Pituitary adenylate cyclase-activating polypeptide (PA CAP) which belongs to the secretin/glucagon/VIP family has been originally isola ted from the sheep hypothalamus on the basis of its ability to stimulate cAMP fo rmation in culture rat anterior pituitary cells. Post-translational processing of the PACAP precursor generates two biologically active molecular forms, PACAP -38 and PACAP-27. The primary structure of PACAP has been remarkably conserved during evolution. The sequence of PACAP-27 exhibits substantial similarities w ith those of vasoactive intestinal polypeptide (VIP), glucagon and secretin. The gene encoding the PACAP precursor is widely expressed in brain and various peri pheral organs, notably in endocrine glands, gastro-intestinal，uro-genital tra cts and respiratory system. In vivo and in vitro studies have shown that PACAP exhibits multiple activities especially a trophic activity during ontogen esis, notably in the adrenal medulla and the central nervous system. The biologi cal effects of PACAP are mediated through three distinct receptor subtypes which exhibit differential affinities for PACAP and VIP. The PAC1 receptor, which sho ws high selectivity for PACAP, is coupled to several transduction systems. In co ntrast, VPAC1 and VPAC2, which bind with the same affinity for PACAP and VIP, ar e mainly coupled to the adenylyl cyclase pathway. In conclusion, PACAP is neurop eptide, and it functions as a hypothalamic hormone, neurohormone, neuromodulator , vasodilator, neurotransmitter or trophic factor in the brain and the various o rgans.

The purpose of this study was to identify specific microRNAs (miRNAs) during differentiation and maturation of interneurons and to predict their possible functions by analyzing the expression of miRNAs during in vitro differentiation of the rat interneuron precursor cell line GE6. In the experiment, the interneuron precursor cell line GE6 was cultured under three different conditions, i. e. the first was that had not added growth factors and the normal differentiation cultured for 4 days (Ge6_4d); the second was that cultured with bone morphogenetic protein-2 (BMP2) for 4 days (Ge6_bmp2); and the third was that cultured with sonic hedgehog (SHH) for 4 days (Ge6_ shh). In addition, another group of undifferentiated GE6 (Ge6_u) was applied as a control. We found in this study that the expression levels of a large number of miRNAs changed significantly during GE6 differentiation. The expression levels of miR-710, miR-290-5p and miR-3473 increased in the GE6 cells with secreted factor BMP2. These miRNAs may play important regulatory roles during interneuron differentiation.
Animals ; Bone Morphogenetic Protein 2 ; chemistry ; Cell Differentiation ; Cell Line ; Hedgehog Proteins ; chemistry ; Interneurons ; cytology ; metabolism ; MicroRNAs ; metabolism ; Rats

Objective To evaluate the effect of genechip in detecting isoniazid-and rifampicinresistance of Mycobacterium tuberculosis (MTB) in China.Methods Studies of genechip in detecting MTB resistance to isoniazid and rifampicin in China,which were published from January 1995 to June 2013,were identified through searches of PubMed,Science Direct,CBMDISC,CNKI and Wanfang database.Meta-Disc1.4 software was used for all analyses.Results Totally 618 articles were identified.Fifteen articles published from 2004 to 2013 were finally included in the study.The pooled sensitivity and specificity of genechip in detecting MTB resistance to isoniazid was 0.79 (95 ％CI:0.77-0.81) and 0.94 (95％CI:0.93-0.95),respectively,with the area under curve (AUC) of 0.86.The pooled sensitivity and specificity of genechip in detecting MTB resistance to rifampin was 0.91 (95％CI:0.89-0.92) and 0.96 (95％CI:0.96-0.97),respectively,with the AUC of 0.97.The pooled sensitivity and specificity of genechip in detecting MTB resistance to multidrug was 0.75 (95％CI:0.72-0.78) and 0.97 (95％ CI:0.96-0.98),respectively.Conclusions The effect of genechip in detecting MTB resistance is moderate for isoniazid,while better for rifampin in China.More studies are needed to evaluate the effect of genechip in detecting multidrug resistance in MTB.

Objective To investigate the clinical efficacy of buttress plating for patients with posterior pilon fracture.Methods From April 2012 to January 2015,12 patients with posterior pilon fracture of the distal tibia were treated in our hospital.They were 7 men and 5 women,30 to 56 years of age (average,41.2 years).According to the CT classification by Haraguchi et al.,5 cases belonged to type I,3 to type Ⅱ and 4 to type Ⅲ.All the patients underwent open reduction and internal fixation with buttress plate via either a posterolateral approach or a dual posterolateral-posteromedial approach.All the patients were available for follow-up.The clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the visual analogue scale (VAS).The radiological evaluation was performed using the osteoarthritis-score (OA-score).Results The patients obtained an average follow-up of 21.2 months (range,from 12 to 30 months).Bone fractures united after an average of 15 weeks (range,from 13 to 19 weeks).The time for full weight walking averaged 16 weeks,ranging from 15 to 23 weeks.The ankle plantar flexion ranged from 36° to 42° (average,40.4°);the ankle dorsal extension ranged from 38° to 44° (average,42.6°).At the final follow-ups,the AOFAS scores ranged from 82 to 97 (average,88.2);the OA-score ranged from 0.6 to 0.8 (average,0.71);the VAS scores during rest,active motion and weight-bearing walking ranged from 0.5 to 0.8 (average,0.66),from 0.6 to 0.9 (average,0.82) and from 1.2 to 1.8 (average,1.41),respectively.No fracture malunion,implant loosening,pain or stiffness of the affected ankle was observed at the final follow-ups.Conclusion Buttress plating for posterior pilon fractures can lead to satisfactory clinical outcomes,because it ensures rigid fixation which in turn enables earlier postoperative mobilization.

Objective To explore the causes and risk factors affecting early death in patients with traumatic cervical spinal cord injury (SCI). Methods Clinical data of 553 patients with traumatic cervical SCI were analyzed retrospectively to discuss the related factors affecting early death of patients with traumatic cervical SCI by using univariate analysis and multivariate logistic regression analysis. Results The early mortality of the patients with traumatic cervical SCI was 4.0% ( 22/553 ). The main causes of the early death were respiratory failure in nine patients (40.9%) and electrolyte disorders in five (22.7%). Univariate analysis showed that age, cervical spinal cord injury severity, complications in respiratory, cardiovascular, digestive systems and electrolyte disturbance as well as tracheotomy were considered statistically significant for early death in patients with traumatic cervical SCI ( P < 0, 05 ). Multivariate logistic regression analysis showed that age, cervical SCI severity, complications in respiratory,cardiovascular system and electrolyte disturbance as well as tracheotomy. Conclusion Severe cervical SCI, combined respiratory, cardiovascular system and electrolyte disorder complications as well as tracheotomy are high risk factors for the early death in patients with traumatic cervical SCI.

Objective To explore the application of 3D printing templates for titanium plate contouring (TrPC) in pelvic ring surgery.Methods From May 2016 to June 2018,12 patients with pelvic ring injury were treated by internal fixation with 24 titanium plates at Department of Orthopedics and Trauma,Sanshui People's Hospital.After solid digital models of the damaged pelves of the patients were reconstructed from their CT images via software,the hollowed ones were created with the wall thickness of 1.2 mm.After the models of damaged pelves were restored to be intact,the templates for titanium plate contouring were designed based on the area of fixation and manufactured via a stereo lithography apparatus.The total manufacturing time and material consumption of 3D printing TTPC were recorded and compared with those of 3D printing solid and hollow models.Before operation,the titanium plates were contoured according to the templates.The time for preoperative shaping the plate and the time for intraoperative preparing the plate before installation were recorded.After operation,all patients underwent CT scan again for reconstruction of 3D models of the postoperative pelves which were compared with their corresponding preoperative ones in the software.Matta criteria were used to evaluate the pelvic reduction and Majeed criteria to evaluate the functional recovery 6 months after operation.Results All patients were followed up for 6 to 28 months (average,16.3 months).The total manufacturing time and material consumption of 3D printing a TTPC were significantly less than those of 3D printing a solid or hollow model (P ＜ 0.05).The time for preoperative shaping the plate was 12.8 ± 4.1 minutes and the time for intraoperative preparing the plate was 1.4 ± 1.1 minutes.The average deviation between the preoperative 3D models and the postoperative ones was 1.4 ± 1.1 mm.According to the Matta criteria for pelvic reduction,6 cases were excellent,4 good and 2 satisfactory.According to the Majeed criteria,the pelvic functions were excellent in 7 cases,good in 4,and fair in one.Conclusion Application of 3D printing TTPC in the surgery for pelvic ring injury is advantageous in lowering the costs of 3D printing and reducing the intraoperative time for contouring the titanium plate,leading to satisfactory outcomes.

The rapid changes in the research and development environment of new anti-tumor drugs in China have brought various challenges to drug innovation. How to explore the clinical advantages of new drugs in the early phase, and design scientific, reasonable and efficient pivotal clinical trials for drug registration accordingly, is one of the key challenges. This article takes innovative new drugs for hematological malignancies as an example, comprehensively elaborates the considerations on the timing for entering the pivotal clinical trial and the key elements of the trial design from the perspective of clinical reviewers.

Objective To analyze the epidemiological characteristics of human brucellosis in northern and southern areas of China,and to develop national strategies for brucellosis prevention and control.Methods Individual data on human brucellosis was collected from the National Notifiable Infectious Disease Reporting Information System to describe the situation of brucellosis in China during 2015-2016.Epidemiological features of the disease in northem and southern areas of China were analyzed.Results A total of 104 125 cases were reported in mainland China during 2015-2016,with an average incidence rate as 3.81/100 000.The overall incidence rate from the northem provinces was 7.77/100 000 in 2016,a 18.6％ decrease from 2015 (9.55/100 000),whereas the incidence rate in the southern provinces was 0.27/100 000 in 2016,with an increase of 28.6％ than 0.21/100 000 in 2015.90.0％ of the newly infected counties mainly distributed in southern China.As for the locations of reporting cases,most of them were in the same counties in the northern areas (52.3％) while most cases in the southern areas (59.6％) were imported from other counties.The median age of the cases was 48 (IQR:38-58) years,with male-to-female ratios as 2.7 ∶ 1 in the north and 2.2 ∶ 1 in the south.Majority of the cases were occupation-related,from both the northern (86.8％) and southern (62.7％) areas.Human brucellosis occurred every month throughout the year but with an obvious seasonal increase between March and July.Conclusions Different epidemiological features of human brucellosis appeared in both northern and southern areas of China.The disease was seen endemic in the northem and dispersal in the southem provinces.Appropriate strategies for brucellosis prevention and control should be developed,according to the different epidemiological characteristics in the northcm or southcm areas.

Objective To investigate the method of modeling, finite element modeling and AnyBody musculoskeletal multi-body dynamics simulation technique analyze the biomechanics of clinical orthopaedic surgery. Methods The AnyBody software was used to establish the musculoskeletal motor model of the individualized upper limbs according to the height, weight and CT data of the volunteers. The flexion motion of the elbow in normal people was simulated, and the muscle force, joint force, torque, constraint condition of the humerus during the flexion movement were derived and used as the boundary conditions of finite element analysis.Then, the 3D reconstruction was conducted in the MIMICS software based on CT data. In the Geomagic Studio software, the humeral curved surface and position coordinate matching were completed, and grid division and material assignment were done in the HyperMesh software. Finally, the 3D reconstruction for finite element model of the humerus was introduced into ABAQUS software. The boundary condition data derived from the AnyBody software were applied and the stress calculation analysis was performed. Results The results of the stress and displacement of the humerus during elbow flexion motion were calculated in the ABAQUS software. The maximum stress and displacement of the humerus were 0.76 MPa and 20 μm when flexion of the elbow joint was about 90°. Conclusions A continuous dynamic analysis of humeral stress and displacement during elbow flexion motion was realized, which was more consistent with the requirements of human physiological anatomy and could provide an efficient analysis platform and a new way for studying clinical orthopedic problems.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*