Objective To screen the anti-Streptococcus pneumoniae(Spn)active ingredients in vitro from different po-lar parts of Pilea peltata,and to examine the combined antibacterial effect of the active ingredient and amoxicillin(AMX).Methods A 96-well plate microdilution method was used to determine the minimum inhibitory concentration(MIC)of different polar parts;the most active polar part was separated by preparative high-performance liquid chromatography,and the active ingre-dients were identified using spectral technology.The fractional inhibitory concentration(FIC)of active ingredients and AMX was determined by the 96-well plate chessboard microdilution method.The crystal violet method was used to investigate the effect of ac-tive ingredients on Spn biofilm.The effect of active ingredients on the appearance and morphology of Spn was investigated under the electron microscope.Results The MICs of the petroleum ether part,chloroform part,ethyl acetate part,n-butanol part,and water part were 1.000,1.000,0.500,1.000,and 2.000 mg·mL-1 respectively,among which the ethyl acetate part had the stron-gest antibacterial activity.Three compounds were isolated from ethyl acetate,namely 5,7,3',4'-tetramethoxyflavone 1,8-O-(p-coumaroyl)-1(10)E,4(5)E-humuladien-8-ol 2 and 1-O-p-coumaroyl copaborneol 3.These compounds were all isolated for the first time from Pilea peltate,their MICs against Spn were 200.000,50.000,and 25.000 μg·mL-1 respectively,and the compound 3 had the strongest antibacterial activity;the FIC value of AMX and compound 3 was 0.50,which had a synergistic antibacterial effect on Spn.Both AMX and compound 3 had inhibitory effects on Spn biofilm,but the biofilm inhibition rate of compound 3(59.10±1.04％)was significantly lower than AMX(87.38±0.84)％(P＜0.01);Moreover,there was no significant difference in biofilm inhibition rate between the combination of the two and AMX(P＞0.05).The scanning electron microscope results showed that the bacterial cells in the compound 3 group had a smooth surface but varying degrees of depression.The surface of the bacteri-al cells in the AMX group and the AMX combined compound 3 group showed severe swelling and rupture.Conclusions Fla-vonoids and sesquiterpenoids are both the anti-Spn active components of Pilea peltate.Among them,sesquiterpenoids have more potent antibacterial activity,and their antibacterial action mechanism is related to inhibiting bacterial biofilms.Compound 3 and AMX have a synergistic antibacterial effect on Spn,but its mechanism of action is not by enhancing biofilm inhibition;although compound 3 cannot destroy the cell wall of Spn,it still has a negative impact on the appearance of the bacteria.

Objective To screen the anti-Streptococcus pneumoniae(Spn)active ingredients in vitro from different po-lar parts of Pilea peltata,and to examine the combined antibacterial effect of the active ingredient and amoxicillin(AMX).Methods A 96-well plate microdilution method was used to determine the minimum inhibitory concentration(MIC)of different polar parts;the most active polar part was separated by preparative high-performance liquid chromatography,and the active ingre-dients were identified using spectral technology.The fractional inhibitory concentration(FIC)of active ingredients and AMX was determined by the 96-well plate chessboard microdilution method.The crystal violet method was used to investigate the effect of ac-tive ingredients on Spn biofilm.The effect of active ingredients on the appearance and morphology of Spn was investigated under the electron microscope.Results The MICs of the petroleum ether part,chloroform part,ethyl acetate part,n-butanol part,and water part were 1.000,1.000,0.500,1.000,and 2.000 mg·mL-1 respectively,among which the ethyl acetate part had the stron-gest antibacterial activity.Three compounds were isolated from ethyl acetate,namely 5,7,3',4'-tetramethoxyflavone 1,8-O-(p-coumaroyl)-1(10)E,4(5)E-humuladien-8-ol 2 and 1-O-p-coumaroyl copaborneol 3.These compounds were all isolated for the first time from Pilea peltate,their MICs against Spn were 200.000,50.000,and 25.000 μg·mL-1 respectively,and the compound 3 had the strongest antibacterial activity;the FIC value of AMX and compound 3 was 0.50,which had a synergistic antibacterial effect on Spn.Both AMX and compound 3 had inhibitory effects on Spn biofilm,but the biofilm inhibition rate of compound 3(59.10±1.04％)was significantly lower than AMX(87.38±0.84)％(P＜0.01);Moreover,there was no significant difference in biofilm inhibition rate between the combination of the two and AMX(P＞0.05).The scanning electron microscope results showed that the bacterial cells in the compound 3 group had a smooth surface but varying degrees of depression.The surface of the bacteri-al cells in the AMX group and the AMX combined compound 3 group showed severe swelling and rupture.Conclusions Fla-vonoids and sesquiterpenoids are both the anti-Spn active components of Pilea peltate.Among them,sesquiterpenoids have more potent antibacterial activity,and their antibacterial action mechanism is related to inhibiting bacterial biofilms.Compound 3 and AMX have a synergistic antibacterial effect on Spn,but its mechanism of action is not by enhancing biofilm inhibition;although compound 3 cannot destroy the cell wall of Spn,it still has a negative impact on the appearance of the bacteria.

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 systematically analyze the efficacy of nasal endoscopic transsphenoidal decompression and glucocorticoid pulse therapy for traumatic optic neuropathy (TON).Methods:PubMed, Web of Science, Cochrane Library, ClinicalTrial.gov, CNKI, Wanfang, China Biomedical and other databases were searched to retrieve clinical studies on endoscopic surgery and hormone therapy for TON since their establishment to November 1, 2020.Two researchers screened the literature and evaluated the quality of the included literatures.The improvement of visual acuity before and after treatment was taken as an effective indicator.RevMan 5.3 statistical software was used for meta-analysis.The sensitivity of the results was analyzed atfer literature exclusion.The publication bias of each study was double checked by funnel plot and Begg test.Results:Eight studies were included, including 7 cohort studies and 1 randomized controlled trial.There was no significant difference between the endoscopic decompression group and glucocorticoid group in the efficiency of visual acuity improvement in the treatment of TON [odds ratio ( OR)=1.65, 95% confidence interval ( CI)∶0.75-3.66, P=0.22], neither in TON patients with residual vision before surgery ( OR=2.17, 95% CI: 0.94-4.98, P=0.07). For nasal endoscopic decompression surgery, early surgery (disease course<7 days) was more effective than late surgery (disease course>7 days) ( OR=4.73, 95% CI: 2.55-8.78, P<0.01). Sensitivity analysis suggested that the results of this literature analysis were not robust.The Begg test showed that there was no literature publication bias. Conclusions:There is no significant difference between nasal endoscopic surgery and glucocorticoid therapy in the treatment of TON.Early endoscopic surgery may help improve visual acuity in patients with residual vision.

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 evaluate the effect of smoking and drinking status on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods    The clinical data of 483 patients with ESCC who underwent surgical treatment in Shannxi Provincial People's Hospital from 2007 to 2016 were retrospectively analyzed. Among them, 352 patients were male and 131 were female, with a median age of 64 (37-80) years. There were 311 smokers and 172 drinkers. The relationship between preoperative drinking or smoking status and the clinicopathological characteristics of patients with ESCC was analyzed. Log-rank method and Cox risk regression were used to conduct univariate and multivariate survival analysis, respectively. Results    The preoperative smoking status was related to the patient's tumor location (P=0.030). Drinking status was associated with tumor location (P=0.001), degree of differentiation (P=0.030), pathological T stage (P=0.024) and pathological N stage (P=0.029). Univariate survival analysis showed that smoking status did not affect the disease-free survival (DFS) (P=0.188) and overall survival (OS) (P=0.127) of patients with ESCC. However, patients who drank alcohol had worse PFS than non-drinking patients (29.37 months vs. 42.87 months, P=0.009). It was further proved that alcohol consumption was an independent risk factor affecting patients' recurrence and metastasis by using multivariate analysis (RR=1.28, P=0.040). Alcohol consumption also reduced the OS of patients by 21.47 months (P=0.014), however, multivariate analysis did not yield significant results. Conclusion    Preoperative drinking status is related to the stage and differentiation of patients with ESCC. It is an independent risk factor affecting the recurrence and metastasis of ESCC.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

Objective:To study the pupillary centroid shift of myopia and characteristics of pupil diameter change from scotopic to photopic condition.Methods:A case series study was carried out, 140 eyes of 70 myopia patients from September to November 2016 in Tianjin Eye Hospital were enrolled.The pupillary centroid shift and pupil diameter parameters were measured by visual quality analyzer from scotopic (0.017 lx) to photopic (10.400 lx) condition.This study followed the Declaration of Helsinki.Results:Under the scotopic and photopic conditions, the pupil diameter was positively correlated between the bilateral eyes (scotopic: rs=0.85, P<0.001; photopic: r=0.85, P<0.001), and the pupil diameter variation from scotopic to photopic condition was positively correlated between the bilateral eyes ( r=0.75, P<0.001). The pupil diameter in scotopic and photopic conditions, and the change of pupil diameter in the right eyes were significantly higher than those in the left eyes (all at P<0.05). The pupillary centroid shift was within 0.2 mm in the left eyes of 94.2% (66/70) subjects and in the right eyes of 97.1%(68/70) subjects.The pupillary centroid shift of all subjects was within 0.3 mm.From scotopic to photopic condition, the pupil centroid was mainly shift to the nasal superior direction.There was no significant correlation between pupil diameter and age or gender.There was no significant correlation between pupillary centroid shift and age, diopter or pupil diameter. Conclusions:The binocular pupillary centroid shift are symmetrical from scotopic to photopic condition in myopic eyes, and the pupil centroid mainly shift to nasal superior direction.

Femtosecond laser has been widely used in corneal refractive surgery.The refractive state, corneal tissue structure and biomechanical properties are changed through cutting the corneal tissue.Femtosecond laser-assisted in situ keratomileusis(FS-LASIK)and small incision lenticule extraction(SMILE)are the most commonly used femtosecond laser corneal refractive surgery.In this study, the structural basis of corneal biomechanical properties, the commonly used methods for corneal biomechanics measuring, biomechanical effect of corneal flap thickness, side-cut angles, residual stromal bed thickness, flap hinge position for F-LASIK and the size of corneal incision, optical zone diameter, cap thickness, tissue cutting thickness for SMILE on corneal biomechanics are reviewed.

Objective To summarize the factors and the corresponding treatments for patients with coronary heart disease (CHD) complicated by thrombocytopenia, and provide medical advises for clinical treatment. Methods Literatures and case reports were analyzed and summarized. Results Thrombocytopenia in patient with CHD could be mainly divided into two types, one group was induced by the antithrombotic therapies for CHD, and the other group was caused by some concurrent diseases or combined non-antithrombotic medications. There were different medical decisions and prognoses according to the causes in different groups. Conclusion The treatment strategies of CHD will be considered in the CHD patients with thrombocytopenia. Identifying thrombocytopenia by monitoring the platelet counts in early stage, finding out the causes quickly and providing proper treatments are the key for the prognosis of the patients.