidence points for the evaluation of antibacterial drugs in the market access process of medical insurance were analyzed.Finally,the author put forward suggestions for China's antibacterial drug access policy based on the opinions of experts in related fields of antibacterial drugs in China.Re-sults Access policies for antimicrobial drugs had already established in the UK,US,EU,Sweden Switzerland,and Republic of Korea.These policies included a series of measures such as evaluation approval rewards,patent extensions,additional reimburse-ment,decoupling sales revenue from sales volume,etc.,with the ultimate goal being to encourage research and development of new antibiotics while reducing resistance rates.The review found that besides evaluating the safety,economy,and cost-effectiveness,some evaluation agencies also consider the actual clinical value and social value of drugs when reviewing the evidence of two types of new antibacterial drugs in the medical insurance access link.Conclusion China can draw upon international framework principles while considering unique demands such as national antibiotic management policy or national healthcare negotiation re-quirements to provide certain policy support throughout the market access process for new antimicrobials due to their unique val-ues so that it can encourage research & development while curbing antibiotic resistance.

Objective:To identify and validate the key genes of ferroptosis in phospholipase A2 receptor (PLA2R) associated membranous nephropathy through bioinformatics analysis and in vitro experiments, and to explore the potential role of ferroptosis in PLA2R associated membranous nephropathy (PMN). Methods:The GSE115857 dataset obtained by retrieving the Gene Expression Omnibus (GEO) database and the ferroptosis-related genes obtained by retrieving the FerrDb database were intersected. The intersected genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key ferroptosis genes associated with PMN were identified by intersecting genes selected using support vector machines-recursive feature elimination and least absolute shrinkage and selection operator regression. The results were validate by real-time PCR, cell counting kit-8, Western blotting and immunofluorescence in human renal podocyte line AB 8/13 from both the control group and model group.Results:A total of 25 genes related to ferroptosis of PMN were obtained, and GO and KEGG analysis showed that these genes were mainly involved in cell ferroptosis metabolism. The key ferroptosis genes of PMN obtained by machine learning method were activating transcription factor 3 ( ATF3) and coiled coil domain containing 6 ( CCDC6). The results of in vitro experiments showed that the human renal podocyte line AB 8/13 in the model group was significantly deformed and retracted compared with the control group. The surface area density of foot processes was significantly reduced, and the podocyte cytoskeleton was allosteric. The morphology of F-actin was disordered and the expression of synaptopodin was decreased. The cell proliferation activity was significantly decreased ( P<0.05). The expression of PLA2R protein was increased ( P<0.05), and the expression of GPX4 protein was decreased ( P<0.01). The protein and mRNA levels of ATF3 and CCDC6 were significantly up-regulated (all P<0.05). Conclusions:Ferroptosis may be one of the key mechanisms in the occurrence and development of PMN. In vitro experiments show that ATF3 and CCDC6 are the key genes in the ferroptosis of PMN podocytes, which provides new insights and ideas for the pathogenesis of PMN.