Objective Zhuanyao decoction is a traditional Chinese herbal compound prescription orignated from Bianzhenglu in Ming Dynasty;Baizhu Zhuanyao decoction(BZZYD),adding spatholobus suberectus,sappanwood,and cyathula root,is intended to enhance the therapeutic effects on the waist and hips.We aimed to investigate the effects of BZZYD on lumbar ligamentum flavum fibrosis and its possible immune regulation mechanism.Methods(i)By using a random number table method,twenty-four male SD rats were divided into the normal,model,chlorophosphate,and BZZYD groups,with six rats per group.The rats in all groups,except for the normal group,were used to establish a rat model of lumbar ligamentum flavum fibrosis using lumbar instability method.The rats in the BZZYD group received Baizhu Zhuanyao decoction through gavage(13.6 g/kg),and the other groups were administered the same amount of saline by gavage once a day for 30 days.The rats in the chlorophosphate group were subcutaneously injected with disodium chlorophosphate liposome(5 g/L,0.5 mL)at the original incision immediately after surgery and at Day 9,18,and 27.After 30 days,the rats were sarcrificed through excessive anesthesia,and the ligamentum flavum was histologically evaluated using HE and Masson staining.The collagen volume fraction(CVF)was calculated.Transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)protein expressions in the ligamentum flavum were detected using immunohistochemical staining.CD163 and TGF-β1 protein expression in M2 macrophages were detected using the immunofluorescence double-labeling method.(ⅱ)M2 macrophage and fibroblast were cultured in the three ways:separately,co-culture,and co-culture of pre-treatment of BZZYD containing serum on M2 macrophage and fibroblast.TGF-β1,TNF-α,and IL-1β mRNA expressions in M2 macrophage and fibroblast were compared using RT-qPCR.Results(ⅰ)Compared with those in the normal group,the ligamentum flavum fibers were dense and twisted,immune cells infiltrated,and the CVF was increased in the model group.TGF-β1,TNF-α,and IL-1β protein expression in the ligamentum flavum tissues of the model group were increased,and TGF-β1 and TNF-α protein expression in the BZZYD group were increased(P<0.05).Compared with that of the model group,extracellular matrix accumulation decreased in the chlorophosphate and BZZYD groups,the CVF was decreased,and TGF-β1,TNF-α,and IL-1β protein expressions in ligamentum flavum tissue were decreased(P<0.05).Compared with that of the chlorophosphate group,extracellular matrix accumulation increased,the CVF was increased,TGF-β1 and IL-1β protein expressions in ligamentum flavum tissue were increased(P<0.05).CD163 and TGF-β1 proteins were not expressed in the normal and chlorophosphate groups.CD163 and TGF-β1 proteins were expressed and co-localized in the model group,and CD163 protein expression was observed in the BZZYD group,however,TGF-β1 expression was low.(ⅱ)The co-culture system increased mRNA expressions of TGF-β1 and IL-1β in M2 macrophages,TNF-α and IL-1β in fibroblasts,compared to the two kinds of cells cultured separately.And after pre-treatment on M2 macrophages,the mRNA expressions all decreased compared co-culture system(P<0.05).Conclusion BZZYD can significantly inhibit lumbar ligamentum flavum fibrosis,reduce TGF-β1 and IL-1β expression in M2 macrophages,affect TNF-α and IL-1β expression in fibroblasts,and inhibit the positive feedback of ligamentum flavum inflammation-fibrosis.

Objective To observe the clinical efficacy of Zhuanyaotang Granules for the treatment of degenerative lumbar spinal stenosis(DLSS).Methods Using a randomized double blind controlled design,104 DLSS patients were divided into an experimental group and a control group using a random number table method,with 52 patients in each group.The treatment group took oral Zhuanyaotang Granules,methylcobalamin tablets and celecoxib capsule simulants.The control group used Zhuanyaotang Granules simulants,methylcobalamin tablets and celecoxib capsules.The course of treatment was 3 weeks for both groups.The follow-ups were conducted at 1 month and 3 months after treatment.The intermittent claudication distance,visual analogue scale(VAS)score and JOA efficacy rating criteria for low back pain score were observed in both groups before treatment,1,2,3 weeks of treatment and 1 month after treatment and 3 months after treatment.Adverse reactions during treatment were recorded.Results There were 5 cases of detachment and 2 cases of exclusion in the experimental group,and 5 cases of detachment and 1 case of exclusion in the control group.Compared with before treatment,there were statistically significant differences in intermittent claudication distance,VAS score,and JOA score between the two groups of patients at various time points during treatment and follow-up(P<0.05);there was no statistically significant difference in intermittent claudication distance,VAS score,and JOA score between the experimental group and the control group before treatment and 1 and 2 weeks of treatment(P>0.05);compared with the two groups at 3 weeks of treatment and 1 and 3 months after treatment,the intermittent claudication distance and JOA score in the experimental group were lower than those in the control group(P<0.05);There was no significant difference in VAS score between the two groups and the control group after 3 weeks of treatment(P>0.05).There were 2 adverse reactions(4.4%)in the experimental group and 5 adverse reactions(10.8%)in the control group,without statistical significance(P>0.05).Conclusion Zhuanyaotang Granules can effectively relieve pain and improve lumbar function in patients with DLSS,which is more effective and safer than oral celecoxib capsules and methylcobalamin tablets.

Background and purpose:Leptomeningeal metastasis is a form of central nervous system metastasis of melanoma.High mobility group A2(HMGA2)has been proven to play an important role in the occurrence and development of various tumors,but its biological functions in leptomeningeal metastatic melanoma cells remain unclear.On the basis of building mouse models of central nervous system metastasis of melanoma,this study investigated the differences in cell migration and cell proliferation among leptomeningeal metastatic melanoma cells,primary site melanoma cells and brain parenchymal metastatic melanoma cells,and further clarified the effects of differentially expressed gene HMGA2 on cell migration and proliferation of leptomeningeal metastatic melanoma cells.Methods:B16 mouse melanoma cells(B16-parental cells,B16-Par)stably expressing tdTomato and luciferase were generated by lentiviral infection.Subsequently,B16 specific brain parenchymal metastatic cells(B16-brain metastatic cells,B16-BrM)and B16 specific leptomeningeal metastatic cells(B16-leptomeningeal metastatic cells,B16-LM)were collected after adaptive screening of metastatic sites in vivo.The differences in migration and proliferation among B16-Par,B16-BrM and B16-LM were assessed by wound healing assay and cell counting kit-8(CCK-8).RNA sequencing(RNA-seq)was used to analyze differential gene expression in B16-Par,B16-BrM and B16-LM,and HMGA2 gene specifically upregulated in B16-LM was screened out.The results were verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Gene ontology(GO)analysis was performed for genes which were upregulated in B16-LM specifically.siRNA was used to interfere with the expression of HMGA2 gene in B16-LM,and the knock-down effect was verified by RTFQ-PCR and Western blot.The effects of knocking down HMGA2 on cell migration and proliferation were detected by wound healing assay and CCK-8 assay.Using GSE174401 data in Gene Expression Omnibus(GEO),the specificity of HMGA2 gene expression in leptomeningeal metastatic melanoma cells from patients was verified.Results:Compared with Par cells,tumor cells screened by the brain environment were more likely to colonize the central nervous system.B16-LM had stronger migration and proliferation abilities,and upregulated the expression of HMGA2 gene.GO analysis revealed that HMGA2 was associated with many biological processes such as angiogenesis and cell proliferation.When the expression of HMGA2 gene was knocked down,the migration and proliferation of B16-LM could be inhibited.HMGA2 was upregulated in leptomeningeal metastatic melanoma cells from patients.Conclusion:Leptomeningeal metastatic melanoma cells had relatively unique cellular characteristics,which promoted cell migration and proliferation by upregulating HMGA2 gene expression.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

Objective : To study the best machine learning method for early prediction of hematoma expansion in hypertensive intracerebral hemorrhage based on head CT plain scan. Methods : The CT images of 130 patients with cerebral hemorrhage were retrospectively analyzed , and the texture features of the head CT plain scan were extracted. The classifier was trained by selecting the features , and the six classic machine learning methods were crossvalidated to evaluate the stability and performanceof predicting cerebral hemorrhage hematoma expansion. Results: The prediction performance of support vector machine (SVM⁃Radial) (AUC 0. 714 ± 0. 144 , accuracy 0. 723 ± 0. 109) , generalized linear model ( GLM) prediction performance ( AUC 0. 643 ± 0. 125 , accuracy 0. 587 ± 0. 136) , random forest (RF) prediction performance (AUC 0. 686 ± 0. 128 , accuracy 0. 680 ± 0. 130) , k ⁃nearest neighbor (kNN) prediction performance ( AUC 0. 657 ± 7C 15 , accuracy 0. 639 ± 39 performance 19) , gradient boosting tree algorithm (GBM) Prediction performance ( AUC 0. 718 ± 0. 141 , accuracy 0. 670 ± 0. 126) , neural network (NNet) prediction performance (AUC 0. 659 ± 0. 162 , accuracy 0. 680 ± 0. 130) , in which support vector machines showed high prediction performance , generalized linear model showed low predictive performance. Conclusion Among the six machine learning methods based on cranial CT radiomics to predict early hematoma expansion in hypertensive intracerebral hemorrhage , support vector machine (SVM⁃Radial) has the best predictive performance and has potential clinical application value.

Virtual reality (VR) is a three-dimensional virtual technology which generates virtual world by computer simulation. VR provides users with the simulation of visual, auditory and tactile senses, so that users can observe things in the virtual space as in the real world. Electroencephalogram(EEG) is the direct reflection of the activation of neurons in the cerebral cortex. The combination of VR and EEG has become an important method of brain science research. However, the existing research lacks a systematic arrangement of combination of VR and EEG. In this paper, the related research of VR combined with EEG in the past 20 years were summarized, the corresponding experimental paradigm, research methods and results were introduced, and finally the future research directions of the combination of VR and EEG were prospected.

Objective To investigate the characteristics of serum lipid levels in centenarians in Hainan province.Methods A total of 899 centenarians were enrolled.Fasting venous blood samples were collected,and serum levels of total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol (HDL-C),apolipoprotein A-1 (Apo A1),apolipoprotein B(Apo B) and lipoprotein (a) [Lp (a)] were determined.Characteristics of serum lipid levels in centenarians with different age and gender were analyzed.Results The ratio of male to female in this study was 1 ∶ 4,101 years of age comprised the largest proportion(20.4 ％,183 cases),and the highest age was 109 years old for men and 116 years old for women.People aged 102 years had the highest levels of TC,TG,LDL-C and Apo B,and also had the lowest levels of HDL-C and Apo A1.Serum levels of TC and LDL-C reached the peak at the age of 102 years and showed downward trends year by year.Serum levels of TC,TG,LDL-C,Apo A1 and Apo B were lower in males than in females(P＜0.01),and HDL-C had no significant difference between males and females(P ＞0.05).The detection rates for abnormal serum lipid levels were higher in females than in males(P＜0.01).Serum Lp(a) level was higher in females than in males.Conclusions Serum lipid levels show a peak expression at a certain age in centenarians of Hainan,and the types and ratio of abnormal blood lipids are higher in female centenarians than in male centenarians.

Objective To study the clinical application value of individualization portal for knee arthroscope meniscoplasty. Methods The clinical data of 100 patients who had underwent knee arthroscope meniscoplasty were retrospectively analyzed. In the patients, 50 cases were performed with routine portal (group A), and other 50 cases were performed with individualization portal (group B). The operation time, curative effect and incidence of complications were compared between 2 groups. Results The operation time in group B was significantly lower than that in group A:(28.8 ± 3.1) min vs. (39.5 ± 5.4) min, and there was statistical difference (t = 12.151, P<0.01). There was no statistical difference in excellent and good rate between group A and group B: 94%(47/50) vs. 96%(48/50),χ2=0.522, P>0.05. The incidence of meniscus and cartilage injury in group B was significantly lower than that in group A: 2% (1/50) vs. 14% (7/50), and there was statistical difference (χ2 = 4.891, P<0.05). There was no statistical difference in incidence of hematoma between 2 groups (P>0.05). There was no ligament injury, infection, vascular and nerve injury, deep vein thrombosis, instrumentation damage and synovial fistula. Conclusions The individualization portal for knee arthroscope meniscoplasty is more convenient. It can shorten operation time and decrease meniscus and cartilage injury. But it has no influence on clinical effect and other complications.

Objective To explore the effect of ceftriaxone combined with rifampicin in the treatment of children with purulent meningitis,thus to provide reference for related studies.Methods 120 children with purulent meningitis were selected and randomly divided into observation group(67 cases) and control group (53 cases) according to the digital table.The control group received treatment of ceftriaxone,and the observation group received ceftriaxone and rifampicin.The clinical effect,recovery time of clinical indicators,total protein (TP),C-reactive protein (CRP),and serum protein C level were observed in the two groups.Results After treatment,the total effective rate of the observation group was 97.01%,which was higher than 86.79% of the control group,the difference was statistically significant(x2=4.457,P<0.05).The recovery time of body temperature,peripheral leukocyte count,and CSF leukocyte in the observation group were (2.35±0.68)d,(5.27±1.56)d,(13.27±1.71)d,respectively,which in the control group were shorter than (3.36±0.36)d,(7.24±2.09)d,(16.74±2.66)d,respectively,the differences were statistically significant(t=-9.713,-5.926,-8.643,all P<0.05).After treatment,the TP and CRP decreased in two groups,serum protein C was increased,and the above indicators of the observation group improved more significantly,there were statistically significant differences(all P<0.05).There was no significant differences in the incidence of complications between the two groups(P>0.05).Conclusion Ceftriaxone combined with rifampicin in the treatment of children with purulent meningitis can reduce inflammation and promote the recovery time of clinical indicators,and it's worthy of reference.

Objective To study and analyze the therapeutic effects of intravenous low dose recombinant tissue plasminogen activator (rt-PA) in the treatment of transient ischemic attack (TIA).Methods A total of 86 TIA patients were selected as the research subjects and divided into observation group (intravenous low dose rt-PA thrombolysis treatment combined with aspirin antiplatelet therapy applied,41 cases) and the control group (single aspirin antiplatelet therapy applied,45 cases) according to the treatment methods.The plasma tissue plasminogen activator (t-PA),the plasminogen activator inhibitor-1 (PAI-1) on admission,at 1,3,7,14 d of the treatment were detected and compared.The control rates of TIA of the patients in the two groups were observed and compared.The patients in the two groups were followed up for 1 year,the ratios of transformation to acute cerebral infarction in the two groups were observed and compared.Results At 1,3 d of the treatment,the plasma t-PA levels of the patients in the observation group were significantly higher than that in the control group,and the differences between the two groups were statistically significant (P ＜ 0.05).At every time points before and after the treatment,the differences of the plasma PAI-1 levels between the two groups were not statistically significant (P ＞ 0.05).There were no statistically significant differences in control rates of TIA in each period of time between the patients in the two groups (P ＞ 0.0 5).During the period of following-up,there were 2 cases and 4 cases of patients with transformation to acute cerebral infarction in the observation group and the control group,respectively,and there was no significant differences in the ratios of transformation to acute cerebral infarction between the two groups (P ＞ 0.05).Conclusion The application of intravenous infusion of low dose of rt-PA for thrombolysis on the basis of the antiplatelet therapy of aspirin can increase the plasma t-PA level in early period of patients with TIA,help to reduce the risk of thrombosis,but has no obvious influences on the plasma PAI-1 levels,the clinical efficacy and the long-term prognosis.