Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase defici...Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.展开更多
Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscle...Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically btamiR-365-3 p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.Results: Firstly, we found that bta-miR-365-3 p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of btamiR-365-3 p significantly reduced the expression levels of cyclin D1(CCND1), cyclin dependent kinase 2(CDK2) and proliferating cell nuclear antigen(PCNA) but stimulated the expression levels of muscle differentiation markers, i.e.,MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3 p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3 p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3 p resulted in the opposite consequences. Finally, we identified that activin A receptor type I(ACVR1) could be a direct target of bta-miR-365-3 p. It was demonstrated that bta-miR-365-3 p can bind to the 3'UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays.Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level.Conclusion: Collectively, these data suggested that bta-miR-365-3 p represses proliferation but promotes differentiation of bovine myoblasts through several biological mechanisms involving downregulation of ACVR1.展开更多
Primary hepatic neuroendocrine tumor(PHNET) is an extremely rare liver tumor. Patients often have no clinical symptoms or have only non-specific symptoms, such as abdominal pain and abdominal mass. The clinical manife...Primary hepatic neuroendocrine tumor(PHNET) is an extremely rare liver tumor. Patients often have no clinical symptoms or have only non-specific symptoms, such as abdominal pain and abdominal mass. The clinical manifestations, disease development, treatment methods, and treatment outcomes of PHNET vary greatly among cases. Here we report a case of PHNET with a confirmed 26-year survival before surgery. The patient was a 56-year-old female. A large right hepatic mass was detected when the patient was 30 years old. The tumor could not be removed during exploratory laparotomy, and constriction of the right hepatic artery and biopsy were conducted. Pathological results indicated a diagnosis of benign tumor, but a confirmed diagnosis was not reached. Twenty-six years after the patient had been living with the tumor, she sought treatment again because of tumor progression. After systematic evaluation of the resectability, the tumor was resected. Based on the examination results of the gastrointestinal tract and lungs, intraoperative examination results, pathological findings, and long-term follow-up results, the diagnosis of PHNET was confirmed. This case represents the longest reported survival time for a PHNET patient before removal of the tumor.展开更多
Introduction: The curative management of primary hyperparathyroidism is based on surgery. We report the case of a patient presenting with elevated parathormone despite surgical removal of the parathyroid adenoma. Obse...Introduction: The curative management of primary hyperparathyroidism is based on surgery. We report the case of a patient presenting with elevated parathormone despite surgical removal of the parathyroid adenoma. Observation: A 48-year-old patient presented for more than 6 months with significant weight loss, polyuria with polydipsia and impaired renal function. The assessment carried out revealed hypercalcaemia at 155 mg/L with hypophastetaemia at 24 mg/L and an elevation of the parathyroid hormone at 218.9 pg/ml. Cervical ultrasound showed a mass at the expense of the lower left parathyroid gland. These results made it possible to conclude primary hyperparathyroidism by parathyroid adenoma which was supported surgically. The postoperative biological assessment revealed a normocalcemia at 85 mg/L associated with an increase in parathormone (PTH) at 271.9 pg/ml. In front of the normalization of calcemia in the subsequent controls and the amendment of all the signs, monitoring was carried out. 9 months after surgery, spontaneous normalization of PTH was observed at 38.4 pg/ml with normal serum calcium at 90 mg/l. Discussion: Primary hyperparathyroidism can be revealed by other manifestations. Post-operative follow-up is generally simple with normalization of PTH and serum calcium. However, there may persist an elevation of PTH with normal self-limiting calcemia.展开更多
Although it offers a direct route to access synthetically valuableα-chiral primary amines,asymmetric transfer hydrogenation of NH imines has been rarely studied,due in large part to the inaccessibility and instabilit...Although it offers a direct route to access synthetically valuableα-chiral primary amines,asymmetric transfer hydrogenation of NH imines has been rarely studied,due in large part to the inaccessibility and instability of NH imines.Herein,we report a Rh-catalyzed asymmetric transfer hydrogenation of a kind of novel and stable NH imines which are prepared via condensation of easily available sulfonylated 2'-aminoacetophenones with NH3 in methanol.With this method,enantioenriched chiral 2-(1-aminoalkyl)anilines,which are privileged pharmacore groups,have been synthesized with good functional group compatibility,and with up to 99%ee.A gram-scale reaction using 0.2 mol%of catalyst has been successfully performed to highlight the practicality.Furthermore,the products can be derivatized into enantiopure bioactive molecules as well as chiral tridentate ligands for metal catalysis.展开更多
目的通过分析原发性恶性骨肿瘤患者在瘤段切除后经不同重建方式治疗的随访资料,探讨手术方案的选择对临床疗效的影响。方法以2016年7月1日至2022年7月1日东部战区总医院单中心收治的四肢原发性恶性骨肿瘤患者为研究对象,根据瘤段切除后...目的通过分析原发性恶性骨肿瘤患者在瘤段切除后经不同重建方式治疗的随访资料,探讨手术方案的选择对临床疗效的影响。方法以2016年7月1日至2022年7月1日东部战区总医院单中心收治的四肢原发性恶性骨肿瘤患者为研究对象,根据瘤段切除后重建方式分为肿瘤型假体置换组和生物重建组。回顾患者的临床随访资料,对比2组患者至随访截止时间的复发率、转移率、生存率以及最终保肢率,并总结生物重建失败的影响因素。同时,采用美国肌肉骨骼肿瘤协会评分(MSTS)、多伦多保肢评分(TESS)评价并比较不同组间患者术后功能的恢复情况。结果共收集并筛选入组患者87例,其中男52例,女35例,年龄8~71岁,平均(38.3±21.2)岁。随访15~70个月,平均随访时间26.5个月。至随访截止时间,共存活67例,死亡20例,总生存率为77.01%;无瘤存活45例,无瘤生存率为51.72%。其中,假体置换组74例、生物重建组13例(瘤体骨灭活再植钢板重建2例、自体腓骨移植钢板重建11例)。生物重建组术后1年的MSTS评分及TESS评分均明显高于假体置换组(28.33±2.09 vs 24.16±4.51、85.62±6.71 vs 80.82±3.85,P<0.01)。假体置换组术后生存率达到了75.68%。而生物重建组患者术后生存率更达到了84.62%,且根据多因素Cox比例风险回归分析结果,不同的手术方式对无瘤生存(TFS)、总生存(OS)均无显著影响(P>0.05),复发和转移发生与否才是影响OS的预测因素(P=0.003和P=0.001)。而进一步的研究显示,两种不同手术方式的选择与患者的生存率(P=0.0843)、复发率(P=0.5206)、转移率(P=0.3217)无显著相关性。假体置换组与生物重建组的二次手术率(29.73%vs 38.46%)及最终保肢率(83.78%vs 84.62%)比较,差异均无统计学意义(P>0.05)。行瘤段切除后自体腓骨移植钢板重建的患者有11例,其中出现移植骨骨不连2例;愈合时间与年龄、术前肿瘤生长部位、术中截骨长度、取骨部位及植骨量均有相关性(P<0.05)。结论随着治疗理念和手术技术的不断进步,针对原发性恶性骨肿瘤瘤段切除后的骨缺损,采用术前精准测量和周密设计的生物重建手术,可以发挥其在关节稳定、肢体功能、保障疗效等各方面的优势,从而取得较假体置换手术更佳的治疗效果。展开更多
基金Supported by National Natural Science Foundation of China, No.81070281
文摘Aldo-keto reductase 1D1(AKR1D1) deficiency,a rare but life-threatening form of bile acid deficiency,has not been previously described in China.Here,we describe the first two primary 4-3-oxosteroid 5β-reductase deficiency patients in China's Mainland diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis.A high proportion of atypical 3-oxo-4-bile acids in the urine indicated a deficiency in 4-3-oxosteroid 5β-reductase.All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents.One patient exhibited compound heterozygous mutations:c.396C>A and c.722A>T,while the other was heterozygous for the mutation c.797G>A.Based on these mutations,a diagnosis of primary 4-3-oxosteroid 5β-reductase deficiency could be confirmed.With ursodeoxycholic acid treatment and fat-soluble vitamin supplements,liver function tests normalized rapidly,and the degree of hepatomegaly was markedly reduced in both patients.
基金supported by the National Natural Science Foundation of China (No.31772574)the Program of National Beef Cattle and Yak Industrial Technology System (CARS-37)the scholarship from the China Scholarship Council (CSC),China。
文摘Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically btamiR-365-3 p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.Results: Firstly, we found that bta-miR-365-3 p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of btamiR-365-3 p significantly reduced the expression levels of cyclin D1(CCND1), cyclin dependent kinase 2(CDK2) and proliferating cell nuclear antigen(PCNA) but stimulated the expression levels of muscle differentiation markers, i.e.,MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3 p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3 p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3 p resulted in the opposite consequences. Finally, we identified that activin A receptor type I(ACVR1) could be a direct target of bta-miR-365-3 p. It was demonstrated that bta-miR-365-3 p can bind to the 3'UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays.Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level.Conclusion: Collectively, these data suggested that bta-miR-365-3 p represses proliferation but promotes differentiation of bovine myoblasts through several biological mechanisms involving downregulation of ACVR1.
文摘Primary hepatic neuroendocrine tumor(PHNET) is an extremely rare liver tumor. Patients often have no clinical symptoms or have only non-specific symptoms, such as abdominal pain and abdominal mass. The clinical manifestations, disease development, treatment methods, and treatment outcomes of PHNET vary greatly among cases. Here we report a case of PHNET with a confirmed 26-year survival before surgery. The patient was a 56-year-old female. A large right hepatic mass was detected when the patient was 30 years old. The tumor could not be removed during exploratory laparotomy, and constriction of the right hepatic artery and biopsy were conducted. Pathological results indicated a diagnosis of benign tumor, but a confirmed diagnosis was not reached. Twenty-six years after the patient had been living with the tumor, she sought treatment again because of tumor progression. After systematic evaluation of the resectability, the tumor was resected. Based on the examination results of the gastrointestinal tract and lungs, intraoperative examination results, pathological findings, and long-term follow-up results, the diagnosis of PHNET was confirmed. This case represents the longest reported survival time for a PHNET patient before removal of the tumor.
文摘Introduction: The curative management of primary hyperparathyroidism is based on surgery. We report the case of a patient presenting with elevated parathormone despite surgical removal of the parathyroid adenoma. Observation: A 48-year-old patient presented for more than 6 months with significant weight loss, polyuria with polydipsia and impaired renal function. The assessment carried out revealed hypercalcaemia at 155 mg/L with hypophastetaemia at 24 mg/L and an elevation of the parathyroid hormone at 218.9 pg/ml. Cervical ultrasound showed a mass at the expense of the lower left parathyroid gland. These results made it possible to conclude primary hyperparathyroidism by parathyroid adenoma which was supported surgically. The postoperative biological assessment revealed a normocalcemia at 85 mg/L associated with an increase in parathormone (PTH) at 271.9 pg/ml. In front of the normalization of calcemia in the subsequent controls and the amendment of all the signs, monitoring was carried out. 9 months after surgery, spontaneous normalization of PTH was observed at 38.4 pg/ml with normal serum calcium at 90 mg/l. Discussion: Primary hyperparathyroidism can be revealed by other manifestations. Post-operative follow-up is generally simple with normalization of PTH and serum calcium. However, there may persist an elevation of PTH with normal self-limiting calcemia.
基金the National Natural Science Foundation of China(22071097,22271307,22378432)the Guangdong Basic and Applied Basic Research Foundation(2021B1515020062)the Shenzhen Science and Technologyy Program(JCYJ20220818100804010).
文摘Although it offers a direct route to access synthetically valuableα-chiral primary amines,asymmetric transfer hydrogenation of NH imines has been rarely studied,due in large part to the inaccessibility and instability of NH imines.Herein,we report a Rh-catalyzed asymmetric transfer hydrogenation of a kind of novel and stable NH imines which are prepared via condensation of easily available sulfonylated 2'-aminoacetophenones with NH3 in methanol.With this method,enantioenriched chiral 2-(1-aminoalkyl)anilines,which are privileged pharmacore groups,have been synthesized with good functional group compatibility,and with up to 99%ee.A gram-scale reaction using 0.2 mol%of catalyst has been successfully performed to highlight the practicality.Furthermore,the products can be derivatized into enantiopure bioactive molecules as well as chiral tridentate ligands for metal catalysis.
文摘目的通过分析原发性恶性骨肿瘤患者在瘤段切除后经不同重建方式治疗的随访资料,探讨手术方案的选择对临床疗效的影响。方法以2016年7月1日至2022年7月1日东部战区总医院单中心收治的四肢原发性恶性骨肿瘤患者为研究对象,根据瘤段切除后重建方式分为肿瘤型假体置换组和生物重建组。回顾患者的临床随访资料,对比2组患者至随访截止时间的复发率、转移率、生存率以及最终保肢率,并总结生物重建失败的影响因素。同时,采用美国肌肉骨骼肿瘤协会评分(MSTS)、多伦多保肢评分(TESS)评价并比较不同组间患者术后功能的恢复情况。结果共收集并筛选入组患者87例,其中男52例,女35例,年龄8~71岁,平均(38.3±21.2)岁。随访15~70个月,平均随访时间26.5个月。至随访截止时间,共存活67例,死亡20例,总生存率为77.01%;无瘤存活45例,无瘤生存率为51.72%。其中,假体置换组74例、生物重建组13例(瘤体骨灭活再植钢板重建2例、自体腓骨移植钢板重建11例)。生物重建组术后1年的MSTS评分及TESS评分均明显高于假体置换组(28.33±2.09 vs 24.16±4.51、85.62±6.71 vs 80.82±3.85,P<0.01)。假体置换组术后生存率达到了75.68%。而生物重建组患者术后生存率更达到了84.62%,且根据多因素Cox比例风险回归分析结果,不同的手术方式对无瘤生存(TFS)、总生存(OS)均无显著影响(P>0.05),复发和转移发生与否才是影响OS的预测因素(P=0.003和P=0.001)。而进一步的研究显示,两种不同手术方式的选择与患者的生存率(P=0.0843)、复发率(P=0.5206)、转移率(P=0.3217)无显著相关性。假体置换组与生物重建组的二次手术率(29.73%vs 38.46%)及最终保肢率(83.78%vs 84.62%)比较,差异均无统计学意义(P>0.05)。行瘤段切除后自体腓骨移植钢板重建的患者有11例,其中出现移植骨骨不连2例;愈合时间与年龄、术前肿瘤生长部位、术中截骨长度、取骨部位及植骨量均有相关性(P<0.05)。结论随着治疗理念和手术技术的不断进步,针对原发性恶性骨肿瘤瘤段切除后的骨缺损,采用术前精准测量和周密设计的生物重建手术,可以发挥其在关节稳定、肢体功能、保障疗效等各方面的优势,从而取得较假体置换手术更佳的治疗效果。
