Objective To analyze the ecological suitability of Codonopsis pilosula;To provide theoretical reference for expanding the planting scale of Codonopsis pilosula in Shanxi Province.Methods Information on the distribution of Codonopsis pilosula samples through the fourth survey of TCM resources in Shanxi Province and literature review;the MaxEnt model and ArcGIS 10.8 geographic information system software were used to analyze the ecological factors affecting the distribution of Codonopsis Radix in Shanxi Province,and the suitable distribution areas of Codonopsis pilosula in Shanxi Province were predicted.Results The predicted distribution areas of Codonopsis pilosula in Shanxi Province by the model were highly consistent with the actual distribution area;the AUC of the training set was 0.945,indicating good prediction results.The predominant ecological factors(contributing)impacting the distribution of Codonopsis pilosula included vegetation type(31.1%),the standard deviation of seasonal temperature fluctuations(25.0%),slope(8.3%),mean January precipitation(5.3%),mean May precipitation(5.0%),and elevation(4.9%)etc.The optimal vegetation types conducive to the proliferation of Codonopsis pilosula were identified as temperate deciduous shrubs,temperate grasslands,temperate coniferous forests,and temperate deciduous broad-leaved forests.The standard deviation of seasonal temperature change was within the range of 92 to 108,the slope gradient was from 14° to 30°,mean January precipitation was of 4 to 6.8 mm,mean May precipitation was of 33.5 to 58 mm,and elevation ranged from 1 100 to 2 800 meters.Codonopsis pilosula was mainly distributed in Lucheng,Qinxian and Qinyuan counties in the eastern part of Taiyue Mountain in Changzhi City;Pu County,Fenxi County,Fenyang City of Lyuliang City in the Lyuliang Mountain Range and Yushe County of Jinzhong City in the northern part of Taiyue Mountain.The most suitable area in Shanxi Province was 14 109.67 km2,the suitable area encompassed 22 837.62 km2,the relatively suitable area covered 41 982.96 km2,while the unsuitable area extended over 77 769.75 km2.Conclusion The geographical distribution data of Codonopsis pilosula resources in Shanxi Province may serve as a basis for further examination of regional zoning,with the establishment of wild cultivation bases for Codonopsis pilosula in proximity to various mountain ranges,such as the Taihang Mountains.Moreover,the artificial cultivation conditions can be modified in accordance with the optimal growth environment of Codonopsis pilosula,thereby optimizing the management of Codonopsis resources.

Objective To analyze the ecological suitability of Codonopsis pilosula;To provide theoretical reference for expanding the planting scale of Codonopsis pilosula in Shanxi Province.Methods Information on the distribution of Codonopsis pilosula samples through the fourth survey of TCM resources in Shanxi Province and literature review;the MaxEnt model and ArcGIS 10.8 geographic information system software were used to analyze the ecological factors affecting the distribution of Codonopsis Radix in Shanxi Province,and the suitable distribution areas of Codonopsis pilosula in Shanxi Province were predicted.Results The predicted distribution areas of Codonopsis pilosula in Shanxi Province by the model were highly consistent with the actual distribution area;the AUC of the training set was 0.945,indicating good prediction results.The predominant ecological factors(contributing)impacting the distribution of Codonopsis pilosula included vegetation type(31.1%),the standard deviation of seasonal temperature fluctuations(25.0%),slope(8.3%),mean January precipitation(5.3%),mean May precipitation(5.0%),and elevation(4.9%)etc.The optimal vegetation types conducive to the proliferation of Codonopsis pilosula were identified as temperate deciduous shrubs,temperate grasslands,temperate coniferous forests,and temperate deciduous broad-leaved forests.The standard deviation of seasonal temperature change was within the range of 92 to 108,the slope gradient was from 14° to 30°,mean January precipitation was of 4 to 6.8 mm,mean May precipitation was of 33.5 to 58 mm,and elevation ranged from 1 100 to 2 800 meters.Codonopsis pilosula was mainly distributed in Lucheng,Qinxian and Qinyuan counties in the eastern part of Taiyue Mountain in Changzhi City;Pu County,Fenxi County,Fenyang City of Lyuliang City in the Lyuliang Mountain Range and Yushe County of Jinzhong City in the northern part of Taiyue Mountain.The most suitable area in Shanxi Province was 14 109.67 km2,the suitable area encompassed 22 837.62 km2,the relatively suitable area covered 41 982.96 km2,while the unsuitable area extended over 77 769.75 km2.Conclusion The geographical distribution data of Codonopsis pilosula resources in Shanxi Province may serve as a basis for further examination of regional zoning,with the establishment of wild cultivation bases for Codonopsis pilosula in proximity to various mountain ranges,such as the Taihang Mountains.Moreover,the artificial cultivation conditions can be modified in accordance with the optimal growth environment of Codonopsis pilosula,thereby optimizing the management of Codonopsis resources.

Objective:This study aimed to primarily discuss the pathogenesis of hereditary coagulation factor Ⅴ (FⅤ) deficiency in a family with a consanguineous cousin marriage.Methods:The coagulation indices of the pedigree (three generations with seven individuals) and the thrombin levels of the proband and his father were assessed. All exons of the F5 gene were analyzed with Sanger sequencing, and a new mutation was confirmed with reverse sequencing. The corresponding sites of the family members were then determined. A set of online software was utilized to predict the conservation and pathogenicity of the mutation site. The pathogenicity of this mutation site was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Results:The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were 52.2 s and 108.3 s, respectively. FⅤ activity (FⅤ∶ C) and FⅤ antigen (FⅤ∶Ag) were greatly decreased by 2% and 4%, respectively. The problem was diagnosed as type Ⅰ F Ⅴ deficiency. PT and APTT of the proband’s father, mother, and grandfather were slightly higher than the upper limit of the reference range, and FⅤ∶C and FⅤ∶Ag were approximately 50% of normal. The thromboplastin generation assay revealed that the amount of thromboplastin produced by the proband and his father was lower than that of the healthy controls and that the proband’s ability to produce thromboplastin was more severely impaired. Sequencing analysis revealed that the proband demonstrated a homozygous missense mutation of c.5128T > C (p.Trp1682Arg) in exon 15 of the F5 gene. The grandfather, father, and mother of the proband were all heterozygous for c.5128 T > C. Conservative analysis revealed that p.Trp1682 was a highly conserved site in the homozygous species, and five online software programs, including Mutation Taster, SIFT, REVEL, PolyPhen-2, and CADD, indicated that the mutation was pathogenic. The ACMG guidelines recommend that the new mutation c.5128 T > C is a possible pathogenic mutation (PM2 + PM3 + PP1 + PP3 + PP4). The comparison of the protein models before and after the mutation revealed that the benzene ring and the hydrogen bond were reduced after the mutation, which changed the local structure of the F Ⅴ protein.Conclusion:The missense mutation c.5128T > C (p. Trp1682Arg) in exon 15 of the F5 gene was initially considered the genetic cause of the FⅤ deficiency family. This mutation is the first report globally, which further enriches the gene-phenotype spectrum of FⅤ deficiency.

Objective To grasp the main environmental factors affecting the growth of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao;To predict the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province;To provide references for the rational distribution of the resources in Shanxi Province.Methods This study utilized the sample point longitude and latitude information collected in the"Fourth Survey of Chinese Materia Medica Resources"database in Shanxi Province.The data were supplemented by searching the China Digital Herbarium and retrieving related literature records.347 sample points distribution data and environmental factors were added to the MaxEnt model.The main environmental factors and contribution rates affecting the geographical distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao were screened out.The ArcGIS software was used to divide the ecological suitable area of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province.Results The area under the ROC curve of the established MaxEnt model was 0.909,indicating that the model prediction results were accurate.The model screened 19 environmental factors.Among them,climate factor was the most important environmental factor,followed by biological factor and topographic factor,and soil factor had the least influence.The potential suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province were mainly distributed in the northern mountainous areas,presenting a trend of gradually decreasing suitability levels from north to south.Under the current climate conditions,the most suitable area for Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province was 15 424 km2,the suitable area was 19 856 km2,the sub suitable area was 59 436 km2,and the unsuitable area was 61 894 km2.Conclusion Based on MaxEnt model and ArcGIS software,this study predicts the distribution of suitable areas of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao in Shanxi Province,which has certain reference value for the protection and rational distribution of Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao resources in Shanxi Province.

Objective:To investigate the relationship between inherited protein S deficiency (PSD) and cerebral venous sinus thrombosis (CVST) by phenotype and gene mutation analysis of 2 inherited PSD pedigrees with nonsense mutations.Methods:Retrospective analysis of clinical and imaging data of 2 patients diagnosed with CVST who were treated in the Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University in July and October 2023 was carried out. The peripheral blood samples were collected from proband 1 and her family members (3 subjects, 2 generations in total), and proband 2 and his family members (8 subjects of 3 generations in total). Their protein S (PS) activity (PS:A), the content of total PS antigen (TPS:Ag) and free PS antigen (FPS:Ag) were measured for definite diagnosis. Polymerase chain reaction was done in all 15 exons of the active PROS1 gene and its 5′ and 3′ untranslated regions and the amplification products were analyzed by direct sequencing. The results were compared with human PROS1 reference sequences, using Chromas software to find the mutation sites. Results:The proband 1 is a female, and the proband 2 is a male. Both of them had young onset and the clinical presentation of CVST. The PS:A level was reduced to 29% in the proband 1 and reduced to about 35% in her mother; PS:A was reduced to 21%-27% in the proband 2 and his 6 family members; a decline in the same proportion of TPS:Ag and FPS:Ag was found in the 2 probands and their family members, therefore they were primarily diagnosed as typeⅠPSD. Gene analysis showed that the proband 1 and her mother had a nonsense mutation of c.1680T>A in exon 14 (p.Tyr560 *) of the PROS1 gene; the proband 2 and his 6 family members had a nonsense mutation of c.1687C>T in exon 14 (p.Gln563 *) of the PROS1 gene. Conclusion:The reduced protein S levels in PSD patients and their family members may be associated with the p.Tyr560 * and p.Gln563 * nonsense mutations of the PROS1 gene, and the clinical manifestations of CVST in PSD patients may be related to these 2 nonsense mutations.

Objective:This study aimed to primarily discuss the pathogenesis of hereditary coagulation factor Ⅴ (FⅤ) deficiency in a family with a consanguineous cousin marriage.Methods:The coagulation indices of the pedigree (three generations with seven individuals) and the thrombin levels of the proband and his father were assessed. All exons of the F5 gene were analyzed with Sanger sequencing, and a new mutation was confirmed with reverse sequencing. The corresponding sites of the family members were then determined. A set of online software was utilized to predict the conservation and pathogenicity of the mutation site. The pathogenicity of this mutation site was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Results:The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were 52.2 s and 108.3 s, respectively. FⅤ activity (FⅤ∶ C) and FⅤ antigen (FⅤ∶Ag) were greatly decreased by 2% and 4%, respectively. The problem was diagnosed as type Ⅰ F Ⅴ deficiency. PT and APTT of the proband’s father, mother, and grandfather were slightly higher than the upper limit of the reference range, and FⅤ∶C and FⅤ∶Ag were approximately 50% of normal. The thromboplastin generation assay revealed that the amount of thromboplastin produced by the proband and his father was lower than that of the healthy controls and that the proband’s ability to produce thromboplastin was more severely impaired. Sequencing analysis revealed that the proband demonstrated a homozygous missense mutation of c.5128T > C (p.Trp1682Arg) in exon 15 of the F5 gene. The grandfather, father, and mother of the proband were all heterozygous for c.5128 T > C. Conservative analysis revealed that p.Trp1682 was a highly conserved site in the homozygous species, and five online software programs, including Mutation Taster, SIFT, REVEL, PolyPhen-2, and CADD, indicated that the mutation was pathogenic. The ACMG guidelines recommend that the new mutation c.5128 T > C is a possible pathogenic mutation (PM2 + PM3 + PP1 + PP3 + PP4). The comparison of the protein models before and after the mutation revealed that the benzene ring and the hydrogen bond were reduced after the mutation, which changed the local structure of the F Ⅴ protein.Conclusion:The missense mutation c.5128T > C (p. Trp1682Arg) in exon 15 of the F5 gene was initially considered the genetic cause of the FⅤ deficiency family. This mutation is the first report globally, which further enriches the gene-phenotype spectrum of FⅤ deficiency.

OBJECTIVE To establish a method for the content determination of patulin in Citri Grandis Exocarpium. METHODS High-performance liquid chromatography-triple quadrupole mass spectrometer（HPLC-MS/MS）was used for the analysis. After water-soluble dispersion and pectinase enzymolysis， the Citri Grandis Exocarpium sample was extracted by acetonitrile with high-speed homogenated. The extracted solution was conducted dispersive solid phase extraction by mixing powder of MgSO4 and NaAC （4∶1，m/m），then purified on SHIMSEN 228 solid phase purification column. Water acetonitrile was used as mobile phase， and the Shim-pack XR-ODS column was used to separate the target compound. And it was detected by electrospray ionization in the negative mode under multiple reaction monitoring， and quantified by the external standard method with matrix- matched standard correction curves. RESULTS Patulin showed good linear correlation in the concentration from 5 to 200 ng/mL （r＝0.999 6）. RSDs of precision， reproducibility and stability tests （12 h） were all lower than 6％. The average recoveries at low， medium， high concentrations were 83.9%， 92.08%， 92.21%， respectively （RSDs were 11.09%， 5.53%， 1.75%， respectively）. The limit of quantitation was 6 μg/kg and limit of detection was 3 μg/kg. Patulin was not detected in 20 batches of samples. CONCLUSIONS Established method can be used for the rapid detection and accurate quantification of patulin in Citri Grandis Exocarpium， which can provide experimental basis and method for safety study and quality control of Citri Grandis Exocarpium.

Objective:To construct an evaluation index system for the elderly stressors, so as to provide a basis for comprehensive and effective stressor assessments for the elderly.Methods:With the bio-psycho-social medicine model as the theoretical guide, the first draft of the evaluation index system for the elderly stressors was drawn up through the literature analysis and the semi-structured interview. The Delphi method was used to conduct two rounds of expert consultations to 13 experts. The analytic hierarchy process was used to determine all levels of indicators and their weights.Results:In two rounds of expert consultations, the expert positive coefficients were 86.67% and 100.00% respectively, and the authority coefficients were both 0.889, and the Kendall coordination coefficients were 0.339 and 0.361 respectively ( P<0.05) . The evaluation index system for the elderly stressors included 4 first-level indicators, 12 second-level indicators and 65 third-level indicators. Conclusions:The evaluation index system for the elderly stressors based on the Delphi method is scientific and practical, and can provide a unified standard for the evaluation of the elderly stressors.