Synthesis of 14-epi-19-nor-22-oxa-1α,25-dihydroxyvitamin D_3

The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functions.

Effect of 1,25-Dihydroxyvitamin D_3 on Regulatory T Cells in Ovariectomized Mice

Objective To investigate the correlation between regulatory T （Treg） cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25（OH）2D3] in relation to Treg cells. Methods Fifty female BALB/c mice were randomly divided into five groups： the basal control （BAS）, Sham, ovariectomy （OVX）, OVX＋diethylstilbestrol （OVX＋DES）, and OVX＋I,2S（OH）2D3. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cy：ometry and quantitative RT-PCR, respectively. Results In comparison with the Sham group, a significant decrease was found in the OV~ group in such indices as trabecular bone volume/tc,tal tissue area （BV/TV）, trabecular number （Tb.N） and trabecular thickness （Tb.Th）. 1,25（OH）2D3 and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRI~：A expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-tr^ated group compared with those in the sham group. 1,25（OH）2D3 and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters. Conclusion The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25（OH）2D3 is related to regulatory T cells.

Enhanced Response of Acute Monocytic Leukemia Cells to Low-dose Cytarabine by 1,25-dihydroxyvitamin D3

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents,such as vitamin D compounds,is a potential regimen to treat acute myeloid leukemia(AML)patients who are unfit for high-intensity chemotherapy.The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3(1,25-D3).Here,firstly,c Bio Portal database was used and we found out that vitamin D receptor(VDR)was highly expressed in acute monocytic leukemia(M5)and high VDR expression was associated with a poor survival of AML patients.Then,we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines(U937,MOLM-13,THP-1)and blasts from M5 patients than in non-monocytic cell lines(KG1 a and K562)and blasts from M2 patient.Finally,it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate,growth inhibition and G0/G1 arrest,while mild changes were found in the apoptosis in acute monocytic leukemia cell lines.Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia,especially for elderly and frail ones.

Synthesis of an optically active intermediate for A-ring of 19-nor-1α,25-dihydroxyvitamin D3

An optically active intermediate 5 for A-ring of 19-nor-1α,25-dihydroxyvitamin D3 2 has been synthesized in five steps, starting from readily available, inexpensive v（＋）-xylose 6 with good yield.

1,25-Dihydroxyvitamin D_(3) effects on the regulation of the insulin receptor gene in the hind limb muscle and heart of streptozotocin-induced diabetic rats

In the present study, we examine the effects of the treatment with 1,25-dihydroxyvitamin D3 [150 IU/Kg (3.75 μg/Kg) once a day, for 15 days] to non-diabetic and streptozotocin-induced diabetic rats. The results indicate that treatment with 1,25-dihydroxyvitamin D3 had minor effects in non-diabetic rats. The same treatment in streptozotocin-induced diabetic rats, although it did not correct the hyperglycemia and hypoinsulinemia induced by the diabetes, caused other actions that could mean beneficial effects on the amelioration of diabetes e.g., it avoided body weight loss, increased calcium and phosphorus plasma levels, and corrected the over-expression of the insulin receptor mRNA species of 9.5 and 7.5 Kb present in the hind limb muscle and heart of these animals. These genomic 1,25-dihydroxyvitamin D3 effects could involve transcriptional mechanisms of repression mediated by vitamin D response elements in the rat insulin receptor gene promoter. Using computer analysis of this promoter, we propose the -249/-235 bp VDRE (5’GGGTGACCCGGGGTT3’) with a pyrimidine (T) in the (+7) position of the3’half-site as the best candidate for negative control by 1,25-dihydroxy-vitamin D3. In addition, posttranscriptional mechanisms of regulation could also be implicated. Thus, computer inspection of the5’untranslated region of the rat insulin receptor pre-mRNA indicated the presence of a virtual internal ribosome entry segment whereas the computer inspection of the3’untranslated region localized various destabilizing sequences, including various AU-rich elements. We propose that through these virtual cis-regulatory sequences, 1,25-dihydroxyvitamin D3 could control the translation and stability of insulin receptor mRNA species in the hind limb muscle and heart of diabetic rats.

Inhibition of Proliferation of Human Megakaryoblastic Leukemic Cells by 1,25-Dihydroxyvitamin D_3 and Retinoic Acid

The effect of 1,25-dihydroxyvitamin D3 [1,25（OH）2D3] and13-cis-retinoic acid（RA）on the proliferation of a novel human megakaryoblasticleukemia cell line（HIMeg）was investigated.At the concentration of 109 106mol/L,1,25（OH）2D3 and RA showed significant inhibition of the proliferation of themegakaryoblastic leukemic cells,which was demonstrated by the count of survival cells,incorporation of3H-TdR and3H-UR,and cloning efficiency in dose-dependent and time-dependent manners.The results can further explain the mechanism of differentiation-inducing agents and the effect of 1 ,25（OH）2D3 on myelofibrosis.It is possible for1,25（OH）2D3 and RA to be used to treat malignant megakaryocytic diseases.

Effect of 1,25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea pigs

Objective:To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase(MCT) in asthmatic guinea pigs.Methods:A total of 60 male or female healthy guinea pigs were randomly divided into control group(group A),asthmatic group(group B).and 1,25-dihydroxyvitamin D3 group(group C),with 20 cases in each group.To establish asthmatic guinea pig models,1ml peanut oil was tilled into stomach in the morning in group A and group B.and 1 ml peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C.Airway resistance(Re) of asthmatic guinea pigs was detected,and the bronchoalveolar lavage fluid(BALF) cells were counted.Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT.Results:After injection of different concentration of acetylcholine chloride,the Re in group B and group C were increased significantly compared with group A(P<0.05):compared with group B.the Re in group C were decreased significantly(t=-5.385.-5.761.-6.184.-13.574.P<0.05):the total number of BALF cells and eosinophils were increased significantly in group B and C(t=19.618.9.598.10.854.5.388.P<0.05);compared with group B.the total number of BALF cells and eosinophils in group C was decreased significantly(t=-5.555.-5.392.P<0.05):the number of tryptase positive cells in group B was increased significantly than that in group A(t=21.312,P<0.05),and in addition to the alveolar septum and submucosa,the cells were also distributed around blood vessels and outside the cells:the number of tryptase positive cells in group C was decreased significantly compared with group B.and the difference was statistically significant(t=5.043.P<0.05).Conclusions:After the asthmatic guinea pigs arc treated with 1,25-dihydroxyvitamin D3,their BALF.Re.infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly.1,25-dihydroxyvitamin D3 has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.

糖调节受损患者血清25(OH)D和免疫相关因子对亚临床动脉粥样硬化影响的研究

目的:研究糖调节受损患者血清25(OH)D和免疫相关因子对亚临床动脉粥样硬化(AS)的影响。方法:选取2019年12月至2021年4月枣庄市立医院收治的142例糖调节受损患者,根据经颈动脉超声检查和臂踝脉搏波传导速度分组,仅糖调节受损患者为对照组(n=86),并发亚临床AS为观察组(n=56)。比较两组患者血清25(OH)D和免疫因子,应用颈动脉超声检测测定颈动脉内中膜厚度,Pearson法测定血清颈动脉内中膜厚度与血清25(OH)D和免疫因子的相关性。采集基线资料和血液学指标,单因素和多因素Logistic回归分析确定亚临床AS的影响因素,应用ROC曲线评估血清25(OH)D和免疫因子对亚临床AS的诊断效能。结果:观察组患者血清25(OH)D[(24.01±4.87)mmol/L vs 3(0.74±5.01)mmol/L,t=7.909,P=0.000)明显低于对照组,观察组患者TNF-α[(48.32±8.02)ng/L vs(33.21±9.00)ng/L,t=10.199,P=0.000)和IL-6[(41.22±9.43)ng/L vs(30.21±7.01)ng/L,t=7.492,P=0.000)明显高于对照组。颈动脉内中膜厚度与血清25(OH)D呈负相关(r=-0.428,P<0.001),颈动脉内中膜厚度与血清TNF-α和IL-6呈正相关(r=0.574,0.577,P<0.001)。Logistic回归分析结果表明,血清25(OH)D(OR=0.520,95%CI:0.401~0.675)、血清TNF-α(OR=1.667,95%CI:1.131~2.457)和血清IL-6(OR=1.478,95%CI:1.213~1.802)等是亚临床AS发生的影响因素。ROC曲线结果显示,血清25(OH)D最佳截断值为28.32 mmol/L,其对应的敏感度为69.64%,特异度为70.93%,AUC为0.803(95%CI:0.749~0.855);血清TNF-α临界值为40.56 ng/L,其对应的敏感度为71.43%,特异度为72.09%,AUC为0.761(95%CI:0.717~0.823);血清IL-6截断值为36.13 ng/L,其对应的敏感度为60.71%,特异度为60.47%,AUC为0.627(95%CI:0.566~0.702);回归分析对应的敏感度为85.71%,特异度为81.40%,AUC为0.889(95%CI:0.830~0.915)。结论:血清25(OH)D与免疫相关因子单独和联合回归检测可有效预测亚临床AS的发生,上述指标与颈动脉内中膜厚度相关,且血清25(OH)D和免疫相关因子是亚临床AS发生的预测指标,临床宜根据指标进行针对性干预,值得进一步研究。

老年血液透析病人衰弱与血清瘦素及25-羟维生素D的相关性研究

目的探究老年血液透析病人血清瘦素及25-羟维生素D[25(OH)D]水平,并分析其与透析病人衰弱的相关性。方法选取2021年4月至2023年4月我院收治的150例老年血液透析病人,依据Fried表型评价病人的衰弱情况,分为非衰弱组(51例),衰弱前期组(74例)和衰弱组(25例)。比较3组一般资料、血清瘦素、25(OH)D及心功能。采用多因素Logistic回归分析老年血液透析病人衰弱的影响因素。结果3组年龄、糖尿病比例、透析龄、左室舒张末期内径,以及白蛋白、镁、IL-6、瘦素、25(OH)D水平比较,差异均有统计学意义(P<0.01)。多因素有序Logistic回归分析显示,年龄、透析龄、糖尿病、镁、IL-6、白蛋白、瘦素、25(OH)D、左室舒张末期内径是老年血液透析病人衰弱的独立影响因素(P<0.05)。结论针对白蛋白水平低、瘦素水平高、25(OH)D水平低的老年血液透析病人采取积极干预措施,有利于延缓衰弱的进展。

糖尿病周围神经病变伴抑郁症状患者血清同型半胱氨酸与25-羟维生素D表达及其临床意义

目的探讨糖尿病周围神经病变(DPN)伴抑郁症状患者血清同型半胱氨酸(Hcy)与25-羟维生素D[25-(OH)D]表达及其临床意义。方法选取DPN伴抑郁症状患者50例设为研究组,DPN未伴有抑郁症状患者32例设为对照组。采用酶循环法检测Hcy水平,电化学发光法检测25-(OH)D水平。比较两组患者Hcy、25-(OH)D水平以及研究组不同抑郁程度患者Hcy、25-(OH)D水平差异。采用Pearson相关分析探讨DPN伴抑郁症状患者的Hcy、25-(OH)D水平与HADM-17评分的相关性,采用Logistic回归分析探讨DPN伴抑郁症状患者抑郁程度的影响因素。结果研究组患者Hcy水平、HAMD-17评分高于对照组,25-(OH)D水平低于对照组(P<0.01)。重度抑郁患者Hcy水平高于轻度、中度抑郁患者,25-(OH)D水平低于轻度、中度抑郁患者(P<0.05)。Pearson相关性分析显示,DPN伴抑郁症状患者Hcy水平与HAMD评分呈显著正相关(r=0.886,P<0.05),25-(OH)D水平与HAMD-17评分呈显著负相关(r=-0.619,P<0.05)。单因素分析结果显示,DPN伴抑郁症状患者性别、收缩压、空腹血糖、文化程度、Hcy、25-(OH)D水平比较,差异有统计学意义(P<0.05或0.01)。Logistic回归分析结果显示,性别、空腹血糖、文化程度、Hcy、25-(OH)D水平是DPN伴抑郁症状患者抑郁程度的影响因素(P<0.01)。结论DPN伴抑郁症状患者Hcy水平升高,25-(OH)D水平降低,性别、空腹血糖、文化程度是DPN伴抑郁症状患者抑郁程度的影响因素。Hcy和25-(OH)D表达在评估DPN患者抑郁严重程度方面具有重要价值,能为患者后续治疗提供生物学信息参考。

基于25⁃羟基维生素D、血清学因子等对老年类风湿性关节炎合并间质性肺疾病Nomogram预测模型的构建和评价

目的基于25-羟基维生素D[25-(OH)D]、血清学因子等构建老年类风湿性关节炎合并间质性肺疾病(RA-ILD)的Nomogram预测模型,并进行模型评价。方法选取2020年5月—2022年10月收治的老年类风湿性关节炎(RA)220例,根据是否合并间质性肺疾病将其分为RA-ILD组(51例)和单纯RA组(169例)2组,比较2组一般资料和实验室相关指标[类风湿因子(RF)、抗环瓜氨酸抗体(anti-CCP)、抗角蛋白抗体(AKA)、类风湿关节炎活动度评分(DAS28)]、25-(OH)D、血清学因子[白细胞介素-33(IL-33)、白细胞介素-35(IL-35)、赖氨酰氧化酶样蛋白-2(LOXL-2)、涎液化糖链抗原-6(KL-6)、基质金属蛋白酶-8(MMP-8)]水平,分析老年RA患者25-(OH)D与各血清学因子的相关性,探讨老年RA-ILD发生的影响因素,根据影响因素、25-(OH)D及血清学因子构建老年RA-ILD的Nomogram预测模型,并对该模型进行评价。结果RA-ILD组和单纯RA组RF、DAS28比较差异有统计学意义(P<0.01);RA-ILD组25-(OH)D、IL-35、KL-6低于单纯RA组,IL-33、LOXL-2、MMP-8高于单纯RA组(P<0.05,P<0.01)。老年RA患者25-(OH)D与IL-35、KL-6呈正相关,与IL-33、LOXL-2、MMP-8呈负相关(P<0.05)。25-(OH)D、IL-35、KL-6、IL-33、LOXL-2、MMP-8、RF和DAS28均为老年RA-ILD发生的影响因素(P<0.01)。在Nomogram预测模型中直接获取各预测因素对应得分,得分之和对应的预测概率即为该老年患者RA-ILD发生的风险概率,该模型对老年RA-ILD发生具有良好预测效能,且具有良好校准度。结论基于25-(OH)D、血清学因子等构建老年RA-ILD发生的Nomogram预测模型,预测效能较高、校准度良好。

Is 1, 25-dihydroxyvitamin D_3 an ideal substitute for dexamethasone for inducing osteogenic differentiation of human adipose tissue-derived stromal cells in vitro?

Background Human adipose tissue-derived stromal cells （hADSCs） can be induced to differentiate along an osteoblastic lineage under stimulation of dexamethasone （DEX）. Recent studies, however, have questioned the efficacy of glucocorticoids such as DEX in mediating the osteogenesis process of skeletal progenitor cells and processed lipoaspirate cells. Is it possible to find a substitute for DEX？ Therefore, this study was designed to investigate osteogenic capacity and regulating mechanisms for osteoblastic differentiation of hADSCs by comparing osteogenic media （OM） containing either 1, 25-dihydroxyvitamin D3 （VD） or DEX and determine if VD was an ideal substitute for DEX as an induction agent for the osteogenesis of hADSCs. Methods Osteogenic differentiation of hADSCs was induced by osteogenic medium （OM） containing either 10 nmol/L VD or 100 nmol/L DEX. Differentiation of hADSCs into osteoblastic lineage was identified by alkaline phosphatase （ALP） staining, von Kossa staining, and reverse transcription-polymerase chain reaction assays for mRNA expression of osteogenesis-related genes such as type Ⅰ collagen （COL Ⅰ）, bone sialoprotein （BSP）, osteocalcin （OC）, bone morphogenetic protein （BMP）-2, BMP-4, BMP-6, BMP-7, runt-related transcription factor 2/core binding factor α1 （Runx2/Cbfal）, osterix （Osx）, and LIM mineralization protein- 1 （LMP- 1）. Results von Kossa staining revealed that the differentiated cells induced by both VD and DEX were mineralized in vitro. They also expressed osteoblast-related markers, such as ALP, COL Ⅰ, BSP, and OC. Runx2/Cbfal, Osx, BMP-6, and LMP-1 were upregulated during VD and DEX-induced hADSC osteoblastic differentiation, but BMP-4, BMP-7 were not. BMP-2 was only expressed in VD-induced differentiated cells. Conclusions VD or DEX-induced hADSCs differentiate toward the osteoblastic lineage in vitro. Runx2/Cbfal, Osx, BMP-2, BMP-6, and LMP-1 are involved in regulating osteoblastic differentiation of hADSCs, but BMP-4, BMP-7 are not. VD, but not DEX, induces expression of BMP-2 during osteogenic induction of hADSCs. VD is an ideal substitute for DEX for osteogenic induction of hADSCs.

2型糖尿病患者血清25-羟维生素D水平与代谢指标的相关性

目的分析2型糖尿病患者25-羟维生素D[25(OH)D]水平,初步了解血清25(OH)D水平与2型糖尿病患者糖化血红蛋白(HbA1c)、胰岛功能等代谢指标的相关性。方法选择新乡市第一人民医院内分泌科2020年1月至2020年12月收治的459例2型糖尿病患者为研究对象。收集患者的临床资料,包括性别、年龄、血清25(OH)D、空腹胰岛素、C肽、HbA1c、空腹血糖、餐后血糖、尿微量白蛋白、尿白蛋白肌酐比值、血钙、血尿酸(UA)、三酰甘油(TG)、总胆固醇(TCH)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)等。根据血清25(OH)D水平将患者分为充足组[n=20,25(OH)D≥30μg·L^(-1)]、不足组[n=95,20μg·L^(-1)≤25(OH)D<30μg·L^(-1)]、缺乏组[n=231,10μg·L^(-1)≤25(OH)D<20μg·L^(-1)]、严重缺乏组[n=113,25(OH)D<10μg·L^(-1)]。比较4组患者各代谢指标的差异,采用Pearson相关分析25(OH)D与各代谢指标的相关性。结果2型糖尿病患者血清25(OH)D水平为3.00~46.59(15.75±0.35)μg·L^(-1),男性患者的血清25(OH)D水平显著高于女性患者(P<0.05)。2型糖尿病患者25(OH)D缺乏的患病率为74.9%(344/459),25(OH)D缺乏主要发生在1、2、3、4、11、12月份。不足组、缺乏组和严重缺乏组患者HbA1c显著高于充足组(P<0.05),缺乏组和严重缺乏组患者HbA1c显著高于不足组(P<0.05);缺乏组和严重缺乏组患者HbA1c比较差异无统计学意义(P>0.05)。充足组与不足组、缺乏组与严重缺乏组患者空腹血糖比较差异无统计学意义(P>0.05);缺乏组和严重缺乏组患者空腹血糖显著高于充足组、不足组(P<0.05)。充足组、不足组、缺乏组患者空腹胰岛素、尿微量白蛋白、日尿白蛋白总量、尿白蛋白肌酐比值比较差异无统计学意义(P>0.05);严重缺乏组患者空腹胰岛素显著低于充足组、不足组和缺乏组,尿微量白蛋白、日尿白蛋白总量、尿白蛋白肌酐比值显著高于充足组、不足组和缺乏组(P<0.05)。4组患者的稳态模型评估的胰岛素抵抗指数(HOMA-IR)、血清白蛋白、血肌酐、餐后1 h血糖、餐后2 h血糖、餐后3 h血糖、空腹C肽、餐后1 h C肽、餐后2 h C肽、餐后3 h C肽、TG、TCH、LDL、HDL、血UA、血钙比较差异均无统计学意义(P>0.05)。Pearson相关性分析结果显示,2型糖尿病患者血清25(OH)D水平与HbA1c、尿微量白蛋白、尿白蛋白肌酐比值呈负相关(r=-0.093、-0.166、-0.157,P<0.05),与空腹胰岛素呈正相关(r=0.089,P<0.05)。2型糖尿病患者血清25(OH)D水平与空腹血糖、HOMA-IR、血清白蛋白、血肌酐、餐后1 h血糖、餐后2 h血糖、餐后3 h血糖、空腹C肽、餐后1 h C肽、餐后2 h C肽、餐后3 h C肽、TG、TCH、LDL、HDL、血UA、血钙等无相关性(P>0.05)。结论2型糖尿病患者25(OH)D缺乏与不足普遍存在,女性患者缺乏更明显。2型糖尿病患者25(OH)D水平与空腹胰岛素呈正相关,与HbA1c、尿微量白蛋白、尿白蛋白肌酐比值呈负相关,25(OH)D缺乏的2型糖尿病患者主要分布在1、2、3、4、11、12月份。

首次复治菌阳肺结核合并糖尿病患者血清IAP、25(OH)D水平及对疗效的预测价值

目的探讨首次复治菌阳肺结核(TB)合并糖尿病(DM)患者血清免疫抑制酸性蛋白(IAP)、25-羟基维生素D[25(OH)D]表达变化及2者对治疗疗效的预测价值。方法选取本院2019年1月至2022年4月首次复治菌阳TB合并DM患者48例为实验组,另选同期单纯TB患者48例为对照组。测定并比较两组患者治疗前后血清IAP、25(OH)D水平;多因素Logistic回归分析影响菌阳TB合并DM患者痰菌阴转的可能因素;受试者工作特征(ROC)曲线评估IAP、25(OH)D对患者痰菌未转阴的预测价值。结果实验组痰菌阴转患者31例(64.58%)显著低于对照组痰菌阴转患者40例(83.33%)。治疗2个月后,实验组、对照组血清IAP均显著降低,25(OH)D水平均显著升高(P<0.05);且治疗2个月后实验组血清IAP水平显著低于对照组,25(OH)D水平显著高于对照组(P<0.05)。多因素Logistic回归分析显示,IAP高水平是首次复治菌阳TB合并DM患者痰菌未阴转的危险因素(P<0.05),25(OH)D高水平是首次复治菌阳TB合并DM患者痰菌未阴转的保护因素(P<0.05)。ROC曲线显示,IAP预测痰菌未阴转的AUC为0.719,25(OH)D预测痰菌未阴转的AUC为0.791,2者联合预测痰菌未阴转的AUC为0.871,明显高于2者单独诊断(Z_(联合vs IAP)=2.605、P=0.009;Z_(联合vs 25(OH)D)=2.408、P=0.016),且灵敏度、特异性分别为78.46%、82.86%。结论首次复治菌阳TB合并DM患者经治疗后血清IAP水平降低、25(OH)D水平升高,2者联合对菌阳TB合并DM患者痰菌未阴转具有一定预测价值。

常见自身免疫性疾病患者血清25-羟维生素D水平的差异分析

目的分析常见自身免疫性疾病患者血清25-羟维生素D[25(OH)D]水平差异及25(OH)D水平与其他实验室指标的相关性。方法选取2022年9月至2023年4月于福建省立医院风湿免疫科就诊的自身免疫性疾病患者229例作为试验组,其中系统性红斑狼疮(SLE)58例、类风湿关节炎(RA)45例、干燥综合征(SS)37例、强直性脊柱炎(AS)60例、皮肌炎(DM)14例和系统性硬化症(SSc)15例;选择同期体检健康人群29例作为对照组。收集血清标本,采用高效液相色谱-串联质谱法对血清标本中的25(OH)D进行检测,分析25-羟维生素D_(2)[25(OH)D_(2)]、25-羟维生素D_(3)[25(OH)D_(3)]和总25(OH)D水平在常见自身免疫性疾病患者中的差异;分析总25(OH)D水平与其他实验室指标之间的相关性。结果试验组的血清总25(OH)D水平表现为缺乏或不足的比例总体上高于对照组。试验组的25(OH)D_(3)和总25(OH)D水平低于对照组,差异有统计学意义(P<0.05),试验组各疾病亚组25(OH)D_(3)、总25(OH)D水平比较,差异有统计学意义(P<0.05),SLE组25(OH)D_(3)和总25(OH)D水平最低,与SS组比较,差异有统计学意义(P<0.05)。女性患者的血清25(OH)D_(3)和总25(OH)D水平低于男性患者,差异有统计学意义(P<0.05)。SLE组血清总25(OH)D水平与红细胞沉降率(ESR)、肌酐(CREA)和尿素氮(BUN)呈负相关(P<0.05),RA组血清总25(OH)D水平与类风湿因子(RF)呈负相关(P<0.05),DM组总25(OH)D水平与ESR呈负相关(P<0.05)。结论自身免疫性疾病患者通常表现为维生素D缺乏或不足,且存在性别差异。在不同的自身免疫性疾病患者中血清总25(OH)D水平与ESR、CREA、BUN及RF表现出不同的相关性。

血清25(OH)D、SII对扩张型心肌病严重程度与预后的评估价值

目的探讨扩张型心肌病(dilated cardiomyopathy,DCM)患者血清25-羟维生素D[25 hydroxy vitamin D,25(OH)D]、系统免疫炎症指数(systemic immune-inflammation index,SII)变化,分析两者与DCM病情严重程度的相关性。方法纳入2020年6月—2023年6月三明市第二医院心内科收治的104例DCM患者作为DCM组,健康体检者104名作为对照组。对比两组生化指标、血压、心脏功能指标、N末端B型脑钠肽前体、25(OH)D、SII差异。根据心功能分级将DCM分成心功能Ⅱ、Ⅲ、Ⅳ级组,按Lee氏心衰积分将DCM分成轻度心力衰竭、中度心力衰竭与重度心力衰竭组,对比各组25(OH)D、SII的差异。Pearson法分析25(OH)D、SII与心功能指标的相关性。受试者工作特征曲线分析25(OH)D、SII对DCM严重程度的评估价值。结果DCM组甘油三酯(triglyceride,TG)(1.77±0.37)mmol/L、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)(2.84±0.81)mmol/L、收缩压(124.23±8.87)mmHg、舒张压(78.44±8.28)mmHg、N末端B型脑钠肽前体(N-terminal B-type brain natriuretic peptide precursor,NT-proBNP)(1509.55±444.53)pg/mL、SII(897.54±107.89)×10^(9)/L、左心房收缩期末内径(left atrial end-systolic diameter,LAD)(45.92±7.17)mm、左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)(64.53±7.10)mm、左心室收缩末期容积(left ventricular end-systolic volume,LVESV)(57.23±4.50)mL、左心室舒张末期容积(left ventricular end-diastolic volume,LVEDV)(87.85±9.38)mL,均高于对照组的(1.63±0.38)mmol/L、(2.53±0.56)mmol/L、(120.39±7.71)mmHg、(74.50±7.60)mmHg、(78.88±10.33)pg/mL、(309.66±59.69)×10^(9)/L、(28.02±3.53)mm、(44.47±2.59)mm、(31.78±3.80)mL、(63.50±4.43)mL,差异有统计学意义(P<0.001);DCM组白蛋白(37.30±3.81)g/L、25(OH)D(28.96±4.31)ng/mL、LVEF(33.97±5.42)%,均低于对照组的(43.10±2.93)g/L、(66.79±5.33)ng/mL、(66.01±6.19)%,差异均有统计学意义(P<0.001)。随着心功能分级、Lee氏心力衰竭积分增加,DCM患者血清25(OH)D逐渐降低,SII逐渐升高,差异均有统计学意义(P<0.001)。Pearson相关分析显示,血清25(OH)D与Lee心力衰竭积分(r=-0.612,P<0.001)、NT-proBNP(r=-0.688,P<0.001)、LVESV(r=-0.586,P=0.006)、LVEDV(r=-0.649,P<0.001)均呈负相关,而与LVEF呈正相关(r=0.704,P<0.001);SII与Lee心力衰竭积分(r=0.721,P<0.001)、NT-proBNP(r=0.662,P<0.001)、LVESV(r=0.674,P<0.001)、LVEDV(r=0.733,P<0.001)均呈正相关,而与LVEF呈负相关(r=-0.589,P=0.002)。受试者工作特征曲线分析显示,25(OH)D、SII预测DCM严重程度的灵敏度分别为80.13%、76.51%,特异度分别为78.44%、86.15%,曲线下面积分别为0.842、0.794。结论DCM患者SII、25(OH)D水平均与DCM病情相关,对DCM病情严重程度与预后具有重要预测价值。

血清25-羟基维生素D与EV71感染手足口病患儿Th1/Th2细胞因子及病情进展关系研究

目的血清25-羟基维生素D[25-(OH)D]与肠道病毒71型(EV71)感染手足口病患儿辅助性T(Th)1/Th2细胞因子及病情进展的关系研究。方法选择2020年10月至2023年10月在我院就诊的135例EV71感染手足口病患儿作为研究对象,依据病情严重程度分为普通型组(n=95)、重型组(n=40),对比两组血清25-(OH)D、Th1/Th2细胞因子[血清白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、血清IL-6]水平,Pearson相关性分析血清25-(OH)D、Th1/Th2细胞因子的关系,多因素Logistic回归模型探讨血清25-(OH)D与病情进展的关系。结果两组血清25-(OH)D水平比较,重型组更低,血清IL-2、TNF-α、IL-6水平比较,重型组更高(P<0.05);血清25-(OH)D与IL-2/TNF-α/IL-6水平负相关(r=-0.344、-0.344、-0.424,P均<0.05);重型组血清25-(OH)D、体液免疫IgG水平及个人卫生习惯良好比例低于普通型组,手足口病病史与白细胞(中性粒细胞)计数升高比例高于普通型组(P<0.05);血清25-(OH)D为患儿病情进展的保护因素(P<0.05),手足口病史、CRP升高为患儿病情进展独立危险因素(P<0.05)。结论血清25-(OH)D与EV71感染手足口病患儿IL-2、TNF-α、IL-6水平均呈负相关,且血清25-(OH)D是EV71感染手足口病患儿病情进展的保护因素,应重视对患儿血清25-(OH)D水平的动态追踪并合理补充维生素D。

代谢综合征患者血清25(OH)D和GDF15水平表达与并发甲状腺结节发生恶性风险的相关性研究

目的探讨代谢综合征(metabolic syndrome,MS)患者血清25羟基维生素D[25(OH)D],生长分化因子15(growth differentiation factor 15,GDF-15)水平表达与并发甲状腺结节(thyroid nodules,TN)发生恶性风险的相关性。方法选取2019年8月~2023年8月在新疆医科大学第一附属医院就诊的185例MS患者作为研究对象,按照甲状腺超声检查结果将其分为MS组(n=73)和MS+TN组(n=112),并根据甲状腺结节恶性分级将MS+TN组患者分为良性组(n=89)及恶性组(n=23);另选取同期体检的68例体检健康者作为对照组。采用酶联免疫吸附法(ELISA)测定各组血清25(OH)D和GDF-15水平;Pearson分析血清25(OH)D和GDF-15水平与MS并发TN患者临床指标之间的相关性;多因素Logistic回归分析MS并发TN患者发生恶性TN的影响因素;绘制受试者工作特征(ROC)曲线评估血清25(OH)D和GDF-15水平对MS并发恶性TN的诊断价值。结果对照组、MS组、MS+TN组血清25(OH)D(30.41±6.73ng/ml,27.23±6.15 ng/ml,24.67±4.38 ng/ml)和GDF-15(167.99±22.56 ng/L,239.75±25.92 ng/L,286.63±26.04 ng/L)水平比较,差异具有统计学意义(F=22.219,472.113,均P<0.05);且与良性组相比,恶性组患者血清25(OH)D(26.28±4.53 ng/ml vs 18.44±3.79 ng/ml)水平明显降低,GDF-15(276.93±24.53 ng/L vs 324.17±31.89 ng/L)水平明显升高,差异具有统计学意义(t=7.631,7.718,均P<0.05)。恶性组患者BMI,年龄、FPG,TG,TSH和TGAb水平明显高于良性组,差异具有统计学意义(t=2.868,3.523,3.542,3.603,4.581,5.516,均P<0.05).Pearson相关分析,MS并发TN患者血清25(OH)D水平与FPG,TSH,TG和TGAb水平均呈负相关(r=-0.302,-0.482,-0.524,-0.546,均P<0.05),GDF-15水平与TG,TSH,TGAb和FPG水平均呈正相关(r=0.467,0.541,0.578,0.623,均P<0.001)。多因素Logistic回归分析,GDF-15(OR=1.673,95%CI:1.146~2.442)为MS患者恶性TN发生的危险因素(P<0.05),25(OH)D(OR=0.744,95%CI:0.604~0.916)为恶性TN发生的保护因素(P<0.05);血清25(OH)D和GDF-15水平单独及联合诊断MS并发恶性TN的AUC分别为0.813,0.799,0.930,联合诊断优于单独诊断(Z=2.088,2.021,P=0.037,0.043)。结论MS并发TN患者血清25(OH)D,GDF-15水平与其结节性质明显相关,血清25(OH)D水平降低和GDF-15水平升高是MS患者发生恶性TN的危险因素。

1α,25-dihydroxyvitamin D 3 inhibits transforming growth factorβ1-induced epithelial-mesenchymal transition viaβ-catenin pathway

Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway plays an important role,notably with regard to TGF-β1.Recent studies have shown that 1α,25-dihydroxyvitamin D 3(1α,25(OH)2D 3)inhibits TGF-β1-induced EMT,although the underlying mechanism have not yet been fully elucidated.Methods::Alveolar epithelial cells were exposed to 1α,25(OH)2D 3,ICG-001,or a combination of both,followed by stimulation with TGF-β1.The protein expression of E-cadherin,α-smooth muscle actin,fibronectin,andβ-catenin was analyzed by western blotting and immunofluorescence analysis.The mRNA transcript of Snail was analyzed using RT-qPCR,and matrix metalloproteinase 9(MMP-9)activity was analyzed by gelatin zymogram.The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results::Both 1α,25(OH)2D 3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells.In addition,the Top/Fop Flash reporters showed that 1α,25(OH)2D 3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes,including MMP-9 and Snail,in synergy with ICG-001.Conclusion::1α,25(OH)2D 3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.

FSH/LH、25(OH)D及AMH对卵巢储备功能及体外受精-胚胎移植结局的预测

目的探讨卵泡刺激素/黄体生成素(FSH/LH)、25-羟维生素D[25(OH)D]及抗苗勒氏管激素(AMH)对卵巢储备功能及体外受精-胚胎移植(IVF-ET)结局的预测价值。方法选取2020年8月至2022年9月于郑州大学第二附属医院行IVF-ET助孕女性112例,根据获卵数分为3个亚组:低反应组(获卵个数≤3个)36例、正常反应组(获卵个数4~15个)48例,高反应组(获卵个数≥16个)28例。对比不同卵巢反应者FSH/LH、25(OH)D、AMH水平;根据COH方案治疗后14 d人绒毛膜促性腺激素(β-HCG)水平,判断患者妊娠结局,收集不同妊娠结局患者临床资料[年龄、不孕类型、不孕病程、优质胚胎数、获卵总个数、受精率、移植胚胎数、LH/FSH、25(OH)D及AMH水平];采用二元Logistic回归分析影响不良妊娠结局的危险因素;计算FSH/LH、25(OH)D、AMH单一及联合对患者不良结局的预测效果。结果不同卵巢反应者中FSH/LH、25(OH)D及AMH水平比较:高反应组>正常反应组>低反应组,差异具有统计学意义(P<0.05)。112例患者中,正常妊娠组77例和非正常妊娠组35例。两组不孕类型、优质胚胎数、不孕病程、获卵总个数、受精率比较差异无统计学意义(P>0.05);两组Gn用量、年龄、移植胚胎数、FSH/LH、25(OH)D及AMH水平比较差异具有统计学意义(P<0.05)。二元Logistic回归分析显示:Gn用量(≥2014.58 U)、年龄(≥39岁)、FSH/LH(≥1.8)、移植胚胎数(≥1.34个)、25(OH)D(≥25.05μg/L)及AMH(≥2.92 ng/mL)为影响妊娠结局的独立危险因素(P<0.05)。ROC结果显示,FSH/LH、25(OH)D、AMH联合预测妊娠结局的敏感度和特异度分别为0.812、0.755,AUC=0.827(95%CI:0.731~0.923),明显高于三指标单独预测(P<0.05)。结论FSH/LH、25(OH)D、AMH水平在高卵巢反应中呈升高状态,三者可作为监测、预防行IVF-ET助孕女性不良妊娠结局的重要指标,且联合预测价值更高。