Objective:To compare the therapeutic effects of combination regimens based on omadacycline or tigecycline in the treatment of patients with carbapenem-resistant acinetobacter baumannii (CRAB) pneumonia.Methods:A retrospective analysis was performed on the case data of 92 patients diagnosed with CRAB pneumonia who were admitted to the Intensive Care Unit (ICU) of Jinhua Municipal Central Hospital between January 2022 and March 2024. Among these cases, 49 patients received combination therapy with omadacycline as the foundation (hereafter referred to as the omadacycline group),A total of 43 cases were treated with tigecycline-based combination therapy (hereafter referred to as the tigecycline group). The demographic and clinical data of the two patient groups, including pre- and post-treatment improvements in inflammatory markers, bacterial clearance rates, ventilator weaning success rates, and 28-day survival rates, were compared.Results:No significant differences were observed in the baseline characteristics between the two patient groups.The body temperature, white blood cell count, C-reactive protein levels, and procalcitonin concentrations in both groups of patients showed significant improvement after 72 hours of treatment.The differences observed were statistically significant ( P<0.05).Following the completion of the treatment regimen, the bacterial clearance rates in the omadacycline and tigecycline groups were 69.4% and 44.2%, respectively ( P = 0.015). Moreover, the success rates for weaning patients from ventilator support were 71.4% and 51.2%, respectively ( P = 0.046).However, no statistically significant difference was observed in the 28-day survival rate.No serious adverse drug reactions were observed in either of the groups. Conclusions:Both omadacycline- and tigecycline-based combination therapies have demonstrated significant efficacy in improving inflammatory markers in patients with CRAB pneumonia. There was no statistically significant difference in the 28-day survival rate between the two patient groups. Furthermore, combination therapy utilizing omadacycline can significantly enhance the efficacy of promoting negative conversion of the etiological agent,minimize the duration of mechanical ventilation.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

Cell Cycle Proteins ; Microtubule-Associated Proteins

Objective To Pulse oximetry saturation has been wildly used clinically.It has been reported that pulse oximetry plethysmographic waveform (POP) reflected the peripheral tissue perfusion.In this study,we parameterized POP,observed the value of POP parameters in normal adults,and established the normal reference value range.Methods A multi-center prospective descriptive study.Total of 1 019 adult volunteers with normovolemia from 7 cities were enrolled in this study.Sex,age,height,weight and pulse oximetry data in awake and spontaneous breathing under in quiet conditions in the room temperature were collected.POP parameters and perfusion index were analyzed using MATLAB 2012a software.The normal reference value ranges of POP parameters,including the amplitude of POP (Amp) and the area under the curve of POP (AUC),were formulated.Results Statistical differences of POP parameters were detected between men and women in the normal adult.The 95％ confidence reference value of POP parameters in normal population was as follows:Amp (104.8-2298.7) PVA and AUC (3265.8-6028.5) PVPGin total,Amp (129.4-2433.6) PVA and AUC (3319.0-5862.2) PVPG in male;Amp (89.5-2138.2) PVA and AUC (3163.9-5929.9) PVPG in female.Conclusions POP,including the amplitude of POP (Amp) and the area under the curve of POP (AUC),had normal reference value ranges in normal adults.