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.

S-methyl-L-cysteine sulfoxide (SMCO) is a non-protein sulfur-containing amino acid with a variety of functions. There are few reports on the enzymes catalyzing the biosynthesis of SMCO from S-methyl-L-cysteine (SMC). In this study, the flavin-containing monooxygenase gene derived from Schizosaccharomyces pombe (spfmo) was heterologously expressed in Escherichia coli BL21(DE3) and the enzymatic properties of the expressed protein were analyzed. The optimum catalytic conditions of the recombinant SpFMO were 30 ℃ and pH 8.0, under which the enzyme activity reached 72.77 U/g. An appropriate amount of Mg²⁺ improved the enzyme activity. The enzyme kinetic analysis showed that the K_m and k_cat/K_m of SpFMO on the substrate SMC were 23.89 μmol/L and 61.71 L/(min·mmol), respectively. Under the optimal reaction conditions, the yield of SMCO synthesized from SMC catalyzed by SpFMO was 12.31% within 9 h. This study provides reference for the enzymatic synthesis of SMCO.
Schizosaccharomyces/genetics* ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Cysteine/biosynthesis* ; Mixed Function Oxygenases/metabolism* ; Schizosaccharomyces pombe Proteins/metabolism* ; Oxygenases/metabolism* ; Kinetics

ObjectiveBased on the quality evaluation experience of "it is better to have a fragrant and strong aroma" summarized by materia medica of past dynasties， the chemical components of Sojae Semen Nigrum（SSN） and Sojae Semen Praeparatum（SSP） were systematically compared and analyzed， and the main fermentation products in different fermentation time were quantitatively analyzed， so as to clarify the transformation law of internal components in the processing process and provide scientific basis for the modern quality control of SSP. MethodUltra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used for the structural identification of the chemical constituents of SSN and SSP， and with the aid of Progenesis QI v2.3 software， the negative ion mode was employed for principal component analysis（PCA） pattern recognition， and the data were analyzed with the aid of orthogonal partial least squares-discriminant analysis（OPLS-DA） for two-dimensional data to obtain S-plot， and components with |P|>0.1 were selected as the differential constituents. The contents of isoflavonoids in SSP during fermentation was determined by UPLC， and the samples were taken every 8 h in the pre-fermentation period and every 2 d in the post-fermentation period， and the dynamic changes of isoflavonoid contents in different fermentation stages were analyzed. The contents of amino acids and nucleosides in SSP and SSN from different fermentation stages were quantitatively analyzed by phenyl isothiocyanate（PITC） pre-column derivatization and high performance liquid chromatography（HPLC） gradient elution， and the contribution of flavor substances to the "delicious" taste of SSP was discussed by taste intensity value（TAV）. ResultA total of 19 kinds of differential components were screened out， mainly soybean saponins and isoflavones， and their contents decreased significantly or even disappeared after fermentation. In the pre-fermentation process of SSP， glycoside bond hydrolysis mainly occurred， and isoflavone glycosides in SSN were degraded and converted into the corresponding aglycones， the content of flavor substances such as amino acids increased gradually. In the post-fermentation process， protein degradation mainly occurred， after 8 d of post-fermentation， the content of isoflavones was basically stable， while the total content of amino acids increased by 8-40 times on average. Different amino acids form the special flavor of SSP， such as the TAV of glutamate is always ahead of other flavor substances， and sweet substances such as alanine and valine have made relatively great contributions to SSP. ConclusionBased on the law of constituent transformation， combined with the traditional evaluation index of "fragrant and strong"， it is difficult to control the fermentation degree of SSP by the existing standards in the 2020 edition of Chinese Pharmacopoeia. It is suggested that description of the characteristics of SSP be refined and changed to "fragrant， delicious and slightly sweet"， and at the same time， the post-fermentation index compounds such as glutamic acid， alanine and valine should be added as the quality control indicators of SSP， so as to standardize the production process and improve the quality of SSP.

ObjectiveBased on the experience of traditional quality evaluation， the quality of Atractylodis Macrocephalae Rhizoma（AMR） with different production methods such as direct seeding， transplanting after seedling raising， topping and non-topping， and difference in growth years was compared. MethodVernier caliper was used to measure the trait data of AMR in different production methods. Paraffin sections of AMR with different production methods were made by saffron solid green staining， and the microstructure was observed. The contents of water-soluble and alcohol-soluble extracts in AMR with different production methods were determined according to the 2020 edition of Chinese Pharmacopoeia. The content of water-soluble total polysaccharides in AMR with different production methods was detected by sulfuric acid-anthrone method. Fiber analyzer was used to detect the content of fiber components in AMR with different production methods. The contents of monosaccharides， oligosaccharides and some secondary metabolites in AMR with different production methods were detected by ultra performance liquid chromatography（UPLC）， and the differences of chemical components were compared by multivariate statistical analysis methods such as principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）. ResultIn terms of traits， the 3-year-old AMR with direct seeding and without topping was close to the high-quality AMR with "phoenix-head and crane-neck， strong sweetness and clear aroma" recorded in ancient materia medica， followed by the 3-year-old AMR with topping after transplanting， while the 2-year-old AMR with topping after transplanting with high market circulation rate was generally fat and strong with mild odor. In the microscopic aspect， the arrangement of xylem vessels and fiber bundles in the 3-year-old samples formed two obvious rings. Compared with the 2-year-old samples cultivated in Bozhou and Zhejiang， the 3-year-old samples without topping after transplanting had more wood fibers. In terms of chemical composition， the contents of 70% ethanol extract， fructose， glucose， sucrose， 1-kestose， atractylenolide Ⅰ， chlorogenic acid， neochlorogenic acid， cryptochlorogenic acid and other components in 3-year-old AMR with direct seeding and without topping were significantly higher than those in the other three samples（P<0.05）. The contents of cellulose， 70% ethanol extract， sucrose， atractylenolide Ⅰ， atractylone and other components in 3-year-old AMR with topping after transplanting were significantly higher than those in the 2-year-old AMR with high market circulation rate（P<0.05）， while the contents of water-soluble extract and water-soluble total polysaccharides in 2-year-old samples with topping after transplanting were significantly higher than those in the 3-year-old AMR with topping after transplanting， direct seeding and without topping（P<0.05）. ConclusionUnder the current mainstream production mode， too much manual intervention makes AMR heavily enriched in polysaccharides and increased the yield， but the accumulation of sweet substances， fragrant substances and fiber substances is insufficient， which affects its quality. The current quality standard of AMR has some shortcomings in guiding the high quality production of it， it is suggested to revise the quality standard of AMR， supplement the quantitative analysis of secondary metabolites， and strengthen the production of imitation wild AMR.

Objective To analyze the occurrence characteristics of adverse events following immunization (AEFI) of 23-valent pneumococcal polysaccharide vaccine (PPSV-23) in Hebei Province and to evaluate the safety of the vaccine. Methods AEFI cases related to vaccination of PPSV-23 in Hebei Province from January 1, 2020 to December 31, 2022 were collected through the AEFI surveillance module of Chinese Center for Disease Control and Prevention Information System. The incidence of reported AEFI cases were then analyzed and compared. Results The reported incidence rate of AEFI of PPSV-23 was 56.12 /100,000 doses, and the incidence rate of adverse reactions was 55.50 /100 000 doses. The incidence rate of common adverse reactions was 53.94/100 000 doses, and the incidence rate of rare adverse reactions was 1.56/100 000 doses. Most of the reported AEFI cases caused by PPSV-23 were common adverse reactions, which occurred mainly within one day after vaccination, and the overall regression was positive. Conclusion The 23-valent pneumococcal polysaccharide vaccine used in Hebei Province is safe，but its safety monitoring still needs to be strengthened.

Objectives:To investigate the prognostic value of soluble growth stimulation expressed gene 2 protein(sST2)combined with N-terminal pro-brain natriuretic peptide(NT-proBNP)in patients with ST-segment elevation myocardial infarction(STEMI)undergoing primary percutaneous coronary intervention(PCI). Methods:A total of 206 patients who were diagnosed with STEMI for the first time and underwent emergency PCI from August 2020 to February 2021 in the People's Hospital of Liaoning Province were enrolled.Patients were followed up for 3 years and divided into major adverse cardiac event(MACE,a composite endpoint event including cardiac death,stroke,heart failure,and ischemia-driven revascularization)group and MACE-free group.Multivariate cox analysis was performed to determine the independent risk factors for the prognosis of primary PCI in STEMI patients;the predictive value of sST2 and NT-proBNP for the occurrence of MACE in STEMI patients undergoing primary PCI was assessed by ROC analysis and the prediction of MACE by each factor by itself and the combined variables was analyzed with the Delong test. Results:There were 62 cases of MACE during the 3-year follow-up.Compared with the MACE-free group,patients in the MACE group had higher levels of sST2 and NT-proBNP,higher proportion of patients with left anterior descending branch lesions,anterior wall myocardial infarction,lower LVEF,and higher proportion of coronary artery slow flow(all P<0.05).Multivariate Cox analysis showed that sST2(HR=1.018,95%CI:1.012-1.024,P<0.001)and NT-proBNP(HR=1.001,95%CI:1.000-1.010,P<0.001)were independent predictors of MACE.According to the statistical analysis of ROC and Delong test,the AUC of combined sST2 and NT-proBNP in predicting MACE was 0.854,the sensitivity was 64.5%,the specificity was 93.1%,and the combined prediction of prognosis was better than that of individual prediction,with statistically significant difference(Z=2.119,P=0.034;Z=2.178,P=0.029). Conclusions:Serum sST2 and NT-proBNP are valuable predictors of MACE after emergency PCI in patients with STEMI,and the predictive efficacy increases with combined assessment of both sST2 and NT-proBNP.

In the past decade, high-throughput sequencing technologies have generated a massive amount of genomic mutation data. The interpretation of mutation data from tumor samples has revealed mutational features highly associated with carcinogenic factors, which are referred to as mutational signatures. These mutational signatures enable the assessment of the contribution rates of various carcinogenic factors during the multi-stage development of tumors. Ionizing radiation-induced gene mutations constitute the molecular basis for its carcinogenic effects. Clarifying the patterns of mutational signatures induced by ionizing radiation is of great importance for a profound understanding of stochastic effects. This review presents the research history and analytical method of mutational signatures as well as a comprehensive summary of the current status of research on mutational signatures induced by ionizing radiation. The future development of this field is also discussed.

The bone-touching acupuncture method, as one of the five-body acupuncture techniques, is widely used and highly effective in the treatment of brain diseases, though its theoretical foundation has been lacking. This paper explores the close connection between bones and the brain in both physiological and pathological states, as described in traditional Chinese medicine (TCM) classics, and explains the "bone-brain axis" concept within the framework of TCM. It summarizes the effects and characteristics of the five-body acupuncture techniques, traces the origins and modern applications of the bone-touching acupuncture method, and discusses its theoretical basis for treating brain diseases. The aim is to provide a reference for future clinical and mechanistic research on bone-touching acupuncture in brain disease treatment and to offer new perspectives and approaches for acupuncture treatment of brain diseases.
Humans ; Acupuncture Therapy/methods* ; Brain/physiopathology* ; Brain Diseases/physiopathology* ; Bone and Bones/physiopathology* ; Medicine, Chinese Traditional/methods*

Objective:To analyze the medication and compatibility law of TCM compound patents in the treatment of diabetic nephropathy (DN) based on data mining method; To provide basis for research and development of new drug in clinic.Methods:TCM compound patents for DN treatment were retrieved from national patent platform. Excel 2019 was used to conduct statistical analysis on drug frequency, property and taste and meridian. SPSS Modeler 18.0 and SPSS Statistic 26.0 were used for drug association rules and clustering analysis. The complex network of co-occurrence of core drugs was constructed with Cytoscape 3.9.0, and the potential of the correlation between new prescriptions and drugs was demonstrated.Results:A total of 261 TCM compound patents were included, including 438 kinds of Chinese materia medica. High-frequency drugs included Astragali Radix, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Lycii Fructus, etc. Drug categories were mainly deficiency tonic drugs. The properties and tastes were mainly cold and sweet, and the meridians were mainly liver and kidney meridians. The commonly used medicinal pair was Ganoderma-Rehmannine Radix. The commonly used triple medicinal combination was Notoginseng Radix et Rhizoma-Angelicae Sinensis Radix-Ganoderma. There were 7 groups of clustering medicines, including Notoginseng Radix et Rhizoma, Ganoderma, Angelicae Sinensis Radix, Euryales Semen, Rehmanniae Radix and Lycii Fructus. There were 5 groups of potential medicines, including Campsis Flos-Caulis Tinosporae Sinensis-Kalopanacis Radix-Fimbristylis Rigiduta Nees-Padicularisdis Dissectae Radix -Korshinsk Peashrub-Alismatis Fructus-Cynanchi Wallichii Radix. The core new prescriptions for treating DN were obtained through topological attribute analysis and screening.Conclusions:The national TCM compounds patents treatment for DN is based on the pathogenesis of this disease, which is characterized by deficiency in nature and excess in superficiality. It often uses methods such as tonifying qi and spleen, nourishing yin and tonifying kidney, promoting blood circulation and resolving blood stasis to improve clinical efficacy, providing ideas for the development of new drugs.

Objectives To explore and compare the clinical characteristics and risk factors for mortality between patients with artificial quartz stone silicosis and those with classic silicosis. Methods A total of 48 patients with artificial quartz stone silicosis (experiment group) and 98 patients with classic silicosis (control group) were recruited as the research subjects using the convenience sampling method. Data of clinical symptoms, laboratory tests, high-resolution computed tomography (HRCT), and pulmonary pathology of the research subjects were retrospectively analyzed. The Cox proportional hazards regression model was used to analyze the influencing factors on the survival time of silicosis patients. Results Patients in the experiment group had shorter years of dust exposure, latency period and time since last exposure than those in the control group (all P<0.01). The positive rate of anti-nuclear antibodies and the expression of neuron-specific enolase in the experiment group were higher than those in the control group (39.6% vs 10.2%, median： 28.44 vs 16.25, both P<0.01). The PaO₂ levels in the experiment group were lower than those in the control group (median： 66.0 vs 89.0, P<0.01). The patients in the experiment group had lower vital capacity, inspiratory reserve volume, forced expiratory volume in the first second (FEV₁), forced vital capacity (FVC), and carbon monoxide diffusion capacity compared to the control group (all P<0.05), but the maximal expiratory flow in 75% vital capacity was higher than the control group (P<0.05). Compared with the control group, patients in the experiment group had the presence of ground-glass opacity (GGO) in both lungs, aggregation and fusion of subpleural nodules, and gradual formation of progressive massive fibrosis (PMF), with higher potential of pneumothorax. Within 5 years after diagnosis, the mortality of patients in the experiment group was higher than that in the control group (27.1% vs 4.1%, P<0.01). The Cox regression model analysis results showed that patients with nodule aggregation on lung HRCT images had a higher risk of mortality than those without nodule aggregation, and lower lung function including vital capacity, FVC, FEV₁ and maximum expiratory flow in 25% vital capacity had higher risk of reduced survival time (all P<0.05). Conclusion Compared with patients with classic silicosis, patients with artificial quartz stone silicosis have higher level of serum neuron-specific enolase, increasing the risk of autoimmune diseases. Pulmonary imaging features in patients with artificial quartz stone silicosis include GGO, PMF and susceptibility to pneumothorax, and rare calcification of mediastinal lymph nodes, leading to a higher mortality rate within 5 years after diagnosis.