Patterns of tocilizumab use in clinical practice of rheumatoid arthritis: a multi-center, non-interventional study in China / 中华风湿病学杂志

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Neuroprotective effect of glutamine supplementation by inhibiting oxidative stress and promoting autophagy responses after traumatic brain injury in rats / 中华临床营养杂志

Objective To investigate the effects and mechanisms of glutamine (Gln) supplementation on oxidative stress,autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Eighty SD rats were randomly divided into 4 groups:sham operation group (group Sham),Sham + glutamine supplementation group (group Sham+ GLN),traumatic brain injury group (group TBI),and TBI + glutamine supplementation group (group TBI+ GLN).We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1,3,7 and 14 after TBI.The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining.The expression of reactive oxygen species (ROS) was tested by ROS kits.Oxidative stress and autophagy related cytokines (HO-1,NQO1,Nrf2,LC3-Ⅱ and Beclin-1) were tested with Western blotting.Results Compared with the TBI group,the neurological function was improved [(9.79±0.43) vs.(8.43±0.30),F =6.775,P =0.010] and the apoptosis rate decreased (19.88％ ± 1.60％ vs.15.35％ ± 1.28％,P =0.013) in the TBI+ GLN group after 7-day treatment.Compared with the Sham group,the protein expression of ROS increased (P=0.000),and the expression of anti-oxidative stress factors (HO-1,NQO1) and Nrf2 pathway significantly decreased in the TBI group.After glutamine supplementation was given,the expression of ROS decreased and the expressions of HO-1 and NQO1 increased.The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2,LC3-Ⅱ and Beclin-1 increasing.Conclusion Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI,thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response,activating Nrf2 pathway and autophagy response.

Effects of enteral nutrition added with glutamine on gastrointestinal functions and prognosis of acute severe traumatic brain injury / 中华创伤杂志

Objective To investigate the effects of enteral nutrition added with glutamine on the incidences of gastrointestinal complications,intestinal mucosal barrier function and inflammatory responses in patients with acute severe traumatic brain injury (sTBI).Methods A prospective case control study was made on 107 patients with sTBI hospitalized from January 2016 to June 2017.The patients were divided into experimental group added with glutamine (n =54) and control group without glutamine (n =53) according to the random number table.The general data of the patients were recorded.After treatment,the incidences of gastrointestinal complications in both groups were compared.The serum levels of intestinal mucosal barrier function indices,namely,diamine oxidase (DAO),Dlactate acid,and intestinal fat acid binding protein (I-FABP) were evaluated by enzymology spectrophotometer method.Meanwhile,the serum levels of C-reactive protein (CRP),tumor necrosis factor-α (TNF-α),and interleukin-6 (IL-6) were also tested with enzyme-linked immunosorbent assay (ELISA).Glasgow coma scale (GCS),acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ),and hospital stay in both groups were compared.Results The two group were comparable with respect to gender,age,injury reasons,body mass index,preoperative GCS,preoperative APACHE Ⅱ,injury type and injury time (P ＞ 0.05).The experimental group had lower incidences of stress ulcer,gastric retention and diarrhea compared with the control group 14 days after treatment (P ＜ 0.05).Within 14 days after treatment,the serum levels of DAO,D-lactate acid and I-FABP were significantly decreased in the experimental group at days 7 and 14 after treatment (P ＜ 0.05).The serum levels of CRP,TNF-α and IL-6 in the experimental group were significantly decreased after treatment (P ＜ 0.05).The experimental group had better prognosis compared with the control group (P ＜ 0.05),with higher GCS scores [(9.3 ± 0.7) points vs.(8.2 ± 0.7) points],lower APACHE Ⅱ scores [(15.3 ± 1.1) points vs.(17.7 ± 1.2) points] at day 14,and shorter hospital stay [(19.1 ± 2.2) days vs.(25.3 ± 2.4) days] (P ＜ 0.01).Conclusions Enteral nutrition added with glutamine can effectively reduce the incidence of gastrointestinal complications,as well as alleviate the intestinal mucosal barrier function damage and the inflammatory responses at early stage after sTBI,which possibly improves prognosis.

Glutamine supplementation provides neuroprotection by inhibiting endoplasmic reticulum stress response after traumatic brain injury in rats / 中华临床营养杂志

Objective To investigate the effects of glutamine (Gln) supplementation on neurologica severity score,brain edema,neuron apoptosis,and endoplasmic reticulum stress (ERS) response after traumatic brain injury (TBI) in rats.Methods TBI rat models were established using modified Feeney's method.Eighty Sprague-Dawley rats were divided into 4 groups with a random number table:sham operation group (Sham group),TBI group,Gln supplementation group (TBI + Gln group) and ERS inducer 2-deoxy-D-glucose group (TBI +Gln + 2-DG group).We measured the rats' neurobehavioral outcomes by modified neurologic severity score (mNSS) on day 1,3,7 and 14 after TBI.Neuron apoptosis was detected using TUNEL staining.Brain water content was measured with wet-dry weight method.The apoptosis-related protein (caspase-12,caspase3,and Bcl-2) and ERS-related cytokines [inositol-requiring enzyme 1 (IRE-1),C/EBP homologous protein (CHOP)] expressions in TBI cerebral cortex were determined by immunohistochemistry staining and Western blot.Results Compared with the Sham group,the levels of brain edema,mNSS,apoptosis-related protein (caspase-12,caspase-3,Bcl-2) and ERS-related proteins (IRE-1,CHOP) were significantly increased in the other three groups (all P =0.00).Compared with the TB1 group,the TBI +Gln group showed significant lower brain water content [3 d:(81.39±0.59)％ vs.(83.54±0.52)％,P=0.04;7 d:(74.86±0.38)％ vs.(77.32±0.66)％,P=0.03],improved mNSS (8.63 ±0.22 vs.10.37±0.29,P=0.03),suppressed expressions of apoptosis-and ERS-related proteins (caspase-12,caspase-3,IRE-1,and CHOP)(P =0.01,P ＜ 0.01),and increased expression of anti-apoptotic protein Bcl-2 (P =0.02).Compared withthe TBI + Gln group,the expression of ERS-related factors (IRE-1 and CHOP),brain edema level,and neurological severity were increased in the TBI + Glu + 2-DG group.Conclusion Glutamine supplementation may have neuroprotection function,demonstrated as reducing brain edema and neuron apoptosis,and improving neurobehaviroal outcomes after TBI,possibly mediated by inhibiting TBI-induced ERS response.

Non-magnetic compliant finger sensor for continuous fine motor movement detection

A non-magnetic MEG compatible device has been developed that provides continuous force and velocity information. Combined with MEG, this device may find utility in characterizing brain regions associated with force and velocity relative to individual digits or movement pattern. 15 healthy right-handed participants were given visual cues to perform random finger movements on the prototype finger sensor for 21 s and then rest for 21 s (7 times). Respective finger flexion data were obtained, during 151-channel MEG brain scanning, by feeding the signal from finger sensor into four input Analog to Digital Converter (ADC) channels in the MEG hardware. The source activity was reconstructed in beta band using a Linearly Constrained Minimum Variance (LCMV) beamformer in the beta band. The ADC channels were used as regressors for a continuous time General Linear Model (GLM) and a Region of Interest (ROI) was identified to examine activity. MEG analysis showed bilateral activation in the primary motor cortex region. Because individual digits could be isolated in the ADC data, somatotopy of the fingers were observed consistent with the homunculus except pinky finger. The total span was calculated to be 5.5662 mm. The study confirms that the finger sensor is magnetically compatible with MEG measurements and may potentially provide a means to study complex sensorimotor functions. Improved isolation of individual digit information along with the use of machine learning algorithms can help retrieve more accurate results.

Effect of omega-3 polyunsaturated fatty acids supplementation on traumatic brain injury in a rat model / 中华临床营养杂志

Objective To investigate the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA)supplementation on brain edema,autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats and the related mechanisms.Methods TBI rat models were established using Feeney's method.Seventy-two SD rats were divided into 4 groups using random number table:sham operation group,TBI group,ω-3 PUFA supplementation group (TBI + ω-3 group) and autophagy inhibitor 3-methyladenine group (TBI + 3-MA group) (all n =18),each group was further divided into 3 sub-groups (n =6) corresponding to 3 time points (days 1,3,and 7 after TBI).On each of the 3 time points,we measured rat behavioral outcomes with modified neurologic severity score (mNSS) tests;brain water content was measured with wet-dry weight method.The mRNA and protein expressions of autophagy-related factors (LC3-Ⅱ and Beclin-1) in TBI cerebral cortex were determined by immunohistochemistry staining,reverse transcription-polymerase chain reaction and Western blot on day 3 after TBI.Results Compared with the sham group,on days 1,3,and 7 after injuary,the TBI group,the TBI + ω-3 group,and the TBI + 3-MA group had significantly higher mNSS scores (TBI group:12.42±0.27vs.1.34±0.32,12.07±0.27vs.1.16±0.29,10.22±0.39vs.1.22±0.30;TBI+ω-3 group:12.05 ±0.23 vs.1.34 ±0.32,11.38 ±0.21 vs.1.16±0.29,8.20 ±0.21 vs.1.22±0.30;TBI +3-MA group:11.93 ±0.20 vs.1.34 ±0.32,11.09 ±0.19 vs.1.16 ±0.29,7.93 ±0.17 vs.1.22 ± 0.30;all P =0.00) and brain water content [TBI group:(79.82 ± 0.61) ％ vs.(71.87 ± 0.43) ％,(83.04±0.42)％ vs.(72.13 ±0.53)％,(75.12 ±0.72)％ vs.(71.78 ±0.38)％;TBI+ω-3 group:(76.81 ±0.63)％ vs.(71.87 ±0.43)％,(79.39 ±0.59)％ vs.(72.13 ±0.53)％,(73.86 ±0.38)％ vs.(71.78 ±0.38)％;TBI+3-MAgroup:(75.98 ±0.49)％ vs.(71.87 ±0.43)％,(77.14 ±0.46)％ vs.(72.13 ±0.53)％,(72.24 ±0.37)％ vs.(71.78 ±0.38)％;all P =0.00].The mRNA and protein expressions of LC3-Ⅱ and Beclin-1 in the brain were also significantly higher on day 3 in the TBI group,the TBI + ω-3 group,and the TBI + 3-MA group (all P =0.00).Compared with the TB1 group,on day 3 and day 7 after injury,the TBI + ω-3 group and the TBI + 3-MA group had significantly lower mNSS scores (TBI + ω-3 group:11.38±0.21 vs.12.07±0.27,P=0.04,8.20±0.21 vs.10.22±0.39,P=0.01;TBI+3-MA group:11.09±0.19vs.12.07 ± 0.27,P=0.01,7.93 ± 0.17 vs.10.22±0.39,P=0.00).Ondays1,3,and 7,compared with the TBI group,the TBI + ω-3 group and the TBI + 3-MA group had significantly lower brain water content [TBI + ω-3 group:(76.81 ± 0.63) ％ vs.(79.82 ± 0.61) ％,P =0.04,(79.39 ±0.59)％ vs.(83.04±0.42)％,P=0.01,(73.86±0.38)％ vs.(75.12±0.72)％,P=0.03;TBI+3-MAgroup:(75.98 ±0.49)％ vs.(79.82 ±0.61)％,P=0.01,(77.14 ±0.46)％ vs.(83.04 ±0.42)％,P =0.00,(72.24 ± 0.37) ％ vs.(75.12 ± 0.72) ％,P =0.02].On day 3,the TBI + ω-3 group and the TBI + 3-MA group had significantly reduced LC3-Ⅱ and Beclin-1 mRNA expression compared with the TBI group (TBI +ω-3 group:P=0.04,P =0.01;TBI +3-MA group:P =0.01,P =0.00) and protein expression (TBI+ω-3 group:P=0.01,P=0.03;TBI +3-MA group:both P=0.00).Conclusion ω-3 PUFA supplementation could markedly reduce brain edema and improve neurological functions after TBI,showing a neuroprotective effect,possibly through inhibiting TBI-induced autophagy responses.

Large decompressive craniectomy for patients with severe traumafic brain injury combined with herniation of brain / 中国综合临床

Objective To investigate the clinical outcome of large decompressive craniectomy in treatment of severe traumatic brain injury combined with herniation of brain.Methods A retrospective analysis was carried out to assess the clinical outcome of large decompressive craniectomy for 98 patients with severe traumatic brain injury combined with herniation of brain enrolled from Jan.2007 to Sep.2010.Results According to the Glasgow outcome scale,there were 27 patients ( GOS 5 points) with good recovery,23 ( GOS 4 points) with moderate deficit,28 (GOS 3 points) with severe deficit,6 (GOS 2 points) under persistent vegetative status and 14 (GOS1 points) deaths at the end of 6 month post injury.We observed a good prognosis rate (good recovery and moderate deficit) of 51％ and a poor prognosis of 49％.Conclusion Large decompressive craniectomy can significanty improve the outcome and reduce complications of patients with severe traumatic brain injury combined with herniation of brain.

Early management of hydrocephalus secondary to large decompressive craniectomy by modified cranioplasty and ventriculoperitoneal shunt: a report of 45 cases / 中华创伤杂志

Objective To explore the role of improved cranioplasty plus ventriculoperitoneal shunt in early treatment of hydrocephalus secondary to decompressive craniectomy for patients with severe craniocerebral injury. Methods A retrospective study was performed on 45 patients complicated by hydrocephalus after decompressive craniectomy for severe craniocerebral injury treated with early stage improved cranioplasty plus ventriculoperitoneal shunt from January 2006 to December 2010.Then,the clinical data,complications and outcomes were summarized. Results All operations were carried out 38-80 days after injury.The postoperative complications were distal obstruction of ventriculoperitoneal shunt in two patients and intracranial infection in one.The clinical symptoms were obviously improved in 36 patients (80％) and the cerebral ventricle was diminished in 34 (76％) one month postoperatively.The Glasgow Outcome Scale (GOS) at discharge was good in eight patients,moderate disability in 19,severe disability in 13 and prolonged coma in five,where better recovery (good recovery and moderate disability) in 27 patients (60％) showed significant improvement compared with preoperation ( x2 =23.47,P ＜0.01 ). Conclusion Early cranioplasty plus ventriculoperitoneal shunt is an effective and safe method for treatment of the complicated hydrocephalus after decompressive craniectomy for severe craniocerebral injury.

Modified large decompressive craniectomy for patients with severe traumatic brain injury combined with acute subdural hematoma / 中华创伤杂志

Objective To investigate the clinical outcome of modified large decompressive craniectomy in treatment of severe traumatic brain injury combined with acute subdural hematoma. Methods A retrospective analysis was carried out to compare the clinical outcome of large decompressive craniectomy (treatment group) for 81 patients with severe traumatic brain injury combined with acute subdural hematoma from July 2007 to June 2010 and that of standard large trauma decompressive craniectomy (control group) for 65 patients with same injuries from July 2004 to June 2007. Results According to the Glasgow outcome scale at the end of month 6 after injury, there were 21 patients (GCS 5 points) with good recovery, 19 (GCS4 points) with moderate deficit, 24 (GCS 3 points) with severe deficit, five (GCS 2 points) under persistent vegetative status and 12 (GCS 1 points) deaths in the treatment group,with good prognosis rate (good recovery and moderate deficit) of 49% (P ＜ 0.05) and poor prognosis rate of 51%. However, only 21 patients got favorable outcome, including 12 patients (GCS 5 points)with good recovery and nine (GCS 4 points) with moderate deficit; 44 patients got unfavorable outcome (68%), including 22 patients (GCS 3 points) with severe deficit, three (GCS 2 points) under persistent vegetative status and 19 (GCS 1 points) deaths in the control group (P ＜0.05). Furthermore, the incidences of delayed intracranial hematomas and subdural collection of fluid in the treatment group were significantly lower than those in the control group (P ＜ 0.05). Conclusion Modified large decompressive craniectomy can significantly improve the outcome and reduce complications of patients with severe traumatic brain injury combined with acute subdural hematoma.

Clinical significance of anti-β2glycoprotein I antibodies in systemic lupus erythematosus / 中华微生物学和免疫学杂志

Objective To investigate the clinical application of anti-β2 glyeoprotein Ⅰ antibodies (IgG, IgM, IgA)in systemic lupus erythematosus(SLE). Methods The anti-β2-GP Ⅰ antibodies and anti-cardiolipin antibodies(ACL) level were measured by ELISA in 100 SLE patients, 39 other rheumatoid arthri-tis patients and 30 healthy control people. Their clinical application was analyzed in SLE diagnose and thera-py. Results The level of anti-β2-GP Ⅰ (IgG, IgM, IgA)were significantly higher in SLE than that in healthy (P < 0. 01 ). Sensitivity, specificity, positive predictive value and negative predictive value were 17.2%, 95.7%, 85.0% and 44. 6%, respectively. There was a significant and positive correlation be-tween anti-β2-GP Ⅰ antibodies and ACL antibodies ( IgG, IgM, IgA) (r = 0.418, 0. 624, 0.518, 0. 583, P <0.01). In multivariate analysis the factors(anti-β2-GP Ⅰ antibodies, ACL antibodies, dsDAN, u1-RNP, Sm, SSA, SSB, Jo-1, Scl-70, P-protein, PT, APTT) associated with SLE disease activity index(SLEDAI) were anti-β2-GP Ⅰ (IgG) and dsDNA. Conclusion anti-β2-GP Ⅰ antibody has high specificity and positive predict value, also is associated with SLE's thrombosis. It has some values in the clinical application.