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简介：摘要Background and aimIn Multiple Sclerosis (MS) spasticity worsen patient′s quality of life. Botulinum NeuroToxin TypeA (BoNT-A) is extensively used in focal spasticity, frequently combined with physical therapies. Radial extracorporeal shock waves (rESW) were already used in association with BoNT-A. Considering that loss of efficacy and adverse events are determinants of BoNT-A treatment interruption, this study aimed to evaluate the possibility to prolong BoNT-A′s effect by using rESW in MS focal spasticity.MethodsSixteen MS patients with spasticity of triceps surae muscles were first subjected to BoNT-A therapy and, four months later, to 4 sections of rESWT. Patients were evaluated before, 30, 90 days after the end of the treatments, by using Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS) and kinematic analysis of passive and active ankle ROM.ResultsBoNT-A determined a significant reduction of spasticity evaluated by MAS with a reduction of positive effects after 4months (P<0.05); MTS highlighted the efficacy only 90 days after injection (P<0.05). rESWT decreased MAS values at the end and 30 days later the treatment (P<0.01); MTS values showed instead a prolonged effect (P<0.01). BoNT-A determined a gain of passive and active ankle ROM, persisting along with treatment and peaking the maximum value after rESWT (P<0.05).ConclusionsrESWT can prolong BoNT-A effect inducing significant reduction of spasticity and improvement in passive and active ankle ROM in MS patients. The use of rESWT following BoNT-A injection is useful to avoid some limitations and to prolong the therapeutic effects of BoNT-A therapy.

简介：摘要ObjectivesTo investigate whether botulinum toxin type A (BTX-A) injection is more effective than radial extracorporeal shock wave therapy in reducing plantar flexor muscle spasticity in subjects with cerebral palsy.MethodsA total of 68 subjects with cerebral palsy were randomly allocated to BTX-A injection (Group 1) or radial extracorporeal shock wave therapy (Group 2) (first experiment; E1). Outcome was evaluated using the Tardieu V1 and V3 stretches, at 3 weeks, 2 months (M2) and M3 after baseline. At M6 subjects in Group 1 received radial extracorporeal shock wave therapy and subjects in Group 2 received BTX-A injection (second experiment; E2); outcome was evaluated as in E1. Treatment success was defined as improvement in foot dorsiflexion ≥10° when performing the V3 stretch at M2 in both experiments.ResultsIn both experiments mean V1 and V3 significantly improved over time. In E1 both treatments resulted in similar treatment success. In E2 fewer subjects treated with BTX-A injection reached the criteria of treatment success than did subjects treated with radial extracorporeal shock wave therapy, which was due to a carry-over effect from E1. No significant complications were observed.ConclusionBTX-A injection is not superior to radial extracorporeal shock wave therapy in the treatment of plantar flexor muscle spasticity in subjects with cerebral palsy.

简介：AbstractPurpose:The incidence of acute lung injury (ALI) in severe trauma patients is 48% and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%. Alveolar epithelial type 1 cells (AEC1s) and type 2 cells (AEC2s) are the key cells in the repair of injured lungs as well as fetal lung development. Therefore, the purification and culture of AEC1s and AEC2s play an important role in the research of repair and regeneration of lung tissue.Methods:Sprague-Dawley rats (3-4 weeks, 120-150 g) were purchased for experiment. Dispase and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells, and then magnetic bead cell sorting was performed to isolate T1α positive cells as AEC1s from the single-cell suspension by using polyclonal rabbit anti-T1a (a specific AEC1s membrane protein) antibodies combined with anti-rabbit IgG microbeads. Afterwards, alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining T1α-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG microbeads. Cell purity was identified by immunofluorescence staining and flow cytometry.Results:The purity of AEC1s and AEC2s was 88.3% ± 3.8% and 92.6% ± 2.7%, respectively. The cell growth was observed as follows: AEC1s stretched within the 12-16 h, but the cells proliferated slowly; while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 days.Conclusion:AEC1s and AEC2s sorted by this method have high purity and good viability. Therefore, our method provides a new approach for the isolation and culture of AEC1s and AEC2s as well as a new strategy for the research of lung repair and regeneration.

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简介：AbstractHereditary spastic paraplegia type 56 (SPG56-HSP) is a rare autosomal recessive disorder caused by loss of function mutations in CYP2U1, leading to an early-onset limbs spasticity, often complicated by additional neurological or extra-neurological manifestations. Given its low prevalence, the molecular bases underlying SPG56-HSP are still poorly understood, and effective treatment options are still lacking. Recently, through the generation and characterization of the SPG56-HSP mouse model, we were able to take few important steps forward in expanding our knowledge of the molecular background underlying this complex disease. Leveraging the Cyp2u1-/- mouse model we were able to identify several new diagnostics biomarkers (vitamin B2, coenzyme Q, neopterin, and interferon-alpha), as well as to highlight the key role played by the folate pathway in SPG56-HSP pathogenesis, providing a potential treatment option. In this review, we discuss the major role played by the Cyp2u1-/- model in dissecting clinical and biological aspects of the disease, opening the way to a series of new research paths ranging from clinical trials, biomarker testing, and to the expansion of the underlying genetic and molecular, emphasizing how basic mouse model characterization could contribute to advance research in the context of rare disorders.

简介：AbstractType 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.

简介：AbstractBackgrounds:Inadequate sleep duration is associated with a higher risk of type 2 diabetes and the relationship is nonlinear. We aim to assess the curve relationship between night sleep duration and the incidence of type 2 diabetes in China.Methods:A cohort of 11,539 participants from the REACTION study without diabetes at baseline (2011) were followed until 2014 for the development of type 2 diabetes. The average number of hours of sleep per night was grouped. Incidence rates and odds ratios (ORs) were calculated for the development of diabetes in each sleep duration category.Results:Compared to people who sleep for 7 to 8 h/night, people with longer sleep duration (≥9 h/night) had a greater risk of type 2 diabetes (OR: 1.27; 95% CI: 1.01-1.61), while shorter sleep (<6 h/night) had no significant difference in risk of type 2 diabetes. When the dataset was stratified based on selected covariates, the association between type 2 diabetes and long sleep duration became more evident among individuals <65 years of age, male, body mass index <24 kg/m2 or with hypertension or hyperlipidemia, no interaction effects were observed. Furthermore, compared to people persistently sleeping 7 to 9 h/night, those who persistently slept ≥9 h/night had a higher risk of type 2 diabetes. The optimal sleep duration was 6.3 to 7.5 h/night.Conclusions:Short or long sleep duration was associated with a higher risk of type 2 diabetes. Persistently long sleep duration increased the risk.

简介：AbstractPurpose:The purpose of this study was to assess and compare elbow range of motion, triceps extension strength and functional results of type C (AO/OTA) distal humerus fractures treated with bilateral triceps tendon (BTT) approach and olecranon osteotomy (OO). At the same time, we are also trying to know whether BTT approach can provide sufficient vision for comminuted intra-articular fractures of the distal humerus, and whether it is convenient to convert to the treatment to total elbow arthroplasty (TEA) or OO.Methods:Patients treated with OO and BTT approaches for type C distal humerus fractures between July 2014 and December 2017 were retrospectively reviewed. Inclusion criteria include: (1) patients' age were more than 18 years old, (2) follow-up was no less than 6 months, and (3) patients were diagnosed with type C fractures (based on the AO/OTA classification). Exclusion criteria include: (1) open fractures (Gustillo type 2 or type 3), (2) treated by other approaches, and (3) presented with combined injuries of ipsilateral upper extremities, such as ulnar nerve. Elbow range of motion and triceps extension strength testing were completely valuated, when the fractures had healed. Assessment of functional results using the Mayo elbow performance score and complications were conducted in final follow-up. The data were compared using the two tailed Student's t-test. All data were presented as mean ± standard deviation.Results:Eighty-six patients of type C distal humerus fractures, treated by OO and BTT approach were retrospectively reviewed between July 2014 and December 2017. Fifty-five distal humerus fractures (23 males and 32 females, mean age 52.7 years) treated by BTT approach or OO were included in this study. There were 10 fractures of type C1, 16 type C2 and 29 type C3 according to the AO/OTA classification. Patients were divided into two surgical approach groups chosen by the operators: BTT group (28 patients) and OO group (27 patients). And the mean follow-up time of all patients was 15.6 months (range, 6-36 months). Three cases in BTT group were converted to TEA, and one converted to OO. Only one case in BTT group presented poor articular reduction with a step more than 2 mm. There were not significantly different in functional outcomes according to the Mayo elbow performance score, operation time and extension flexion motion are values between BTT group and OO group (p > 0.05). Complications and reoperation rate were also similar in the two groups. Triceps manual muscle testing were no significant difference in the two groups, even subdivided in elder patients (aged >60 years old).Conclusion:BTT is a safe approach to achieve similar functional result comparing with OO. BTT were not suitable for every case with severe comminuted pattern, but it avoids the potential complications related to OO, and has no complications concerning with triceps tendon. It is convenient for open reduction internal fixation and flexible to be converted to OO, as well as available to be converted to TEA in elder patients.

简介：AbstractPurpose:Stable Weber B ankle fractures are treated by a walking boot for 6 weeks and bearing full weight through the boot as tolerated. The aim of the present study was to assess the outcome parameters of this treatment protocol, evaluate the efficacy of using the walking boot, and investigate any possible predicting factors that could affect the outcomes.Methods:All the patients with stable Weber B ankle fractures, treated in our hospital between January 2018 and December 2018, were prospectively included to the study. The patients were evaluated clinically, and the patient-reported outcome measures data were collected at the 2 and 6 weeks post-injury. Chi square, Spearman's rho test, independent samples and paired sample t-tests were used for the monovariant analysis.Results:A total of 128 consecutive patients (aged 52.2 ± 19.1 years) with supination external rotation type 2 fracture were finally included to the study. At the 2 weeks follow-up, the reported outcome measures scores were in moderate levels, but improved significantly at the 6 weeks follow-up (p < 0.0001). Multivariant analysis revealed that the ability to bear full weight without the boot at the 2 weeks after diagnosis was the only variable, which made statistically unique contribution to the foot and ankle disability index score at the 6 weeks (p = 0.005).Conclusion:Conservative treatment using a walking boot with advice to bear full weight of stable ankle Weber B fractures can bring to good functional outcomes. The ability to bear full weight without the aid of the walking boot at 2 weeks after diagnosis was the only significant predicting factor for better outcomes at 6 weeks after diagnosis.

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简介：AbstractSchatzkter type-I tibial plateau fracture is a split fracture of the lateral tibial plateau in sagittal plane, consequent to valgus impaction caused by low velocity of trauma. However, a deep understanding of the different columns of the tibial plateau and patho-mechanisms of the injury led to the unmasking of atypical fractures around the tibial plateau. We have encountered 2 cases with unusual fracture pattern of the lateral tibial condyle caused by road traffic accidents. The fracture pattern and severity of injury deviate from the original description of Schatzker type 1; in view of dual plane split, there is rotation of the posterolateral column fragment along its sagittal plane plus grade-III medial collateral ligament injury. The patients were initially treated with knee spanning external fixator and after a latency of 5 days, definitive fracture specific fixation was done, combined with repair of grade-III medial collateral ligament injury. At the 6 months follow-up both the patients achieved satisfactory knee functions (knee society score case 1:100 and case 2: 92) and returned to their jobs. The severity of fracture pattern and displacement as described should prompt for examination of associated ligament injury. Because of timely diagnosis, early and appropriate care promised an excellent function outcome even in such a severe nature of knee injury. To prompt the description of injury pattern we coined the name "dual split and dislocation" of lateral tibial plateau, as a complex injury variant of split fracture of lateral tibial plateau fracture.

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简介：AbstractBackground:Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM).Methods:In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm2.Results:Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P < 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595–0.866, P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (all P for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients.Conclusions:There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.

简介：AbstractBackground:Little was known about the association among time in range (TIR), time above range (TAR), time below range (TBR), and cancer mortality among patients with type 2 diabetes. We aimed to investigate the association among TIR, TAR, TBR, and the risk of cancer mortality among patients with type 2 diabetes.Methods:A total of 6225 patients with type 2 diabetes were prospectively recruited in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline and was defined as the average percentage of time in the target glucose range during a 24 h period. Cox proportion hazard regression analysis was used to determine the association between TIR and the risk of cancer mortality.Results:During a mean follow-up of 7.10 years, we confirmed 237 death events related to cancer. The multivariable-adjusted hazard ratio (HR) for cancer mortality was 1.32 (95% confidence interval [CI]: 1.01-1.75) in patients with TIR ≤70% compared with those with TIR >70%. When TIR was considered as a continuous variable, the multivariable-adjusted HR for cancer mortality associated with each 10% decrease in TIR was 1.07 (95% CI: 1.02-1.14). In the site-specific analysis, a significant association between TIR as a continuous variable and the risk of hepatocellular cancer was found (HR: 1.24; 95% CI: 1.09-1.41). However, no relationship between hemoglobin A1c and cancer mortality was observed (HR: 1.04; 95% CI: 0.97-1.10).Conclusions:The present study found an inverse association of TIR with the risk of cancer mortality among patients with type 2 diabetes. New evidence of TIR was added into the clinical practice that TIR may be an optimal target of glycemic control among patients with type 2 diabetes.

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简介：AbstractBackground:Time in range (TIR) refers to the time an individual spends within their target glucose range, which now has been popularized as an important metric to classify glycemic management and also recognized as an important outcome of current diabetes therapies. This study aimed to investigate the association between TIR and the severity of the urinary albumin excretion rate (UAER) in patients with type 2 diabetes mellitus (T2DM).Methods:We retrospectively analyzed the data of 1014 inpatients with T2DM at the Department of Endocrinology and Metabolism of Peking University International Hospital, China. TIR was defined as the percentage of blood glucose within the target range of 3.90-10.00 mmol/L. Urine samples for assessment of UAER were collected for 3 consecutive days from the start of hospitalization.Results:The TIR values for patients with normal urine levels of albumin, microalbuminuria, and macroalbuminuria were 70% ± 20%, 50% ± 20%, and 30% ± 20%, respectively (all P < 0.001). The patients were stratified according to quartiles of TIR as follows: quartile (Q) 1, <55%; Q2, 55%-72%; Q3, 73%-83%; and Q4, >83%. The incidences of microalbuminuria in Q1, Q2, Q3, and Q4 were 41.1%, 21.6%, 7.1%, and 5.5% (all P < 0.001), respectively. The respective incidences of macroalbuminuria were 24.2%, 1.1%, 1.4%, and 0% (all P < 0.001). In multinomial logistic regression analyses, TIR was significantly correlated with microalbuminuria (odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.52-0.65, P < 0.001) and macroalbuminuria (OR 0.26, 95% CI: 0.18-0.38, P < 0.001) after adjusting for age, sex, body mass index, diabetes duration, systolic blood pressure, and levels of triglycerides, glycosylated hemoglobin A1c, and creatinine.Conclusion:The proportion of blood glucose in TIR is closely related to the severity of UAER in patients with T2DM.