Outcome of COVID-19 Infection in Patients With Multiple Sclerosis Who Received Disease-Modifying Therapies: A Systematic Review and Meta-Analysis

Background@#and Purpose A systematic review and meta-analysis was performed of the outcome of Coronavirus disease 2019 (COVID-19) infection in patients with multiple sclerosis (MS) who received disease-modifying therapies (DMTs). @*Methods@#Relevant studies published before November 2022 in the PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, and Web of Science databases were retrieved using the following search expression: (“multiple sclerosis” OR “MS”) AND (“DMT” OR “disease modifying therapies”) AND (“COVID-19”). Two authors independently screened the articles and extracted the data. Qualitative analyses and a meta-analysis constituted 22 of the 794 retrieved articles. Differences in the hospitalization and mortality rates were used as the main measures of efficacy, and the meta-analysis was performed using RevMan software. @*Results@#22 clinical trials were selected. The hospitalization rate was lower in the 3,216 patients who received DMTs than in the 774 patients who did not receive any treatment, with a moderate effect size of 0.43 (p<0.00001). The mortality rate was also lower among patients with MS treated using DMTs than in controls (odds ratio [OR]=0.19, 95% confidence interval [CI]=0.13–0.27, p<0.00001). The hospitalization rates for COVID-19 infection in patients with MS treated with anti-CD20 therapy also increased markedly (OR=3.32, 95% CI=2.63–4.20, p<0.00001). However, there was no significant difference between patients with MS who did and did not receive DMTs. @*Conclusions@#In summary, the application of DMTs was found to be valuable for patients with MS infected with COVID-19. However, more clinical studies are needed to determine the use of anti-CD20 drugs in patients with MS during the COVID-19 pandemic.

Research progress of statins on immune regulation of multiple sclerosis and experimental allergic encephalomyelitis

Objective The aim of this study is to summarize studies on statins used to treat multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) and its underlying mechanisms. Methods We searched some representing databases. Some studies were included if the effects of statins were tested on MS and EAE. The methodological quality was evaluated by the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies checklist. Results Studies have confirmed that statins have immunomodulatory, neuroprotective and anti-inflammatory effects, and can be used in combination with immunomodulators of different mechanisms to treat MS and EAE. Statins have been shown to improve the following symptoms MS, reduce the number of attacks and the number of lesions, through immunomodulatory, neuroprotective and anti-inflammatory effects, and has a good safety profile. Conclusions In short, statins represent an attractive new measure for treating MS. Some studies indicate that in addition to immunomodulatory effects, statins may have neuroprotective and neuro-repairing effects. The combination of statins with other immunosuppressive drugs has also produced encouraging results. This can be broadly prospects prospected to treat MS and EAE. It is hoped that in the near future, a combination of statins with less adverse reactions and high efficacy combined with other immunomodulators will bring exact results to patients with MS (AU)

Dynamic expression of autophagy-related factors in autoimmune encephalomyelitis and exploration of curcumin therapy.

Curcumin has been used in the study of central nervous system immune-related diseases and exerts a substantial neuroprotective effect. However, the mechanism remains unclear. The AKT/mTOR autophagy-related signalling pathway plays an important role in tumour therapy, but whether curcumin plays a therapeutic role in multiple sclerosis (MS) through this signalling pathway remains to be determined. As an animal model of MS, experimental autoimmune encephalomyelitis (EAE) is induced by the myelin glial glycoprotein MOG35-55 in female C57BL/6 mice. We first evaluated the changes in autophagy levels in EAE mice. Then, curcumin was intraperitoneally injected into the mice, and the expression of AKT/mTOR autophagy signalling pathway-related proteins was evaluated. Our data show that 1. autophagy defects can cause neuronal damage in EAE mice; and 2. curcumin may regulate the activation of autophagy in EAE mice by affecting the AKT/mTOR autophagy signalling pathway, further balancing central nervous system and peripheral autophagy.

Systematic review of vitamin D as add-on therapy in multiple sclerosis / 中国免疫学杂志

Objective:To evaluate a Meta-analysis of randomized controlled trials ( RCTs) in multiple sclerosis ( MS) patients to evaluate the efficacy of vitamin D as add-on therapy. Methods: Searched Pubmed,EMbase,the Cochrane Library,CNKI,Wanfang Data base and so on up to february 2016 using the keywords:multiple sclerosis or MS and the drug names:vitamin D orCholecalciferol. Two authors independently selected the articles and extracted the data. We performed meta-analysis using Review Manager ( RevMan) version 5. 3 software. Results:Four RCTs with a total of 247 patients were selected.①Compared to the placebo, the EDSS score[MD=-0. 33,95% Confidence interval (CI)= (0. 68,0. 01),P=0. 05],the annual relapse rate[MD=-0. 08, 95%CI=(-0.37,0.21),P=0.60]and the number of gadolinium-enhancing lesions[MD=-0.16,95%CI=(-0.57,0.25),P=0. 45] showed no significant difference at 12 months,meanwhile the EDSS score[MD=-0. 48,95%CI=(0. 87,-0. 09),P=0. 02] and the annual relapse rate[MD=-0. 27,95%CI=(-0. 52,-0. 02),P=0. 03] were significantly less in the vitamin D group at 24 months.②Safety evaluation:There was no hypercalcaemia in vitamin D treated patients in each studies,main adverse events reported were diarrhoea, fever, constipation, dyspepsia, headache and so on. These symptoms were mild, after stopping drug can relieve the general. Conclusion: Vitamin D as an added in the treatment of MS showed as same as the placebo in some clinical indicators. However,after a longer treatment, the clinical indicators were significantly lower in the vitamin D group. Due to limited quantity and quality of the included studies,further larger and more prolonged studies are merited to verify the above conclusion.

Effects of Foot Three-needle Therapy on Colonic Cystathionine Gamma-lyase and Myeloperoxidase in Postoperative Rats / 广州中医药大学学报

Objective To observe the effect of acupuncture on cystathionine gamma-lyase(CSE)and myeloperoxidase (MPO) in the colonic tissues of rats and to explore its mechanism for recovering the function of interstitial cells of Cajal(ICCs)in rats after colonic anastomosis . Methods Thirty SD rats were randomized into normal control group, model group(receiving colonic anastomosis) and acupuncture group. The acupuncture group received foot three-needle therapy on bilateral Zusanli(ST36), Sanyinjiao(SP6) and Taichong(LR3), once a day for 3 days after colonic anastomosis. And then the propulsive rate of the small intestine was measured. The count of ICCs with positively expressive c-kit in rat colonic tissues was measured by immunohistochemistry, the activity of CSE was observed by enzyme-linked immunosorbent assay (ELISA) and the activity of MPO was tested by biochemical method. Results Compared with the normal control group, the small intestinal propulsive rate in the model group was decreased, the number of ICCs with positively expressive c-kit was reduced, while the activities of CSE and MPO were increased(P<0.05). The acupuncture group had higher intestinal propulsive rate, more ICCs with positively expressive c-kit, and lower CSE and MPO activities than the model group(P<0.05).Conclusion Acupuncture can promote the recovering of postoperative gastrointestinal function, and its mechanism may be related to the regulation of CSE and MPO activities in the colonic tissues and to the restoration of ICCs function in the focus with positive c-kit.

A meta-analysis to determine efficacy and safety of alemtuzumab in multiple scle-rosis / 中国免疫学杂志

Objective:To perform a meta-analysis of randomized controlled trials ( RCTs) in multiple sclerosis ( MS) patients to evaluate the efficacy and safety of alemtuzumab.Methods: We searched PubMed,EMBASE,the Cochrane Library and so on up to February 2015 using the keywords:′multiple sclerosis′or ′MS′and the drug names:alemtuzumab.Two authors independently selected the articles and extracted the data.We performed meta-analysis using Review Manager ( RevMan) version 5.3 software.Results:Three RCTs with a total of 1 695 patients were selected.Compared to the interferon beta,the number of gadolinium-enhancing lesions ( odds ratio (OR)=0.33,95% Confidence interval (CI)=[0.23,0.48],P<0.000 01),the cumulative probability of sustained disability (Or=0.51,95%CI=[0.38,0.69],P<0.000 1) and the proportion of patients who had at least one relapse of MS(Or=0.42,95%CI=[0.34,0.52],P<0.000 1) were significantly less in the alemtuzumab group,meanwhile the number of new T2-hyperintense lesions (Or=0.10,95%CI=[0.01,1.75],P=0.11) showed no significant difference.Comparing adverse events between two groups, alemtuzumab treatment did not increase the frequency of serious adverse events (Or=1.00,95% CI=[0.80,1.26],P=0.99) but increase the frequency of any adverse events (Or=2.29,95% CI=[1.40,3.75],P=0.001).Conclusion: Alemtuzumab is a relatively effective and safe treatment for MS.

Effect of Acupuncture Combined with Antidepressant on Behavioral Changes, and mRNA Expression of 5-Hydroxytryptamine Receptors in Nucleus Raphes Dorsalis of Sleep Deprivation Depression Rats / 广州中医药大学学报

Objective To investigate the effect of acupuncture combined with antidepressant on behavioral changes and 5-hydroxytryptamine 1A and 2A receptor ( 5-HT1AR and 5-HT2AR) mRNA expression in nucleus raphes dorsalis (NRD) of sleep deprivation depression (SDD) rats. Methods Eight normal Sprague Dawley (SD) rats were caged together without any stimulus or treatment, serving as the normal group. Thirty-two SD rats were given solitary raise for 21 days, together with chronic unpredictable mild stress ( CUMS) and rapid eye movement ( REM) sleep deprivation to establish the model. Twenty-eight rats completed the modeling successfully, and were divided into model group, acupuncture group, medicine group, and combination group, 7 rats in each group. Rats in the model group were given modeling treatment but without any intervention. Rats in the acupuncture group were given acupuncture on acupoint Yintang, Shenting and bilateral Taichong, acupuncture stimulation lasting 15 s every 10 min and acupuncture retention for 20 min in each day. Rats in the medicine group were given gastric gavage of Zoloft solution (0.83 mg·kg-1·d-1) and Alprazolam solution (0.067 mg· kg-1·d-1) , and rats in the combination group were given both acupuncture and medicine intervention. The intervention for the three intervention groups lasted for 7 days. Results Compared with the normal group, body weight, Open-field scores and sucrose preference of the model rats were significantly decreased on modeling day 7, 14, 21 (P<0.05). On modeling day 28, body weight and Open-field scores of each intervention group were significantly increased compared with those of the model group (P<0.05), and Open-field scores of combination group differed from those of acupuncture group and medicine group ( P<0.05). Only sucrose preference of combination group was improved significantly compared with the model group (P<0.05). Compared with the model group, NRD 5-HT1AR mRNA expression level was increased in the combination group (P<0.05), and NRD 5-HT2AR mRNA expression level was down-regulated in all of the three intervention groups ( P<0.05). Conclusion Acupuncture and antidepressant treatment covering 7 days can evoke rapid effect on SDD rats, which can improve the slow effect of antidepressant.

Effects of acupuncture on NO and NOS in restoration environment of interstitial cells of Cajal after colonic anastomosis / 中国针灸

<p><b>OBJECTIVE</b>To explore the mechanism of acupuncture on promoting the restoration of interstitial cells of Cajal (ICCs).</p><p><b>METHODS</b>Thirty SD rats were randomly divided into a blank group, a model group and an acupuncture group, ten rats in each one. The rats in the model group and acupuncture group were treated with colonic anastomosis to establish the model. After successful establishment of the model, the rats in the acupuncture group were treated with acupuncture at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Taichong" (LR 3) for 15 min, once a day for 10 days. Rats in the model group and blank group were put into the fixator for 15 min at the same time daily. The propulsive rate of small intestine was measured in each group. Colonic tissues were collected to detect c-kit expression by using immunohistochemistry. The nitricoxide (NO) content was measured by nitrate reductase method and nitric oxide synthase (NOS) activity was measured by method of L-arginine.</p><p><b>RESULTS</b>Compared with the blank group, the propulsive rate of small intestine in the model group was decreased; NO content was increased; iNOS activity was elevated; cNOS activity was declined; total NOS (tNOS) activity was increased and the counting of c-kit positive ICCs was decreased (all P < 0.05). Compared with the model group, the propulsive rate of small intestine in the acupuncture group was increased; NO content was decreased; iNOS activity was reduced; cNOS activity was elevated; NOS activity was decreased and the counting of c-kit positive ICCs was increased (all P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture can regulate NO content and NOS activity in postoperative restoration environment of ICCs, which may participate in the process of acupuncture promoting the restoration of ICCs.</p>

Effects of Prescription of Nourishing Blood and Stretching of Stoke on TXB2 and 6-Keto-PGF1αof Patients with Acute Ischemic Cerebrovascular Disease / 中国中医药信息杂志

Objective To investigate the effects of prescription of nourishing blood and stretching of stoke (PNBSS) on the levels of TXB2 and 6-Keto-PGF1αin serum of patients with acute ischemic cerebrovascular disease (AICD);To discuss its action mechanism in AICD treatment. Methods Ninety patients with AICD were randomly divided into trial group and control group, 45 cases in each group. The control group received western routine treatment, while the trail group received the western routine treatment plus PNBSS, one dose per day, for one week. Rating scale of neurologic deficit was employed to evaluate treatment effectiveness. Venous blood was collected before the treatment and on the 3rd and 7th days of treatment. Levels of TXB2 and 6-Keto-PGF1αin serum were detected respectively. Results The score of neurologic deficit of post-treatment in two groups apparently decreased compared with baseline (P<0.01), and score of neurologic deficit in trial group on 7th day was lower than that of control group (P<0.05). The total effective rate in trial group was 93.3%, which was apparently higher than that of control group (84.4%). The level of TXB2 in serum and ratio of TXB2/6-Keto-PGF1α (T/P) in two groups on 3rd and 7th days remarkably decreased compared with baseline (P<0.01), while the level of 6-Keto-PGF1α in two groups on 3rd and 7th days was higher than that of baseline (P<0.01). Meanwhile, the level of TXB2 and ratio of T/P in two groups on 7th day were apparently lower than that of 3rd day (P<0.01), and the level of 6-Keto-PGF1αon 7th day was higher than that of 3rd day (P<0.01). The level of TXB2 in serum and ratio of T/P on 3rd and 7th days in trial group were apparently lower than that of control group (P<0.01, P<0.05), while the level of 6-Keto-PGF1α on 3rd and 7th days in trial group was apparently higher than that of control group (P<0.01, P<0.05). Conclusion One of the mechanisms of PNBSS for AICD appears to inhibit overavtivity of thrombocyte, and regulate the misadjustment of ratio of T/P.