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Background: Surgical treatment of both-column acetabular fractures is challenging because of the complex acetabular fracture patterns and the curved surface of the acetabulum. Seldom study has compared the application of three-dimensional (3D) printing technology and traditional methods of contouring plates intra-operatively for the surgical treatment of both-column acetabular fractures. We presented the use of both 3D printing technology and a virtual simulation in pre-operative planning for both-column acetabular fractures. We hypothesized that 3D printing technology will assist orthopedic surgeons in shortening the surgical time and improving the clinical outcomes. Methods: Forty patients with both-column acetabular fractures were recruited in the randomized prospective case-control study from September 2013 to September 2017 for this prospective study (No. ChiCTR1900028230). We allocated the patients to two groups using block randomization (3D printing group, n = 20; conventional method group, n = 20). For the 3D printing group, 1:1 scaled pelvic models were created using 3D printing, and the plates were pre-contoured according to the pelvic models. The plates for the conventional method group were contoured during the operation without 3D printed pelvic models. The operation time, instrumentation time, time of intra-operative fluoroscopy, blood loss, number of times the approach was performed, blood transfusion, post-operative fracture reduction quality, hip joint function, and complications were recorded and compared between the two groups. Results: The operation and instrumentation times in the 3D printing group were significantly shorter (130.8 ± 29.2 min, t = －7.5, P < 0.001 and 32.1 ± 9.5 min, t = －6.5, P < 0.001, respectively) than those in the conventional method group. The amount of blood loss and blood transfusion in the 3D printing group were significantly lower (500 [400, 800] mL, Mann-Whitney U= 74.5, P < 0.001 and 0 [0,400] mL, Mann-Whitney U = 59.5, P < 0.001, respectively) than those in the conventional method group. The number of the approach performed in the 3D printing group was significantly smaller than that in the conventional method group (pararectus + Kocher-Langenbeck [K-L] approach rate: 35% vs. 85%; x2 = 10.4, P < 0.05). The time of intra-operative fluoroscopy in the 3D printing group was significantly shorter than that in the conventional method group (4.2 ± 1.8 vs. 7.7 ± 2.6 s; t = －5.0, P < 0.001). The post-operative fracture reduction quality in the 3D printing group was significantly better than that in the conventional method group (good reduction rate: 80% vs. 30%; x2 = 10.1, P < 0.05). The hip joint function (based on the Harris score 1 year after the operation) in the 3D printing group was significantly better than that in the conventional method group (excellent/good rate: 75% vs. 30%; x2 = 8.1, P < 0.05). The complication was similar in both groups (5.0% vs. 25%; x2 = 3.1, P = 0.182). Conclusions: The use of a pre-operative virtual simulation and 3D printing technology is a more effective method for treating bothcolumn acetabular fractures. This method can shorten the operation and instrumentation times, reduce blood loss, blood transfusion and the time of intra-operative fluoroscopy, and improve the post-operative fracture reduction quality. Clinical trail registration: No.ChiCTR1900028230; http://www.chictr.org.cn Key words: Both-column; Acetabulum fractures; Computer simulation; Three-dimensional printing; Internal fracture fixation

Innate lymphoid cells (ILCs) are a group of lymphocytes without diversified antigen receptors encoded by gene rearrangement on T and B cells. ILCs, which are tissue-resident innate immune cells, expressed particularly in the mucosa or the barrier surface, contribute to the formation of lymphoid organs, the maintenance of tissue homeostasis, and the regulation of antimicrobial defenses. It has been recently reported that ILCs were enriched at the maternal–fetal interface. During a successful pregnancy, the maternal immune system must tolerate a fetus as an allograft. With the new defined of ILCs, a number of studies have shown that three types of ILCs are involved in embryonic development and pregnancy maintenance as well as the occurrence and development of pregnancy-related complications. This article reviews the types and roles of ILCs in normal pregnancy and pregnancy-related diseases.

Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan–Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22,491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over eightfold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the > eightfold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan–Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 62 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

Background Lung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database. Methods Four cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the differently expressed genes (DEGs) between non-small cell lung cancer (NSCLC) and normal lung tissues. After the DEGs functions were analyzed, the protein–protein interaction network (PPI) of DEGs were constructed, and the core gene in the network which has high connectivity degree with other genes was identified. We analyzed the association of the gene with the development of NSCLC as well as its prognosis. Lastly we explored the conceivable signaling mechanism of the gene regulation during the development of NSCLC. Results A total of 92 up regulated and 214 down regulated DEGs were shared in four cDNA expression profiles. Based on their PPI network, TOP2A was connected with most of other genes and was selected for further analysis. Kaplan–Meier overall survival analysis (OS) revealed that TOP2A was associated with worse NSCLC patients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of expression in cancer comparing to normal tissues. The clinical significance of TOP2A and probable signaling pathways it involved in were further explored, and a positive correlation between TOP2A and TPX2 expression was found in lung cancer tissues. Conclusion Using bioinformatic analysis, we revealed that TOP2A could be adopted as a prognostic indicator of NSCLC and it potentially regulate cancer development through co-work with TPX2. However, more detailed experiments are needed to clarify its drug target role in clinical medical use.

PURPOSE The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). Methods Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed. RESULTS We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs. CONCLUSION The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

Background: Early extubation can reduce pulmonary complications in children undergoing cardiac surgery. The aim of this study is to evaluate the effects of sugammadex for postoperative respiratory management in children with congenital heart disease. Methods: Sixty children with congenital heart disease undergoing elective cardiac surgery were divided into group S and group C (30 children in each group). When post tetanic twitches count (PTC) = 1-2 and train-of-four (TOF) = 0, the children in group S received sugammadex4 mg/kg for reversal of neuromuscular block at the end of surgery, and the children in group C received the same volume of normal saline. The recovery time to TOF of 0.9, the mechanical ventilation and extubation times were recorded. On the other side, the hemodynamic parameters before and 5 min after administration, and side effects were also recorded. The levels of C-reactive protein (CRP) and procalcitonin (PCT) before and 24 h after surgery were measured. Results: The recovery time to TOF of 0.9 and extubation time were significantly shorter in the group S than in the group C (4.2 ± 1.4 vs 108.2 ± 26.7 min, 66.3 ± 6.5 vs 171.6 ± 23.1 min, respectively, P 0.05) with respect to side effects. Conclusion: Sugammadex is rapid and effective in reversing rocuronium-induced neuromuscular block, and significantly reduces the extubation time and the release of postoperative CRP and PCT in children with congenital heart diseases.

Patterns of relative timing between consonants and vowels appear to be conditioned in part by phonological structure, such as syllables, a finding captured naturally by the two-level feedforward model of Articulatory Phonology (AP). In AP, phonological form – gestures and the coordination relations between them – receive an invariant description at the inter-gestural level. The inter-articulator level actuates gestures, receiving activation from the inter-gestural level and resolving competing demands on articulators. Within this architecture, the inter-gestural level is blind to the location of articulators in space. A key prediction is that intergestural timing is stable across variation in the spatial position of articulators. We tested this prediction by conducting an Electromagnetic Articulography (EMA) study of Mandarin speakers producing CV monosyllables, consisting of labial consonants and back vowels in isolation. Across observed variation in the spatial position of the tongue body before each syllable, we investigated whether inter-gestural timing between the lips, for the consonant, and the tongue body, for the vowel, remained stable, as is predicted by feedforward control, or whether timing varied with the spatial position of the tongue at the onset of movement. Results indicated a correlation between the initial position of the tongue gesture for the vowel and C-V timing, indicating that inter-gestural timing is sensitive to the position of the articulators, possibly relying on somatosensory feedback. Implications of these results and possible accounts within the Articulatory Phonology framework are discussed.

Our previous study revealed that early application of electrical field stimulation (EFS) with the anode at the lesion and the cathode distal to the lesion reduced injury potential, inhibited secondary injury and was neuroprotective in the dorsal corticospinal tract after spinal cord injury (SCI). The objective of this study was to further evaluate the effect of EFS on protection of anterior horn motoneurons and their target musculature after SCI and its mechanism. Rats were randomized into three equal groups. The EFS group received EFS for 30 minutes immediately after injury at T10. SCI group rats were only subjected to SCI and sham group rats were only subjected to laminectomy. Luxol fast blue staining demonstrated that spinal cord tissue in the injury center was better protected; cross-sectional area and perimeter of injured tissue were significantly smaller in the EFS group than in the SCI group. Immunofluorescence and transmission electron microscopy showed that the number of spinal cord anterior horn motoneurons was greater and the number of abnormal neurons reduced in the EFS group compared with the SCI group. Wet weight and cross-sectional area of vastus lateralis muscles were smaller in the SCI group to in the sham group. However, EFS improved muscle atrophy and behavioral examination showed that EFS significantly increased the angle in the inclined plane test and Tarlov's motor grading score. The above results confirm that early EFS can effectively impede spinal cord anterior horn motoneuron loss, promote motor function recovery and reduce muscle atrophy in rats after SCI.

Checkpoint with Forkhead-associated and Ring finger domains (CHFR) is a G2/M checkpoint and tumor-suppressor gene. Recent publications showed the correlation of CHFR promoter methylation with clinicopathological significance of non-small cell lung cancer (NSCLC), however, the results remain inconsistent. The aim of this study is to investigate the Clinicopathological significance of CHFR promoter methylation in NSCLC with a meta-analysis. A total of nine studies were included in the meta-analysis that 816 patients were involved. Our data indicated that the frequency of CHFR promoter methylation was higher in NSCLC than in normal lung tissue, Odd Ratios (OR) was 9.92 with 95% corresponding confidence interval (CI) 2.17-45.23, p = 0.003. Further subgroup analysis revealed that CHFR promoter was more frequently methylated in squamous cell carcinoma (SCC) than in adenocarcinoma (ADC), OR was 4.46 with 95% CI 1.65-12.05, p = 0.003, suggesting the mechanism of SCC pathogenesis is different from ADC. Notably, CHFR promoter methylation was correlated with smoking behavior in NSCLC. In conclusion, CHFR could be a biomarker for diagnosis of NSCLC, and a promising drug target for development of gene therapy in SCC. CHFR promoter methylation is potentially associated with poor overall survival, additional studies need to be carried out for confirmation in future.

Wheat (Triticum aestivum L.) is a staple food of more than 50% of global population. Rhizoctonia cerealis is the causal agent of sharp eyespot, a devastating disease of cereal crops including wheat. Cutinases produced by fungal pathogens play important roles in host-pathogen compatible interactions, but little is known about cutinases in R. cerealis. In this study, we identified a total of six cutinase encoding genes from R. cerealis genome, designated as RcCUT1-RcCUT6, analyzed their expression patterns during the infection, and determined virulence role for RcCUT1. All the proteins, RcCUT1-RcCUT6, contain a highly conserved GYSKG motif and another conserved C-x(3)-D-x(2)-C-x(2)-[GS]-[GSD]-x(4)-[AP]-H motif in the carbohydrate esterase 5 domain. The RcCUT1, RcCUT2, RcCUT4, and RcCUT5 are predicted to be secreted proteins containing four cysteine residues. These six cutinase genes had different expression patterns during the fungal infection process to wheat, among which RcCUT1 was highly expressed across all the infection time points but RcCUT6 was not expressed at all and the others were expressed only at certain time points. Further, RcCUT1 was heterologously expressed in Escherichia coli to obtain a purified protein. The purified RcCUT1 was shown to possess the cutinase activity and be able to induce necrosis, H2O2 accumulation, and expression of defense-related genes when infiltrated into wheat and Nicotiana benthamiana leaves. In contrast, RcCUT1 protein with serine mutation at the first motif had no cutinase activity, consequently lost the ability to induce necrosis. Noticeably, application of the purified RcCUT1 with R. cerealis led to significantly higher levels of the disease in wheat leaves than application of the fungus alone. These results strongly suggest that RcCUT1 serves as a virulence factor for the fungus. This is the first investigation of the cutinase genes in R. cerealis and the findings provide an important insight into pathogenesis mechanisms of R. cerealis on wheat.

Wheat (Tritium aestivum L.) production is essential for global food security. Infection of barley yellow dwarf virus-GAV (BYDV-GAV) results in wheat showing leaf yellowing and plant dwarfism symptom. To explore the molecular and ultrastructural mechanisms underlying yellow dwarf symptom formation in BYDV-GAV-infected wheat, we investigated the chloroplast ultrastructure via transmission electron microscopy (TEM), examined the contents of the virus, H2O2, and chlorophyll in Zhong8601, and studied the comparative transcriptome through microarray analyses in the susceptible wheat line Zhong8601 after virus infection. TEM images indicated that chloroplasts in BYDV-GAV-infected Zhong8601 leaf cells were fragmentized. Where thylakoids were not well developed, starch granules and plastoglobules were rare. Compared with mock-inoculated Zhong8601, chlorophyll content was markedly reduced, but the virus and H2O2 contents were significantly higher in BYDV-GAV-infected Zhong8601. The transcriptomic analyses revealed that chlorophyll biosynthesis and chloroplast related transcripts, encoding chlorophyll a/b binding protein, glucose-6-phosphate/phosphate translocator 2, and glutamyl-tRNA reductase 1, were down-regulated in BYDV-GAV-infected Zhong8601. Some phytohormone signaling-related transcripts, including abscisic acid (ABA) signaling factors (phospholipase D alpha 1 and calcineurin B-like protein 9) and nine ethylene response factors, were up-regulated. Additionally, reactive oxygen species (ROS)-related genes were transcriptionally regulated in BYDV-GAV infected Zhong8601, including three up-regulated transcripts encoding germin-like proteins (promoting ROS accumulation) and four down-regulated transcripts encoding peroxides (scavenging ROS). These results clearly suggest that the yellow dwarf symptom formation is mainly attributed to reduced chlorophyll content and fragmentized chloroplasts caused by down-regulation of the chlorophyll and chloroplast biosynthesis related genes, ROS excessive accumulation, and precisely transcriptional regulation of the above-mentioned ABA and ethylene signaling- and ROS-related genes in susceptible wheat infected by BYDV-GAV.

Objective: To investigate the immunomodulating mechanisms of a Chinese herbal medicine Yi Shen Juan Bi (YJB) in treatment of adjuvant arthritis (AA) in rats. Materials and Methods: Levels of serum tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) were measured by the Enzyme-Linked Immunosorbent Assay (ELISA). Expression of TNF-α mRNA and IL-1β mRNA in synovial cells was measured with the semi-quantitative technique of reverse transcription-polymerase chain reaction (RT-PCR), while caspase-3 was examined by western blot analysis. Results: The administration of YJB significantly decreased the production of serum TNF-α and IL-1β. It also decreased significantly the TNF-α mRNA, IL-1β mRNA, and caspase-3 expression in synoviocytes. Conclusions: YJB produces the immunomodulatory effects by downregulating the over-activated cytokines, while it activates caspase-3, which is the key executioner of apoptosis in the immune system. This may be the one of the underlying mechanisms that explains how YJB treats the rheumatoid arthritis.

The present study aimed to evaluate the therapeutic effects of polysaccharides fromInonotus obliquus(PIO) on streptozotocin- (STZ-) induced diabetic symptoms and their potential mechanisms. The effect of PIO on body weight, blood glucose, damaged pancreaticβ-cells, oxidative stresses, proinflammatory cytokines, and glucose metabolizing enzymes in liver was studied. The results show that administration of PIO can restore abnormal oxidative indices near normal levels. The STZ-damaged pancreaticβ-cells of the rats were partly recovered gradually after the mice were administered with PIO 6 weeks later. Therefore, we may assume that PIO is effective in the protection of STZ-induced diabetic rats and PIO may be of use as antihyperglycemic agent.

Background Asthma has become an important public health issue and approximately 300 million people have suffered from the disease worldwide. Nowadays, the use of acupuncture in asthma is increasing. This study intended to systematically analyze and compare the gene expression profiles between the asthmatic and acupuncture-treated asthmatic rat lung, and tried to gain insight into the molecular mechanism underlying the early airway response (EAR) phase of asthma treated by acupuncture. Methods Four tag libraries of serial analysis of gene expression (SAGE) were established from lung tissues of control rats (CK), asthmatic rats (AS), asthmatic rats treated by acupuncture (ASAC), and control rats treated by acupuncture (CKAC). Bioinformatic analyses were carried out by using the methods including unsupervised hierarchical clustering, functional annotation tool of the database for annotation, visualization, and integrated discovery (DAVID), gene ontology (GO) tree machine, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Results There were totally 186 differentially expressed tags (P < 0.05, PCK/AS) between the libraries of CK and AS, 130 differentially expressed tags between libraries of AS/ASAC (P < 0.05, PAS/ASAC), and 144 differentially expressed tags between libraries of CK/CKAC (P < 0.05, PCK/CKAC). The gene expression profiles of AS and ASAC were more similar than other libraries via unsupervised SAGE clustering. By comparison of PCK/AS and PAS/ASAC, the DAVID genes functional classification was found to be changed from "immune response" to "response to steroid hormone stimulus", and the GO term "antigen processing and presentation of peptide antigen" disappeared in PAS/ASAC. Totally 3 same KEGG pathways were found among the three groups. Moreover, 21 specific tags of the acupuncture in treating asthma were detected using Venn diagrams. Conclusion Our SAGE research indicates that the gene expression profile of the EAR phase of asthma could be effectively and specifically regulated by acupuncture, which suggests that the gene expression of immune response and steroid hormone may play an important role in the treatment.

AIM:To find out the relationship between the gene transcription of different types of procollagen and the deposition of the relevant collagens in the liver tissue and to confirm the types of collagen producing cells in liver fibrogenesis.METHODS:Dynamic changes of the expression of alpha1(I), alpha1(III) and alpha1(IV) procollagen mRNA and relevant collagens and the distribution of collagen producing cells during liver fibrogenesis of rat induced by CCl(4) (20 weeks) were investigated with Northern blot analysis, in situ hybridization and immunohistochemical techniques.RESULTS: The increased expression of alpha 1(III) procollagen mRNA by Northern blot analysis was the most predominant one among the three mRNAs during fibrogenesis. However, the enhanced expression of alpha1(IV) procollagen mRNA occurred very early while the expression of alpha1(I) mRNA was not enhanced much until the middle stage of the experiment. Desmin (Dm) positive hepatic stellate cells (HSCs) and few myofibroblasts (MFs) in and around the necrotic areas expressed alpha1(I), alpha1(III) and alpha1(IV) procollagen mRNA signals detected by in situ hybridization at the early stage of the experiment. All the three procollagen mRNA signals thereafter mainly localized in fibroblasts (Fbs) and MFs in fibrotic septa during the middle and late stages of fibrosis, which distributed parallel to the corresponding collagens detected by immunohistochemical study. In addition, the endothelial cells of sinusoids and the small blood vessels within the septa also showed alpha1(IV) procollagen mRNA and type IV collagen expression.CONCLUSION:It is considered that "HSC-MF-Fb effect cell system is the major cellular source of collagen production in liver fibrosis, in which HSCs are collagen producing precursor cells in the early liver fibrogenesis, thereafter the synthesis of type I, III and IV collagens (Col I, Col III and Col IV) mainly derives from MFs and Fbs, which play a very important role in the progress of liver fibrosis. The endothelial cells along sinusoids, as another source of Col IV production, might participate in the capillization of liver sinusoids.