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.

Image 1.

This study aims to research the relationship between arterial stiffness and serum indirect bilirub in levels(IBIL)in patients with type 2 diabetes by measuring brachial-ankle pulse wave velocity (baPWV). The clinical data of 1 327 patients with T2DM admitted to Qingdao Huangdao District People′s Hospital from July 1st, 2018 to March 1st, 2024 were retrospectively and cross-sectionally analyzed (609 men and 718 women; age range, 45.3-79.5 years; median age, 60.3 years; mean age, 61.4 years). The subjects were stratified based on gender-specific quartiles of IBIL values(male, Q1:<6.7 μmol/L, Q2:6.7-8.9 μmol/L, Q3:8.9-12.3 μmol/L, Q4:≥12.3 μmol/L;female, Q1:<6.4 μmol/L, Q2:6.4-7.9 μmol/L, Q3:7.9-10.4 μmol/L, Q4:≥10.4 μmol/L), and a high baPWV was defined as greater than 18.37 m/s (75th percentile). The results showed that the serum IBIL concentration was negatively correlated with the duration of diabetes ( r=-0.142, P=0.010), the SBP ( r=-0.158, P=0.005) and the baPWV ( r=-0.194, P<0.001) in women and was positively correlated with TC (men: r=0.282, P<0.001; women: r=0.237, P<0.001), HDL-C (men: r=0.171, P=0.011; women: r=0.287, P<0.001) and LDL-C (men: r=0.196, P=0.009; women: r=0.233, P<0.001) levels in both genders. Dividing IBIL levels into quartiles, there were significant statistical differences in the incidence of high baPWV among different subgroups of female patients ( χ 2=36.468, P<0.001), and the incidence of high baPWV showed a decreasing trend with increasing IBIL levels. After adjusting for confounding factors, the IB levels were inversely associated with a greater risk of a high baPWV both as a continuous variable [a 1-SD difference; odds ratio ( OR):0.836; 95% confidence interval ( CI):0.774-0.942; P=0.009] and when categorized in quartiles (the highest vs. the lowest quartile; OR:0.381; 95% CI:0.162-0.897; P=0.025) in women but not in men. Low IBIL levels were significantly associated with arterial stiffness in middle-aged and elderly women with type 2 diabetes. In conclusion, the serum IBIL levels were independent protective factors for macrovascular disease in middle-aged and elderly diabetic women.

Objective To observe the value of CT radiomics machine learning(ML)model for predicting stone free rate(SFR)of urinary calculi after retrograde intrarenal surgery(RIRS).Methods Totally 216 patients with urinary calculi who underwent RIRS were retrospectively enrolled and divided into residual group(n=73)and non-residual group(n=143).Univariate and multivariate logistic regression(LR)were performed to analyze clinical data and CT manifestations of stones to screen independent predictors of SFR after RIRS.Window width and window level normalization combined with max-min normalization(denoted as method a),max-min normalization(denoted as method b),window width and window level normalization(denoted as method c)and non-normalization(denoted as method d)of pre-RIRS abdominal CT were performed,respectively,and the best radiomics features of stones were extracted and screened to establish ML models,including support vector machine(SVM),LR and stochastic gradient descent(SGD)models,and the best ML model was screened.RUSS and modified S.T.O.N.E scores were evaluated based on pre-RIRS CT for predicting SFR of urinary calculi after RIRS.A combined model was then constructed with the independent predictors and the best ML model.The predictive efficacy of each model and scoring system were assessed.Results The number of stones,CT value and volume of the maximum stone were all independent predictors of SFR after RIRS(all P＜0.05).The area under the curve(AUC)of SVM model constructed with images preprocessed by method b was the highest(0.861),higher than that of the total scores of RUSS and modified S.T.O.N.E(AUC=0.750,0.759,both P＜0.05)but not different from that of combined model(AUC=0.853,P=0.775).Conclusion Radiomics SVM model based on max-min normalization preprocessed CT could effectively predict SFR of urinary calculi after RIRS.

This study aims to research the relationship between arterial stiffness and serum indirect bilirub in levels(IBIL)in patients with type 2 diabetes by measuring brachial-ankle pulse wave velocity (baPWV). The clinical data of 1 327 patients with T2DM admitted to Qingdao Huangdao District People′s Hospital from July 1st, 2018 to March 1st, 2024 were retrospectively and cross-sectionally analyzed (609 men and 718 women; age range, 45.3-79.5 years; median age, 60.3 years; mean age, 61.4 years). The subjects were stratified based on gender-specific quartiles of IBIL values(male, Q1:<6.7 μmol/L, Q2:6.7-8.9 μmol/L, Q3:8.9-12.3 μmol/L, Q4:≥12.3 μmol/L;female, Q1:<6.4 μmol/L, Q2:6.4-7.9 μmol/L, Q3:7.9-10.4 μmol/L, Q4:≥10.4 μmol/L), and a high baPWV was defined as greater than 18.37 m/s (75th percentile). The results showed that the serum IBIL concentration was negatively correlated with the duration of diabetes ( r=-0.142, P=0.010), the SBP ( r=-0.158, P=0.005) and the baPWV ( r=-0.194, P<0.001) in women and was positively correlated with TC (men: r=0.282, P<0.001; women: r=0.237, P<0.001), HDL-C (men: r=0.171, P=0.011; women: r=0.287, P<0.001) and LDL-C (men: r=0.196, P=0.009; women: r=0.233, P<0.001) levels in both genders. Dividing IBIL levels into quartiles, there were significant statistical differences in the incidence of high baPWV among different subgroups of female patients ( χ 2=36.468, P<0.001), and the incidence of high baPWV showed a decreasing trend with increasing IBIL levels. After adjusting for confounding factors, the IB levels were inversely associated with a greater risk of a high baPWV both as a continuous variable [a 1-SD difference; odds ratio ( OR):0.836; 95% confidence interval ( CI):0.774-0.942; P=0.009] and when categorized in quartiles (the highest vs. the lowest quartile; OR:0.381; 95% CI:0.162-0.897; P=0.025) in women but not in men. Low IBIL levels were significantly associated with arterial stiffness in middle-aged and elderly women with type 2 diabetes. In conclusion, the serum IBIL levels were independent protective factors for macrovascular disease in middle-aged and elderly diabetic women.

Objective To observe the value of CT radiomics machine learning(ML)model for predicting stone free rate(SFR)of urinary calculi after retrograde intrarenal surgery(RIRS).Methods Totally 216 patients with urinary calculi who underwent RIRS were retrospectively enrolled and divided into residual group(n=73)and non-residual group(n=143).Univariate and multivariate logistic regression(LR)were performed to analyze clinical data and CT manifestations of stones to screen independent predictors of SFR after RIRS.Window width and window level normalization combined with max-min normalization(denoted as method a),max-min normalization(denoted as method b),window width and window level normalization(denoted as method c)and non-normalization(denoted as method d)of pre-RIRS abdominal CT were performed,respectively,and the best radiomics features of stones were extracted and screened to establish ML models,including support vector machine(SVM),LR and stochastic gradient descent(SGD)models,and the best ML model was screened.RUSS and modified S.T.O.N.E scores were evaluated based on pre-RIRS CT for predicting SFR of urinary calculi after RIRS.A combined model was then constructed with the independent predictors and the best ML model.The predictive efficacy of each model and scoring system were assessed.Results The number of stones,CT value and volume of the maximum stone were all independent predictors of SFR after RIRS(all P＜0.05).The area under the curve(AUC)of SVM model constructed with images preprocessed by method b was the highest(0.861),higher than that of the total scores of RUSS and modified S.T.O.N.E(AUC=0.750,0.759,both P＜0.05)but not different from that of combined model(AUC=0.853,P=0.775).Conclusion Radiomics SVM model based on max-min normalization preprocessed CT could effectively predict SFR of urinary calculi after RIRS.

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 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 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.