ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Objective : To characterize MMP12 as a pan-cancer marker and assess its screening value as a tumor serum marker. Methods : Bioinformatics tools such as GEPIA2,GSCA,cBioPortal,and GeneMANIA were used to analyze the pan-cancer features of MMP12 in TCGA datasets,including encompassing differential gene expression analysis,prognostic analysis,DNA methylation analysis,gene structural variation analysis and immune microenvironment analysis.Furthermore,serum samples we collected from patients with lung adenocarcinoma,breast invasive carcinoma,esophageal squamous cell carcinoma,stomach adenocarcinoma,liver hepatocellular carcinoma,and healthy individuals.ELISA was used to detect MMP12 expression in serum,and the screening performance was evaluated using the area under the ROC curve.Additionally,we followed up 28 ESCC patients and compared serum MMP12 levels between 19 patients with disease progression and 9 patients with stable disease. Results: The pancancer feature analysis revealed a significant negative correlation between MMP12 mRNA expression and its promoter DNA methylation(P<0.05),as well as a positive correlation with gene copy number variations(P<0.05).MMP12 mRNA expression was up-regulated in 14 cancer tissues compared to normal tissues next to cancer(P<0.05) and was associated with poor prognosis of cancer patients(P<0.05).Immunocorrelation analysis showed that MMP12 was significantly associated with immunity,infiltration of stromal cells,tumor mutational burden(TMB) and microsatellite instability(MSI)(P<0.05).ROC curve analysis indicated that MMP12 could serve as a potential biomarker for screening lung adenocarcinoma,breast invasive carcinoma,esophageal squamous cell carcinoma,stomach adenocarcinoma,and liver hepatocellular carcinoma.In a 30-month follow-up study of esophageal squamous cell carcinoma patients,the expression of MMP12 was higher in the disease progression group than that in the stable group. Conclusion MMP12 serves as a potential prognostic and screening marker of pan-cancer.

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Objective To investigate the differential expression genes(DEGs)related to angiogenesis in rosacea(RA)by utilizing bioinformatics analysis in order to screen the key genes and verify their mRNA expression levels.Methods The gene microarray dataset GSE65914 was retrieved from the Gene Expression Omnibus(GEO)repository.Analyzed by R programming,the dataset was refined to identify DEGs related to RA,and then cross-referenced with angiogenesis-related genes from the GeneCards database to get a subset specific to RA angiogenesis.The process of identifying key genes was augmented by employing protein-protein interaction(PPI)network analysis and Cytoscape-based computational algorithms.The mRNA expression levels of the aforementioned pivotal genes were detected by real-time fluorescent quantitative reverse transcription PCR(RT-qPCR).Results A total of 947 RA-associated DEGs were identified from GEO dataset,and then 202 genes related to RA angiogenesis were further delineated.PPI network analysis and Cytoscape algorithm finally identified 3 key genes,that is,CXCL8,IL-1B,and STAT1.The results of RT-qPCR showed that the mRNA expression levels of MIP-2,GCP-2,IL-1B and STAT1 in RA lesions were significantly higher than those in normal controls(P<0.05).Conclusion With aid of bioinformatics analysis,our study has screened and validated key genes associated with angiogenesis in RA,namely CXCL8,IL-1B,and STAT1,which providing a theoretical basis for elucidating the potential mechanisms underlying RA-induced angiogenesis and developing targeted therapeutic strategies.

BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.

A three-dimensional(3D)medical image segmentation network(CA-SegResNet)which incorporates a 3D coordinate attention mechanism is proposed to address the issue of segmenting identified vertebral bones from spinal computed tomography(CT)images.The network extracts image features through a deep residual convolutional neural network and fuses the feature maps from each encoder layer with the input of the corresponding decoder layer.Subsequently,a 3D coordinate attention module is introduced to capture inter-channel relationships as well as directional and positional information,establishing long-range dependencies across different spatial directions,thereby enabling precise segmentation of the identified vertebral bones.For the segmentation tasks involving the identified cervical vertebra(the 7th cervical vertebra)and the identified thoracic vertebra(the 12th thoracic vertebra)across 105 cases,CA-SegResNet achieves average Dice similarity coefficients(DSC)of 0.934 5 and 0.918 9 on the test set,with average Hausdorff distances(HD)of 7 and 8 mm.Compared with U-Net results,the average DSC is improved by 0.014 5 and 0.0463,while average HD is reduced by 176 and 388 mm.The results demonstrate that the network can realize the precise segmentation of identified vertebral bones from CT images.

Objective To explore the performance of routine blood test parameters,bone marrow parameters and the risk factors of leukemia conversion in higher-risk patients with myelodysplastic syndrome(MDS)treated with Bushen Jiedu Huayu Method in the real world.Methods The clinical data of 162 patients with higher-risk MDS who were admitted to the Department of Hematology,Xiyuan Hospital,China Academy of Chinese Medical Sciences from September 2017 to September 2022 were collected,and their clinical data,blood routine parameters,and bone marrow parameters were analyzed.Results A total of 162 higher-risk MDS patients were included,and the overall effective rate of the combination of traditional Chinese and Western medicine treatment,mainly using Bushen Jiedu Huayu Method being 48.8%.Patients with higher-risk MDS who were younger than 70 years old were more likely to obtain curative effect when treated with Bushen Jiedu Huayu Method combined with chemotherapy(P<0.05).After treatment with Bushen Jiedu Huayu Method,PLT levels in higher-risk MDS patients were significantly higher than those before treatment(P<0.05),and PLT levels in the ineffective group increased more significantly(P<0.05).After treatment,the HGB level in the effective group significantly increased(P<0.05).After treatment,the proportion of bone marrow granulocytes,megakaryocytes and lymphocytes in higher-risk MDS patients were significantly higher than those before treatment(P<0.05).Conclusion Bushen Jiedu Huayu Method,mainly using arsenic containing TCM compound,can treat higher-risk MDS.It can increase the HGB content and PLT level of patients,increase the proportion of bone marrow granulocytes,megakaryocytes and lymphocytes,and also play a certain role in reducing the proportion of bone marrow primitive cells,namely demethylation.

Objective:To evaluate the predictive value of stress+ rest gated myocardial perfusion imaging (G-MPI) in assessing all-cause mortality risk in patients with familial hypercholesterolemia (FH).Methods:From June 2010 to March 2022, 72 patients (39 males, 33 females; age (21.1±12.3) years) who diagnosed with FH clinically and genetically and underwent stress+ rest G-MPI in Beijing Anzhen Hospital, Capital Medical University were retrospectively followed up. Image analysis was performed using the 17-segment 5-point method to obtain left ventricular myocardial perfusion and functional parameters. Patients were followed for all-cause mortality events, and predictors associated with the risk of all-cause mortality were analyzed using Cox regression. The efficiencies of predictors were evaluated by ROC curve analysis, and the Kaplan-Meier method and log-rank test were used to compare the differences in the incidence of all-cause mortality in different groups of patients with FH. Independent-sample t test or Mann-Whitney U test was used to analyze the data. Results:The follow-up time of 72 patients was 7(4, 10) years, and all-cause death occurred in 16(22.2%) patients during the follow-up period. There were statistically significant differences in total cholesterol (TC), low density lipoprotein cholesterol (LDLC), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), stress end-systolic volume (SESV), stress ejection fraction (SEF), rest end-diastolic volume (REDV), rest end-systolic volume (RESV) and rest ejection fraction (REF) between the death group and the survival group ( t values: from -2.65 to 4.47, z values: from -3.43 to -1.98, all P<0.05). Cox regression analysis showed that SDS (hazard ratio ( HR)=1.337, 95% CI: 1.114-1.604, P=0.002), SESV ( HR=1.019, 95% CI: 1.008-1.030, P<0.001) and LDLC ( HR=1.355, 95% CI: 1.049-1.749, P=0.020) were independent predictors associated with the risk of all-cause mortality in patients with FH. The optimal cut-off value of SESV for predicting mortality in patients with FH determined by ROC curve analysis was 35.5 ml, with the AUC of 0.701 (95% CI: 0.517-0.885). The incidence of all-cause mortality in the group with SESV≥35.5 ml was significantly higher than that in the group with SESV<35.5 ml (28.6% vs 6.9%; χ2=5.15, P=0.023). Conclusion:Stress+ rest G-MPI is an important imaging method for all-cause mortality risk assessment in patients with FH, and SDS, SESV and LDLC are important factors in predicting mortality in patients with FH.

Objective:To investigate the optimal concentration of ropivacaine in continuous epidural anesthesia combined with general anesthesia for radical resection of esophageal cancer.Methods:A retrospective case series study was conducted. A total of 100 patients with esophageal cancer undergoing radical surgery in Shanxi Province Cancer Hospital from February 2020 to February 2022 were collected. According to the concentration of ropivacaine in continuous epidural anesthesia combined with general anesthesia, all patients with esophageal cancer were divided into 0.25% concentration group and 0.50% concentration group, 50 cases in each group. The vital signs, analgesic effects, time of recovery from anesthesia and satisfaction with anesthesia of the 2 groups at entering the operating room (T 0), 5 minutes after general anesthesia induction (T 1), and time of extubation (T 2) were compared. Results:There were statistically significant differences in the age, gender, body mass of the both groups (all P > 0.05). The heart rate, mean arterial pressure (MAP) at T 1 were lower than those at T 0 and T 2 (all P < 0.05), but there were no significant differences in heart rate and MAP at T 0 and T 2 (all P > 0.05); at T 0, T 1 and T 2, there were no significant differences in HR and MAP between the both groups (all P > 0.05). The static visual analogue scale (VAS) score of patients in the 0.25% concentration group was lower than that in the 0.50% concentration group [(1.24±0.28) scores vs. (2.58±0.41) scores, t = 19.09, P < 0.05], and the dynamic VAS score in the 0.25% concentration group was lower than that in the 0.50% concentration group [(2.86±0.47) scores vs. (4.02±1.16) scores, t = 6.55, P < 0.05]. The recovery time of spontaneous respiration, the extubation time and the time of complete consciousness in the 0.25% concentration group was shorter than those in the 0.50% concentration group (all P < 0.05). The anesthesia satisfaction in the 0.25% concentration group was higher than that in the 0.50% concentration group [94% (47/50) vs.78% (39/50), χ2 = 5.32, P < 0.05]. Conclusions:The optimal concentration of ropivacaine in continuous epidural anesthesia combined with general anesthesia for radical resection of esophageal cancer is 0.25%.