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Efficacy of intelligent diagnosis with a dynamic uncertain causality graph model for rare disorders ofsex development

Dongping Ning, Zhan Zhang, Kun Qiu, Lin Lu, Qin Zhang, Yan Zhu, Renzhi Wang

《医学前沿（英文）》 2020年 第14卷 第4期   页码 498-505 doi: 10.1007/s11684-020-0791-8

摘要： Disorders of sex development (DSD) are a group of rare complex clinical syndromes with multiple etiologies. Distinguishing the various causes of DSD is quite difficult in clinical practice, even for senior general physicians because of the similar and atypical clinical manifestations of these conditions. In addition, DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD. Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses. On the basis of the principles and algorithms of dynamic uncertain causality graph (DUCG), a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence. “Chaining” inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information. Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis. The model had an accuracy of 94.1%, which was significantly higher than that of interns and third-year residents. In conclusion, the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSD-related diseases.

关键词： disorders of sex development (DSD)     intelligent diagnosis     dynamic uncertain causality graph    

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Progress in studies of sex determination mechanisms and sex control techniques in

Qian ZHOU,Songlin CHEN

《农业科学与工程前沿（英文）》 2016年 第3卷 第2期   页码 113-123 doi: 10.15302/J-FASE-2016093

摘要： The (half-smooth tongue sole) is a marine flatfish of great commercial value for fisheries and aquaculture in China. It has a female heterogametic sex determination system (ZW/ZZ) and environmental factors can induce sex-reversal of females to phenotypic males, suggesting that it is a promising model for the study of sex determination mechanisms. Additionally, females grow much faster than males and it is feasible to improve the aquaculture production through sex control techniques. This paper reviews the progress in research on sex determination mechanisms research in our laboratory. We have completed whole-genome sequencing and revealed the genome organization and sex chromosome evolution of . A putative male determining gene was identified and DNA methylation was verified as having a crucial role in the sex reversal process. Genetic maps and sex-specific biomarkers have been used in a marker-assisted selection breeding program and for differentiation of the fish sex. Development and improvement of sex control technologies, including artificial gynogenesis and production of breeding fry with high proportion of females, is also reviewed. These research advances have provided insight into the regulation of sex determination and enabled efficient sex management in artificial culturing of .

关键词： Cynoglossus semilaevis     sex determination     sex control technique    

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Genomic regions associated with the sex-linked inhibitor of dermal melanin in Silkie chicken

Ming TIAN,Rui HAO,Suyun FANG,Yanqiang WANG,Xiaorong GU,Chungang FENG,Xiaoxiang HU,Ning LI

《农业科学与工程前沿（英文）》 2014年 第1卷 第3期   页码 242-249 doi: 10.15302/J-FASE-2014018

摘要： A unique characteristic of the Silkie chicken is its fibromelanosis phenotype. The dermal layer of its skin, its connective tissue and shank dermis are hyperpigmented. This dermal hyperpigmentation phenotype is controlled by the sex-linked inhibitor of dermal melanin gene ( ) and the dominant fibromelanosis allele. This study attempted to confirm the genomic region associated with . By genotyping, was found to be closely linked to the region between GGA_rs16127903 and GGA_rs14685542 (8406919 bp) on chromosome Z, which contains ten functional genes. The expression of these genes was characterized in the embryo and 4 days after hatching and it was concluded that , encoding methylthioadenosinephosphorylase, would be the most likely candidate gene. Finally, target DNA capture and sequence analysis was performed, but no specific SNP(s) was found in the targeted region of the Silkie genome. Further work is necessary to identify the causal mutation located on chromosome Z.

关键词： sex-linked inhibitor of dermal melanin (Id)     Silkie     chromosome Z    

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Therapeutic effects of thalidomide in hematologic disorders: a review

null

《医学前沿（英文）》 2013年 第7卷 第3期   页码 290-300 doi: 10.1007/s11684-013-0277-z

摘要：

The extensive autoimmune, anti-inflammatory, and anticancer applications of thalidomide have inspired a growing number of studies and clinical trials. As an inexpensive agent with relatively low toxicity, thalidomide is regarded as a promising therapeutic candidate, especially for malignant diseases. We review its therapeutic effects in hematology, including those on multiple myeloma, Waldenstroem macroglobulinemia, lymphoma, mantle-cell lymphoma, myelodysplastic syndrome, hereditary hemorrhagic telangiectasia, and graft-versus-host disease. Most studies have shown satisfactory results, although several have reported the opposite. Aside from optimal outcomes, the toxicities and adverse effects of thalidomide should also be examined. The current work includes a discussion of the mechanisms through which the novel biological effects of thalidomide occur, although more studies should be devoted to this aspect. With appropriate safeguards, thalidomide may benefit patients suffering from a broad variety of disorders, particularly refractory and resistant diseases.

关键词： thalidomide     multiple myeloma     lymphoma    

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Isolation and characterization of a bacterial strain that efficiently degrades sex steroid hormones

JI Shulan, LIU Zhipeng, REN Haiyan, LIU Zhipei

《环境科学与工程前沿（英文）》 2007年 第1卷 第3期   页码 325-328 doi: 10.1007/s11783-007-0055-8

摘要： A bacterial strain, ZY3, growing on sex steroid hormones as the sole source of carbon and energy was isolated from the sewage treatment plant of a prophylactic steroids factory. ZY3 degrades the 3-methoxy-17-hydroxy-1,3,5(10),8(9)--4-estren (MHE). This strain was preliminarily identified as sp. ZY3 according to its morphology and its 16S rRNA gene sequence. During the experimental period (72 h), the optimum temperature, pH and 3-MHE concentration for the degradation of hydride by the strain ZY3 were 35vH, 10 and 10 mg/L, respectively. The degradation rate of the sex steroid hormones increased to 87% and 85% after the addition of maltose and peptone, respectively.

关键词： maltose     optimum temperature     prophylactic     3-methoxy-17-hydroxy-1     3     5     addition    

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Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

《医学前沿（英文）》 2019年 第13卷 第2期   页码 138-151 doi: 10.1007/s11684-018-0627-y

摘要： As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., “subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://clinicaltrials.gov) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

关键词： mesenchymal stem cell     clinical transition     immune disorders    

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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function

《医学前沿（英文）》 doi: 10.1007/s11684-023-1006-x

摘要： Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants in TMEM141 (c.270G>A, p.Trp90*), DDHD2 (c.411+767_c.1249-327del), and LHFPL5 (c.250delC, p.Leu84*) were identified. A Tmem141p.Trp90*/p.Trp90* mouse model was generated. Behavioral studies showed impairments in learning ability and motor coordination. Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells. Transmission electron microscopy showed abnormal mitochondrial morphology. Furthermore, studies on a human in vitro neuronal model (SH-SY5Y cells) with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function, possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model. Conclusively, panoramic variation analysis revealed that multilocus genomic variations of TMEM141, DDHD2, and LHFPL5 together caused variable phenotypes in patient. Notably, the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder     autosomal recessive intellectual disability     consanguinity     spastic paraplegia     hearing loss     TMEM141    

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Physiological functions and clinical implications of the N-end rule pathway

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 258-270 doi: 10.1007/s11684-016-0458-7

摘要：

The N-end rule pathway is a unique branch of the ubiquitin-proteasome system in which the determination of a protein’s half-life is dependent on its N-terminal residue. The N-terminal residue serves as the degradation signal of a protein and thus called N-degron. N-degron can be recognized and modifed by several steps of post-translational modifications, such as oxidation, deamination, arginylation or acetylation, it then polyubiquitinated by the N-recognin for degradation. The molecular basis of the N-end rule pathway has been elucidated and its physiological functions have been revealed in the past 30 years. This pathway is involved in several biological aspects, including transcription, differentiation, chromosomal segregation, genome stability, apoptosis, mitochondrial quality control, cardiovascular development, neurogenesis, carcinogenesis, and spermatogenesis. Disturbance of this pathway often causes the failure of these processes, resulting in some human diseases. This review summarized the physiological functions of the N-end rule pathway, introduced the related biological processes and diseases, with an emphasis on the inner link between this pathway and certain symptoms.

关键词： N-end rule pathway     Ate1     cardiovascular development     neurogenesis     spermatogenesis     neurodegenerative disorders     Johanson–Blizzard syndrome    

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Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

《医学前沿（英文）》 2019年 第13卷 第4期   页码 471-481 doi: 10.1007/s11684-019-0686-8

摘要： Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus . Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

关键词： antibiotics     tacrolimus     glucose disorders     microbiome    

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Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic

XU Leping, JI Juying, DUAN Yiyang, SHI Hui, ZHANG Bin, SHAO Yaqin, SUN Jian

《医学前沿（英文）》 2007年 第1卷 第3期   页码 316-319 doi: 10.1007/s11684-007-0061-z

摘要： The aim of this study was to observe the changes in glucose metabolism after antipsychotic (APS) therapy, to note the influencing factors, as well as to discuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin (HbAc) levels. One hundred and fifty-two patients with schizophrenia, whose fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) in the oral glucose tolerance test (2HPG) were normal, were grouped according to the HbAc levels, one normal and the other abnormal, and were randomly enrolled into risperidone, clozapine and chlorpromazine treatment for six weeks. The FPG and 2hPG were measured at the baseline and at the end of the study. In the group with abnormal HbA1c and clozapine therapy, 2HPG was higher after the study [(9.5±1.8) mmol/L] than that before the study [(7.2±1.4) mmol/L] and the difference was statistically significant (〈0.01). FPG had no statistically significant difference before and after the study in any group (〉0.05). HbAc levels and drugs contributing to 2HPG at the end of study had statistical cross-action (〈0.01). In the abnormal HbAc group, 2HPG after the study was higher in the clozapine treatment group [(9.5±1.8) mmol/L] than in the risperidone treatment group [(7.4±1.7) mmol/L] and the chlorpromazine treatment group [(7.3±1.6) mmol/L]. The differences were statistically significant (〈0.01). In the normal HbAc group there was no statistically significant difference before and after the study in any group (〉0.05). 2HPG before [(7.1±1.6) mmol/L] and after the study [(8.1±1.9) mmol/L] was higher in the abnormal HbAc group than in the normal HbAc group [(6.2±1.4) mmol/L (6.5±1.4) mmol/L] with the difference being statistically significant (〈0.01 〈0.001). As compared with normal HbAc group, the relative risk (RR) of glucose metabolism disease occurrence was 4.7 in the abnormal HbAc group with the difference being statistically significant (〈0.001). Patients with abnormal HbAc are more likely to have a higher risk of having glucose metabolism disorders after APS treatment.

关键词： significant difference     occurrence     hemoglobin     risperidone treatment     abnormal    

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人工智能算法在精神疾病中的应用简述 Review

刘光迪, 李雨辰, 张伟, 章乐

《工程（英文）》 2020年 第6卷 第4期   页码 462-467 doi: 10.1016/j.eng.2019.06.008

摘要：

为了研究精神疾病的病因和发病机制，各国开展了大量脑研究计划。尽管精神疾病是脑科学研究的重要部分，但精神疾病的诊断仍然依靠医生的主观经验，而非疾病的病理生理学指标。因此，为了开发有效的治疗方式和干预措施，我们迫切需要对重大精神疾病的病因和致病机制有一个清晰的认识。当前，人工智能（AI）技术在精神疾病的应用研究发展迅速，但缺少对其进行系统化的总结和展望。因此，本研究简要回顾了用于研究精神疾病的三种主要观测技术，即磁共振成像（MRI）、脑电图（EEG）和基于体势学的诊断（与模式识别相关的AI算法）。最后，我们讨论了AI应用面临的挑战、机遇和未来的发展方向。

关键词： 人工智能     精神疾病     神经影像学    

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微针递送系统用于皮肤疾病的局部增效治疗——应用、挑战和前景 Review

龚明宇, 陈杨燕, 胡婉姗, 陆超, 潘昕, 彭婷婷, 陈天祥, 吴传斌

《工程（英文）》 2023年 第30卷 第11期   页码 170-189 doi: 10.1016/j.eng.2023.05.009

摘要：

微针能直接将治疗药物递送到皮肤病变部位，从而提高治疗效果和降低副作用，因而可用于皮肤疾病的局部治疗。微针可以递送不同种类的治疗药物（如小分子药物、大分子药物、纳米药物、活细胞、细菌和外泌体）来治疗各种皮肤疾病，包括浅表肿瘤、伤口、皮肤感染、炎症性皮肤病和异常皮肤外观。微针的治疗效率可以通过以下几种策略来提高：①整合不同治疗方法的优点来进行联合治疗；②对微针的结构进行仿生设计或者赋予微针内外源响应性释药性能来提高药物的经皮递送效率。一些研究提出将无药物微针发展为一种有前景的机械治疗方法，即通过微针的机械刺激产生机械转导信号来促进伤口愈合、疤痕消退和毛发再生。虽然微针具有诸多优点，但微针的实际应用还存在工业化生产和临床评价难等问题，进而制约微针的临床转化。本文总结了微针在皮肤疾病中的各种应用、新出现的挑战和发展前景，为微针的临床转化思路提供借鉴。

关键词： 微针     经皮给药系统     皮肤疾病     治疗     挑战     前景    

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肠道菌群是调节神经系统功能紊乱的潜在靶点 Review

武万强, 孔庆敏, 田培郡, 翟齐啸, 王刚, 刘小鸣, 赵建新, 张灏, Yuan Kun Lee, 陈卫

《工程（英文）》 2020年 第6卷 第4期   页码 415-423 doi: 10.1016/j.eng.2019.07.026

摘要：

众所周知，肠道菌群在调节宿主生理功能方面具有重要作用，如调节免疫和代谢平衡。近年来，越来越多证据表明肠道菌群能够通过肠-脑轴调节中枢神经系统功能，这为研究肠道和大脑间的相互作用关系开辟了一条新路径。本文首先介绍了肠道菌群与大脑相互作用的肠–脑轴分子机制，以及肠道菌群失调引发的神经系统功能紊乱；然后介绍了调节肠道菌群失衡是干预神经系统功能紊乱的潜在策略，如益生菌、益生元、合生元以及饮食等干预措施。目前关于肠道菌群–肠–脑轴方面的研究尚处在起步阶段，但继续深入阐明肠道菌群调节神经系统功能的分子机制不仅能揭示神经系统功能紊乱的新型病理机制，而且能够为神经系统功能紊乱提供潜在的诊断标志物和干预策略。

关键词： 肠道菌群     肠-脑轴     神经系统功能紊乱     干预策略    

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中药生物活性成分对糖脂代谢紊乱疾病的治疗作用和机制 Review

张莹, 鞠佳明, 焦磊, 杨宝峰

《工程（英文）》 2023年 第29卷 第10期   页码 73-82 doi: 10.1016/j.eng.2023.03.004

摘要：

胆固醇和葡萄糖稳态异常在心血管疾病、脑血管疾病、中枢神经系统疾病和癌症等多种疾病的发生发展中起着至关重要的作用。 越来越多的研究表明，体内脂肪堆积过多与2型糖尿病或胰岛素抵抗有关，高胆固醇和高血糖将加重上述疾病的发展进程。因此，稳定患者的血脂和血糖水平是改善心脑血管和中枢神经系统疾病患者症状的主要策略。中药（CHM）在中国已有两千多年的历史，建立了独特的中医理论，积累了丰富的临床经验。此外，中药在国内外广泛应用于心脑血管疾病的治疗和预防，具有防治高脂血症、糖尿病和高血压等疾病的优势。然而，中药在西方国家的使用仍然相当有限，部分原因是对其多种复杂成分的了解不完整，药理机制不确定。本文就中药生物活性成分及其制剂治疗高脂血症和高血糖症的作用、分子机制和临床研究进展进行综述和讨论。

关键词： Chinese herbal medicines     Hyperlipidemia     Hyperglycemia     Cardiovascular and cerebrovascular diseases    

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Metabonomic study of the biochemical profiles of heterozygous myostatin knockout swine

Jianxiang XU,Dengke PAN,Jie ZHAO,Jianwu WANG,Xiaohong HE,Yuehui MA,Ning LI

《农业科学与工程前沿（英文）》 2015年 第2卷 第1期   页码 90-99 doi: 10.15302/J-FASE-2015045

摘要： Myostatin is a transforming growth factor-β family member that normally acts to limit skeletal muscle growth. Myostatin gene ( ) knockout (KO) mice show possible effects for the prevention or treatment of metabolic disorders such as obesity and type 2 diabetes. We applied chromatography and mass spectrometry based metabonomics to assess system-wide metabolic response of heterozygous KO ( ) swine. Most of the metabolic data for swine were similar to the data for wild type (WT) control swine. There were, however, metabolic changes related to fatty acid metabolism, glucose utilization, lipid metabolism, as well as BCAA catabolism caused by monoallelic depletion.The statistical analyses suggested that: (1) most metabolic changes were not significant in swine compared to WT swine; (2) only a few metabolic properties were significantly different between KO and WT swine, especially for lipid metabolism. Significantly, these minor changes were most evident in female KO swine and suggested differences in gender sensitivity to myostatin.

关键词： myostatin     transforming growth factor-β family     skeletal muscle     metabolic disorders     chromatography     mass spectrometry     metabonomics    

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标题 作者 时间 类型 操作

Efficacy of intelligent diagnosis with a dynamic uncertain causality graph model for rare disorders ofsex development

Dongping Ning, Zhan Zhang, Kun Qiu, Lin Lu, Qin Zhang, Yan Zhu, Renzhi Wang

期刊论文

Progress in studies of sex determination mechanisms and sex control techniques in

Qian ZHOU,Songlin CHEN

期刊论文

Genomic regions associated with the sex-linked inhibitor of dermal melanin in Silkie chicken

Ming TIAN,Rui HAO,Suyun FANG,Yanqiang WANG,Xiaorong GU,Chungang FENG,Xiaoxiang HU,Ning LI

期刊论文

Therapeutic effects of thalidomide in hematologic disorders: a review

null

期刊论文

Isolation and characterization of a bacterial strain that efficiently degrades sex steroid hormones

JI Shulan, LIU Zhipeng, REN Haiyan, LIU Zhipei

期刊论文

Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

期刊论文

Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function

期刊论文

Physiological functions and clinical implications of the N-end rule pathway

null

期刊论文

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

期刊论文

Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic

XU Leping, JI Juying, DUAN Yiyang, SHI Hui, ZHANG Bin, SHAO Yaqin, SUN Jian

期刊论文

人工智能算法在精神疾病中的应用简述

刘光迪, 李雨辰, 张伟, 章乐

期刊论文

微针递送系统用于皮肤疾病的局部增效治疗——应用、挑战和前景

龚明宇, 陈杨燕, 胡婉姗, 陆超, 潘昕, 彭婷婷, 陈天祥, 吴传斌

期刊论文

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