Objective:Glioblastoma(GBM)and brain metastases(BMs)are the two most common malignant brain tumors in adults.Magnetic resonance imaging(MRI)is a commonly used method for screening and evaluating the prognosis of brain tumors,but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited.In recent years,deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system.This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases(SBMs),and to further explore the impact of multimodality data fusion on classification tasks. Methods:Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed.First,structural T1-weight,T1C-weight,and T2-weight were selected as 3 inputs to the entire model,regions of interest(ROIs)were manually delineated on the registered three modal MR images,and multimodality radiomics features were obtained,dimensions were reduced using a random forest(RF)-based feature selection method,and the importance of each feature was further analyzed.Secondly,we used the method of contrast disentangled to find the shared features and complementary features between different modal features.Finally,the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. Results:The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs.Furthermore,compared with single-modal data,the multimodal fusion models using machine learning algorithms such as support vector machine(SVM),Logistic regression,RF,adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT)achieved significant improvements,with area under the curve(AUC)values of 0.974,0.978,0.943,0.938,and 0.947,respectively;our comparative disentangled multi-modal MR fusion method performs well,and the results of AUC,accuracy(ACC),sensitivity(SEN)and specificity(SPE)in the test set were 0.985,0.984,0.900,and 0.990,respectively.Compared with other multi-modal fusion methods,AUC,ACC,and SEN in this study all achieved the best performance.In the ablation experiment to verify the effects of each module component in this study,AUC,ACC,and SEN increased by 1.6%,10.9%and 15.0%,respectively after 3 loss functions were used simultaneously. Conclusion:A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.

Objective:To investigate the clinical effects of adjustable external fixation traction combined with arthroscopic microfracture in the treatment of osteochondral lesions of the talus (OLT).Methods:A retrospective study was conducted to analyze the data of 27 OLT patients who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from May 2017 to March 2022. There were 16 males and 11 females, aged (32.4±7.2) years. Lesion site: 23 medial and 4 lateral cases; Hepple staging: 7 cases at stage Ⅰ, 15 cases at stage Ⅱ, and 5 cases at stage Ⅲ; disease duration: (10.6±3.3) months. All the patients were treated by adjustable external fixation traction combined with arthroscopic microfracture. Recorded were the patients' visual analogue scale (VAS) pain scores and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at 6 months and 12 months after surgery, levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor- α (TNF- α) at 1 month after surgery, lesion area at 12 months after surgery, and incidence of complications. Results:The follow-up time for this cohort was (16.2±6.7) months. The AOFAS score was (61.52±6.75) points before surgery, (84.15±5.56) points at 6 months after surgery and (95.67±4.30) points at 12 months after surgery. The VAS score was (5.88±1.02) points before surgery, (2.12±0.48) points at 6 months after surgery and (0.66±0.36) points at 12 months after surgery. The two-by-two comparisons between the 3 time points for the above items were statistically significant ( P<0.05). IL-1 was (32.37±6.64) pg/mL, IL-6 (34.04±7.12) pg/mL, and TNF- α (17.89±4.96) ng/L at 1 month after surgery in the 27 patients, all of which were significantly lower than their preoperative levels [(96.63±14.80) pg/mL, (102.33±20.42) pg/mL, and (54.48±9.33) ng/L] ( P<0.05). The lesion area was (28.66±6.52) mm 2 at 12 months after surgery, significantly smaller than the value before surgery [(128.52±11.32) mm 2] ( P<0.05). Infection at the adjustable external fixation needle track occurred in 1 patient and lower limb thrombosis in 2 patients. Conclusion:In the treatment of OLT, adjustable external fixation and traction combined with arthroscopic microfracture can achieve satisfactory results and improve symptoms for the patients.

Objective To study the effect of leucine rich repeat kinase 2(LRRK2)on pain sensitivity in neuro-pathic pain(NP)rats and explore its possible mechanism.Methods 48 SD rats were randomly divided into four groups:sham surgery(Sham),model,LRRK2 inhibitor(MLi-2),and LRRK2 inhibitor+p3 8 mitogen activated pro-tein kinase(MAPK)agonist(MLi-2+Anisomycin),with 12 rats in each group.The NP rat model was induced by chronic constriction injury(CCI)of the sciatic nerve.Intrathecal injection of MLi-2(1 mg/kg,10 μl)or Anisomy-cin(20 μmol/L,10 μl)was started from the 8th day after surgery,once a day for 7 consecutive days.Pain sensi-tivity tests were conducted before surgery(day 0)and on postoperative days 7 and 14,respectively.The changes in mechanical withdrawal threshold(MWT)and paw withdraw thermal latency(PWTL)were analyzed in each group of rats.ELISA was used to detect the levels of interleukin-1 β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)in the dorsal horn of the rat spinal cord.Nissl staining was used to observe the pathological changes of neurons in rat spinal cord tissue.Immunofluorescence staining was used to observe the expression levels of ionized calcium-binding adapter molecule-1(Iba-1),a marker of microglia in the spinal cord of rats.Western blot was used to detect the protein expression levels of LRRK2,p-p38 mitogen activated protein kinase(MAPK),p38 MAPK,and Iba-1 in the dorsal horn of the rat spinal cord.Results Compared with the sham group,the model group showed a significant decrease in MWT and PWTL in the right hind limb of rats(P＜0.01).The levels of IL-1,IL-6,and TNF in the spi-nal dorsal horn tissue,as well as the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK pro-tein ratio significantly increased(P＜0.01).The proportion of Iba-1 positive cells in the spinal cord tissue signifi-cantly increased(P＜0.01),while Nissl bodies were significantly reduced(P＜0.01).Compared with the model group,the MLi-2 group showed a significant increase in MWT and PWTL in the right hind limb of rats(P＜0.01),a significant increase in Nissl bodies(P＜0.01),a significant decrease in the proportion of Iba-1 positive cells in the spinal cord tissue(P＜0.01),and a significant decrease in the levels of IL-1,IL-6,and TNF and the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK protein ratio(P＜0.01).However,Anisomychin in-tervention could activate the p38 MAPK signaling pathway and partially reverse the beneficial effects of MLi-2 on pain sensitivity and neuroinflammation in rats with neuropathic pain.Conclusion Inhibiting the expression of LRRK2 can alleviate pain sensitivity in NP rats induced by microglia activation mediated neuroinflammation,and its mechanism of action may be related to regulating the p38 MAPK signaling pathway.

Objective To investigate the role and mechanism of silent information regulator 1(SIRT1)-NOD-like receptor protein 3(NLRP3)axis in the effect of remifentanil against ischemia-reperfusion injury(IRI)in rat livers.SD rats were randomly divided into sham operation group(sham group),IRI group,IRI+remifentanil pretreatment group(IRI+RPC group),IRI+SIRT1 inhibitor EX-527 group(IRI+EX-527 group)and IRI+RPC+EX-527 group,with 8 rats in each group.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),interleukin(IL)-1β and IL-18 of rats in each group were detected.The liver tissue pathology was observed.The apoptosis rate of hepatocytes in rats was detected.The expressions of SIRT1,NLRP3,cleaved cysteinyl aspartate specific proteinase-1(Cleaved Caspase-1)and Gasdermin D(GSDMD)proteins in rat liver tissue were detected.Results Compared with the sham group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were decreased,the relative expression of SIRT1 protein in liver tissue was increased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were decreased;the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased,the ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI+RPC group,the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased,the levels of ALT,AST,LDH,IL-1β,and IL-18 were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis.

OBJECTIVE To study the anti-inflammatory effect and mechanism of the ethanol extract and the drug-containing serum of Zhuang medicine Stahlianthus involucratus on lipopolysaccharide （LPS）-induced RAW264.7 cell inflammation. METHODS The drug-containing serum or blank serum was obtained by intragastrical administration of ethanol extract of S. involucratus （75.35 g/kg） or purified water. Using RAW264.7 cells as objects， RAW264.7 cells were divided into normal control group， LPS group （1 μg/mL）， S. involucratus ethanol extract high-dose， medium-dose and low-dose groups （50， 25， 12.5 μg/mL）， 4% or 15% blank serum groups， 4% or 15% blank serum+LPS groups， 4% or 15% drug-containing serum groups， 4% or 15% drug-containing serum+LPS groups. After culturing for 24 h， cell viability， the contents of nitric oxide tumor necrosis factor α （TNF-α）， interleukinand IL-6 as well as mRNA expressions of Toll-like eceptor 4 （TLR4） and nuclear factor κB （NF- κB） and protein expressions of nitric oxide synthase （NOS） and cyclooxygenase 2 （COX-2） were all detected in each group. 0771-4953513。E-mail：zhuhuagx@163.com RESULTS After culturing for 24 h， there was no statisticalsignificance in the difference of cell viability. Compared with normal control group， the contents of NO， TNF-α， IL-1β and IL-6， mRNA expressions of TLR4 and NF-κB， and protein expressions of NOS and COX-2 were increased significantly in LPS group （P＜0.05）. Compared with 4% or 15% blank serum groups， the levels of above indexes were increased significantly in 4% or 15% blank serum+LPS groups （P＜0.05）. Compared with LPS group， the levels of above indexes were decreased significantly in S. involucratus ethanol extract groups （P＜0.05）. Compared with 4% or 15% blank serum+LPS groups， the levels of above indexes were decreased significantly in 4% or 15% drug-containing serum+LPS groups （P＜0.05）. CONCLUSIONS The ethanol extract and the drug-containing serum of S. involucratus can significantly alleviate LPS-induced inflammatory reaction， the mechanism of which may be associated with inhibiting the activity of TLR4/NF-κB signaling pathway， down-regulating the protein expressions of COX-2 and NOS， and reducing the release of inflammatory factors.

Humans ; East Asian People ; Psoriasis/drug therapy* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Treatment Outcome ; Severity of Illness Index

The real-world data of Hainan Boao Lecheng International Tourism Pilot Zone has the advantage of supporting pre-market clinical evaluation of medical devices. Based on the relevant requirements of clinical evaluation of medical devices and based on the practical experience of pilot devices in the early stage, the application of Boao Lecheng real-world data in the pre-market clinical evaluation path of medical devices from the perspective of review is discussed. At the same time, the elements that should be considered in real-world study design and the way of data quality evaluation are proposed. Expect to provide a reference in order to allow registration applicants to use real world data wisely to help declare device registration for marketing.
Device Approval ; Marketing ; Research Design

Objective To observe the value of quantitative CT(QCT)for predicting the efficacy of medical thoracoscopic giant emphysematous bullae(GEB)volume reduction.Methods Data of chest QCT and pulmonary function tests before and 6 months after medical thoracoscopic volume reduction in 26 chronic obstructive pulmonary disease(COPD)patients complicated with GEB who underwent medical thoracoscopic GEB volume reduction were retrospectively analyzed.According to the improvement rate of lung function(forced expiratory volume in one second[FEV1])6 months after treatment compared with that before treatment,the patients were divided into significant improvement group(FEV1 improvement rate≥15％,n=20)and non-significant improvement group(FEV1 improvement rate＜15％,n=6).QCT parameters before treatment were compared between groups,and the correlations of QCT parameters being significantly different between groups with FEV1 improvement 6 months after treatment were analyzed.Then receiver operating characteristic(ROC)curves were drawn to evaluate the efficacy of the above parameters for predicting the curative effect of medical thoracoscopic volume reduction of GEB.Results Significant differences of preoperative target lung lobe volume,total lung volume and bullae volume were found between groups(all P＜0.05).Preoperative target lung lobe volume,total lung volume,target lobar bullae volume and total lung bullae volume were positively correlated with FEV1 improvement(r/rs=0.600,0.470,0.699,0.523,all P＜0.05),with the area under the curve(AUC)for predicting FEV1 improvement of 0.817,0.817,0.892 and 0.833(all P＜0.05),respectively.Conclusion QCT could effectively predict the efficacy of medical thoracoscopic GEB volume reduction.

Randomized controlled trials (RCT) have long been considered the gold standard for assessing clinical efficacy. However, RCT are inappropriate for some diseases due to related ethical issues and costs, such as rare diseases that are seriously life-threatening but without adequate treatment. Using real world data (RWD) as external control for RCT could make recruitment less complicated and reduce time and cost. This paper introduces common application scenarios, data sources, study design, basic principles, and statistical methods of RWD as an external control based on the latest guidelines related to RWD and combined with our team's previous research experience. This study could provide references for scholars and sponsors who want to conduct RWD research.

OBJECTIVE To study the spectru m-toxicity relationship of in vitro hepatotoxicity of aqueous extract from Euodia rutaecarpa. METHODS The aqueous extract from 16 batches of E. rutaecarpa from different habitats were prepared. The fingerprints of aqueous extract from E. rutaecarpa were established by ultra high performance liquid chromatography （UPLC） method and Similarity Evaluation System of TCM Fingerprint （2012A edition ），and common peaks were identified and the similarity was evaluated. Using normal human hepatocytes L 02 as subject ，inhibitory effect of aqueous extract from 16 batches of E. rutaecarpa to them were investigated. The spectrum-toxicity relationship of UPLC fingerprint of aqueous extract from E. rutaecarpa with the hepatotoxicity of hepatocytes L 02 was analyzed by grey relational analysis （GRA）and partial least squares regression analysis （PLSR）. The corresponding compound of the chromatographic peak with the greatest correlation with the in vitro hepatotoxicity of E. rutaecarpa were isolated ，prepared and identified. RESULTS There were 27 common peaks in UPLC fingerprints of aqueous extract from 16 batches of E. rutaecarpa ，with similarity of 0.375-0.995. Totally 9 peaks were confirmed ，i.e. neochlorogenic acid （peak 5），chlorogenic acid （peak 9），cryptochlorogenic acid （peak 10），caffeic acid （peak 12），rutin （peak 16），hyperin（peak 17），dehydroevotarine（peak 19），evotarine（peak 24），rutecarpine（peak 25）. The aqueous extract from 16 batches of E. rutaecarpa showed significant inhibitory effect on the growth of L 02 cells（P＜0.05 or P＜0.01），and the inhibitory rate ranged from 6.68％ to 67.95％. GRA showed that there were 18 common peaks with correlation degree greater than 0.8，which were peak 8＞peak 3＞peak 23＞peak 7＞peak 4＞peak 9＞peak 12＞peak 2＞peak 19＞peak 6＞ 4928381。E-mail：799247687@qq.com peak 15＞peak 5＞peak 1＞peak 17＞peak 21＞peak 26＞ peak 20＞peak 14 in descending order of correlation degree. PLSR showed that there were 14 peaks with regression coefficient＞0 and variable importance projection value ＞1，and the order of regression coefficient was peak 8＞peak 3＞peak 23＞ peak 2＞peak 7＞peak 4＞peak 12＞peak 9＞peak 19＞peak 5＞peak 17＞peak 26＞peak 10＞peak 15. Peak 8 had the greatest correlation with in vitro hepatotoxicity，and the corresponding compound of this peak was identified as 6-O-trans caffeoyl gluconic acid. CONCLUSIONS The in vitro hepatotoxicity of aqueous extract from E. rutaecarpa is the result of multiple component interaction，among which 6-O-trans caffeoyl gluconic acid shows closest relation with in vitro hepatotoxicity.