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Objective:To explore the effect of enriched environment on pain sensitivity, anxiety- and depressive-like behavior in selective nerve injury(SNI) rats model and its potential mechanism.Methods:A total of 36 male clean grade SD rats aged 6-8 weeks were randomly divided into three groups( n=12 in each group): sham operation+ standard environment group (sham group), SNI+ standard environment group (standard environment group), SNI+ enriched environment group (enriched environment group). The rat model of neuropathic pain was established by SNI.The rats in the enriched enviroment group were placed in an enriched enviroment 7 days before operation until 21 days after operation.The paw withdraw threshold(PWT) and paw withdraw latency (PWL) were performed to assess hyperalgesia.The open field test, elevated plus maze test, novelty suppressed feeding test and forced swimming test were used to assess anxiety and depression like behavior.The expressions of cAMP response element binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95) and neuroligin 2 (NLGN2) were detected by Western blot.The expression of CREB and BDNF in contralateral ACC were measured by immunofluorescence.GraphPad prism 8.0 and SPSS 23.0 were used for data analysis.One way ANOVA was used for inter group comparison, repeated measurement ANOVA was used to analyze PWT and PWL results, and Tukey test was used for pairwise comparison. Results:(1) In PWT and PWL experiments, the interaction effect between group and time, group main effect and time main effect of PWT were significant ( F=13.4, 39.6, 369.6, all P<0.05), and the interaction effect between group and time, group main effect and time main effect of PWL were significant ( F=3.8, 10.3, 58.8, all P<0.05). Compared with sham group, PWT((8.0±3.5) g, (2.4±1.4) g, (2.3±1.1) g, (2.2±1.6) g, (1.6±0.5) g) and PWL((8.6±1.3) s, (7.3±1.5) s, (7.9±1.0) s, (6.6±1.1) s, (7.7±1.4) s) in standard environment group decreased at each time point (all P<0.05). (2) Compared with sham group, the number of entrying into the central area (1.3±1.7), the time of entrying into the central area((1.6±1.3) s), the proportion of entering open arms ((8.0±7.8) %) and the proportion of time in the open arms ((1.3±1.2) %) all significantly decreased in standard environment group ( t=4.585, 5.423, 4.682, 5.202, all P<0.05). The eating latency ((365.2±94.4) s) and immobility time ((127.6±24.3) s) dramatically increased ( t=6.008, 14.290, both P<0.05). The number and time of entrying into central area of enriched environment group were both higher than those of standard environment group(both P<0.05), while the eating latency and immobility time of enriched environment group were both lower than those of standard environment group(both P<0.05). (3) Compared with sham group(CREB: (1.6±0.2), (0.8±0.5); BDNF: (0.8±0.5), (1.0±0.4)), the expression of CREB ((1.8±0.1), (1.5±0.2)), BDNF ((0.9±0.6), (1.4±0.3)) in spinal cord and ACC of standard environment group increased (spinal: t=3.283, 4.989; ACC: t=5.502, 4.257, all P<0.05). The expression of PSD-95 ((1.6±0.2), (1.0±0.2) and NLGN2 ((1.5±0.5), (1.1±0.2)) also increased in ACC of standard enviroment group ( t=4.257, 2.214, both P<0.05). Compared with standard environment group, the expression of CREB (1.3±0.3), BDNF (0.7±0.4), PSD-95(1.0±0.3) and NLGN2(1.1±0.4) in spinal cord of enriched environment group decreased ( t=5.007, 2.166, 2.358, 2.322, all P<0.05). The expression of PSD-95(1.2±0.3) and NLGN2(1.1±0.2) also decreased in ACC of enriched environment group ( t=2.674, 2.944, both P<0.05). However, the expression of p-CREB (1.7±0.6) and BDNF (2.4±0.2) increased in ACC ( t=4.180, 7.610, P<0.05). Conclusion:Enriched environment can improve neuropathic pain and anxiety- and depressive-like behavior in SNI rats, which may be related to the change of synaptic plasticity in spinal cord and ACC.
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T helper 17 (Th17) cells are closely associated with the pathogenesis of several autoimmune and inflammatory diseases, and selective suppression of Th17 cell production and pathogenicity is an effective strategy for the treatment of these diseases. There is growing evidence that cellular metabolism is associated with the development of autoimmune diseases and determines the differentiation and effector functions of Th17 cells, which undergoes a metabolic reorganization during differentiation from an oxidative phosphorylation-based catabolism to a glucose-based anabolic metabolism in the initial T cells. This paper focused on reviewing recent findings regarding the importance of metabolism in T cell differentiation and autoimmune diseases, especially in Th17 cells, and discussing the regulatory mechanisms of glycolysis in Th17 cell differentiation. This review summarized the regulation of metabolism on T-cell activation and differentiation, revealed metabolic targets with specific regulation on Th17 cells, and provided reference for finding potential therapeutic targets for Th17 cell-mediated autoimmune diseases.
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Background@#and Purpose: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe central nervous system disorder mediated by NMDAR antibodies that damages neurons. We investigated the correlation between cytoskeletal autoantibodies and the clinical severity in patients with anti-NMDAR encephalitis. @*Methods@#Non-NMDAR autoantibodies were identified by screening matched cerebrospinal fluid (CSF) and the serum samples of 45 consecutive patients with anti-NMDAR encephalitis and 60 healthy individuals against N-methyl-D-aspartate receptor 1-transfected and nontransfected human embryonic kidney 293T cells. Immunocytochemistry was performed to assess antibody binding in rat brain sections and primary cortical neurons. Cell-based assays and Western blotting were applied to identify autoantibodies targeting medium neurofilaments (NFMs). We compared clinical characteristics between patients with NMDAR encephalitis who were positive and negative for anti-NFM-autoantibodies. @*Results@#Anti-NFM autoantibodies were detected in both the serum and CSF in one patient (2%) and in the serum only in six patients (13%). No antibodies were detected in the serum of healthy controls (7/45 vs. 0/60, p=0.0016). Four of the seven patients with anti-NFM autoantibodies in serum were children (57%), and three (43%) had abnormalities in brain magnetic resonance imaging. These patients responded well to immunotherapy, and either no significant or only mild disability was observed at the last follow-up. Anti-NMDAR encephalitis did not differ with the presence of anti-NFM autoantibodies. @*Conclusions@#Anti-NFM autoantibodies may be present in patients with anti-NMDAR encephalitis, indicating underlying neuronal damage. A large cohort study is warranted to investigate the clinical differences between patients with NMDAR encephalitis according to their antiNFM antibody status.
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OBJECTIVE@#To assess the value of mapping allele with resolved carrier status (MaReCs) technology for the determination of balanced translocation carrier status for embryos.@*METHODS@#Blastocysts produced by 25 reciprocal translocation carriers and 15 Robertsonian translocation carriers were detected by MaReCs. After genetic counseling, transplantable blastocysts were selected. Amniocentesis was performed to check fetal chromosomes at 16 to 20 gestational weeks, and the consistency of amniocentesis and MaReCs was determined.@*RESULTS@#No significant difference was found in the normal rate for chromosome copy number variations (CNVs) in blastocysts between reciprocal translocation carriers and Robertsonian translocation carriers (28.6% vs. 32.0%, P> 0.05). For 12 (48%) reciprocal translocation carriers and 8 (32%) Robertsonian translocation carriers, the status of translocation carrier of embryos was successfully determined. The results of amniocentesis were consistent with that of MaReCs in all 11 pregnancies.@*CONCLUSION@#MaReCs is a reliable method to distinguish the translocation carrier status of embryos of balanced translocation carriers. It can help a certain proportion of balanced translocation carriers to select completely normal embryos while reduce transfer of embryo carrying a balanced translocation.
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Myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD) are newly recognized immune-mediated inflammatory demyelinating diseases of the central nervous system. The diseases can be manifested as a single-phase or recurrent course, recurrent episodes of which can leave serious neurological dysfunction, and control of acute attacks and prevention of recurrence is the focus of treatment, including steroids, immunosuppressants and biological agents. This article will review the progress of immunotherapy for MOGAD.
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Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG. In C57BL/6 mice and Sprague-Dawley rats, MOG-IgG only caused lesions in the presence of complement. Interestingly, AQP4-IgG induced astroglial damage, while MOG-IgG mainly caused myelin loss. MOG-IgG also induced astrocyte damage in mouse brains in the presence of complement. Importantly, we also observed ultrastructural changes induced by MOG-IgG and AQP4-IgG. These findings suggest that MOG-IgG directly mediates cell death by activating complement in vitro and producing NMOSD-like lesions in vivo. AQP4-IgG directly targets astrocytes, while MOG-IgG mainly damages oligodendrocytes.
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This retrospective study aims to demonstrate the effect of antitubercular treatment (ATT) on the pregnancy outcomes and prognoses of patients with genital tuberculosis (GTB) who had received laparoscopy and/or hysteroscopy. This study included 78 patients with infertility and who were diagnosed with GTB through laparoscopy and/or hysteroscopy over the period of November 2005 to October 2015. The recruited patients were divided into ATT and nonATT groups on the basis of ATT duration. The GTB recurrence rates, menstrual patterns, and pregnancy outcomes of the patients were determined at follow-up. Among the 78 patients, 46 received ATT and 32 did not receive ATT. The menstrual volumes of patients in the ATT group significantly decreased relative to those of patients in the nonATT group. GTB did not recur among all patients regardless of treatment. A total of 11 pregnancies (36.7%) in the ATT group and 19 pregnancies (63.3%) in the nonATT group were observed. Pregnancy rates significantly differed (P = 0.002) between the two groups. ATT may decrease the menstrual volume and pregnancy rates of patients who were diagnosed with GTB through laparoscopy and/or hysteroscopy. In addition, ATT did not improve the prognosis of patients with chronic GTB.
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Adult , Female , Humans , Pregnancy , Young Adult , Antitubercular Agents , Therapeutic Uses , China , Fertilization , Hysteroscopy , Infertility, Female , Laparoscopy , Pregnancy Outcome , Pregnancy Rate , Prognosis , Retrospective Studies , Tuberculosis, Female Genital , Drug TherapyABSTRACT
Objective@#To observe the therapeutic effect of vitrectomy combined with single-layer inverted internal limiting membrane (ILM) flap covering technique for rhegmatogenous retinal detachment(RRD) complicated with macular hole (MH).@*Methods@#A retrospective case analysis. From January 2015 to August 2019, 29 eyes of 29 patients with RRD and MH diagnosed in the First People's Hospital Affiliated to Shanghai Jiaotong University were included in this study. There were 16 males (16 eyes) and 13 females(13 eyes). All the eyes were peripheral RRD and involving the macular area, while complicated with MH and proliferative vitreoretinopathy in stage less than C. All the eyes were examined by BCVA and OCT. The BCVA examination was performed using the Snellen visual acuity chart, which was converted into logMAR visual acuity. Before 2017, 18 eyes were treated with vitrectomy combined with ILM peeling (ILM peeling group); after 2017, 11 eyes were treated with vitrectomy combined with single-layer inverted ILM flap covering technique (ILM inverted group). The differences of age (t=0.360), onset time (t=1.235), number of holes except MH (t=0.060), RRD range (t=1.232), gas filled eyes (χ2=0.324) between the two groups were not statistically significant (P>0.05). The average follow-up time after surgery was 4.5 months. The BCVA, retinal reattachment and MH closure at the last follow-up in the two groups were comparatively observed. U-shaped or V-shaped retina was defined as MH closure.@*Results@#At the last follow-up, retinal reattachments were achieved in all the eyes. In ILM peeling group, 5 eyes (27.8%, 5/18) were completely closed in typeⅠ . In ILM inverted group, 9 eyes (81.8%, 9/11) were completely closed in typeⅠ . There was a statistically significant difference of closure rate in type Ⅰ closure between the two groups (χ2=5.968, P=0.015). The mean logMAR BCVA in ILM peeling group and ILM inverted group were 1.24±0.28 and 0.97±0.39, respectively. The difference of logMAR BCVA between the two groups was statistically significant (t=2.179, P=0.038).@*Conclusion@#Vitrectomy combined with single-layer inverted ILM flap covering technique can increase the BCVA and MH closure rates in RRD patients with MH.
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Objective To observe the therapeutic effect ofvitrectomy combined with single-layer inverted internal limiting membrane (ILM) flap covering technique for rhegmatogenous retinal detachment (RRD) complicated with macular hole (MH).Methods A retrospective case analysis.From January 2015 to August 2019,29 eyes of 29 patients with RRD and MH diagnosed in the First People's Hospital Affiliated to Shanghai Jiaotong University were included in this study.There were 16 males (16 eyes) and 13 females (13 eyes).All the eyes were peripheral RRD and involving the macular area,while complicated with MH and proliferative vitreoretinopathy in stage less than C.All the eyes were examined by BCVA and OCT.The BCVA examination was performed using the Snellen visual acuity chart,which was converted into logMAR visual acuity.Before 2017,18 eyes were treated with vitrectomy combined with ILM peeling (ILM peeling group);after 2017,11 eyes were treated with vitrectomy combined with single-layer inverted ILM flap covering technique (ILM inverted group).The differences of age (t=0.360),onset time (t=1.235),number of holes except MH (t=0.060),RRD range (t=1.232),gas filled eyes (x2=0.324) between the two groups were not statistically significant (P＞0.05).The average follow-up time after surgery was 4.5 months.The BCVA,retinal reattachment and MH closure at the last follow-up in the two groups were comparatively observed.U-shaped or V-shaped retina was defined as MH closure.Results At the last follow-up,retinal reattachmnents were achieved in all the eyes.In ILM peeling group,5 eyes (27.8％,5/18) were completely closed in type Ⅰ.In ILM inverted group,9 eyes (81.8％,9/11) were completely closed in type Ⅰ.There was a statistically significant difference of closure rate in type Ⅰ closure between the two groups (x2=5.968,P=0.015).The mean logMAR BCVA in ILM peeling group and ILM inverted group were 1.24± 0.28 and 0.97 ± 0.39,respectively.The difference of logMAR BCVA between the two groups was statistically significant (t=2.179,P=0.038).Conclusion Vitrectomy combined with single-layer inverted ILM flap covering technique can increase the BCVA and MH closure rates in RRD patients with MH.
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Exudative or wet age-related macular degeneration (AMD) is characterized by the progressive growth of choroidal neovascularization (CNV).Anti-vascular endothelial growth factor (VEGF) drugs have been used in the control of the development of CNV and vision improvement,but there are still defects like frequent injections,drug resistance and so on.Radiotherapy can deactivate local inflammatory cell populations,and make CNV unstable in the absence ofpericytes and VEGF stimulation,which induce apoptosis of the vascular endothelial cells.Therefore,radiotherapy is considered as a potential adjuvant treatment of anti-VEGF therapy.The current clinical approaches include epimacular brachytherapy (EMBT) and long-range stereotactic radiotherapy (SRT).SRT may be a preferred adjuvant treatment for patients receiving anti-VEGF therapy.Knowing the progress of radiotherapy for the treatment of exudative AMD may help us to fully understand the pathogenesis of wAMD in China
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Objective To investigate the variation characteristics of adenovirus type 55 (HAdV-B55) gene on plateaus.Methods Throat swabs were collected from HAdV-B55 infected patients and used for virus isolation in HEp-2 cells.The whole-genome sequence was obtained by PCR and sequencing.HAdV-B55 gene sequence was blast with the previously reported virus.Results HAdV-B55 strains were isolated from throat swabs, which were named LS89/Tibet/2016.The whole-genome sequence was obtained and submitted to GenBank with the accession number of KY002683.No large fragment gene recombination was found between this HAdV-B55 strain and previous strains, and the sequence similarity with QS-DLL strain was 99.9%.Conclusion This study provides more information for the evolution patterns of adenovirus 55 and will contribute to the prevention and control of HAdV-B55 infection in the future.
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This study was aimed to systematically evaluate the clinical efficacy and safety of brucea javanica oil emulsion injection combined with gemcitabine plus cisplatin (GP) regimen in the treatment of non-small cell lung cancer.Literatures were retrieved from databases of CNKI,Wanfang database,VIP,CBM,Pubmed from the date of database establishment to March 2017.Journals on related fields were also manually searched.The randomized controlled trials (RCTs) of brucea javanica oil emulsion injection combined with GP regimen in the treatment of non-small cell lung cancer were collected.The results showed that there were 12 included RCTs with 1 118 patients.The meta-analysis results showed that compared with single using of GP regimen,there were statistical significance in the partial remission rate [OR =1.59,95％ CI (1.23,2.05),P =0.000 4],the total remission rate [OR =1.72,95％ CI (1.33,2.22),P ＜ 0.000 1],the KPS (Karnofsky) score improvement [OR =2.59,95％ CI (1.96,3.43),P ＜ 0.000 01],the deterioration of KPS score [OR =0.33,95％ CI (0.25,0.46),P ＜ 0.000 01],the incidence of bone marrow suppression [OR =0.48,95％ CI (0.35,0.65),P ＜ 0.000 01],and the incidence of gastrointestinal adverse reactions [OR =0.46,95％ CI (0.23,0.91),P =0.03] by brucea javanica oil emulsion injection combined with GP regimen in the treatment of non-small cell lung cancer.It was concluded that brucea javanica oil emulsion injection combined with GP regimen can increase clinical efficacy,decrease myelosuppression rate and gastrointestinal adverse reactions.
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BACKGROUND:The aid treatment of aphasia is mainly achieved through computer training system, and the applied software of the market at present is mainly Chinese aphasia training system software. The software for a native Uighur aphasia patient does not apply and no research of Uygur language aphasia training software has been reported. OBJECTIVE:To design a clinic oriented training software for Uighur aphasia, based on training specifications of rehabilitative therapist in the treatment of Uighur aphasia patients. METHODS:The experiment was conducted from January 2013 to December 2013 in South and North areas of Xinjiang Uygur Autonomous Region, deeply researching the common and familiar life material of the Uyghur’s and combining the life custom of the Uyghur’s, to screen the relevant materials of the speech rehabilitation training, preliminary build up the living language material database of the Uyghur’s. Basing on this database, we designed the computer-assisted application software which has the Uygur and Chinese double interface. The software is designed by the software research and development personnel in accordance with the requirements of the members of our group, with Uygur and Chinese double interface speech rehabilitation training software. 30 Uygur aphasiac patients after stroke in Xinjiang were screened for clinical trials and evaluation, the software after many corrections, detailed recorded the valuable dates and the problems existing in the experimental stage. And we constantly communicate with the software designers so as to repeatedly revise the wrong in the process of training, and eventualy developing a set of basic mature Uygur language aphasia and training software. RESULTS AND CONCLUSION:A set of basic mature Uygur aphasia training software was designed. With the research and development of the Uighur aphasia training software, speech therapists of Xinjiang get a fuly functional, easy operation, flexible extension training tool, which help to reduce the workload of speech therapists and improve the clinical efficiency.
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Objective To investigate the effectiveness of heart valve replacement in the same period of radiofrequency ablation in the treatment of atrial fibrillation.Methods Eighty-six patients with atrial fibrillation underwent heart valve replacement in the same period of bipolar radiofrequency ablation system according to the maze heart valve replacement operation principle.And optimized the operation method.Results No death occurred during operation.The average ablation time was (23 ± 8) minutes with a range of 16-56 minutes.Sinus rhythm of the heart was restored after surgery in all patients (100％).The long-term success rate was 98.8％ (85/86).Conclusion Our optimization of heart valve replacement in the same period of radiofrequency ablation enhanced the success rate of the operation,simplified the procedures,meanwhile it might need widely application clinically.
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Objective To study the protective effect of normothermic ex vivo perfusion to prevent donor-lung injury.Method After being flushed with perfadex solution through the pulmonary artery and vein,the donor lungs were divided to control group (preserved with 4℃ cold static preservation,n =8) and experimental group (preserved with ex vivo oxygenated blood continuous perfusion,n =8).Pulmonary function indexes,including pulmonary vascular resistance (PVR),lung ventilation resistance(LVR),the left inferior pulmonary vein(LIPV) blood PO2,and lung water content,were evaluated.Lung injury were studied by light microscopic observation and detecting the expression of proimflammatory factor IL-1β was detected.Result (1) Lung function evaluation:in both group,PVR,LVR and lung water content gradually increased,LIPV PO2 gradually declined;But in the same time point PVR and LVR in group were were significantly less than in control group (P＜0.05),LIPV PO2 in experimental group were were significantly more than in control group(P＜0.05).(2)Lung injury evaluation:Lung tissue edema classification in both group were significantly higher than in normal lung(P＜0.05),but classification in experimental group were significantly lower than in control group(P＜0.05).The expression of IL-1β in experimental group (0.422 ± 0.132) were significantly lower than in control group(0.578 ± 0.163,P＜0.05).Conclusion Ex vivo oxygenated blood continuous perfusion without ventilator is a feasible technique for lung preservation.It ameliorates hypothermic time-dependent ischemic injury.But further systems evaluation in complete physiologic condition is necessary.
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Objective To investigate the feasibility and efficacy of treating atrial fibrillation(AF)in beating heart surgery using bipolar Radiofrequency Ablation(RFA)system. Methods Treating AF in beating heart under normal temperature CBP surgery with bipolar RFA following the circuit of maze operation,2 - 6 times each place,until sinus rhythm appeared,then perform AVR or MVR in the stopped beating heart. Results All 18 cases survived the surgery. Sinus rhythm appeared in all cases. The average treating time was 28 minutes. Conclusions Application of bipolar RFA in the treatment of AF in beating heart is a safe and efficacy method. It is recommended to be applied widely.
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OBJECTIVE: To prepare Nimodipine hydrogel patch and to investigate the effects of different factors on the in vitro percutaneous permeability of nimodipine.METHODS: Nimodipine hydrogel patch was prepared with sodium carboxymethylcellulose as matrix.The permeation flux of nimodipine through excised mice skin in vitro was determined using Franz diffusion cell.The content of nimodipine was measured by HPLC.Accumulative transdermal delivery of nimodipine(Q) and transdermal speed constant(Js) were calculated.The loading amounts,type of transdermal enhancer(menthol,azone and oleic acid) and their content were optimized with the value of Q and Js as index.RESULTS: The best loading amount was 4 mg?cm-2.Different transdermal enhancers were found to increase the percutaneous permeability of nimodipine.5% oleic acid had the best penetration enhancing effect.The permeation of samples containing 5% oleic acid was in accordance with the zero-order kinetics.Nimodipine hydrogel transdermal patch presented high Js of 28.10 ?g?cm-2?h-1 and Q of 342.58 ?g?cm-2 in 12 h.CONCLUSION: Nimodipine hydrogel patch has good potential for transdermal delivery.