Objective To observe the effects of electroacupuncture on central inflammatory response and neurotransmitter release in rats with post stroke spasticity(PSS);To exploring the mechanism in treating PSS based on IL-6/JAK2/STAT3 signaling pathway.Methods Totally 30 male SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 10 rats in each group.The PSS model was prepared by the method of suture and N-methyl-D-aspartic acid receptor injection into internal capsule.The rats in the electroacupuncture group were electroacupulated on the affected side of the body at"Quchi"and"Yanglingquan"for 30 min/d for consecutive 7 d.The sham-operation group and the model group were only fixed without any interventions.The Zea Longa neurological function score and the modified Ashworth muscle tension score were evaluated before and after treatment in each group;the pathological changes of the cortex on the ischemic side were observed by HE staining;the contents of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and γ-aminobutyric acid(GABA)in cortex on the ischemic side were detected by ELISA;the content of glutamate(Glu)was detected by biochemical kit;Western blot was used to detect the expressions of tyrosine kinase 2(JAK2),p-JAK2,signal transduction and transcription activating factor 3(STAT3)and p-STAT3 protein in ischemic cortex;RT-PCR was used to detect the mRNA expressions of JAK2 and STAT3 in ischemic cortex.Results Compared with the sham-operation group,neurological function score and muscle tension score significantly increased in the model group(P<0.01),with disorganized neurons in cerebral cortex,nucleus accumbens,the contents of IL-6,TNF-α and Glu significantly increased,the content of GABA significantly decreased(P<0.01),and p-JAK2,p-STAT3 proteins and JAK2 and STAT3 mRNA expression significantly increased(P<0.01,P<0.05).Compared with the model group,the neurological function score and muscle tension score of rats in the electroacupuncture group were significantly decreased(P<0.05),the degree of neuronal damage in cerebral cortex was reduced,the cell contour was clear,the content of IL-6,TNF-α and Glu were significantly decreased,and the content of GABA significantly increased(P<0.05,P<0.01),p-JAK2,p-STAT3 protein and JAK2,STAT3 mRNA expression significantly decreased(P<0.01).Conclusion Electroacupuncture may alleviate central inflammatory response and improve limb spasticity of PSS model rats by inhibiting the IL-6/JAK2/STAT3 signaling pathway.

Objective To observe the effects of electroacupuncture on post-stroke spasticity(PSS)rats and the relationship between microglia polarization-mediated neuroinflammation and neurotransmitter glutamate(Glu)and γ-aminobutyric acid(GABA)in cerebral cortex;To investigate the possible mechanism of electroacupuncture to relieve PSS.Methods Male SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 10 rats in each group.A rat model of PSS was prepared using suture method combined with internal capsule injection of NMDA receptor.The electroacupuncture group selected"Quchi"and"Yanglingquan"electroacupuncture for 30 minutes per day,for 7 days,the model group and the sham-operation group were fixed at the same time without intervention.Zea Longa neurological function score and modified Ashworth muscular tone score were evaluated,and electrophysiology was tested;kits were used to GABA,Glu,tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)content in ischemic cortex;Western blot was used to detect the expression of GABRA1 and GAD67 protein in ischemic cortex;The co-expression of ionized calcium-binding protein 1(Iba-1),inducible nitric oxide synthase(iNOS)and Arg-1 were detected by immunofluorescence staining.Results Compared with the sham-operation group,the neurological function score and muscle tone score of the model group rats significantly increased(P<0.01),and muscle tone significantly increased(P<0.01);the contents of GABA and IL-10 in ischemic cortex significantly decreased(P<0.01),and the contents of TNF-α and Glu significantly increased(P<0.01),Glu/GABA ratio increased(P<0.01),GABRA1 and GAD67 protein expression significantly decreased(P<0.01),the co-expression of Iba-1 and iNOS significantly increased(P<0.01),while the co-expression of Iba-1 and Arg-1 was significantly decreased(P<0.01).Compared with the model group,the nerve function score and muscle tone score of the electroacupuncture group rats were significantly reduced(P<0.05),and muscle tone was significantly reduced(P<0.01);the contents of GABA and IL-10 in ischemic cortex significantly increased(P<0.01),and the contents of TNF-α and Glu significantly decreased(P<0.01),Glu/GABA ratio decreased(P<0.01),the protein expressions of GABRA1 and GAD67 significantly increased(P<0.01),the co-expression of Iba-1 and iNOS significantly decreased(P<0.01),while the co-expression of Iba-1 and Arg-1 significantly increased(P<0.05).Conclusion Electroacupuncture can effectively alleviate PSS,and its mechanism of action may be related to electroacupuncture regulating microglia polarization and reduing neuroinflammation.

Neurodevelopmental disorders(NDDs)are chronic developmental brain disorders that can affect cognition,motor,social adaptation,behavior and so on due to multiple genetic or acquired causes.Natural polysaccharides are synthesized by living organisms,located in the cell wall,inside and between cells,and outside the cells,and are essential components of life activities.Previous studies have found that natural polysaccharides play an important role in neurological diseases,which mainly ameliorate the behavioral abnormalities and clinical symptoms caused by anti-oxidative stress,anti-neuronal apoptosis,anti-neuroinflammation,anti-excitatory amino acid toxicity,and regulation of the brain-gut axis.This review summarizes the intervention role of 17 bioactive polysaccharides from plants and fungi in neurological diseases,aiming to provide new ideas for the research and treatment of NDDs.

Objective:To establish a feasible mouse model of post-stroke dysphagia(PSD).Methods:Thirty C57BL/6 male mice were randomly divided into a sham-operated group(Sham)and a model group(PSD),and the PSD mouse model was made by the photothrombosis method(PT)method,and the sham-operated group was only injec-ted with rose bengal staining solution in the tail vein.The cerebral blood flow of the mice was measured by laser scatter imaging,the ratio of cerebral infarct area was detected by TTC staining,the electromyographic area of the in vivo pha-ryngeal muscle group of mice swallowing was recorded by a multi-conductor physiological recorder MP160,the drinking function of the mice was measured by the 4-min water drinking experiment,and the weight changes were recorded,respectively,at 1,3,and 7 d.Results:Cerebral blood flow decreased at all time points,with a sharp drop in cerebral blood flow at 1 d,gradual recovery of cerebral blood flowat 3 and 7 d,establishment of collateral circulation,and gradu-al reduction of cerebral infarction area;compared with the Sham group,the myoelectric area of the PSD group was reduced at 1 and 3 d(P＜0.05),but with a trend of gradual recovery,and there was no significant difference between the PSD group and the Sham group at 7 d,and water consumption and weight decreased at 4 min at 1,3,and 7 d(P＜0.05).Conclusion:The mice showed some degree of dysphagia symptoms and are expected to be a translational model for PSD.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Objective:To observe the effects of electroacupuncture on the expression of cortical solute carrier family 7 member 11(SLC7A11),glutathione(GSH)and glutathione peroxidase 4(GPX4)in rats with post stroke spasticity(PSS),and to explore the mechanism of electroacupuncture in the treatment ferrozosis in PSS.Methods:Thirty SD male rats were randomly divided into sham group,model group and electroacupuncture group.A modified Zea-Longa wire bolus+internal capsule injection NMDA method was used to produce a rat model of PSS.In the electroacupunc-ture group,the affected side of Yanglingquan and Quchi were needled once/day for 30 min/time for 7 d.In the sham group and the model group,only fixation without intervention was performed during the same period.Zea-Longa Neuro-logical Function Score was used to detect the neurological function of rats,electrophysiological tracing method was used to detect the muscle tone of rat quadriceps,Western Blot was used to detect the protein expression of rat cortical SLC7A11 and GPX4,Enzyme-linked immunosorbent assay(ELISA)was used to detect the GSH content of rat cortex,and real time RT-PCR was used to detect the mRNA of rat cortical SLC7A11 and GPX4 mRNA expression.Results:Neurological function scores were elevated;quadriceps muscle tone was increased;GSH content was decreased;the protein expression of SLC7A11 and GPX4 was significantly decreased;the expression of SLC7A11 mRNA and GPX4 mRNA was significantly decreased.Electroacupuncture treatment resulted in lower neurological function scores,lower quadriceps muscle tone,increased GSH content in rat cortex,significantly up-regulated protein expression of SLC7A11 and GPX4,and significantly increased expression of SLC7A11 and GPX4 mRNA.Conclusion:Electroacupuncture on"Yanglingquan"and"Quchi"could improve limb spasticity and promote the recovery of neurological function in PSS rats,and its mechanism of action may be related to the inhibition of ferroptosis of cortical cells by electroacupuncture regulating the SLC7A11 and GPX4 expression.

Objective:To investigate the synergistic effect of physical intervention and chemotherapeutic drug therapy on tumor growth by blocking tumor microvessels and injecting chemotherapy drug Endostar (ecombinant human vascular endostatin injection) to inhibit tumor neovascularization by low intensity ultrasound induced microbubble cavitation combined with hemocoagulase.Methods:Seventy-five male NU/NU mice bearing human-derived lung adenocarcinoma, weighing 25-30 g, were randomly divided into microbubble-enhanced ultrasonic cavitation+ Endostar group (MEUC+ Endostar), microbubble-enhanced ultrasonic cavitation+ hemocoagulase+ Endostar group (MEUC+ HC+ Endostar), microbubble-enhanced ultrasonic cavitation (MEUC), Endostar group (Endostar) and sham group. Fifteen mice in each group were given the corresponding treatment intervention for 4 consecutive days followed by 4 days of aseptic feeding. Two-dimensional ultrasound and contrast-enhanced ultrasound (CEUS) were performed before intervention, immediately after intervention and 4 days after intervention, respectively. Tumor tissues were obtained for vascular endothelial growth factor immunofluorescence staining, and microvessel density (MVD) was observed.Results:There was no difference in tumor volume between the groups before the intervention ( P>0.05). Immediately after the intervention, filling defects were observed in MEUC+ Endostar group, MEUC+ HC+ Endostar group and MEUC group, while filling was good in Endostar group and sham group; 4 days after the intervention, filling defects were observed in MEUC+ Endostar group and MEUC+ HC+ Endostar group. The filling defect was still present in Endostar group, while partial recovery of perfusion was performed in MEUC group, and PI and AUC were still significantly lower in MEUC+ HC+ Endostar group than in the other groups ( P<0.05). When tumor tissues were obtained 4 days after the intervention, the MVD in MEUC+ HC+ Endostar group was significantly lower than that in the remaining groups, and the difference of MVD in tumor tissue was statistically significant ( P<0.05). Conclusions:Low intensity ultrasound induced microbubble cavitation combined with hemocoagulase and Endostar can produce a synergistic effect in blocking tumor microvessels and inhibiting tumor angiogenesis, which can more effectively inhibit tumor growth.

Objective:To compare the clinical results of different endovascular thrombus reduction techniques in the treatment of acute lower extremity arterial thrombosis.Methods:The clinical data of 96 consecutive patients with acute femoral popliteal arterial thrombosis who were treated with catheter directed thrombolysis (CDT) and mechanical thrombus aspiration system (PMT) between Jan 2016 and Dec 2018 at Cangzhou People's Hospital and Peking University People's Hospital were retrospectively analyzed.Results:Ninty-six patients underwent thrombolytic surgery,including 36 with CDT thrombolysis, 28 with AngioJet aspiration alone and 32 with Rotarex aspiration alone. Angiojet thrombus aspiration reduced thrombus rate by 89.3% (25/28) and clinical success rate by 92.8% (26/28).The thrombus reduction rate of Rotarex group was 87.5% (28/32), and the clinical success rate was 96.8% (31/32). In the CDT thrombolytic group, the thrombolytic reduction rate was 61.1% (22/36), including 8 patients who underwent thrombectomy and 6 patients with PMT, with a clinical success rate of 86.1% (31/36). The rate of distal arterial embolization, puncture point and local subcutaneous hematoma and vascular rupture was 21.4%, 10.7% and 2.1%, respectively. There were no amputation cases reported during a mean 13 months follow-up.The survival rate was 97.9%. The first-stage patency rate of 67.8%, while the second-stage artery patency rate of 85.7% during the follow-up.Conclusion:Compared with CDT, PMT has higher efficiency and lower complication rate in the treatment of acute lower extremity arterial thrombosis.

Objective:To report our experience in diagnosis and treatment of posterior atlantoaxial dislocation with odontoid retrolisthesis.Methods:A retrospective study was conducted of the 5 patients who had been treated from July 2012 to August 2018 at Department of Orthopaedics, General Hospital of Southern Theater Command for posterior atlantoaxial dislocation. They were 4 men and one woman, aged from 34 to 67 years (average, 47 years). All of them had a history of trauma. Of them, 4 were complicated with odontoid fracture and one with congenital free os odontoideum. Their posterior atlantoaxial dislocation ranged from 3 to 9 mm (average, 6 mm). By the American Spinal Injury Association (ASIA) grading system, their preoperative spinal injury was rated as grade B in one, as grade C in 3 cases and as grade D in one. All the 5 patients underwent skull traction at 10° flexion. Surgical trans-oralpharyngeal atlantoaxial reduction and internal fixation was performed for the one patient whose reduction had not been achieved by traction while posterior atlantoaxial screw-rod fixation or anterior odontoid screwing was conducted for the 4 patients whose reduction had been achieved by traction. The distance of posterior atlantoaxial dislocation was measured to evaluate their reduction and ASIA grade system was used to assess their spinal function after operation.Results:The postoperative distance of posterior atlantoaxial dislocation was 0 mm, showing a reduction rate of 100%. The 5 patients were followed up for 6 to 36 months (average, 15 months). By the ASIA grade system, the postoperative functional recovery of the spine was grade D in 4 cases and grade C in one. No implant loosening or breakage occurred.Conclusion:As a kind of high-energy hyperextension injury, posterior atlantoaxial dislocation is rare in clinic, but an appropriate treatment can be adopted to deal with its different clinical types to achieve good outcomes.

Objective:To construct and validate a prediction model combined machine learning with imaging omics characteristics in differentiating anaplastic glioma from glioblastoma.Methods:Imaging data of 241 patients with anaplastic glioma or glioblastoma, confirmed by pathology in our hospital from August 2005 to August 2012, were retrospectively collected. These patients were divided into a training group ( n=140) and a verification group ( n=101) according to random number table method. MRIcron software was used to delineate tumor boundaries of patients from the training group on preoperative T1 enhanced MR imaging. The regions of interest (ROIs) were outlined on preoperative T1 enhanced MR imaging, and the radiomic features were extracted from ROIs by Matlab software. Least absolute shrinkage and selection operator (LASSO) regression model was used to screen the features, and then, the selected features were used to construct the prediction model by support vector machine (SVM) classifier. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of the model. Results:In these 241 patients, 101 were with anaplastic glioma and 140 were with glioblastoma confirmed by pathology. In the training group and validation group, there was statistical difference in age between patients with anaplastic glioma and glioblastoma ( P<0.05); there was no significant difference in gender distribution, tumor location, and percentages of tumor necrosis or edema between patients with anaplastic glioma and glioblastoma ( P>0.05). Totally, 431 radiomic features were extracted; 11 radiomic features were screened by LASSO regression model and the prediction model was established. The AUC of ROC curve was 0.942 and 0.875, respectively, in the training group and validation group. Conclusion:The prediction model combined machine learning and imaging omics characteristics can effectively discriminate anaplastic glioma from glioblastoma.