Vitamin D and Diseases of Mineral Homeostasis: A Cyp24a1 R396W Humanized Preclinical Model of Infantile Hypercalcemia Type 1

Infantile hypercalcemia type 1 (HCINF1), previously known as idiopathic infantile hypercalcemia, is caused by mutations in the 25-hydroxyvitamin D 24-hydroxylase gene, CYP24A1. The R396W loss-of-function mutation in CYP24A1 is the second most frequent mutated allele observed in affected HCINF1 patients. We have introduced the site-specific R396W mutation within the murine Cyp24a1 gene in knock-in mice to generate a humanized model of HCINF1. On the C57Bl6 inbred background, homozygous mutant mice exhibited high perinatal lethality with 17% survival past weaning. This was corrected by crossbreeding to the CD1 outbred background. Mutant animals had hypercalcemia in the first week of life, developed nephrolithiasis, and had a very high 25(OH)D₃ to 24,25(OH)₂D₃ ratio which is a diagnostic hallmark of the HCINF1 condition. Expression of the mutant Cyp24a1 allele was highly elevated while Cyp27b1 expression was abrogated. Impaired bone fracture healing was detected in CD1-R396^w/w mutant animals. The augmented lethality of the C57Bl6-R396W strain suggests an influence of distinct genetic backgrounds. Our data point to the utility of unique knock-in mice to probe the physiological ramifications of CYP24A1 variants in isolation from other biological and environmental factors.     

天玑骨科机器人联合O臂导航系统辅助经皮微创治疗骨盆后环损伤

目的评价天玑骨科机器人联合O臂导航系统辅助经皮微创治疗骨盆后环损O24;的疗效。方法回顾分析2016年1月—2021年6月收治的76例骨盆后环损O24;患者临床资料，其中45例采用天玑骨科机器人联合O臂导航系统辅助经皮微创骶髂螺钉内固定术治疗（研究组），31例仅在C臂X线机引导下行经皮微创骶髂螺钉内固定术治疗（对照组）。N24;组患者性别、年龄、致O24;原因、骨折Tile分型、受O24;至24b;术时间等一般资料比较差异均无统计学意义（P>0.05）。记录N24;组患者24b;术时间、术中出血量、钉道调整次数和术中透视次数，采用Matta评分评价骨折复位质量；末次随访时采用Majeed评分评估患者骨盆功能恢复情况。 结果研究组共植入螺钉72枚，每例患者植入螺钉1（1，2）枚；对照组共植入螺钉47枚，每例患者植入螺钉1（1，2）枚；N24;组每例患者植入螺钉数比较差异无统计学意义（Z=−0.392，P=0.695）。研究组24b;术时间、术中出血量、钉道调整次数和术中透视次数均显著少于对照组（P<0.05）。240;有患者均获随访，随访时间6～24个月，平均14个月。术后和随访过程中均未见严重并发症。术后1周采用Matta评分评价骨折复位质量，N24;组差异无统计学意义（Z=−1.135，P=0.256）。末次随访时采用Majeed评分评价骨盆功能，N24;组差异无统计学意义（Z=−1.279，P=0.201）。 结论天玑骨科机器人联合O臂导航系统辅助治疗骨盆后环损O24;是一种可靠的24b;术方式，与C臂X线机引导下的传统24b;术方式相比减少了24b;术时间和透视次数，提高了24b;术安全性、准确性和24b;术效率。     

严重创伤患者早期外周血淋巴细胞变化与预后之间的关系

目的探讨严重创O24;早期外周血淋巴细胞变化趋势与预后间的关系。方法选取2017年6月至2020年6月北京大学人民医院创O24;救治中心收治的严重多发O24;患者作为研究对象进行回顾性研究, 观察入院后连续5 d血常规中淋巴细胞变化趋势并进行分组, 第1组: 淋巴细胞减少后在5 d内恢复正常; 第2组: 淋巴细胞减少后未恢复正常; 第3组: 淋巴细胞一直处于正常水平, 并记录各组患者在住院28 d后的转归情况。对收集的临床资料进行统计学分析, 了解创O24;早期淋巴细胞变化趋势与预后间的关系。同时, 为排除年龄的影响, 依据年龄是否≥65岁进行分层, 并根据住院时间是否≥28 d分为住院时间延长组和住院时间非延长组, 在不同年龄组中分别探讨淋巴细胞变化与住院时间的关系。结果共纳入患者83例, 其中男性66例, 女性17例, 主要受O24;机制为车祸O24;和高处坠落O24;, 创O24;严重程度评分(injury severe score, ISS)为(30±11)分。根据连续5 d淋巴细胞变化趋势分组, 第1组32例, 第2组33例, 第3组18例。第2组33例患者中, 在住院28 d内死亡5例, 死亡率为15.2%(5/33), 未出院9例, 均高于其他N24;组(P < 0.05)。进一步按年龄进行分层后, 发现在高年龄患者中淋巴细胞处于低水平是住院时间≥28 d的危险因素, 但在低年龄患者中, 发现中性粒细胞持续偏高与预后不良相关。结论严重创O24;后外周血淋巴细胞一直处于低水平与预后不佳密切相关, \24;其在高年龄患者中明显, 淋巴细胞可作为一项可靠指标用于预后评估。     

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.     

一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损的疗效分析

目的观察一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损的疗效。方法回顾分析2021年7月—2022年2月符合选择标准的13例采用一次性皮肤拉拢装置治疗的难闭性皮肤软组织缺损患者临床资料。其中男9例，女4例；年龄15～71岁，平均39.8岁。致O24;原因：摔O24;5例，交通事故O24;5例，高处坠落O24;3例。皮肤软组织缺损原因：开放骨折4例，O24;口感染4例，骨髓炎3例，脱套O24;1例，植皮坏死1例。损O24;部位：小腿8例，跟骨3例，骨盆1例，足底1例。皮肤软组织缺损范围为5.0 cm×2.0 cm～10.5 cm×6.5 cm。记录O24;口情况（包括O24;口闭合和O24;口愈合）及有无并发症等情况。结果13例患者均获随访，随访时间32～225 d，中位时间164 d。O24;口闭合时间5～14 d，平均8.8 d；O24;口闭合速度0.7～13.7 cm²/d，平均3.6 cm²/d。240;有O24;口均甲级愈合，均未发生皮缘损O24;、O24;口坏死、感染、裂开、水肿等并发症，患者均未诉疼痛不适等，随访时未发现明显瘢痕形成等情况。O24;口愈合时间17～28 d，平均21.7 d。其中1例使用该装置后因肺癌病情变化转科，术后17 d随访时O24;口未经缝合已直接愈合。 结论一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损疗效确切，O24;口闭合时间短，并发症少，操作简便。     

The seasonal relationships between household dietary diversity and child growth in a rural Timor‐Leste community

Both child growth and dietary diversity are poor in rural Timor‐Leste. The rainy season is associated with food scarcity, yet the association between seasonal scarcity, food diversity, and child growth is underdocumented. This study assesses the relationship between household dietary diversity and children''s standardized growth across the 2018 food‐scarce (April–May; post‐rainy period) and post‐harvest (October) seasons in the agricultural community of Natarbora, on the south‐coastal plains of Timor‐Leste. We conducted household interviews and collected anthropometric data across 98 and 93 households in the post‐rainy and post‐harvest periods, respectively. Consumed household foods were obtained via 24‐h diet recalls and were subsequently categorized into a nine‐food‐group dietary diversity score (DDS; number of different food groups consumed). The DDS was related to children''s standardized short‐term growth (z‐weight, z‐body mass index [BMI] and percent change in weight over the harvest season) via linear mixed models. Across seasons, DDS increased from 3.9 (standard deviation [SD] = 1.0) to 4.3 (SD = 1.4; p < 0.05). In the post‐rainy season, children in high DDS households had higher z‐weight than those in low DDS households and higher z‐BMI than children in medium and low DDS households. In the post‐harvest period, household DDS did not predict children''s z‐weight but predicted z‐BMI. Consumption of protein‐rich foods, particularly animal‐source foods and legumes, in low‐ and medium‐DDS households may be associated with improved child growth. While consuming more animal‐source foods in the post‐rainy season would be ideal, promoting the consumption of locally grown legumes, such as beans and pulses, may facilitate better nutritional outcomes for more children in rural Timor‐Leste.     

Dietary Patterns of 479 Indonesian Adults and Their Associations with Sodium and Potassium Intakes Estimated by Two 24-h Urine Collections

The excess sodium (Na) intake and insufficient potassium (K) intake are frequently observed all over the world, including Indonesia. This study explored the dietary patterns of Indonesian people and evaluated their associations with Na and K intakes. Na and K intakes were assessed by repeated 24-h urine collection. The dietary patterns of the previous month were extracted by factor analysis using the Indonesian Food Frequency Questionnaire. The participants were community-dwelling Indonesian men and women (n = 479) aged 20 years and over. We identified four dietary patterns in each sex. After controlling for confounding factors, the high quantile of ‘Noodle, oil, and salty sea products’ pattern was associated with the high Na intake in both men and women (p = 0.02 and <0.001, respectively). The ‘Meat, vegetable, oil, and fruit’ pattern statistically significantly contributed to the high K intake in men (p = 0.04), but not in women (p = 0.26). The ‘Vegetable, non-oil, and milk’ pattern in men and ‘Meat, vegetable, and fruit’ pattern in women were associated with low Na:K ratios (p = 0.03 and 0.01, respectively). Neither ‘bread’ nor ‘fish’ appeared as a major determinant of any dietary patterns in this population. The ‘Noodle, oil, and salty sea products’ pattern should be avoided to reduce sodium intake.     

人类免疫缺陷病毒新近感染及其检测技术的研究进展

人类免疫缺陷病毒（HIV）感染使全球面临严重问题,而对HIV新近感染的检测是估算HIV新发感染趋势研究的新方向。HIV核心蛋白p24抗原可早期检出因而用于HIV新近感染的检测,但因其敏感性低,对群体发病率的估计存在局限性;HIV核酸检测用于新近感染的判断敏感性和特异性都较高．尤其是集合核酸技术的应用降低了核酸检测技术本身的高成本;BED（指HIV-1特异的B、E和D亚型）捕获酶联免疫法的数据结果则更能反映出新近感染高危因素以及其他方面的变化规律,对评估HIV新发感染动态趋势起到积极作用。     

瑞香狼毒水提物小鼠血清对人膀胱癌T24细胞增殖的影响

目的：探讨瑞香狼毒水提物（SCLA）的抗癌作用及机制。方法：以不同剂量SCLA灌胃给药后,于不同时间采集小鼠血清,处理体外培养的人膀胱癌T24细胞,用MTS比色法,于酶标仪上测定吸光度值,观察SCLA对细胞增殖的影响。结果：SCLA小鼠血清显著降低T24细胞增殖。结论：瑞香狼毒抑制人膀胱癌T24细胞增殖,可能成为膀胱癌新的治疗药物。     

糖尿病肾病动态血压模式的特点及其与尿蛋白的关系

目的 :观察糖尿病肾损害不同时期患者的血压模式的变化 ,及其在糖尿病肾病发生机制中所起的作用。方法 :分别选取血糖稳定、临床血压正常的 、 、 期 2型糖尿病肾损害患者 ,进行动态血压测定 ,观察他们日夜血压模式的特点并与正常对照组进行对比。结果 :实验组患者的共同特点为夜间血压的升高及非勺型曲线的出现率增高 ,且后者与尿蛋白的水平成正相关。结论 :糖尿病肾损害患者的血压模式的改变 ,先于血压的升高及尿蛋白的明显增多 ,提示自主神经功能的受损 ,是糖尿病肾病的发病机制之一。