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Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.
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Objective To study the effect of scopolamine butylbromide injection combined with tamsulosin oral auxiliary extracorporeal shock wave lithotripsy(ESWL) in the treatment of urinary calculi,and to investigate its effect on serum inflammatory factors.Methods From January 2016 to May 2017,96 patients with urinary calculi in the People's Hospital of Lanxi were selected and randomly divided into control group(n =42) and observation group(n =54).The control group received scopolamine butylbromide assisted ESWL treatment,the observation group treated with tamsulosin on the basis of the control group.The VAS score,clinical efficacy,adverse reactions and serum C reactive protein(CRP),tumor necrosis factor alpha(TNF-alpha) and other inflammatory factors were compared between the two groups.Results Before treatment,no statistically significant difference in VAS score was found between the two groups (t =0.274,P ＞ 0.05).After treatment,the VAS score of the observation group was (2.21 ± 0.28) points,which was significantly lower than that of the control group[(4.75 ± 0.63) points] (t =7.935,P ＜ 0.05).The stone clearance rate in the observation group was 96.30％ (52/54),which was significantly higher than that in the control group[71.43％ (30/42)] (x2 =6.712,P ＜ 0.05).The time of disappearance of pain in the observation group was (10.86 ± 1.54) d,which was significantly lower than that in the control group [(7.02 ± 1.25) d] (t =7.468,P ＜0.05).The lithecbole time of the observation group was (9.01 ± 1.53) h,which was significantly shorter than that of the control group[(13.25 ± 2.21) h] (t =8.035,P ＜ 0.05).Before treatment,there were no statistically significant differences in serum CRP and TNF-levels between the two groups (t =0.152,0.185,all P ＞0.05).After treatment,the serum level of CRP in the observation group was (11.64 ± 1.75) mg/L,which was significantly lower than that in the control group [(18.94 ± 2.03) mg/L] (t =7.008,P ＜ 0.05).After treatment,the serum TNF-level in the observation group was (13.95 ± 2.01)mg/L,which was significantly lower than that in the control group[(20.76 ±3.18) mg/L] (t =7.008,P ＜0.05).The incidence rate of adverse reactions of the observation group was 5.56％,which was significantly lower than 26.19％ of the control group (x2 =9.572,P ＜ 0.05).Conclusion Urinary calculi underwent intravenous infusion of scopolamine butylbromide combined with tamsulosin oral adjuvant ESWL therapy,can effectively reduce the pain of patients,reduce the serum levels of inflammatory cytokines,improve the stone clearance rate,and with less complications,it is worthy of clinical popularization and application.
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Objective To evaluate the clinical value of the the hypopharynx and chest esophageal carcinoma. Methods 20 patients surgical treatment data of the hypopharynx and chest esophageal carcinoma from January 2013 to July 2019 were reviewed. Results The simultaneous hypopharynx and esophageal carcinoma 11 cases. The heterochronic hypopharynx and chest esophageal carcinoma 9 cases. 20 cases are all squamous cell carcinoma. The synchronus operation included total pharyn-golaryngo esophagectomy, gastric tube interposition pharyngo gastric anastomic, neck and mediastinal lymph nodes dissection, tracheostomy. The heterochronic operation included the first stage radical hypopharygealectomy, the second stage radical esoph-agealectomy. Postoperative complications included in hospital death in one, double pneumonia in 3 and anastomosis stricture in one case. Pharynx gastric fistula in 2. Swallowing function were all recovered. Conclusion Although laryngo pharyngo esoph-agectomy and pharyngogastric anastomoses for the hypopharynx and chest esophageal carcinoma is a simple and acceptable pro-cedure, the quality of life is not satisfactory. And although colon interpasation for esophageal replacement is complicated the quality of life is the best.
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Objective@#To evaluate the clinical value of the the hypopharynx and chest esophageal carcinoma.@*Methods@#20 patients surgical treatment data of the hypopharynx and chest esophageal carcinoma from January 2013 to July 2019 were reviewed.@*Results@#The simultaneous hypopharynx and esophageal carcinoma 11 cases. The heterochronic hypopharynx and chest esophageal carcinoma 9 cases. 20 cases are all squamous cell carcinoma. The synchronus operation included total pharyngolaryngo esophagectomy, gastric tube interposition pharyngo gastric anastomic, neck and mediastinal lymph nodes dissection, tracheostomy. The heterochronic operation included the first stage radical hypopharygealectomy, the second stage radical esophagealectomy. Postoperative complications included in hospital death in one, double pneumonia in 3 and anastomosis stricture in one case. Pharynx gastric fistula in 2. Swallowing function were all recovered.@*Conclusion@#Although laryngo pharyngo esophagectomy and pharyngogastric anastomoses for the hypopharynx and chest esophageal carcinoma is a simple and acceptable procedure, the quality of life is not satisfactory. And although colon interpasation for esophageal replacement is complicated the quality of life is the best.
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BACKGROUND:Studies have shown that lung cancer stem cels can be isolated from the lung cancer cel lines, But there are few reports on in vitro isolation, culture and identification of lung cancer stem cels in patients with lung squamous carcinoma. OBJECTIVE:To establish the feasible methods of harvesting lung cancer stem cels from fresh lung cancer tissues in patients with lung squamous carcinoma, and to investigate the alterations in cel number and function during primary culture. METHODS: Side population cels were isolated by colagenase digestion, Ficol density gradient centrifugation and Hoechst 33342 efflux properties. The isolated cels were isolated and cultured in conditioned medium. Flow cytometry method was used to detect lung cancer stem cels based on the cel surface markers CD133 and CD44, and the positive rates of CD133+, CD44+ and CD133+/CD44+ were recorded. The single cel clones assay, flat colony formation assay and the cel sphere formation assay were used to identify the stem-like characteristics of lung cancer stem cels between the first and fourth generations. RESULTS AND CONCLUSION:The positive rates of CD133+, CD44+ and CD133+/CD44+ cels at the fourth generation were increased significantly, and the positive rates of CD133+ and CD133+/CD44+ cels at passage 4 were significantly higher than those at the first generation. The abilities of single cel clone formation, the flat colony formation and the cel sphere formation in the fourth-generation cels were greatly enhanced compared with the first-generation cels. Experimental findings showed that stem cel-like lung cancer cels were obtained from fresh lung cancer tissue in patients with lung squamous carcinoma, which stably and rapidly amplified in vitro, laying the foundation for the further study of the heterogeneity and drug resistance of lung cancer stem cels.
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BACKGROUND:Studies have shown that lung cancer stem cel s can be isolated from lung cancer cel lines. But there are few reports about in vitro isolation, culture and identification of lung cancer stem cel s in patients with lung squamous carcinoma. OBJECTIVE:To explore the feasible methods of harvesting lung cancer stem cel s from fresh lung cancer tissue in patients with lung squamous carcinoma. METHODS:Side population cel s were isolated by col agenase digestion, Ficol density gradient centrifugation and Hoechst 33342 solution. The isolated cel s were suspended in conditioned medium for isolated culture. Flow cytometry method was used to detect lung cancer stem cel s based on the cel surface markers CD133 and CD44, and the positive rates of CD133+, CD44+and CD133+/CD44+cel s were recorded. RESULTS AND CONCLUSION:Cel s adhered at 0.5 hour after incubation;typical cel colony was formed at 4 days of culture;cel s showed paving stone-shape at 7 days in a total number of 10 8. The positive rates of CD133+, CD44+and CD133+/CD44+cel s at passage 4 were increased significantly. These findings indicate that stem cel-like lung cancer cel s were obtained from fresh lung cancer tissue in patients with lung squamous carcinoma, which were stably and rapidly amplified in vitro, laying the foundation for the further study on the heterogeneity and resistance of lung cancer stem cel s in the future.
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BACKGROUND:Lung cancers are highly heterogeneous and resistant to available therapeutic agents, with a five year survival rate of less than 15%. It has been difficult to determine the basis of lung cancer heterogeneity and drug resistance. Cancer stem cellmodel has attracted a significant amount of attention in recent years as a viable explanation for the heterogeneity, drug resistance, dormancy and recurrence and metastasis of various tumors. OBJECTIVE:To summarize the current understanding of lung cancer stem cells, including their histological types and tumor growth areas, and to discusses the prognosis of lung cancer and its relationship with lung cancer stem cells, in an effort to eradicate these cells to combat lung cancer. METHODS:In order to search relevant articles about the lung cancer stem celland its relationship with lung cancer from PubMed and Sciencedirect databases (from 1990 to 2014), a computer-based search was performed, using the key words of“lung cancer, cancer stem cell, lung cancer stem cell, lung cancer occur, tumor heterogeneity, drug resistance, gene mutation, signal pathways”in English. After eliminating literatures which were irrelevant to research purpose or containing a similar content, 48 articles were chosen for further analysis. RESULTS AND CONCLUSION:The cancer stem cellmodel has gained considerable support recently in context of lung cancers and stem-like cells that are associated with aggressive cancer behavior, metastatic progression, resistance to therapy and relapse. Since lung cancer stem cells are thought to consist of a heterogeneous population depending on the histology and site of tumors, and multiple signaling pathways might have to be targeted to effectively eliminate lung cancer stem cells for therapeutic benefit. It can be imagined that the multidisciplinary efforts currently under way to characterize and target stem-like cells in lung cancer wil reap significant therapeutic benefits in the future.
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Prosthesis for femoral head surface replacement was designed. Between January 2002 and December 2005,28 patients underwent femoral head surface replacement in Anyang People's Hospital. The diameter of the normal femoral head was determined by CT,and the prosthesis was selected according to the measured value ±1 mm. With the muscle gap approach,the center of the femoral head was determined according to the measured distance between the femoral head center and the culminated point of the round ligament fossa based on the mark of the culminated point of the round ligament pit. Additionally,the diameter of the femoral head was measured again to ensure the precise match of the prosthesis and acetabulum. X-ray films at 24-48 months show no loosening or dislocation of the prosthesis,which was well matched with acetabulum. Furthermore,the joint space did not remarkably change. The mean score was 63 before operation and 91.5 after operation respectively according to Harris sore. The successful rate is 92.86% (excellent in 23cases,good in 3,and improved in 2). The results show that femoral head surface replacement is an effective method for young patients with avascular necrosis of the femoral head at the stage of ARCO HI.