ObjectiveTo compare the differences in color， odor， coumarin content and microbial community composition of Angelicae Dahuricae Radix（ADR） during different drying processes， and to explore the correlation between changes in microbial community composition and changes in quality indexes of ADR. MethodsThe fresh ADR was processed at three drying temperatures（50， 70， 100 ℃） by drying and steaming cutting， semi-fresh cutting and drying， fresh cutting and drying， and sulfur fumigation methods. The color values of samples were extracted by Adobe Photoshop 2022 software and subjected to principal component analysis（PCA）， electronic nose was used to identify the odor information of medicinal powders and subjected to loadings analysis， PCA， and linear discriminant analysis（LDA）， and high performance liquid chromatography（HPLC） was used to determine the contents of five coumarins（bergapten， oxypeucedanin， imperatorin， phellopterin， isoimperatorin）. The samples for microbial detection were taken from fresh dried samples， 50 ℃（dried and steamed cut， sulfur fumigated） samples， and 100 ℃（dried and steamed cut） samples when the water content was 50% and 14%， respectively. And the changes of microbial community composition during processing were determined by high-throughput sequencing method. The relationship between the changes of microbial community composition and the changes of odor， color and active component content of ADR during drying process was analyzed by Pearson correlation analysis. ResultsThe color quantification results showed that an increase in drying temperature led to the decrease of brightness value（L）， and the increases of red-green value（a） and yellow-blue value（b）， and the change of processing method had no obvious effect on the color of medicinal materials. The results of odor quantification showed that W1S， W2S， W5S， W2W and W1W sensor were sensitive to the odor changes of ADR and could be used to distinguish ADR decoction pieces from different processing methods. The results of HPLC showed that the coumarin content of ADR decreased with the increase of drying temperature and the delay of processing time， the optimal processing method was drying and steaming cutting method， and the optimal temperature was 50 ℃. High-throughput sequencing results showed that the dominant bacteria in ADR during processing were Achromobacter， Agrobacterium， Nocardioides， Mycobacterium and Enterobacter， the dominant fungi were Coprinopsis， Meyerozyma and Apiotrichum. The results of correlation analysis showed that the quality indexes of ADR were positively correlated with Agrobacterium， Mycobacterium in bacteria， Candida in fungi， and negatively correlated with Bacillus in bacteria. ConclusionThere are significant differences in the color， odor， coumarin content and microbial community composition of ADR in different drying processes， and the best drying method is drying and steaming cutting at 50 ℃. The relative abundance changes of 9 bacterial genera and 4 fungal genera are closely related to the quality formation of ADR during the drying process.

Objective To observe the value of intratumoral and peritumoral CT radiomics for evaluating KRAS gene status in patients with colorectal adenocarcinoma.Methods Totally 245 patients with colorectal adenocarcinoma were retrospectively enrolled and divided into mutant group(n=139)and wild group(n=106)according to KRAS gene status,also divided into training set(n=171)and test set(n=74)at a ratio of 7∶3.Clinical data were compared between groups,and clinical factors were screened with logistic regression analysis to establish a clinical model.Based on enhanced venous phase CT images,intratumoral volume of interest(VOI),peritumoral VOI,and intratumoral+peritumoral VOI were delineated,radiomics features were extracted,and radiomics models were constructed.The combination model was constructed based on the best radiomics model combined with clinical factors.The value of each model for evaluating KRAS gene status in patients with colorectal adenocarcinoma was analyzed.Results Significant differences of patients’gender and carcinoembryonic antigen(CEA)were found between mutant group and wild group(both P＜0.05),which were independent impact factors of KRAS gene status in patients with colorectal adenocarcinoma(both P＜0.05).The area under the curve(AUC)of clinical model for evaluating KRAS gene status in patients with colorectal adenocarcinoma in training set and test set was 0.633 and 0.658,respectively.Intratumoral+peritumoral 3 mm model was the best radiomics model,with AUC of 0.921 and 0.894 in training set and test set,respectively.AUC of the combination model in training set and test set was 0.949 and 0.956,respectively.In training set,significant differences of AUC were found between clinical model and intratumoral+peritumoral 3 mm model,also between clinical model and combination model(both P＜0.001),while in test set,significant differences of AUC were found between each two models(all P＜0.05).Conclusion Intratumoral+peritumoral 3 mm radiomics based on enhanced venous phase CT could help to evaluate KRAS gene status in patients with colorectal adenocarcinoma.Combining with patients’gender and CEA could further improve efficacy of this model.

Objective To observe the value of contrast-enhanced CT radiomics combined with clinical and hematology indicators for predicting lymph node(LN)metastasis(LNM)of esophageal squamous cell carcinoma(ESCC).Methods Totally 218 ESCC patients were retrospectively enrolled.Stage pN1 and pN2 were clustering as LNM(n=90),while stage pN0 were taken as non-LNM(n=128).The patients were divided into training set(n=174)and test set(n=44)at the ratio of 8∶2.In training set,clinical and LN imaging features which could be used to independently judge LNM were screened and a clinical-imaging model was constructed.The hematological indicators that might be associated with ESCC LNM were screened,and a hematological model was constructed.Radiomics features in LN ROI and ESCC volume of interest(VOI)were extracted based on venous-phase contrast-enhanced CT images,and those might be associated with LNM were screened,and a radiomics model was constructed.Finally a combined model was constructed based on all the above features.The efficacy of each model for diagnosing LNM was evaluated with the area under the curve(AUC)of receiver operating characteristic curves,and the clinical net benefit was evaluated using decision curve analysis(DCA).Results Body mass index(BMI)and internal necrosis of target LN were both independent judging factors for ESCC LNM(both P＜0.05),and AUC of clinical-imaging model for diagnosing LNM in training and test sets was 0.747 and 0.687,respectively.Seven hematological indicators were included in hematological model,and AUC in training and test sets was 0.623 and 0.583,respectively.Ten LN radiomics features and 15 ESCC radiomics features were included in radiomics model,and AUC in training and test sets was 0.769 and 0.745,respectively.AUC of the combined model for diagnosing LNM in training and test sets was 0.822 and 0.739,respectively,better than other models in training set(all P＜0.05),but no significantly different in test set(all P＞0.05).DCA showed that combined model had higher net gain than the other models in 0.55-0.80 threshold probability interval.Conclusion Combined model based on venous-phase contrast-enhanced CT radiomics and clinical and hematology indicators could relatively effectively evaluate ESCC LNM,which might bring some promotions in clinical benefit.

Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P＞0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P＞0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21％accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.

BACKGROUND:Microglia cells play a major role in maintaining the balance as well as the development and function reconstruction of the central nervous system.As a histone deacetylase inhibitor,Scriptaid can inhibit neuroinflammation and enhance neuroprotection. OBJECTIVE:To investigate the effect of silk fibroin methacryloyl hydrogel loaded with Scriptaid on the behaviors of microglia cells. METHODS:Microglia(BV2 cells)were cultured in medium containing different concentrations of Scriptaid(0,0.1,0.5,1,2,5,10 μmol/L).The optimal concentration of Scriptaid was screened by the CCK-8 assay and live/dead cell staining.Silk fibroin methacryloyl hydrogels loaded with or without Scriptaid were prepared using photocuring.The micromorphology,swelling properties,mechanical properties,slow release properties,and hydrophilicity of the hydrogels were characterized.Microglia(BV2 cells)were inoculated in the subventricular region of 24-well Transwell and cultured in five groups.In the control group,the cell culture medium was added to the lower chamber.In the lipopolysaccharide group,Scriptaid group,hydrogel group,and drug-loaded hydrogel group,cell culture media containing lipopolysaccharide were added into the lower chamber.After 24 hours of lipopolysaccharide intervention,in the Scriptaid group,hydrogel group and drug-loaded hydrogel group,Scriptaid,silk fibroin methacryloyl hydrogel,and silk fibroin methacryloyl hydrogel loaded with Scriptaid were added to the upper chamber,respectively.The culture medium was replaced with ordinary culture medium and continued to culture for 24 hours.The cell viability was detected by CCK-8 assay,and the cell phenotype was detected by immunofluorescence staining of induced nitric oxide synthase and arginase 1. RESULTS AND CONCLUSION:(1)Compared with the group without Scriptaid,the viability and number of BV2 cells were decreased after Scriptaid added.When Scriptaid 2 μmol/L or above was added,the cell viability was lower than the standardized cell viability(70%),and the number of BV2 cells was significantly reduced.Therefore,1 μmol/L Scriptaid was selected to be loaded into the hydrogel.(2)Characterization experiments showed that the addition of Scriptaid did not affect the microscopic morphology,swelling rate of water absorption,compression modulus and hydrophilicity of silk fibroin methacryloyl hydrogel,and silk fibroin methacryloyl hydrogel had slow release performance.(3)The result of CCK-8 assay showed that compared with the control group,silk fibroin methacryloyl hydrogel significantly increased the viability of BV2 cells(P<0.001).(4)Immunofluorescence staining showed that compared with the control group,the expression of inducible nitric oxide synthase was increased in the lipopolysaccharide group(P<0.01);the expression of inducible nitric oxide synthase was decreased(P<0.01)and the expression of arginase 1 was increased(P<0.001)in the drug-loaded hydrogel group;the expression of arginase 1 was increased in the Scriptaid group(P<0.01).(5)The results indicate that Scriptaid-loaded silk fibroin methacryloyl hydrogel is able to promote polarization of microglia to the M2 type after lipopolysaccharide induction.

Objective:To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. Methods:A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c. 548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+ PM2_Supporting+ PP3+ PP4). Conclusion:Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.

Objective: To investigate the prognostic utility of radiomics features extracted from 18 F-fluorodeoxyglucose (FDG) PET/CT combined with clinical factors and metabolic parameters in predicting progression-free survival (PFS) and overall survival (OS) in individuals diagnosed with extranodal nasal-type NK/T cell lymphoma (ENKTCL). Materials and Methods: A total of 126 adults with ENKTCL who underwent 18 F-FDG PET/CT examination before treatment were retrospectively included and randomly divided into training (n = 88) and validation cohorts (n = 38) at a ratio of 7:3.Least absolute shrinkage and selection operation Cox regression analysis was used to select the best radiomics features and calculate each patient’s radiomics scores (RadPFS and RadOS). Kaplan–Meier curve and Log-rank test were used to compare survival between patient groups risk-stratified by the radiomics scores. Various models to predict PFS and OS were constructed, including clinical, metabolic, clinical + metabolic, and clinical + metabolic + radiomics models. The discriminative ability of each model was evaluated using Harrell’s C index. The performance of each model in predicting PFS and OS for 1-, 3-, and 5-years was evaluated using the time-dependent receiver operating characteristic (ROC) curve. Results: Kaplan–Meier curve analysis demonstrated that the radiomics scores effectively identified high- and low-risk patients (all P < 0.05). Multivariable Cox analysis showed that the Ann Arbor stage, maximum standardized uptake value (SUVmax), and RadPFS were independent risk factors associated with PFS. Further, β2-microglobulin, Eastern Cooperative Oncology Group performance status score, SUVmax, and RadOS were independent risk factors for OS. The clinical + metabolic + radiomics model exhibited the greatest discriminative ability for both PFS (Harrell’s C-index: 0.805 in the validation cohort) and OS (Harrell’s C-index: 0.833 in the validation cohort). The time-dependent ROC analysis indicated that the clinical + metabolic + radiomics model had the best predictive performance. Conclusion The PET/CT-based clinical + metabolic + radiomics model can enhance prognostication among patients with ENKTCL and may be a non-invasive and efficient risk stratification tool for clinical practice.

OBJECTIVE To develop an individualized medication list for elderly patients by evidence-based pharmacy method， and to support clinical decisions on rational use of METHODS　Firstly， drugs with risk genetic information were screened out by systematically reviewing evidence-based pharmacy information. Secondly， researchers investigated the included drugs in lists from different data E- sources. Drugs included in three or more data sources and drugs proposed by the expert committee were then included in the medication list. Thirdly， for the drugs included in two data sources， researchers designed questionnaires to investigate the necessity of drug-related gene testing. According to the scoring results of the expert questionnaire， drugs with higher scores were included in the list. Data sources included real-world data （list of high frequency medication in hospitals， high frequency medication for elderly outpatients and inpatients in National Health Care Claims Data， drugs related to frequent medication errors and so on） and evidence-based pharmacy evidence （the websites of Clinical Pharmacogenomics Implementation Consortium， Dutch Pharmacogenetics Working Group， Food and Drug Administration and so on）. RESULTS　The study obtain 68 drugs with risk genetic information which were included in three data sources. Combined with 23 drugs proposed by the expert committee， a list containing 74 drugs was preliminarily formed after de-duplication. A total of 37 drugs included in two databases with risk genetic information were scored through the questionnaire survey to form a supplementary list of 26 drugs. This is the final composition of the list of 100 drugs developed in this study. Among them， there are 43 drugs for the central nervous system， 15 drugs for the cardiovascular system， 12 anti-tumor drugs and so on. Twelve drugs were included in six or more data sources， which mainly consisted of drugs for digestive system， all proton pump inhibitors. CONCLUSION　In this study， a list of 100 commonly used drugs which require individualized medication for the elderly was developed by evidence-based pharmacy method. The drug list will be updated in time as available evidence changes， and can provide guidance for rational use of medicines for elderly patients.

Objective:To investigate the value of intratumoral and peritumoral radiomics features of multi-parameter MRI in evaluation of the status of human epithelial growth factor receptor 2 in breast cancer.Methods:The clinical, pathological and imaging data of 340 patients with pathologically confirmed breast cancer in Henan Provincial People′s Hospital from September 2019 to December 2020 were retrospectively collected. All patients were female, 48 (42, 55) years old. All patients underwent multi-parameter breast MRI before surgery, including dynamic contrast-enhanced T 1WI (DCE-T 1WI), fat-suppressed T 2WI (T 2WI) and diffusion-weighted imaging (DWI). The region of interest (ROI) for lesions were manually delineated and the segmented ROIs were zoomed in ring shape by 4 mm to acquire ROI intra and ROI prei, respectively. Then six sets of radiomics features were extracted from ROI intra and ROI prei of DCE-T 1WI, T 2WI and DWI. The cases were divided into a training set (272 cases) and a test set (68 cases) by stratified sampling at a ratio of 4∶1. The Mann-Whitney U test, Select K Best and minimum absolute contraction and selection operator were used for feature selection of the 6 sets of radiomics features. The feature subsets after reduction were used to construct independent and combined radiomics signatures with support vector machine algorithm to predict the HER2 status of breast cancer. Receiver operating characteristic curve was generated and area under curve (AUC) was calculated to compare the prediction performance of different models. Results:Of the 340 patients, 80 were HER2-positive and 260 were HER2-negative. Among the radiomics signatures based on single sequence, the DWI peri showed the best performance in predicting HER2 status of breast cancer, with an AUC of 0.678 for the test set. Among the combination of intratumoral and peritumoral radiomics signatures based on same sequence, the DWI intra+DWI peri had the highest prediction value, achieving an AUC of 0.774 for the testing set. Among the intratumoral or peritumoral radiomics signatures derived from two different sequences, the DCE-T 1WI intra+DWI intra and T 2WI peri+DWI peri showed the best predictive performance, yielding AUC of 0.766 and 0.769 in the testing set, respectively. Among the combination of intratumoral or peritumoral radiomics signatures derived from all 3 sequences or combinations of all features, the DCE-T 1WI intra+T 2WI intra+DWI intra+DCE-T 1WI peri+T 2WI peri+DWI peri obtained the highest prediction efficiency, with an AUC of 0.913 for the testing set. Conclusion:The radiomics features of intratumoral and peritumoral regions based on multi-parameter MRI have a certain value in non-invasive evaluation of HER2 status of breast cancer, which can help clinicians to provide scientific basis for decision-making of targeted therapy in patients with breast cancer.

Objective:To investigate the application value of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosome aneuploidy.Methods:A total of 5 730 pregnant women who were screened for fetal chromosomal diseases in the Quzhou Maternal and Child Health Hospital from January 2017 to March 2019 were included in this study. All of them underwent noninvasive prenatal DNA screening and nuchal translucency thickness measurement. The results of amniocentesis were used as the gold standard to evaluate the diagnostic efficacy of noninvasive prenatal DNA screening, nuchal translucency thickness measurement and their combination.Results:Noninvasive prenatal DNA screening revealed that 64 (1.12%) women out of 5 730 pregnant women had high risk of developing chromosomal abnormalities. Ultrasound examination results showed that nuchal translucency was thickened in 140 (2.44%) women. The outcome of adverse pregnancy increased with the increase of nuchal translucency thickness. Among the 68 pregnant women who underwent amniocentesis, 51 women developed chromosomal abnormalities, with trisomy 21 syndrome being the majority (23/51,45.10%). The diagnostic efficacy of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosomal aneuploidy reached the ideal level.Conclusion:Noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement has a high clinical application value. The combined method can be used as the main prenatal DNA screening method for pregnant women and it can effectively avoid the birth of children with chromosomal abnormalities.