神经外科重症监护病房住院医师规范化培训教育的思考

重症神经外科是神经外科住院医师规范化培训的难点和重点之一。通过对重庆医科大学附属第一医院神经外科重症监护病房的住院医师进行以急救技能培训、理论与实践相辅相成的多模态病例分析、神经影像学及电生理知识的拓展、手术操作及围手术期管理的专科知识培训、定期病例讨论等方式构成的系统性、规范化的培训,他们的临床思维更加地成熟,对神经外科重症监护病人管理方法的掌握时间明显地缩短,参与临床实践的主动性也较前明显地增加,对神经外科患者围手术期管理的方法有了更深刻的认识,有效地提升了神经外科重症监护室的带教成效。     

骨转换标志物PINP和β⁃CTX在帕金森病患者发生骨质疏松中的预测价值

目的：研究骨转换标志物Ⅰ型胶原氨基端前肽（procollagen type Ⅰ N-terminal propeptide,PINP）、Ⅰ型胶原羧基端前肽（β-cross-linked ctelopeptide of type I collagen,β-CTX）在帕金森病（Parkinson’s disease,PD）并发骨质疏松中的预测价值。方法：纳入PD患者105例,根据是否合并骨质疏松分为骨质疏松组和非骨质疏松组,对所有患者检测25（OH）D、甲状旁腺激素、骨钙素、β-CTX、PINP等骨代谢指标,分析各指标与骨质疏松发生之间的关系。结果：①骨质疏松组少动强直型比例、女性比例、PINP、骨钙素、β-CTX水平均高于非骨质疏松组,骨质疏松组25（OH）D水平低于非骨质疏松组,差异均具有统计学意义; ②相关分析结果显示PD患者骨质疏松发生与骨钙素（r=0.28,P=0.005）、β-CTX（r=0.36,P=0.001）、PINP（r=0.40,P＜0.001）均呈正相关,与25（OH）D（r=-0.30,P=0.002）、PINP/β-CTX（r=-0.56,P＜0.001）均呈负相关,差异具有统计学意义;③多因素二元Lo- gistic 回归分析显示,25（OH）D（OR=0.95,95%CI：0.84~0.98,P=0.041）、PINP/β-CTX（OR=0.90,95%CI：0.83~0.98,P=0.017）是 PD病合并骨质疏松的独立危险因素;④ROC曲线分析示25（OH）D联合PINP/β-CTX时ROC曲线下面积最大,AUC=0.82,灵敏性=0.80,特异性=0.84,P＜0.001。结论：血清25（OH）D水平及PINP/β-CTX比值与PD患者骨质疏松发生密切相关,在PD患者骨质疏松的发生中具有重要的预测价值,二者联合检测时诊断价值更高。     

血清Tg、TgAb对甲状腺癌根治术联合131I治疗后随访期间复发/转移的评估价值

目的 研究血清甲状腺球蛋白（Tg）、甲状腺球蛋白抗体（TgAb）对甲状腺癌根治术联合¹³¹I治疗后随访期间复发/转移的评估价值。方法 回顾性分析2018年6月—2020年6月中国贵航集团三〇二医院收治的106例分化型甲状腺癌患者的临床资料,患者均接受甲状腺癌根治术治疗,术后均采用¹³¹I进行清除残留的甲状腺组织（清甲）治疗。随访24个月,将患者分为复发转移组（21例）和未复发转移组（85例）。比较两组临床资料、¹³¹I治疗情况及血清促甲状腺激素（TSH）、Tg、TgAb。绘制受试者工作特征（ROC）曲线分析血清Tg、TgAb检测对甲状腺癌根治术联合¹³¹I治疗后复发/转移的预测价值。采取非条件一般Logistic回归模型进行多因素分析。结果 与未复发转移组比较,复发转移组原位肿瘤T₄分期、手术方式为腺叶切除或近全切、残余甲状腺质量≥1 g、手术至¹³¹I治疗时间> 3个月、24 h摄¹³¹I率≤ 20%患者的占比均较高（P <0.05）;复发转移组血清Tg和TgAb水平均较高（P <0.05）;ROC曲线分析结果显示：血清Tg预测甲状腺癌根治术联合¹³¹I治疗后复发或转移的最佳截断值为1.674 μg/L,AUC为0.803（95% CI：0.721,0.884）,敏感性为81.1%（95% CI：0.724,0.898）,特异性为63.8%（95% CI：0.585,0.691）;血清TgAb预测的最佳截断值为44.19 3 IU/mL,AUC为0.911（95% CI：0.859,0.963）,敏感性为89.2%（95% CI：0.813,0.971）,特异性为72.5%（95% CI：0.674,0.774）。非条件Logistic一般回归分析结果显示：原位肿瘤T₄分期［O^R=2.916（95% CI：1.325,6.417）］、腺叶切除或近全切［O^R=3.243（95% CI：2.174,4.838）］、残余甲状腺质量≥ 10 g［O^R=1.835（95% CI：1.514,2.224）］、手术至¹³¹I治疗时间> 3个月［O^R=1.962（95% CI：1.371,2.808）］、24 h摄¹³¹I率≤ 20%［O^R=2.638（95% CI：1.219,5.709）］、血清Tg ≥ 1.674 μg/L［O^R=2.503（95% CI：1.430,4.360）］、血清TgAb≥ 44.193 IU/mL［O^R=2.944（95% CI：2.016,4.299）］可能是甲状腺癌根治术联合¹³¹I治疗后复发或转移的危险因素（P <0.05）;风险因素预测模型预测甲状腺癌根治术联合¹³¹I治疗后复发/转移的ROC曲线下面积为0.961（95% CI：0.935,0.987）,标准误为0.010,临界值为73.162,敏感性为91.9%（95% CI：0.863,0.957）,特异性为88.2%（95% CI：0.845,0.922）。结论 甲状腺癌根治术联合¹³¹I治疗后出现复发/转移的患者血清Tg、TgAb水平明显升高,Tg、TgAb对预测复发/转移具有较好的价值,联合其他危险因素建立风险因素预测模型可进一步提高预测价值。     

Three-dimensional reconstruction of adult female mouse submandibular gland secretory structures

Computer-assisted reconstructions of adult female mouse submandibular gland have been used to positionally characterize within the three-dimensional structure likely intermediates in secretory cell replacement. The locations of striated granular duct cells and granular intercalated duct cells are consistent with a role as intermediates between intercalated duct cells and granular duct cells or acinar cells, respectively. Average volumes of the two putative intermediate cell types are also consistent with this role. The reconstructions suggest that, in addition to a "streaming" mechanism for secretory cell replacement, formation of new secretory structures composed of multiple acini and second-order intercalated ducts may also contribute to the cell replacement process.     

Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms

Osteopontin (OPN) plays a pivotal role in various immune responses and inflammatory diseases. OPN is expressed in various granulomatous diseases; however, the cellular and molecular role of OPN in these diseases is not well known. We analyzed the role of OPN in a beta-glucan-induced hepatic granuloma model. First, we found that neither OPN deficiency nor overexpression of OPN affected the number and the size of hepatic granulomas at day 7, indicating that OPN is not involved in the formation of hepatic granulomas at the early stages. Importantly, OPN did not influence the liver tissue damage as defined by alanine aminotransferase and aspartate aminotransferase levels at early stages. Second, OPN deficiency resulted in the reduction of IL-12 and IFN-gamma production at early stages. Third, at late stages, OPN deficiency resulted in a decrease in the number and size of hepatic granulomas, and a reduction of liver tissue injury. This was due to the reduction of the cellular recruitment including macrophages, CD4 T cells and dendritic cells into the liver, and the reduction of tumor necrosis factor (TNF)-alpha production in the liver. In contrast, overexpression of OPN resulted in the persistence of granuloma formation. These data suggest that OPN affects the persistence of hepatic granuloma formation. Our results indicate that OPN up-regulates the production of IL-12 and IFN-gamma within the granulomas at early stages, and OPN has an additional role in the regulation of cellular recruitment and TNF-alpha production at late stages that determine the severity of liver tissue injury.     

Diagnosis of Kala-Azar by Nested PCR Based on Amplification of the Leishmania Mini-Exon Gene

To diagnose visceral leishmaniasis (kala-azar), we have developed a nested PCR method based on amplification of the mini-exon gene, which is unique and tandomly repeated in the Leishmania genome. Nested PCR was sufficiently sensitive for the detection of DNA in an amount equivalent to a single Leishmania parasite or less. We examined the usefulness of this PCR method using bone marrow aspirates and buffy coat cells collected from kala-azar patients who had or had not received chemotherapy in northwest China. We obtained PCR positivity for all of the parasitologically positive bone marrow samples from the patients. Some ambiguities with the primary PCR results were eliminated by the subsequent nested PCR. The buffy coat samples from 7 of 12 patients with splenomegaly were positive by the nested PCR, although only 2 of them were positive for parasites by culture. However, buffy coat samples from nine children, whose splenomegaly has been reduced and clinically cured by antimony treatment, were all negative. Thus, this nested PCR method represents a new tool for the diagnosis of kala-azar with patient blood samples instead of bone marrow or spleen aspirates obtained by more invasive procedures.     

A homozygous MITF mutation leads to familial Waardenburg syndrome type 4

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in MITF in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in MITF and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.     

中国人群DXS102座位多态性鉴定及其应用

目的探讨中国人群中ＤＸＳ１０２座位的多态分布。方法应用ＰＣＲ扩增片段长度多态性（Ａｍｐ－ＦＬＰ）研究了无亲缘关系的２３４条Ｘ染色体。结果ＤＸＳ１０２座位等位片段有８个，核心单元ＡＣ二核苷酸重复数为１３～２１，频率分布在０．０１３～０．１５６之间，杂合度观察值和无偏估测值分别为０．８７和０．８０，多态信息含量（ＰＩＣ）０．８０，女性基因型数为２２个，男性基因型数为８个，该座位多态分布符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡定律。ＤＸＳ１０２座位在中国人群和欧洲人群的分布有明显的种族差异，在中国人群中发现了两个新的等位片段。应用ＤＸＳ１０２座位的短串联重复序列多态性对一接受基因治疗的血友病Ｂ家系进行分析和携带者筛查。结论ＤＸＳ１０２座位连锁分析有望成为一种有效的血友病Ｂ基因诊断的方法。     

Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage

The bone morphogenetic proteins (BMPs), TGFβ superfamily members, play diverse roles in embryogenesis, but how the BMPs exert their action is unclear and how different BMP receptors (BMPRs) contribute to this process is not known. Here we demonstrate that the two type I BMPRs, BMPR-IA and BMPR-IB, regulate distinct processes during chick limb development. BmpR-IB expression in the embryonic limb prefigures the future cartilage primordium, and its activity is necessary for the initial steps of chondrogenesis. During later chondrogenesis, BmpR-IA is specifically expressed in prehypertrophic chondrocytes. BMPR-IA regulates chondrocyte differentiation, serving as a downstream mediator of Indian Hedgehog (IHH) function in both a local signaling loop and a longer-range relay system to PTHrP. BMPR-IB also regulates apoptosis: Expression of activated BMPR-IB results in increased cell death, and we showed previously that dominant-negative BMPR-IB inhibits apoptosis. Our studies indicate that in TGFβ signaling systems, different type I receptor isoforms are dedicated to specific functions during embryogenesis.     

A study on facial features of children with Williams syndrome in China based on three‐dimensional anthropometric measurement technology

To describe special facial features of children with Williams syndrome in China by using method of three‐dimensional craniofacial anthropometry. Using three‐dimensional stereo photogrammetric device, 14 craniofacial anthropometric measurements were performed and five indices were calculated in 52 children with Williams syndrome and 208 age and sex matched controls of Han Chinese ethnicity. Except intercanthal width, mouth breadth, morphological face height, nasal height‐breadth index, nasal breadth‐depth index, morphological ear index, the Williams syndrome group under 3 years old were smaller than the control group in the other 12 variables. Compared with the control group, the Williams syndrome group aged 3–5 years old had smaller biocular breadth, nasal length, nasorostral angle, bitragal breadth, ear width, morphological ear index and face depth. The Williams syndrome group aged above 6 years old had smaller biocular breadth, nasal breadth, bitragal breadth, ear width, ear length and face depth than the control group. The craniofacial variability index of the Williams syndrome group was greater than the control group. Greater variation was found among children with Williams syndrome than normal in China, specifically at eye, nose, ear and face shape, which demonstrate the usefulness of three‐dimensional stereo photogrammetric analysis in supporting accurate diagnose of the patient with Williams syndrome.