Clinical analysis of 1301 children with hand and foot fractures and growth plate injuries.

BACKGROUND: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. METHODS: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. RESULTS: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. CONCLUSIONS: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.

Epidemiology and management of 10,486 pediatric fractures in Shenzhen: experience and lessons to be learnt.

PURPOSE: To explore and analyze the causes and related influencing factors of pediatric fractures, and provide theoretical basis for reducing the incidence and adverse effects of pediatric fractures. METHODS: This study retrospectively analyzed the epidemiological characteristics of fractures in pediatric aged ≤18 years old who were admitted to the our hospital between July 2015 and February 2020. RESULTS: A total of 10,486 pediatric patients were included in the study, of whom 6961 (66.38%) were boys, and 3525 (33.62%) were girls. For the fracture incidence, age group of the 3-6 years reached the peak. 5584 (60.76%) children were operated upon within 12 h after admission. The top three types of fractures were the distal humerus (3843 sites, 27.49%), distal ulna (1740 sites, 12.44%), and distal radius (1587 sites, 11.35%). The top three causes of injury were falls (7106 cases, 82.10%), car accidents (650 cases, 65.72%), and clipping (465 cases, 5.37%). Fractures predominantly occurred between July and November (4664 cases, 48.87%) and on Saturdays and Sundays (3172 cases, 33.24%). The highest number of hospital visits occurred between 20:00 and 00:00 (4339 cases, 45.46%). CONCLUSION: For pediatric fractures, we should take appropriate and effective preventive measures to reduce the incidence of children's fractures according to the distribution characteristics of age, gender, cause of injury, and fracture site.

Epidemiology of skeletal trauma and skull fractures in children younger than 1 year in Shenzhen: a retrospective study of 664 patients.

BACKGROUND: Unintentional injury is one of the top three causes of death for infants. However, the epidemiological studies of skeletal trauma and skull fractures in infants younger than 1 year were poorly understood in China. Therefore, our study aimed to examine accidental and emergency attendance in infants under 1 year. It also tried to determine the prevalence and severity of accident types in infants. METHODS: A retrospective analysis was performed on the demographic characteristics of infants younger than 1 year with skeletal trauma and skull fractures who visited the Shenzhen Children's Hospital from January 1, 2016 to December 31, 2019. Age, gender, fracture site and type, mechanism of injury, length of visit, length of hospital stay, hospitalization cost, and treatment methods were analyzed. RESULTS: A total number of 675 fractures in 664 infants were included, the median age was 187days (IQR,90-273days), including 394 males and 270 females. The top three fracture sites were the skull (430 sites, 63.70 %), long bones of the limbs (168 sites, 24.89 %), and clavicle (53 sites, 7.85 %). The top three causes of injury were locomotion injuries (256 cases, 38.55 %), falls or trips from low height (from beds, tables, chairs, etc.) (130 cases, 19.58 %), and birth injuries (97 cases, 14.61 %). The greatest amount of fractures occurred in children 1-28 days of life (d) reached a top of 101 cases, followed by 331-365 days, accounting for 15.21 and 10.24 %, respectively. The number of fractures reached a trough of 29 cases in the 29-60d group (4.37 %). And increased again to 65 cases in the 151-180d group (9.79 %). The proportion remained relatively constant at 9 % in the 181-210d group (9.19 %) and 211-240d group (9.64 %). The interval between injury and visiting our hospital was ≤ 72 h in 554 cases. CONCLUSIONS: Special attention should be given to the demographic characteristics of fractures in infants under 1 year of age, and appropriate outreach should be implemented. For example, health education should be provided to aid in the prevention especially for frequently occurring locomotion injuries, and prompt access to specialist medical care should be recommended for skull fractures, which are prone to delayed treatment. In addition, multidisciplinary collaboration should be implemented in trauma care, while also promoting the establishment of trauma centers in specialist children's hospitals with a stronger capacity to treat pediatric trauma, and a regional system for pediatric trauma treatment.

TIPE1 suppresses invasion and migration through down-regulating Wnt/ß-catenin pathway in gastric cancer.

Epithelial-mesenchymal transition (EMT) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE1 is a newly identified member of the TIPE (TNFAIP8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE1 in well-differentiated gastric cancer cell line (AGS) inhibited these processes. Mechanistically, we found that TIPE1-medicated Wnt/ß-catenin signalling was one of the critical signal transduction pathways that link TIPE1 to EMT inhibition. Importantly, TIPE1 dramatically restrained the expression and activities of MMP2 and MMP9 which are demonstrated to promote tumour progression and are implicated in EMT. Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE1 in progression and metastasis of gastric cancer and suggest that TIPE1 may be an innovative diagnostic and therapeutic target of gastric cancer.

Muscle texture features on preoperative MRI for diagnosis and assessment of severity of congenital muscular torticollis.

OBJECTIVES: To develop an objective method based on texture analysis on MRI for diagnosis of congenital muscular torticollis (CMT). MATERIAL AND METHODS: The T1- and T2-weighted imaging, Q-dixon, and T1-mapping MRI data of 38 children with CMT were retrospectively analyzed. The region of interest (ROI) was manually drawn at the level of the largest cross-sectional area of the SCM on the affected side. MaZda software was used to obtain the texture features of the T2WI sequences of the ROI in healthy and affected SCM. A radiomics diagnostic model based on muscle texture features was constructed using logistic regression analysis. Fatty infiltration grade was calculated by hematoxylin and eosin staining, and fibrosis ratio by Masson staining. Correlation between the MRI parameters and pathological indicators was analyzed. RESULTS: There was positive correlation between fatty infiltration grade and mean value, standard deviation, and maximum value of the Q-dixon sequence of the affected SCM (correlation coefficients, 0.65, 0.59, and 0.58, respectively, P < 0.05).Three muscle texture features-S(2,2)SumAverg, S(3,3)SumVarnc, and T2WI extreme difference-were selected to construct the diagnostic model. The model showed significant diagnostic value for CMT (P < 0.05). The area under the curve of the multivariate conditional logistic regression model was 0.828 (95% confidence interval 0.735-0.922); the sensitivity was 0.684 and the specificity 0.868. CONCLUSION: The radiomics diagnostic model constructed using T2WI muscle texture features and MRI signal values appears to have good diagnostic efficiency. Q-dixon sequence can reflect the fatty infiltration grade of CMT.

Influence of bFGF on in vitro expansion and chondrogenic construction of articular cartilage-derived progenitor cells.

Background: Articular cartilage-derived progenitor cells (ACPCs) possess the properties of both chondrocytes and bone marrow mesenchymal stem cells (BMSCs). However, the number of ACPCs in articular cartilage is low, and an effective culture system is needed for their expansion. Basic fibroblast growth factor (bFGF) promotes the expansion of chondrocytes and BMSCs, as well as the chondrogenic differentiation of BMSCs. Therefore, the aim of this study was to clarify whether bFGF could be used for in vitro expansion of ACPCs and whether bFGF promoted chondrogenic construction of ACPCs. Methods: We applied the fibronectin adhesion method to sort mice ACPCs and compared the proliferative, osteogenic, and chondrogenic abilities of ACPCs by adding various concentration of bFGF (0, 2, and 5 ng/mL) to the cell culture medium. Then used the best system to construct cartilage with ACPCs in vitro and in vivo. Results: The results indicated that bFGF promoted ACPCs proliferation, inhibited osteogenesis, and promoted chondrogenesis, and that a cell culture system containing 2 ng/mL bFGF was optimal for these effects. ACPCs constructed cartilage using the filtered culture system presented homogeneous cartilaginous histological structure in vitro and in vivo. Conclusions: By applying this cell culture system, homogenous cartilage tissue was constructed in vitro and in vivo by chondrogenic induction, which provides a stable cell expansion culture method for the application of ACPCs in cartilage repair.

Identification of Key Genes and Pathways in Osteoarthritis via Bioinformatic Tools: An Updated Analysis.

OBJECTIVE: Osteoarthritis (OA) is a severe and common degenerative disease; however, the exact pathology of OA is undefined. Our study is designed to investigate the underlying molecular mechanism of OA with bioinformatic tools. DESIGN: Three updated GEO datasets: GSE55235, GSE55457, and GSE82107 were selected for data analyzing. R software was utilized to screen and confirm the candidate differentially expressed genes in the development of OA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway were performed to identify the enriched GO terms and signaling pathways. Protein and protein interaction (PPI) models were built to observe the connected relationship among each potential protein. RESULTS: A total of 113 upregulated genes and 161 downregulated genes were found by integrating 3 datasets. GO enrichment indicated that cell differentiation, cellular response to starvation, and negative regulation of phosphorylation were important biological processes. KEGG enrichment indicated that FoxO, IL-17 signaling pathways, and osteoclast differentiation mainly participated in the progression of OA. Combining the molecular function and PPI results, ubiquitylation was identified as a pivotal bioactive reaction involved in OA. CONCLUSION: Our study provided updated candidate genes and pathways of OA, which may benefit further research and treatment for OA.

Calcaneal skeletal traction versus elastic intramedullary nailing of displaced tibial shaft fractures in children.

BACKGROUND: The objective of this study was to compare the outcomes and complications of patients who underwent either the calcaneal skeletal traction (CST) or the elastic intramedullary nails (EIN) procedure. METHODS: We retrospectively reviewed data of patients who underwent EIN or CST surgery for tibia shaft fracture at our center from 2013 to 2018. The patient demographics, fracture characteristics, radiographic information, length of hospital stay, and medical expenses were recorded. All patients were clinically followed-up until they started to walk or for at least 6 months. The treatment outcomes and postoperative complications of the two procedures were compared. RESULTS: Overall, 186 patients who underwent EIN and CST were included in the study. The EIN patients had more low-energy mechanism of injury. In radiographic evaluation, significant differences were observed in distributions of fracture classification and location. Moreover, associated fibula fractures were higher in the EIN group than in the CST group. The CST procedure had faster surgical time, cast duration and lower expenses, and longer hospitalization time. Although they required more clinical visits, patients in the EIN group began exercising and endured weight-bearing earlier than those in the CST group. The average time for bone healing was 68.5 days in the EIN group, and 69.6 days in the CST group. However, the CST provided slight better results of coronal correction than EIN. Moreover, CST patients had less malalignment (> 5°) in complications. None had delay union, nonunion, and shortening over 10 mm at final assessment. CONCLUSIONS: Both EIN and CST patients showed similar treatment outcomes. Hence, not only the characteristics of the patient and fracture, but also the individual's situation and expectation should be considered when choosing the best approach.

Comparison of the Wiltse Approach and Percutaneous Pedicle Screw Fixation Under O-arm Navigation for the Treatment of Thoracolumbar Fractures.

OBJECTIVES: The aim of this study was to evaluate the clinical outcomes of the Wiltse approach and percutaneous pedicle screw placement under O-arm navigation for the treatment of thoracolumbar fracture. METHODS: We enrolled a total of 54 patients with neurologically intact thoracolumbar fracture who received minimally invasive treatments between October 2014 and October 2018 in this retrospective study. Among these, 28 patients (22 males and six females, with a mean age of 48.6 ± 9.6 years) were treated with pedicle screw fixation through the Wiltse approach (WPSF), and another 26 (15 males and 11 females, with a mean age of 45.7 ± 10.6 years) received percutaneous pedicle screw fixation under O-arm navigation (OPSF). Statistical methods were used to perform a detailed comparison of clinical outcomes, radiologic findings, and complications between the two groups obtained preoperatively, postoperatively, and at last follow-up. RESULTS: All patients underwent surgery successfully and finished a follow-up of more than 12 months. No serious complications, such as infection, blood vessel injury, or spinal cord or nerve root injury occurred. Visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, local Cobb angle (LCA), vertebral wedge angle (VWA), and R value were notably improved after surgery, though there was no clear discrepancy between the groups at each time point (P > 0.05). During the follow-up period, no patients developed neurological impairment or implant-related complications, and no patients underwent revision surgery. The WPSF group had a significantly shorter operation time than the OPSF group (68.1 ± 9.8 vs 76.1 ± 9.0 minutes, P = 0.005). Moreover, the WPSF group showed less cost of surgery than the WPSF group (48142.1 ± 1430.1 vs 59035.4 ± 1152.7 CNY, P < 0.001). There were no significant differences between the two groups in terms of the intraoperative bleeding, length of incision, or postoperative hospitalization time (P > 0.05). The accuracy of pedicle screw placement was 95.2% (160/168) in the WPSF group and 96.8% (151/156) in the OPSF group, with no significant difference between the groups (P = 0.432). CONCLUSION: Both WPSF and OPSF were safe and effective for the treatment of thoracolumbar fracture. Although the two groups showed favorable clinical and radiologic outcomes through to final follow-up, we recommended the minimally invasive WPSF given its shorter operation time and lower cost of surgery.

Bortezomib Rescues Ovariectomy-Induced Bone Loss via SMURF-Mediated Ubiquitination Pathway.

A balance between bone formation by osteoblasts and bone resorption by osteoclasts is necessary to maintain bone health and homeostasis. As a cancer of plasma cells, multiple myeloma (MM) is accompanied with rapid bone loss and fragility fracture. Bortezomib has been used as a first-line for treating MM for decades. Recently, the potential protection of bortezomib on osteoporosis (OP) is reported; however, the specific mechanism involving bortezomib-mediated antiosteoporotic effect is undetermined. In the present study, we assessed the effects of in vitro bortezomib treatment on osteogenesis and osteoclastogenesis and the protective effect on bone loss in ovariectomized (OVX) mice. Our results indicated that bortezomib treatment increased osteogenic differentiation of MC3T3-E1 cells as evidenced by increased levels of matrix mineralization and osteoblast-specific markers. In bortezomib-treated bone marrow monocytes (BMMs), osteoclast differentiation was suppressed, substantiated by downregulated tartrate-resistant acid phosphatase- (TRAP-) positive multinucleated cells, areas of actin rings, pit formation, and osteoclast-specific genes. Mechanistically, bortezomib exerted a protective effect against OP through the Smad ubiquitination regulatory factor- (SMURF-) mediated ubiquitination pathway. Furthermore, in vivo intraperitoneal injection of bortezomib attenuated the bone microarchitecture in OVX mice. Accordingly, our findings corroborated that bortezomib might have future applications in the treatment of postmenopausal OP.

TIPE2 acts as a negative regulator linking NOD2 and inflammatory responses in myocardial ischemia/reperfusion injury.

UNLABELLED: Although recent studies have highlighted the importance of innate pattern-recognition receptors (PRRs) in the pathogenesis of cardiovascular diseases by mediating inflammatory responses, their molecular mechanisms of PRRs in cardiovascular diseases are still largely unknown. The present study was designed to explore the contribution of NOD2, an intracellular PRR, to the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. We found that NOD2 was upregulated in ischemic myocardium and NOD2 deficiency ameliorated cardiac injury in myocardial I/R mice accompanied by the decreased levels of pro-inflammatory mediators and cardiac inflammatory cell infiltration. We further found that TIPE2, a recently identified immune regulator, was negatively mediated by NOD2. In vitro, we demonstrated that TIPE2 inhibited NOD2-induced activation of MAPK and NF-κB signaling pathways, thereby reducing the production of pro-inflammatory cytokines in macrophages. Finally, in vivo gene silencing of TIPE2 by lentiviral gene delivery counteracted the reduced inflammation and myocardial injury in NOD2-deficient ischemic mice. Collectively, this study for the first time demonstrates that TIPE2 serves as a negative regulator of immunity, at least in part, by NOD2-mediated inflammatory responses in I/R-induced myocardial injury. A better understanding of NOD2-TIPE2 signaling pathways will provide unexpected opportunities for developing new therapies for ischemic cardiovascular disease. KEY MESSAGE: NOD2 deficiency ameliorates myocardial ischemia reperfusion injury. NOD2 deficiency reduces the inflammatory response after myocardial I/R. TIPE2 inhibits NOD2-induced activation of MAPK and NF-κB signaling pathways. TIPE2 silencing counteracts the reduced inflammation and myocardial injury in NOD2(-/-) ischemic mice. TIPE2 acts as a negative regulator linking NOD2 and inflammatory responses.

Vascular endothelial growth factor affects dendritic cell activity in hypertensive disorders of pregnancy.

Vascular endothelial growth factor (VEGF) activity is involved in the growth and stability of the placenta, and its signaling has been implicated in the development of pregnancy­induced hypertension (PIH). The present study sought to evaluate VEGF levels and dendritic cell (DC) profiles in patients with PIH, and to investigate the effects of VEGF expression on DC phenotypes. The present study assessed 162 patients, 112 of whom were diagnosed with PIH. Serum VEGF was measured by ELISA, while myeloid DC (mDC; (Lin1­HLA­DR+CD11c+) and plasmacytoid DC (pDC; Lin1­HLA­DR+CD123+) counts were determined using flow cytometry. In order to determine the effect of VEGF treatment on DC phenotypes, immature DCs (iDCs) were separated from monocytes by culturing in the presence of cytokines (GM­CSF, IL­4), and then pretreated with VEGF or lipopolysaccharide (LPS). The phenotype of dendritic cells (CD14, CD80, CD83, or CD86) was determined by flow cytometry. The levels of VEGF in the serum of patients with PIH were significantly lower than those in control subjects (P<0.05). The percentage of pDCs found in the serum of patients with preeclampsia was significantly lower than that in the other groups. The percentage of mDCs in the serum of patients with preeclampsia and eclampsia was significantly higher than that in the control and hypertensive disorder groups (P<0.05). The percentage of mDCs was significantly negatively correlated with the levels of VEGF in the preeclamptic and eclamptic patients (r=­0.34 and r=­0.42, respectively; P<0.05). Detected levels of CD80, CD83 and CD86 in DCs treated with VEGF were significant lower than those in DCs treated with LPS alone (P<0.05). In conclusion, abnormal expression of VEGF and an altered dendritic cell profile may be involved in the development of PIH.

Dendritic cells derived from preeclampsia patients influence Th1/Th17 cell differentiation in vitro.

Immune regulation plays important but as-yet-unclear roles in the development of preeclampsia. This study explored potential contributions to immune regulation by dendritic cells (DCs) derived from peripheral blood of preeclampsia patients on the differentiation of Th1 and Th17 cells. Pregnant women with preeclampsia (n = 73) and healthy pregnant women (n = 80) were included in the study. Peripheral blood samples were collected from each participant, and DCs were derived from peripheral blood mononuclear cells in vitro. The phenotypes of DCs, identified by CD14, CD80, CD83, and CD86 expression, were detected by flow cytometry, and secretion of interleukin-23 (IL-23) into the culture medium by DCs was measured by ELISA. CD4 + T cells were separated by the magnetic beads and subjected to flow cytometry to determine their ability to differentiate to Th1 or Th17 cells. Compared with DCs derived from healthy pregnant women, DCs derived from preeclampsia patients expressed higher levels of CD83, CD80, and CD86 (P < 0.05). Additionally, secretion of IL-23 was higher in DCs derived from the preeclampsia group than from the control group (P < 0.001). DCs derived from preeclampsia patients also had a stronger ability to promote the differentiation of CD4 + T cells into Th1/Th17 cells when cultured with different cytokines (P < 0.01). Thus, altered phenotypes and functions of DCs may promote the abnormal balance of Th1 and Th17 in the development of preeclampsia.

[Effect of dendritic cells on the differentiation of Th1/Th17 in peripheral blood from preeclampsia patients].

OBJECTIVE: To observe the effect of dendritic cells (DCs) derived from peripheral blood monouclear cells (PBMCs) on the differentiation of Th1 and Th17 in normal pregnancy women and preeclampsia patients. METHODS: PBMCs were obtained from 32 preeclampsia patients and 20 normal pregnancy controls, respectively. Then DCs were sorted from peripheral blood monocytes cultured in the presence of cytokines (GM-CSF, IL-4) and LPS for 8 d. The phenotypes of DCs (CD14, CD80, CD83, CD86) were detected by flow cytometry (FCM). The content of IL-23 in the supernatant was detected by ELISA. CD4(+);T lymphocytes were separated using the magnetic BD IMag Cell Separation System according to the manufacturer's instructions. Purified CD4(+);T lymphocytes were clutured with mature DCs derived from normal pregnancy women (N-DC) and IL-2, or with mature DCs derived from preeclampsia patients (P-DC) and IL-2, or with N-DC and IL-1ß, IL-6, or with P-DC and IL-1ß, IL-6. At 6 days after culture, CD4(+);IFN-γ(+);T(Th1) and CD4(+);IL-17(+);T(Th17) subsets were determined by FCM. RESULTS: Compared with N-DC, P-DC expressed the higher levels of CD83, CD80, CD86 and manifestated the stronger ability of promoting the differentiation of CD4(+);T into Th1/Th17 when cultured with different cytokines (P<0.01). CONCLUSION: The changes in phenotype and function of DCs might be related to immune imbalance and be an important reason for preeclampsia.

[Changes in the subsets of dendritic cells and T cells in peripheral blood of patients with preeclampsia].

OBJECTIVE: To investigate the immunoregulation in pathogenesis of pregnancy induced hypertension (PIH) by observing the changes in the subsets of dendritic cells (DC) and T cells in the peripheral blood of patients with preeclampsia. METHODS: The study included 32 preeclampsia patients, 20 normal pregnancy subjects and 20 non-pregnant healthy controls. We harvested their peripheral blood cells and counted the percentages of myeloid DC (mDC) and plasmacytoid DC (pDC) in whole blood cells, and the numbers of CD4(+); IFN-γ(+);T (Th1), CD4(+); IL-4(+);T (Th2) and CD4(+); IL-17(+);T (Th17) subsets in peripheral blood mononuclear cells by flow cytometry, and worked out the ratio of Th1 to Th2. RESULTS: The percentage of mDC (0.33±0.12)% and the ratio of mDC/pDC (2.96±1.65) in preeclampsia patients were significantly higher than those in normal pregnancy subjects (P<0.05). The percentage of pDC (0.16±0.13)% was lower than that in normal pregnancy subjects (0.21±0.12)% (P<0.05). The percentages of IFN-γ, IL-4 and IL-17 in preeclampsia patients were (18.67±1.96)%, (1.88±0.51)% and (1.36±0.59)%, respectively, all with statistically significant difference from those of normal late pregnancy (P<0.01). In preeclampsia patients, mDC/pDC ratio was significantly positively correlated with Th1/Th2 (r=0.637, P<0.01) and the percentage of Th17 cells was negatively correlated with pDC cells and positively correlated with mDC/pDC (r=-0.670, 0.772, respectively; P<0.01). CONCLUSION: Preeclampsia patients suffered the changes in dendritic cell subsets and abnormal expressions of Th1, Th2 and Th17, which might be an important reason for immune imbalance in preeclampsia patients.

NOX2 deficiency ameliorates cerebral injury through reduction of complexin II-mediated glutamate excitotoxicity in experimental stroke.

Although NADPH oxidase (NOX)-mediated oxidative stress is considered one of the major mechanisms triggering the pathogenic actions of ischemic stroke and very recent studies have indicated that NADPH oxidase is a major source of reactive oxygen species (ROS) production controlling glutamate release, how neuronal NADPH oxidase activation is coupled to glutamate release is not well understood. Therefore, in this study, we used an in vivo transient middle cerebral artery occlusion model and in vitro primary cell cultures to test whether complexins, the regulators of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes necessary for vesicle fusion, are associated with NOX2-derived ROS and contribute to glutamate-mediated excitotoxicity in ischemic stroke. In this study, we first identified the upregulation of complexin II in the ischemic brain and evaluated its potential role in ischemic stroke showing that gene silencing of complexin II ameliorated cerebral injury as evidenced by reduced infarction volume, neurological deficit, and neuron necrosis accompanied by decreased glutamate levels, consistent with the results from NOX2(-/-) mice with ischemic stroke. We further demonstrated that complexin II expression was mediated by NOX2 in primary cultured neurons subjected to oxygen-glucose deprivation (OGD) and contributed to OGD-induced glutamate release and neuron necrosis via SNARE signaling. Taken together, these findings for the first time provide evidence that complexin II is a central target molecule that links NADPH oxidase-derived ROS to glutamate-mediated neuronal excitotoxicity in ischemic stroke.