Advances in Disease-Modifying Therapy of Neuromyelitis Optic Spectrum Disorders / 罕见病研究

Neuromyelitis optic spectrum disorders (NMOSD) is a serious inflammatory demyelinating disease. Clinical treatment of NMOSD mainly involves acute phase treatment and remission phase prevention treatment. Disease-modifying therapy (DMT) in remission phase of NMOSD can effectively reduce disease recurrence and delay disability progression. At present, the drugs commonly used for DMT at home and abroad include classical immunosuppression, B-cell surface antigen monoclonal antibody, complement targeting monoclonal antibody, IL-6 receptor-targeting monoclonal antibody, etc. This paper mainly reviews the DMT drugs efficacy, safety, as well as the marketing status of NMOSD.

Advances in the Adjunctive Treatment of Lennox-Gastaut Syndrome with Clobazam and Cannabidiol / 罕见病研究

Lennox-Gastaut syndrome (LGS) is a severe, epileptic encephalopathy.In recent years, a variety of drugs have been approved for the treatment of LGS. The U.S. Food and Drug Administration approved clobazam and cannabidiol as adjunctive therapy for LGS in October 2011 and June 2018, respectively. This article provides an overview of clobazam and cannabidiol, including their chemical structures, pharmacological actions, curative effects, safety profile, drug interactions, to introduce the current state of research and the achievements of both drugs.

Progress in the Diagnosis and Treatment of Infantile Epileptic Spasm Syndrome / 罕见病研究

Infantile epileptic spasm syndrome (IESS) is a new concept proposed recently. IESS is a unique and age-specific refractory epilepsy syndrome. The recent advances in molecular biology, neuroimmunology and the in-depth study of anti-epileptic mechanism in antiepileptic drugs have led to the achievements in the definition and treatment of infantile epileptic spasm. At present, the use of traditional antiepileptic drugs is decreasing, while the use of new antiepileptic drugs is increasing. In this paper, based on the relevant literature in recent years, the authors discuss the pathogenesis, epidemiology, etiology, diagnosis, treatment, therapeutic drugs, clinical progress, efficacy, and safety of infantile epileptic spasm, hoping to introduce the latest status in research and achievements of IESS.

Pharmacokinetic Characteristics of Siponimod in Healthy Volunteers and Patients With Multiple Sclerosis: Analyses of Published Clinical Trials.

Objectives: This study aimed to investigate the pharmacokinetic characteristics of siponimod in healthy volunteers and patients with MS based on aggregated data from published clinical trials, and to explore the factors influencing siponimod exposure. Methods: A total of 476 siponimod plasma concentrations aggregated from 28 dosage groups (corresponding to 294 healthy volunteers and 207 patients with MS) were collected from published clinical trials. Population pharmacokinetic (PPK) analysis was performed using a nonlinear, mixed-effect modeling approach. The pharmacokinetic properties of siponimod in healthy volunteers and patients with MS were compared, and the influence of covariates on siponimod exposure was evaluated using both PPK analysis and noncompartmental analysis (NCA). Results: A one-compartment model with first-order absorption and elimination adequately described siponimod pharmacokinetics. The typical population parameter estimates of clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (ka) were 3.17 L/h, 112.70 L, and 0.38 h-1, respectively. An 11.85% lower siponimod clearance was estimated for patients with MS relative to healthy volunteers. Subgroup analyses using NCA assessments revealed that siponimod presented an accumulation index of approximately 2 after multiple administration. Compared with nonobese participants, obese participants had a relatively lower dose-corrected area under the concentration-time curve (AUC0-∞/D) (0.31 vs. 0.42 h/L) and V/F (120.95 vs. 133.75 L), and a relatively higher CL/F (3.25 vs. 3.21 L/h). Participants with CYP2C9*2/*3, *1/*3, and *3/*3 genotypes experienced an increased (1.3- and 3.4-fold, respectively) AUC0-∞/D and a decreased (0.7- and 0.3-fold, respectively) CL/F compared with those in participants with the CYP2C9*1/*1, *1*2, and *2*2 genotypes. Fluconazole combination led to a decrease in CL/F (approximately 0.5 times) and an increase in AUC0-∞/D (approximately 1.3 times). Conclusion: Siponimod pharmacokinetic properties in healthy volunteers and patients with MS were explored using complementary model-based meta-analysis (MBMA) and NCA approaches. A slightly lower siponimod clearance was observed in patients with MS than in healthy volunteers. The dosage regimen, body mass index, CYP2C9 genetic polymorphism and fluconazole combination may had influences on siponimod pharmacokinetics. Such model paves the road to more population-based analyses in different patient populations with MS to quantify the effect of any influencing factors on siponimod pharmacokinetics.

Development and reliability and validity testing of the assessment scale for patients with persistent vegetative state or minimally conscious state discharge from the anesthesia recovery room / 中国实用护理杂志

Objective:To develop and test the reliability and validity of the assessment scale for patients with persistent vegetative state (PVS) or minimally conscious state (MCS) discharge from the anesthesia recovery room after operation.Methods:From September 2018 to October 2020, three dimensions and 17 item pools were determined through literature review and discussion among the project members. Two rounds of expert consultation were conducted to determine the respiratory (R), circulatory (C), oxygenation (O), bispectral index (B) and neuromuscular monitoring (N) scale (RCOBN scale), the reliability and validity were tested. 87 patients with PVS or MCS after operation Affiliated Sichuan Bayi Rehabilitation Center of Chengdu University of Traditional Chinese Medicine were selected to verify the effectiveness.Results:In the first round, 23 questionnaires were distributed. The total score of experts was 50 ± 3, F=9.24, CV were 0.00-0.43. The Cronbach α coefficient of each dimension was 0.782-0.846, and the Cronbach α coefficient of the total scale was 0.813. In the second round, 10 questionnaires were distributed. The item-level content validity index was 0.7-1.0, the probability of random consistency ( Pc) was 0.001-0.117, the adjusted kappa value ( k*) was 0.567-1.000, and the sum of the index scores corresponding to k* > 0.74 was 8. The scale-level content validity index of the overall consistency was 0.87. The ratio of patients transferred out of PACU by two rounds of evaluation method was 100 : 96.55, and the difference was not statistically significant ( χ2=3.05, P>0.05). The time of the first round of assessment was significantly longer than that of the second round, which were (197 ± 52) s and (58 ± 14) s respectively. The difference was statistically significant ( t=26.52, P < 0.01). Conclusions:The RCOBN scale has high reliability and validity. It can be used as an assessment scale for patients with PVS or MCS to transfer out of PACU after surgery, and those with a total score of 8 can be transferred out of PACU.

Efficay of different doses of remimazolam for anesthesia induction during reoperation in asthenic patients with tracheotomy / 中华麻醉学杂志

Objective:To evaluate the efficay of different doses of remimazolam for anesthesia induction during reoperation in asthenic patients with tracheotomy.Methods:One hundred and twenty patients of both sexes, aged 19-64 yr, with a modified frailty index score ≥3, of American Society of Anesthesiologists physical status Ⅳ, scheduled for reoperation after tracheotomy, were divided into 4 groups ( n=30 each)using a random number table method: propofol group (group C) and different doses of remimazolam groups (R 1, R 2 and R 3 groups). Anesthesia was induced with intravenous sufentanil 5 μg, propofol 1.5 mg/kg in group C and with remimazolam 0.1, 0.2 and 0.3 mg/kg in R 1, R 2 and R 3 groups, respectively.The tracheotomy cannula was replaced with a reinforced endotracheal intubation (ID=6.0 mm) when bispectral index value ≤ 65.Mean arterial pressure and heart rate were recorded before induction (T 0), immediately before replacement of the tube (T 1) and immediately after replacement of the tube (T 2). The onset time of anesthesia and adverse reactions such as hypotension, bradycardia and bucking during replacement of the tube, and requirement for rescue sedation were recorded. Results:Compared with group C, mean arterial pressure was significantly increased at T 1, 2 in group R 1 and group R 2, the onset time of anesthesia was significantly prolonged, the incidence of hypotension and bradycardia was decreased in R 1, R 2 and R 3 groups, and the requirement for rescue sedation in group R 1 and incidence of bucking in group R 1 and group R 2 were increased ( P<0.05 or 0.01). Compared with group R 1, heart rate at T 2 was significantly decreased, the onset time of anesthesia was shortened, and the requirement for rescue sedation and incidence of bucking were decreased in C, R 2 and R 3 groups, and the incidence of hypotension was significantly increased in group R 3 ( P<0.05 or 0.01). Compared with group R 2, the onset time of anesthesia was significantly shortened in group R 3 ( P<0.05). Conclusions:Remimazolam 0.2 mg/kg provides good efficacy when used for anesthesia induction with fewer side effects during reoperation in asthenic patients with tracheotomy.

Efficacy of remimazolam combined with low-dose propofol for sedation during induction of anesthesia / 中华麻醉学杂志

Objective:To evaluate the efficacy of remimazolam combined with low-dose propofol for sedation during induction of anesthesia.Methods:A total of 228 patients of both sexes, aged 18-64 yr, with body mass index of 19-35 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic cholecystectomy, were divided into 2 groups ( n=114 each) by a random number table method: remimazolam combined with low-dose propofol group (group R) and propofol group (group P). Anesthesia was induced with intravenous injection of sufentanil 0.3 μg/kg, remimazolam 0.3 mg/kg, propofol 0.5 mg/kg and micuronium 0.2 mg/kg in group R, and sufentanil 0.3 μg/kg, propofol 2 mg/kg and micuronium 0.2 mg/kg in group P. Endotracheal intubation was performed when bispectral index value ≤ 50.Before induction (T 0), immediately before intubation (T 1), at 1 min (T 2) and 3 min (T 3) after intubation, mean arterial pressure (MAP) and heart rate (HR) were recorded.The anesthesia induction time and the incidence of hypotension and bradycardia were recorded in the two groups. Results:There was no significant difference in MAP and HR at T 0 between the two groups ( P>0.05). Compared with the value at T 0, MAP in two groups and HR were significantly decreased at T 1-3 in group P ( P<0.01). Compared with group P, the anesthesia induction time was significantly prolonged, and hypotension and bradycardia was decreased in group R ( P<0.05). Conclusion:The combination of remimazolam and low-dose propofol exerts better efficacy for sedation during induction of anesthesia than propofol alone.

Cobalamin metabolism and the clinical application in its different forms / 中华实用儿科临床杂志

Cobalamin, also known as Vitamin B 12, is the most complex vitamin in nature, and also one of essential vitamins in human body, which involved in many physiological activities, including homocysteine metabolism and translation of methylmalonyl-CoA to succinyl-CoA as a biological coenzyme.As a higher organism, human cannot synthesize cobalamin by themselves, so cobalamin needs to be supplemented by diet or medicine.At present, there are various forms of cobalamin, including cyanocobalamin (a common form of Vitamin B 12), hydroxylcobalamin, mecoba-lamin and 5′-adenosylcobalamin.These different forms of cobalamin are similar in structures and physiochemical pro-perties, but have some differences in the pharmacokinetics of absorption, distribution, metabolism and elimination, as well as clinical application and therapeutic efficacy.Among them, cyanocobalamin and hydroxycobalamin are widely used in Europe and the United States.Mecobalamin is more commonly used in Asia.5′-adenosylcobalamin has been approved in China, but less widely used in the world.Cyanocobalamin and mecobalamin are mainly used for the treatment of diseases caused by peripheral neuropathy and cobalamin deficiency.Hydroxycobalamin has been approved as an antidote to cyanide and has shown some potential in the treatment of methylmalonic acidemia in recent years.Now, the chemical structures, physiochemical properties, pharmacokinetic characteristics and clinical applications of the four cobalamins were compared and distinguished, so as to provide references for clinicians in clinical rational drug use and to avoid confusion.

Research on anti-cancer active component in red wine / 中国医学装备

Objective:To detect the anti-cancer component, trans-resveratrol in red wine by high performance liquid chromatography, and to determine the influence of environmental factors on its content. Methods: A method for determining trans-resveratrol in red wine by HPLC is described. The operating conditions were ZORBAX-C18 column(4.6 mm×250 mm, 5μm) at room temperature, 30%acetonitrile as mobile phase at a flow of 1ml/min and UV detection at 306 nm. Results:The content of trans-resveratrol in Changyu dry red wine and Great Wall Claret Cabernet are (1.01±0.03)mg/L and (2.36±0.02)mg/L, respectively. The results show that, sunlight, high temperature and poor seal condition can decrease the content of trans-resveratrol. Conclusion:The content of trans-resveratrol varies in different brands of red wine. Red wine should be stored in cool, dark and sealed conditions.

Mechanism of nerve root stretch injury / 中国组织工程研究

BACKGROUND:Under physiological conditions, nerve roots can move along with the movement of limbs and spine. However, the mechanisms of nerve root stretch injury under physiological conditions and the neurological dysfunction after injury are unclear. OBJECTIVE:To review the reason of nerve root stretch injury, and to analyze the mechanism of nerve function from biomechanics, pathology and neurophysiology. METHODS:A computer-based online search of PubMed database was undertaken by the first author to identify the articles related to the research of nerve root injury and nerve stretch injury between 1990 and 2012, with the key words of“nerve root, nerve, stretch injury”. A total of 391 articles were screened out. The articles on the anatomy and biomechanics research of nerve root were included, as wel as the pathology and neurophysiology research after nerve root stretch injury. Final y, 44 articles were included for review. RESULTS AND CONCLUSION:Nerve root can be stretched along with limbs and spine movement. However, diseases or trauma may cause pathological nerve root stretch, and thus leading neurological dysfunction. The nerve root is often influenced stretch because of its anatomical and tissue structure. Mechanical injury mechanism of stretch composes of peripheral (peripheral nerve conduction stress) and central mechanism (displacement of spinal cord content). Pathological studies found that the local fibrosis is caused by the extracted serum protein that difficult to remove after injury, and this is because of the shortage of lymphatic system in nerve roots. Fibrosis can cause nerve root ischemia, affect the nerve function, and change the biomechanical properties of nerve root. Nerve root injury can cause primary and secondary injury of internal axons, and this is the main reason for neurological dysfunction after injury.

Clinical experience of VATS diagnosis and treatment of pulmonary nodules less than 20 mm in size / 中华胸心血管外科杂志

Objective To evaluate the technique of finger palpation in thoracoscopic localization in patients with pulmonary nodules,and to summarize its technical details,especially with exploit of chest computed tomography (CT) facilitating it.Methods 95 patients with total amount of 109 pulmonary nodes 20 mm or smaller in size shown with lung window of CT,were reviewed.They were located subpleurally,with a median depth of 8.2 mm and a median size of 10.0 mm.The value of their depth over their size (D/d value) could be used as the extent of localizing difficulty.Each node had its own radiographic fealures for being localized,which was built preoperatively.Under thoracoscopic vision,nodules were finger-palpated by index finger via the 4th or 5th intercostal space on anterior axillary line,followed by wedgectomy or lobectomy for instant histopathological diagnosis to further decide the final surgical type.The distance between the nodule and the origin of segmental bronchus (L value) were also calculated out,as it might be relevant to the way the nodule could be biopsied.Results All nodules were successfully localized and resected for biopsy goal,105 by wedgectomy,4 by lobectomy.After intraoperative diagnosis was made by the pathologist,VATS lobectomy and lymph node dissection were further performed in 55 patients.L value of 4 cases being biopsied by lobectomy ranged from 18.3 to 30.3 mm,averaging 26.1 mm.Conclusion Finger palpation is viable in any cases of pulmonary nodules.Detailed reference of CT digital information,and enough detachment of mediastinal pleura,can greatly facilitate thoracoscopic localization by finger palpation.Lobectomy or segementectomy is preferable when L value is less than 30 mm.