Utility of Differential White Cell Count and Cell Population Data for Ruling Out COVID-19 Infection in Patients With Community-Acquired Pneumonia

IntroductionThe main aim of this study was to assess the utility of differential white cell count and cell population data (CPD) for the detection of COVID-19 in patients admitted for community-acquired pneumonia (CAP) of different etiologies.MethodsThis was a multicenter, observational, prospective study of adults aged ≥18 years admitted to three teaching hospitals in Spain from November 2019 to November 2021 with a diagnosis of CAP. At baseline, a Sysmex XN-20 analyzer was used to obtain detailed information related to the activation status and functional activity of white cells.ResultsThe sample was split into derivation and validation cohorts of 1065 and 717 patients, respectively. In the derivation cohort, COVID-19 was confirmed in 791 patients and ruled out in 274 patients, with mean ages of 62.13 (14.37) and 65.42 (16.62) years, respectively (p < 0.001). There were significant differences in all CPD parameters except MO-Y. The multivariate prediction model showed that lower NE-X, NE-WY, LY-Z, LY-WY, MO-WX, MO-WY, and MO-Z values and neutrophil-to-lymphocyte ratio were related to COVID-19 etiology with an AUC of 0.819 (0.790, 0.846). No significant differences were found comparing this model to another including biomarkers (p = 0.18).ConclusionsAbnormalities in white blood cell morphology based on a few cell population data values as well as NLR were able to accurately identify COVID-19 etiology. Moreover, systemic inflammation biomarkers currently used were unable to improve the predictive ability. We conclude that new peripheral blood biomarkers can help determine the etiology of CAP fast and inexpensively.     

Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.     

艾拉莫德联合甲氨蝶呤治疗类风湿性关节炎的临床疗效及对患者骨代谢的影响

目的 探讨艾拉莫德联合甲氨蝶呤治疗类风湿性关节炎(RA)的临床效果及对患者骨代谢的影响。方法 将我院收治的86例RA患者随机分为两组各43例。对照组采用甲氨蝶呤治疗,观察组采用艾拉莫德联合甲氨蝶呤治疗。比较两组的临床疗效、骨代谢指标(β-CTX、 TPINP、 N-MID)及不良反应发生情况。结果 观察组治疗总有效率为95.35%,明显高于对照组的81.40%(P<0.05)。治疗后,两组的β-CTX水平降低, TPINP、 N-MID水平升高(P<0.05);观察组的β-CTX水平明显低于对照组, TPINP、 N-MID水平高于对照组(P<0.05)。两组的不良反应发生率(9.30%vs. 6.98%)比较差异无统计学意义(P>0.05)。结论 艾拉莫德联合甲氨蝶呤治疗RA效果显著,可有效改善患者的骨代谢,且安全性较高。     

新化合物Elixir-X对肝切及辐射所致衰老小鼠的抗衰老作用

目的 探讨蜂巢提取物Elixir-X对自然衰老及辐射衰老小鼠的影响，为Elixir-X的进一步研发提供药理学基础。方法 采用小鼠肝脏切除术建立自然衰老小鼠模型，将其分为空白对照组、Elixir-X组、白藜芦醇组及模型组，连续给药7 d后，检测小鼠70%肝脏切除后的再生过程中，衰老细胞、肝脏功能恢复与肝脏再生的变化，观察Elixir-X对自然衰老的影响；采用60CO辐射法建立辐射衰老小鼠模型，将其分为模型组、空白对照组、白藜芦醇组、Elixir-X高、低剂量组，通过检测小鼠肠隐窝干细胞再生、小肠绒毛结构以及衰老细胞的变化，对比不同剂量Elixir-X对辐射后衰老的影响。结果 在肝脏切除术的小鼠模型中，Elixir-X组的肝功能水平明显低于模型组的肝脏自然再生小鼠，显著促进了肝功能恢复（P＜0.05）；同时与模型组相比，Elixir-X组清除了肝脏切除后再生过程中产生的衰老细胞（P＜0.05），Ki-67的着色斑块明显增加，促进肝脏的再生，且肝血窦的扫描电镜影像结果中Elixir-X组肝血窦再生加快。60CO辐照小鼠模型中，与模型组相比，Elixir-X组有效促进辐照后肝脏功能恢复（P＜0.05），Elixir-X高剂量组体重也恢复到正常水平，与空白对照组无显著差异；与模型组相比，Elixir-X低剂量组小肠的β-Gal着色细胞减少，Elixir-X高剂量组甚至能更有效地减少衰老细胞（P＜0.05）；小肠HE染色的结果中，Elixir-X组小肠绒毛结构得到恢复；Ki-67的IHC染色中，与模型组相比，Elixir-X组着色板块更多，且着色区域都在肠隐窝干细胞位置。结论 Elixir-X能有效清除肝脏切除术引起的自然衰老与辐射引起的损伤性衰老细胞，对衰老具有显著地抑制作用。     

肥胖型PCOS患者的生物学特征和临床特征

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是一种内分泌代谢紊乱综合征,临床表现高度异质性。肥胖是PCOS异质性临床表现之一,超过50%的PCOS患者超重或肥胖。肥胖型PCOS主要表现为高雄激素血症、中心型肥胖和糖脂代谢紊乱,非肥胖型PCOS主要表现为黄体生成激素（luteinizing hormone,LH）水平异常升高。尽管肥胖型和非肥胖型PCOS均存在内分泌代谢异常,然而肥胖可加重PCOS糖脂代谢紊乱;肥胖型PCOS还表现脂肪代谢的异常。综述肥胖型PCOS患者的临床特征、性激素水平、糖脂代谢特征,旨在为肥胖型和非肥胖型PCOS患者新的分型诊治提供参考。     

ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.