BACKGROUNDHemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses. This study was conducted to investigate the early pathophysiological changes of CD4(+)CD25(+)Foxp3(+) Treg and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation.

METHODSA rat model of controlled hemorrhagic shock with no fluid resuscitation was established. Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation. Three color flow cytometry was used to detect Tregs, Th1, Th2, Tc1 and Tc2 cells in the samples.

RESULTSIn the peripheral blood of rats, the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P = 0.001). The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08 ± 8.98)% to (23.91 ± 15.36)%, and from (40.40 ± 21.56)% to (65.48 ± 23.88)%, respectively.

CONCLUSIONSAt an early stage, the advent of hemorrhagic shock is related to an early decrease of Tregs, and a mild shift in the Th1/Th2, Tc1/Tc2 balance toward Th1 and Tc1 dominance. These changes are part of a hyper-inflammatory state of the host, and will deteriorate the maintenance of immune balance. Further influences and detailed mechanisms need to be investigated.

Animals ; CD4 Antigens ; metabolism ; Forkhead Transcription Factors ; metabolism ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Resuscitation ; Shock, Hemorrhagic ; immunology ; metabolism ; T-Lymphocytes, Cytotoxic ; metabolism ; T-Lymphocytes, Regulatory ; metabolism ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

Objective To investigate a shorter and safer route for contralateral C_7 nerve root transfer. Methods Eight male patients were treated from Dec2005 to Nov.2006Their range of age was from 22 to 43 years with an average of 30 yearsFive cases had total brachial plexus avulsion.The operative delay was from 2 to 6 months(mean:4 months).The sealenus anterior muscle was transected before a prespinaJ & ret- ropharyngeal tunnel was madeThe contralateral C_7 nerve root was used to repair the upper trunk or the infra- clavicular lateral cord and posterior cord of injured side via this routeusing direct anastomosis or nerve graft- ing.Results The length of the harvested contralateral C_7 nerve root was(4.67?0.52em in the early 5 casesThe nerve graft was6.25?0.35)em long for repairing supraclavicular brachial plexus and(8.56?0.45cm long for repairing infraclavicular brachial plexusThe length of the harvested contralateral C_7 nerve root averaged 6.85cm in the other 3 cases2 of which had direct anastomosis to the residual nerve C_5 and C_6 nerve roots and the other used nerve graft of 3 cm in lengthTransient contralateral sensory symptoms were re- ported in most patientsAt 3 months followups6 patients had tingling sensation on the contralateral fingers with percussion on the injured cervical areaIpsilateral SSEP could be recorded by stimulating at 2 cm above sternoclavicular joint on the injured sideAt 7 months follow ups of 5 patientsCMAP could be recorded in bi- cepsdeltoids and infraspinatus or triceps with stimulation at Erb's pointHoweverno clinical movements was noticedAt 12 months follow ups of 3 patientswe could observe early motor and sensory function recovery of those patients to different extent.Conclusion Transection of anterior scalenus muscle shortens the length of the transfer route and allows more efficient neurotizationThe procedure is convenient and safeprovided certain precautions being usedThe principal of contralateral C_7 nerve transfer are reconstruct the anterior divi- sions of upper trunkposterior divisions of upper trunk and suprascapular nerve when repairing the supraclavic- ula brachial plexusReconstruct the lateral cord and posterior cord when repairing the infraclavicula brachial plexusPostsurgical fasting for 4 days included foods and liquids will benefit of healing of anastomosed nerves and regenerationaud avoid complications.

OBJECTIVETo evaluate the value of 640-slice 3D CT angiography (3D-CTA) plus 3D printing for improving the outcomes of surgeries for intracranial aneurysms.

METHODSSixty patients with intracranial aneurysm were randomly divided into trial group (n=30) and control group (n=30). The control group received routine surgery, and the simulation models of the intracranial aneurysm in trial group was printed using a 3D printer using the imaging data from 3D-CTA. Using the simulation model, the surgery was designed and planned before operation (including surgical approaches and placement of clips) and simulation surgery was also conducted. The coincidence rates between preoperative and intraoperative findings of the intracranial aneurysms on 3D-CTA were compared. CT scan was performed at 1 and 3 days after the operation to detect potential cerebral infarction or bleeding associated with the operation; CTA was performed both at the same time and at 3-6 months after the operation to detect stenosis, occlusion and aneurysm clipping. The patients were followed up for 3-6 months to assess the outcomes using Glasgow Outcome Scale (GOS).

RESULTSThe preoperative 3D-CTA findings were basically consistent with the intraoperative findings in all the 60 patients. Nine patients in the control group and 2 patients in the trial group had short-term adverse operation events; 11 patients in control group and 4 patients in trial group had long-term adverse events; 18 patients in control group and 25 patients in trial group had good neurologic function. The incidences of short-term and long-term adverse events associated with the operation was significantly lower in the trial group than in the control group (χ=5.364, P=0.021; χ=4.841, P=0.028), and the outcomes were significantly better in the trial group than in the control group (χ=4.633, P=0.031).

CONCLUSIONThe simulation model of intracranial aneurysm is helpful to improve the quality of surgery and patients outcomes.

To compare the early effects of hypertonic and isotonic saline resuscitation on heme oxygenase-1 (HO-1) expression in organs of rats with hemorrhagic shock. Rats were randomly divided into hypertonic saline resuscitation (HTS), normal saline resuscitation (NS) and sham groups. HO-1 mRNA, protein expression and apoptosis were evaluated in organs. In the HTS group, significant difference was noted in HO-1 protein in small intestinal mucosa and liver compared with the NS and sham groups, and in HO-1 mRNA in liver and kidney compared with the sham group. The apoptosis of small intestinal mucosa, liver, heart, and lung was significantly lower in the HTS group than that in the NS group. In this study, small volume resuscitation with HTS can efficiently up-regulate the expression level of HO-1 in small intestinal mucosa and liver, which may be one of the mechanisms alleviating organ damage.
Animals ; Base Sequence ; Blood Pressure ; DNA Primers ; Gene Expression Regulation, Enzymologic ; drug effects ; Heme Oxygenase-1 ; metabolism ; Intestine, Small ; enzymology ; Kidney ; enzymology ; Liver ; enzymology ; RNA, Messenger ; genetics ; Rats ; Resuscitation ; methods ; Reverse Transcriptase Polymerase Chain Reaction ; Saline Solution, Hypertonic ; pharmacology ; Shock, Hemorrhagic ; enzymology

BACKGROUNDHemorrhagic shock is usually associated with complicated immune and inflammatory responses, which are sometimes crucial for the prognosis. As regulators of the immune and inflammatory system; proliferation, migration, distribution and activation of myeloid-derived suppressor cells (MDSCs) are intimately linked to the inflammation cascade.

METHODSIn a model of severe hemorrhagic shock, thirty-five rats were randomly divided into control, sham, normal saline resuscitation (NS), hypertonic saline resuscitation (HTS), and hydroxyethyl starch resuscitation (HES), with seven in each group. MDSCs were analyzed by flow cytometric staining of CD11b/c(+)Gra(+) in peripheral blood mononuclear cells (PBMC), spleen cell suspensions, and bone marrow nucleated cells (BMNC). Simultaneously, the expressions of arginase-1 (ARG-1) and inducible nitric oxide synthase (iNOS) mRNA in MDSCs were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

RESULTSIn the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the MDSCs in the PBMC of NS, HTS and HES groups markedly increased, and MDSCs in BMNC of these groups decreased accordingly, significantly different to the control group. In hemorrhagic shock rats infused with HTS at the early resuscitation stage, MDSCs in PBMC increased about 2 and 4 folds, and MDSCs in BMNC decreased about 1.3 and 1.6 folds, as compared to the sham group respectively, with statistically significant difference. Furthermore, compared to the NS and HES groups, the MDSCs in PBMC of HTS group increased 1.6 and 1.8 folds with statistically significant differences; the MDSCs decrease in BMNC was not significant. However, there was no statistically significant difference in MDSCs of spleen among the five groups. In addition, compared to the control, sham, NS and HES groups, the ARG-1 and iNOS mRNA of MDSCs in PBMC, spleen and BMNC in the HTS group had the highest level of expression, but no statistically significant differences were noted.

CONCLUSIONSIn this model of rat with severe and controlled hemorrhagic shock, small volume resuscitation with HTS contributes to dramatically early migration and redistribution of MDSCs from bone marrow to peripheral circulation, compared to resuscitation with NS or HES.

Animals ; Arginase ; genetics ; metabolism ; Blood Pressure ; physiology ; Disease Models, Animal ; Flow Cytometry ; Fluid Therapy ; methods ; Leukocytes, Mononuclear ; metabolism ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Saline Solution, Hypertonic ; therapeutic use ; Shock, Hemorrhagic ; immunology ; metabolism ; therapy

BACKGROUNDNeuroimaging studies have found that functional changes exist in patients with Parkinson's disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.

METHODSSeventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.

RESULTSCompared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected).

CONCLUSIONSThe baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease's progression in patients with PD.

Adult ; Aged ; Brain ; pathology ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Parkinson Disease ; diagnosis

Objective To observe the treatment effect of edaravone plus mild hypothermia treatment on patients with acute severe traumatic brain injury (TBI).Methods One hundred and forty-three patients with TBI,admitted to our hospital from February 2008 to September 2012,were randomly divided into 4 groups:control group (group A,routine treatment,n=35),mild hypothermia treatment group (group B,routine treatment plus temperature control at the range of33～34 ℃ for 2-14 days,n=36),edaravone treatment group (group C,routine treatment plus edaravone up to 14 days,30 mg per time,twice per day,n=36) and mild hypothermia plus edaravone treatment group (group D,routine treatment combined with mild hypothermia plus edaravone n=36).Intracranial pressure (ICP) and arterial blood glucose were determined at admission,and 24 and 72 h after admission; Glasgow Outcome Scale (GOS) scores were assessed 3 months after the treatment.Results At 24 and 72 h after admission,the mean ICP of group B and group C was significantly lower than that of group A (P＜0.05); that of group D was significantly lower than that of group B and group C (P＜0.05).The mean blood glucose of group B and group C was obviously lower than that of group A (P＜0.05); group D was obviously lower than group B and group C (P＜0.05).The rate of good neurologic function (GOS scores 4-5) in group D was better than that of group B and group C (P＜0.05),which was significantly better than that of group A (P＜0.05).Conclusion It is much more effective to use mild hypothermia plus edaravone treatment than simple mild hypothermia or edaravone treatment in the early treatment of acute severe TBI.

Due to the diversity and complexity, the change of chemical components in medicinal plant according to the time, cultivated varieties or ecological condition is difficult to recognize using traditional phytochemistry method. In order to analyze the pharmacodynamics material basis in Uighur medicinal plant Artemisia rupestris L. in an effective and comprehensive way, a plant metabolomics approach was established based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study firstly focused on the effect of extraction solvents,redissolve solvents and ultrasonic time on the untargeted metabolomics, then the optimal preparation condition was selected according to metabolites coverage. After methodology validation, the approach was applied to acquire metabolic information in root, stem, branchlet, leaf and flower of Artemisia rupestris L. The results showed that the metabolome in flower was obviously different with the other organs. Coupling with multivariate statistical analysis, a batch of differential metabolites were picked out, in which 61 flavonoids, 97 rupestonic acid derivatives, 7 chlorogenic acids and 15 other compounds were primarily recognized according to the characteristic fragmentation rules of specific structure type and database retrieval. Additionally,the distribution characteristics of the above 180 differential metabolites was illustrated by cluster heat map. In conclusion,this study provided important information about the rational utilization of effective parts from Artemisia rupestris L.,and offered a novel strategy for quality control,variety improvement and reasonable development of medicinal plants.

Using beta-2 adrenergic receptor, 5-hydroxytryptamine and angiotensin II type 1 receptor as control, we here established a method for rapid prediction of the initial position amino acids of N-terminal, C-terminal, intracellular loops, extracellular loops and transmembrane (TM) regions in G protein-coupled receptors (GPCRs), and successfully predicted the structure of Mas-related G protein-coupled receptors X3 (MRGPRX3). To achieve this purpose, nanoluciferase (Nluc) was inserted into the different sites of these GPCRs′ sequence by sequence and ligation-independent cloning (SLIC) method, and the luminescence value were measured to distinguish the different parts of GPCRs. The results showed that luminescence values of NLuc luciferase at TM region were less than 100 000, and the values were higher than 1 000 000 at N terminal, C terminal, or extracellular loops and intracellular loops, and the values were between 100 000 and 500 000 at junction. The predicted MRGPRX3 structure was analyzed in detail and was compared with AlphaFold predicted structure. In conclusion, this method could provide useful information of GPCR structure model for the ligand virtual screening, and could provide certain experimental basis for structural pharmacology.

BACKGROUNDThe domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.

METHODSThe study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.

DISCUSSIONThe study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).