Autism spectrum disorder(ASD)is a pervasive neurodevelopmental disorder with onset in infancy or early childhood.Mendelian randomization(MR)is a statistical method used to infer causal relationships between exposures and outcomes.This article summarizes MR studies related to ASD.Existing research supports a causal relationship between maternal inflammatory bowel disease in children with ASD,parental education levels,screen time exposure,obesity,insomnia,serum transferrin,decreased blood selenium,abnormal signals in brain functional MRI,interleukin-6,phosphodiesterase 2A,mitogen-activated protein kinase kinase 3,mitochondrial ribosomal protein L33,serotonin,and ASD.However,it does not support a causal relationship between parental rheumatoid arthritis,systemic lupus erythematosus,neonatal jaundice in children with ASD,cytomegalovirus infection,asthma,oral ulcers,vitamin D levels,and ASD.This article reviews the etiological factors related to ASD and MR studies,aiming to explore and deepen the understanding of the pathophysiology of ASD.It provides strong statistical support for the prevention,diagnosis,and treatment of ASD,and offers new methods and strategies for the etiological analysis of complex traits.

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.
Female ; Pregnancy ; Humans ; Adult ; Blood Component Transfusion ; Plasma ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Mutation ; Purpura, Thrombocytopenic, Idiopathic ; ADAMTS13 Protein/therapeutic use*

OBJECTIVE: To compare the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and post-remission chemotherapy (PR-CT) in treatment of intermediate risk acute myeloid leukemia with negative for FLT3-ITD, NPM1 or biallelic CEBPA mutation. METHODS: The clinical data of patients with intermediate risk NPM1/non-CEBPA/FLT3-ITD AML from October 2009 to May 2016 were retrospectively analyzed. RESULTS: The overall survival rate of the patients treated with PR-CT, MSD-HSCT or hi-HSCT was 63.7%, 71.7%, 75.5%, respectively (P＜0.05); the disease-free survival (DFS) rate was 52.8%, 67.1%, 71.3% respectively (P＜0.001); the cumulative incidence of relapse was 24.7%, 16.9%, 14.4% respectively (P＜0.05); the non-relapse mortality was 26.2%, 17.3%, 14.4% reapectively (P＞0.05). The analysis of transplantation, related adverse events showed that II-IV grade of aGVHD in the MSD-HSCT group and hi-HSCT group was 48.9% and 45.6% respectively (P＞0.05); the extensive cGVHD event was 21.6% and 8.8% (P＜0.05) respectively. CONCLUSION The efficiency of hi-HSCT and MSD-HSCT is superior to that of PR-CT for treatment of patients with intermediate risk NPM1/non-CEBPA/FLT3-ITD AML after CR1, there is no statistically significant difference in the efficiency of consolidatorg treatment and the transplantation-related mortality between hi-HSCT and MSD-HSCT.
CCAAT-Enhancer-Binding Proteins ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Nuclear Proteins ; Prognosis ; Retrospective Studies ; fms-Like Tyrosine Kinase 3

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.

Objective To study the mechanism of right ventricular pulmonary artery coupling by fitting the pressure volume loop of pulmonary arterial hypertension patients and calculating the related parameters.Methods During January of 2015 to December of 2015,34 patients with pulmonary hypertension and 5 patients with patent oval foramen(PFO)were admitted in Wuhan Asian Heart Hospital,. Inclusion criteria for the pulmonary hypertension group were in accordance with the newest European guidelines for pulmonary hypertension . All of the patients were conducted invasive pressure catheter intervention and MRI. All the pressure data were digitized by GetData software and the CMR tools3D was used to derive right ventricular volume data, fitting the pressure volume loop and calculate the Pmax, Ees, Ea and other related parameters. 5 patients with PFO and 34 patients with pulmonary hypertension were divided into three groupswhich included:the control group (i.e. the patients with PFO), patients with pulmonary artery mean pressure less than 50 mmHg as group A and pulmonary artery mean pressure greater than or equal to 50 mmHg as group B. The pressure volume loop of the three groups were compared and the related parameters were calculated.Results The right ventricular Pmax were(53.05±12.87) mmHg, (134.73±26.38) mmHg, (207.88±65.67) mmHg, in the control group, group A and B respectively. There were significant differences when compared among the 3 groups. There was no statistical difference in Ees between the control group and group A(P>0.05). The Ees of group B was significantly higher than the control group[(1.53±0.97)vs.(0.60±0.28),P<0.05]. The Ea of group B was higher than the control[(1.34±0.74) vs.(0.39±0.15),P<0.05]. The overall ratio of Ees/Ea was lower in group B as compared to the control group [(1.12±0.47)vs.(1.62±0.51),P<0.05].Conclusions In the early stage of pulmonary hypertension, right ventricular contractility preserves and can overcome the slightly elevated afterload .The right ventricle and pulmonary artery coupled with good work. With the increasing mean pulmonary artery,the afterload of right ventricular increases and right ventricular contractility needs further increase to fight against the elevated afterload. The elevation of contractility cannot overcome the change of afterload, resulting in the off paired of mechanical efflciency, causing the right ventricle- pulmonary artery coupling decreases.

OBJECTIVETo study the effect of Erigeron Breviscapus (EB) at different concentrations and different intervention time points on the mRNA and protein expression of OPG/RANKL/RANK in MG63 osteoblast-like cells and RAW264. 7 pre-osteoclast cells cultured in vitro, thus exploring roles EB played in bone rebuilding and its mechanisms.

METHODSMG63 osteoblast-like cells and RAW264.7 pre-osteoclast cells were cultured in vitro. The 3rd passage cells were divided into the control group and different experimental groups. Total RNA and protein were respectively isolated from cells treated with different concentrations of EB (0, 0.001, 0.01, 0.1, and 1.0 mg/mL) for 48 h. Meanwhile, the protein was extracted from 0 and 1 mg/mL EB groups at 12, 24, and 48 h respectively. Expression of OPG mRNA and RANKL mRNA in MG63 osteoblast-like cells, and expression of RANK mRNA in RAW264.7 pre-osteoclast cells were detected by semi-quantitative RT-PCR. Expression of OPG protein and RANKL protein in MG63 osteoblast-like cells, and expression of RANK protein in RAW264. 7 pre-osteoclast cells were detected by Western blot.

RESULTSAlong with increased EB concentration, expression of OPG mRNA and protein in MG63 osteoblast-like cells was gradually lowered (P < 0.05) after 48-h intervention of EB, the expression of RANKL mRNA and protein in MG63 osteoblast-like gradually increased (P < 0.05); the expression of RANK mRNA in RAW264.7 pre-osteoclast cells increased (P < 0.05). But the expression of RANK mRNA was slightly lower in the 0.1 mg/mL EB group than in the 0.01 mg/mL EB group, and the expression of RANK protein in RAW264.7 pre-osteoclast cells gradually increased (P < 0.05). After treatment with 1 mg/mL EB for 12, 24, 48 h, the expression of OPG protein in MG63 osteoblast-like cells gradually decreased as time went by (P < 0.05), and the expression of RANKL protein in MG63 osteoblast-like and RANK protein in RAW264.7 pre-osteoclast cells gradually increased (P < 0.05). The expression of RANKL protein in RAW264.7 pre-osteoclast cells increased as time went by (P < 0.05).

CONCLUSIONEB could inhibit the expression of OPG in osteoblasts in a dose- and time-dependent manner, promote the expression of RANKL in osteoblasts and the secretion of RANK in pre-osteoclast, indicating EB might play roles in promoting bone resorption.

Animals ; Cell Differentiation ; Cell Line ; Drugs, Chinese Herbal ; pharmacology ; Erigeron ; Humans ; Mice ; Osteoblasts ; drug effects ; metabolism ; Osteoclasts ; drug effects ; metabolism ; Osteoprotegerin ; metabolism ; RANK Ligand ; metabolism ; RNA, Messenger ; genetics ; Receptor Activator of Nuclear Factor-kappa B ; metabolism

OBJECTIVETo evaluate the effect of comprehensive control strategy of schistosomiasis with emphasis on infection source control in Anhui province.

METHODSForty endemic villages in Guichi district, Chizhou city, Anhui province were selected as national pilot villages in the years from 2006 to 2008, and another 10 provincial pilot villages were respectively selected from 10 highly endemic villages in 7 cities in 2007. The comprehensive infection source control measures, including "replace cattle with machines", "raise livestock in pens", "improve the sanitary toilets", "supply safe water " and so on were carried out among the above pilot villages. At the end of 2008, 13 national pilot villages and 6 provincial pilot villages were selected to investigate the popularity of schistosomiasis, and the effect of the comprehensive control strategy in those villages were compared.

RESULTSAfter implementing the comprehensive control strategy, the infectious rate of schistosomiasis in national pilot villages decreased from 4.57% (487/10 659) to 1.76% (147/8370), with the reduction rate at 61.49%, whose difference showed statistical significance (χ(2) = 115.16, P < 0.01); and the density of infected snails decreased from 0.0067/0.1 m(2) to 0.0008/0.1 m(2), the infectious rate of snails decreased from 0.28% to 0.04%, whose reduction rates were 88.06% and 85.71% respectively. While as to the provincial pilot villages, the infectious rate of schistosomiasis decreased from 1.27% (54/4254) to 0.21% (14/6592), with the reduction rate at 83.46%, whose difference showed statistical significance (χ(2) = 94.57, P < 0.01); and the density of infected snails decreased from 0.0025/0.1 m(2) to 0.0003/0.1 m(2), the infection rate of snails decreased from 0.13% to 0.05%, whose reduction rates were 88.00% and 61.54% respectively.

CONCLUSIONThe comprehensive control strategy with emphasis on infection source control implemented in marshland and lake regions can effectively control the transmission of schistosomiasis.

Animals ; China ; epidemiology ; Disease Reservoirs ; parasitology ; Humans ; Infection Control ; methods ; Livestock ; Pilot Projects ; Rural Health ; Schistosomiasis ; epidemiology ; parasitology ; prevention & control ; Snails ; parasitology

Objective To study the effect and molecular mechanism of epigallocaechin-3-gallate (EGCG) on epithelial-mesenchymal transition (EMT) in vitro induced by human recombinant TGF-β1 protein in squamous cell carcinoma of the head and neck.Methods EMT morphological changes of Tu686 cells were observed after sequential treatment of 5 ng/ml TGF-β1 and 20 μmol/L EGCG.Tu686 cells were collected after the treatment of 5 ng/ml TGF-β1 for 24 h and EGCG with different concentrations (0,10,20,30 μmol/L) for another 24 h or 20 μmol/L EGCG treatment for different time phase(6,12,24 h).Then RT-PCR and Western-blot were applied to detect mRNA and protien expression level of epithelial cell marker E-cadherin,mesenchymal cell marker Vimentin and Smad7,an inhibit molecule of TGF-β1 mediated pathway in Tu686 cells.Results TGF-β1 successfully induced characterized EMT morphological and molecular changes in Tu686 cells,in which expression of E-cadherin decreased,Vimentin increased and Smad7 declined.However,EGCG could reverse the TGF-β1 mediated process of EMT by downregulating the expression of Vimentin and upregulating the expression of E-cadherin and Smad7.Conclusion EGCG significantly inhibits TGF-β1-mediated EMT inTu686 cell lines of SCCHN,which maybe associated with the upregulated-expression of Smad7,an inhibitor in TGF-β1 signaling pathway.

OBJECTIVETo evaluate the expression of EphA2 protein in tissue specimens and cell lines of laryngeal squamous cell carcinoma (LSCC), and to further study the correlation of EphA2 protein expression with clinicopathological characteristics and prognosis in LSCC.

METHODSWestern blot was applied to assess the EphA2 protein expression in LSCC cell line Hep-2 cells and the head and neck immortalized epithelial cell line NP-69 cells. Immunohistochemical staining was performed on paraffin sections of 88 cases of LSCC specimens and 16 cases of adjcent normal tissue samples to investigate the EphA2 protein expression, and to futher elucidate its correlation with clinicopathological characteristics.

RESULTSCompared with the NP-69 cells, EphA2 expression in LSCC cell line Hep-2 cells was upregulated. The positive rates of EphA2 expression in LSCC and adjcent normal tissues samples were 80.7% and 43.8%, respectively, with a significant difference between the two groups (P < 0.001). EphA2 overexpresion was closely correlated with clinical stage (I + II/III + IV, P = 0.005), metastasis (P = 0.025) and recurrence (P = 0.021) in LSCC. Furthermore, patients with EphA2 overexpression had poorer tumor-free survival and 5-year overall survival compared with that in patients with low EphA2 expression (33.3% vs. 63.2%, P = 0.003; 46.7% vs. 81.6%, P = 0.002). EphA2 expression combined with clinical stage provided a better predictive value in prognosis. Univariate and multivariate Cox regression analysis revealed that EphA2 expression is an independent prognostic factor for patients with LSCC (P = 0.019).

CONCLUSIONSThe results of this study demonstrate that EphA2 protein expression is significantly increased in LSCC tissues and cell lines, and EphA2 protein overexpression is associated with tumor recurrence, metastasis and poorer prognosis in LSCC patients. These results suggest that EphA2 may play a critical role in the initiation and progression of LSCC, implicating EphA2 as a valuable marker for the prediction of recurrence, metastasis and prognosis in LSCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Cell Line ; Cell Line, Tumor ; Disease-Free Survival ; Epithelial Cells ; metabolism ; Female ; Follow-Up Studies ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neck ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, EphA2 ; metabolism ; Survival Rate

OBJECTIVE: To establish a new animal model of grading skeletal muscle contusions that could be controllable and repetitive. METHODS: The rats' gastrocnemius was injured by a new weight-dropping device designed. The force acting on gastrocnemius with a comparatively constant duration and inducing elastic deformation of the gastrocnemius was expressed with velocity (v) and deformation (DF). Instant velocity was changed to create gastrocnemius contusions. Pathological changes of gastrocnemius were graded by the gross and histological examinations of 39 rats. RESULTS: At low level of impact (v: 2 m/s, DF: 5.5 mm), mild injuries were detected in epimysium and superficial layer of gastrocnemius. At moderate level of impact (v: 2.5 m/s, DF: 6.5 mm), the injuries were observed in epimysium and whole gastrocnemius. At high level of impact (v: 3 m/s, DF: 7.5 mm), severe injuries were seen deeper to soleus with more extensive skeletal muscle damage. CONCLUSION Grading of skeletal muscle blunt force contusion is created by parameter of velocity and muscle deformation. The model could be used for further research on skeletal muscle contusions.
Animals ; Contusions/classification* ; Disease Models, Animal ; Forensic Pathology ; Male ; Muscle, Skeletal/injuries* ; Rats ; Rats, Sprague-Dawley ; Wounds, Nonpenetrating