Targeting cardiac resident CCR2+ macrophage-secreted MCP-1 to attenuate inflammation after myocardial infarction.

After myocardial infarction (MI), cardiac resident CCR2+ macrophages release various cytokines and chemokines, notably monocyte chemoattractant protein-1 (MCP-1). MCP-1 is instrumental in recruiting CCR2+ monocytes to the damaged region. The excessive arrival of these monocytes, which then become macrophages, perpetuates inflammation at the site of injury. This continuous inflammation leads to adverse tissue remodeling and compromises cardiac function over time. We hypothesized that neutralizing the MCP-1 secreted by cardiac resident CCR2+ macrophages can mitigate post-MI inflammation by curtailing the recruitment of monocytes and their differentiation into macrophages. In this work, we developed nanoparticles that target the infarcted heart, specifically accumulating in the damaged area after intravenous (IV) administration, and docking onto CCR2+ macrophages. These nanoparticles were designed to slowly release an MCP-1 binding peptide, HSWRHFHTLGGG (HSW), which neutralizes the upregulated MCP-1. We showed that the HSW reduced monocyte migration, inhibited pro-inflammatory cytokine upregulation, and suppressed myofibroblast differentiation in vitro. After IV delivery, the released HSW significantly decreased monocyte recruitment and pro-inflammatory macrophage density, increased cardiac cell survival, attenuated cardiac fibrosis, and improved cardiac function. Taken together, our findings support the strategy of MCP-1 neutralization at the acute phase of MI as a promising way to alleviate post-MI inflammation. STATEMENT OF SIGNIFICANCE: After a myocardial infarction (MI), CCR2+ macrophages resident in the heart release various cytokines and chemokines, notably monocyte chemoattractant protein-1 (MCP-1). MCP-1 is instrumental in attracting CCR2+ monocytes to the damaged region. The excessive arrival of these monocytes, which then become macrophages, perpetuates inflammation at the site of injury. This continuous inflammation leads to adverse tissue remodeling and compromises cardiac function over time. In this work, we tested the hypothesis that neutralizing the MCP-1 secreted by cardiac CCR2+ macrophages can mitigate post-MI inflammation by curtailing the recruitment of monocytes.

A new classification for emergency critically ill patients and analysis of their adverse events during intrahospital transport: A cluster analysis.

BACKGROUND: Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before transporting them from the emergency department and focusing on managing high-risk patients are critical. At present, no unified classification method exists; all the current approaches are subjective. AIMS: To ensure transportation safety, we conducted a cluster analysis of critically ill patients transferred from the emergency department to the intensive care unit. STUDY DESIGN: Single-centre cohort study. This study was conducted at a comprehensive first-class teaching hospital in Beijing. Convenience sampling and continuous enrolment were employed. We collected data from 1 January 2019, to 31 December 2021. All patients were transferred from the emergency department to the intensive care unit, and cluster analysis was conducted using five variables. RESULTS: A total of 584 patients were grouped into three clusters. Cluster 1 (high systolic blood pressure group) included 208 (35.6%) patients. Cluster 2 (high heart rate and low blood oxygen group) included 55 (9.4%) patients. Cluster 3 (normal group) included the remaining 321 (55%) patients. The oxygen saturation levels of all the patients were lower after transport, and the proportion of adverse events (61.8%) was the highest in Cluster 2 (p < .05). CONCLUSIONS: This study utilized data on five important vital signs from a cluster analysis to explore possible patient classifications and provide a reference for ensuring transportation safety. RELEVANCE TO CLINICAL PRACTICE: Before transferring patients, we should classify them and implement targeted care. Changes in blood oxygen levels in all patients should be considered, with a focus on the occurrence of adverse events during transportation among patients with high heart rates and low blood oxygen levels.

Oxygenated Scaffolds for Pancreatic Endocrine Differentiation from Induced Pluripotent Stem Cells.

A 3D microenvironment is known to endorse pancreatic islet development from human induced pluripotent stem cells (iPSCs). However, oxygen supply becomes a limiting factor in a scaffold culture. In this study, oxygen-releasing biomaterials are fabricated and an oxygenated scaffold culture platform is developed to offer a better oxygen supply during 3D iPSC pancreatic differentiation. It is found that the oxygenation does not alter the scaffold's mechanical properties. The in situ oxygenation improves oxygen tension within the scaffolds. The unique 3D differentiation system enables the generation of islet organoids with enhanced expression of islet signature genes and proteins. Additionally, it is discovered that the oxygenation at the early stage of differentiation has more profound impacts on islet development from iPSCs. More C-peptide+ /MAFA+ ß and glucagon+ /MAFB+ α cells formed in the iPSC-derived islet organoids generated under oxygenated conditions, suggesting enhanced maturation of the organoids. Furthermore, the oxygenated 3D cultures improve islet organoids' sensitivity to glucose for insulin secretion. It is herein demonstrated that the oxygenated scaffold culture empowers iPSC islet differentiation to generate clinically relevant tissues for diabetes research and treatment.

Co-Delivery of Bioengineered Exosomes and Oxygen for Treating Critical Limb Ischemia in Diabetic Mice.

Diabetic patients with critical limb ischemia face a high rate of limb amputation. Regeneration of the vasculature and skeletal muscles can salvage diseased limbs. Therapy using stem cell-derived exosomes that contain multiple proangiogenic and promyogenic factors represents a promising strategy. Yet the therapeutic efficacy is not optimal because exosomes alone cannot efficiently rescue and recruit endothelial and skeletal muscle cells and restore their functions under hyperglycemic and ischemic conditions. To address these limitations, we fabricated ischemic-limb-targeting stem cell-derived exosomes and oxygen-releasing nanoparticles and codelivered them in order to recruit endothelial and skeletal muscle cells, improve cell survival under ischemia before vasculature is established, and restore cell morphogenic function under high glucose and ischemic conditions. The exosomes and oxygen-releasing nanoparticles, delivered by intravenous injection, specifically accumulated in the ischemic limbs. Following 4 weeks of delivery, the exosomes and released oxygen synergistically stimulated angiogenesis and muscle regeneration without inducing substantial inflammation and reactive oxygen species overproduction. Our work demonstrates that codelivery of exosomes and oxygen is a promising treatment solution for saving diabetic ischemic limbs.

The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model.

Objective: Semaphorin3E (Sema3E) mediates reorganization of the actin cytoskeleton, and plays an important role in ensuring the specificity of synapse formation and angiogenesis. However, the role of Sema3E in allergic asthma (AS) and eosinophilic bronchitis (EB) is still elusive. This study aimed to investigate the relationship between Sema3E in vagal ganglion and lung tissue, airway reactivity, and eosinophilic inflammation. Methods: The frequency of coughs and airway reactivity as well as the airway inflammation were observed in ovalbumin- (OVA-) induced AS and EB mouse models. The expression of Sema3E was examined in the vagal ganglion and lung tissues by immunofluorescence staining and western blotting analyses. In the Sema3E treatment protocol, exogenous Sema3E was administrated intranasally before challenge in AS model to study the effect of Sema3E on airway hyperresponsiveness, airway inflammation, mucus production, and collagen deposition. Results: The similar higher frequency of coughs and airway eosinophilic inflammation could be seen in AS and EB groups compared with nasal saline (NS) and dexamethasone (DXM) groups. The absence of the airway hyperresponsiveness was observed in EB and DXM group, while AS group showed increase in airway reactivity to methacholine. The expression of Sema3E in vagal ganglion and lung tissue was remarkably decreased in AS and DXM group compared with EB group. Sema3E-treated asthma mice displayed ameliorated airway hyperresponsiveness, mucus production, and collagen deposition. Conclusion: Sema3E in lungs and vagal ganglia is related to eosinophilic inflammation and has a protective effect on OVA-induced AHR in asthma.

Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFß pathways promote diabetic wound healing.

Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFß receptor II inhibitor (PTßR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTßR2I inhibits the TGFß1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTßR2I does not interfere with the TGFß1/Smad2/3 pathway that is required to regulate myofibroblasts, a critical cell type for wound healing. The hydrogel's ability to scavenge ROS in diabetic wounds further decreases inflammation. Single-dose application of the wound dressing significantly accelerates wound healing with complete wound closure after 14 days. Overall, using wound dressings capable of adaptively modulating TGFß pathways provides a new strategy for diabetic wound treatment.

Collagen VI deposition mediates stromal T cell trapping through inhibition of T cell motility in the prostate tumor microenvironment.

The tumor extracellular matrix (ECM) is a barrier to anti-tumor immunity in solid tumors by disrupting T cell-tumor cell interaction underlying the need for elucidating mechanisms by which specific ECM proteins impact T cell motility and activity within the desmoplastic stroma of solid tumors. Here, we show that Collagen VI (Col VI) deposition correlates with stromal T cell density in human prostate cancer specimens. Furthermore, motility of CD4+ T cells is completely ablated on purified Col VI surfaces when compared with Fibronectin and Collagen I. Importantly, T cells adhered to Col VI surfaces displayed reduced cell spreading and fibrillar actin, indicating a reduction in traction force generation accompanied by a decrease in integrin ß1 clustering. We found that CD4+ T cells largely lack expression of integrin α1 in the prostate tumor microenvironment and that blockade of α1ß1 integrin heterodimers inhibited CD8+ T cell motility on prostate fibroblast-derived matrix, while re-expression of ITGA1 improved motility. Taken together, we show that the Col VI-rich microenvironment in prostate cancer reduces the motility of CD4+ T cells lacking integrin α1, leading to their accumulation in the stroma, thus putatively inhibiting anti-tumor T cell responses.

Meta-Analysis of Electroencephalographic Correlates and Cognitive Performance for Acute Exercise-Induced Modulation.

INTRODUCTION: Although abundant research delving into the acute exercise-induced modulation of cognitive performance and the P300-ERP component has been conducted, there is a lack of consensus regarding whether or not this type of intervention has a beneficial effect on cognition and how it relates to the P300-ERP. METHODS: To examine the possible sources of this discrepancy, we conducted a meta-analysis of ERP results together with cognitive performance that were systemically stratified by relevant demographic and methodological moderators. RESULTS: Our results indicate that while acute exercise exerted an overall stable effect on cognitive improvement, associated with enlarged P300 amplitudes, the effect size varied across factors of age, biological sex, exercise intensity, exercise type, control type, and experimental design. Future research taking into consideration modulating factors as to avoid misestimating the beneficial effects of acute exercise are encouraged. CONCLUSION: All in all, and to our knowledge, this is the first meta-analysis quantitatively summarizing the relevant literature on the associations between P300-ERP correlates, acute exercise, and its positive influence on attention and cognitive performance in healthy individuals.

Cytotoxic steroids from the stems of Strophanthus divaricatus.

Phytochemical investigation on the stems of Strophanthus divaricatus led to the isolation of four undescribed cardiac glycosides and one undescribed C21 pregnane, together with eleven known steroids. Their structures were elucidated by a comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 16 was determined by comparison of the experimental and computed ECD spectra. Compounds 1-13 and 15 displayed potent to significant cytotoxicity against human cancer cell lines K562, SGC-7901, A549 and HeLa with IC50 values of 0.02-16.08, 0.04-23.13, 0.06-22.31 and 0.06-15.13 µM, respectively.

Chinese Medicine Plaster as A New Treatment for Surgical Site Infection in Patients with Cesarean Delivery: A Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial. METHODS: This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments. RESULTS: During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group. CONCLUSIONS: CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626).

Establishment of a simplified score for predicting risk during intrahospital transport of critical patients: A prospective cohort study.

AIMS AND OBJECTIVES: To establish a simple score that enables nurses to quickly, conveniently and accurately identify patients whose condition may change during intrahospital transport. BACKGROUND: Critically ill patients may experience various complications during intrahospital transport; therefore, it is important to predict their risk before they leave the emergency department. The existing scoring systems were not developed for this population. DESIGN: A prospective cohort study. METHODS: This study used convenience sampling and continuous enrolment from 1 January, 2019, to 30 June, 2021, and 584 critically ill patients were included. The collected data included vital signs and any condition change during transfer. The STROBE checklist was used. RESULTS: The median age of the modelling group was 74 (62, 83) years; 93 (19.7%) patients were included in the changed group, and 379 (80.3%) were included in the stable group. The five independent model variables (respiration, pulse, oxygen saturation, systolic pressure and consciousness) were statistically significant (p < .05). The above model was simplified based on beta coefficient values, and each variable was assigned 1 point, for a total score of 0-5 points. The AUC of the simplified score in the modelling group was 0.724 (95% CI: 0.682-0.764); the AUC of the simplified score in the validation group (112 patients) was 0.657 (95% CI: 0.566-0.741). CONCLUSIONS: This study preliminarily established a simplified scoring system for the prediction of risk during intrahospital transport from the emergency department to the intensive care unit. It provides emergency nursing staff with a simple assessment tool to quickly, conveniently and accurately identify a patient's transport risk. RELEVANCE TO CLINICAL PRACTICE: This study suggested the importance of strengthening the evaluation of the status of critical patients before intrahospital transport, and a simple score was formed to guide emergency department nurses in evaluating patients.

Chinese Medicine Plaster as A New Treatment for Surgical Site Infection in Patients with Cesarean Delivery: A Randomized, Double-Blind, Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy of Chinese plaster containing rhubarb and mirabilite on surgical site infection (SSI) in patients with cesarean delivery (CD) by performing a randomized controlled trial.@*METHODS@#This randomized controlled trial included 560 patients with CD due to fetal head descent enrolled at a tertiary teaching center between December 31, 2018 and October 31, 2021. Eligible patients were randomly assigned to a Chinese medicine (CM) group (280 cases) or a placebo group (280 cases) by a random number table, and were treated with CM plaster (made by rhubarb and mirabilite) or a placebo plaster, respectively. Both courses of treatment lasted from the day 1 of CD, followed day 2 until discharge. The primary outcome was the total number of patients with superficial, deep and organ/space SSI. The secondary outcome was duration of postoperative hospital stay, antibiotic intake, and unplanned readmission or reoperation due to SSI. All reported efficacy and safety outcomes were confirmed by a central adjudication committee that was unaware of the study-group assignments.@*RESULTS@#During the recovery process after CD, the rates of localized swelling, redness and heat were significantly lower in the CM group than in the placebo group [7.55% (20/265) vs. 17.21% (47/274), P<0.01]. The durution of postoperative antibiotic intake was shorter in the CM group than in the placebo group (P<0.01). The duration of postoperative hospital stay was significantly shorter in the CM group than in the placebo group (5.49 ± 2.68 days vs. 8.96 ± 2.35 days, P<0.01). The rate of postoperative C-reactive protein elevation (≽100 mg/L) was lower in the CM group than in the placebo group [27.6% (73/265) vs. 43.8% (120/274), P<0.01]. However, there was no difference in purulent drainage rate from incision and superficial opening of incision between the two groups. No intestinal reactions and skin allergies were found in the CM group.@*CONCLUSIONS@#CM plaster containing rhubarb and mirabilite had an effect on SSI. It is safe for mothers and imposes lower economic and mental burdens on patients undergoing CD. (Registration No. ChiCTR2100054626).

Rescuing Cardiac Cells and Improving Cardiac Function by Targeted Delivery of Oxygen-Releasing Nanoparticles after or Even before Acute Myocardial Infarction.

Myocardial infarction (MI) causes massive cell death due to restricted blood flow and oxygen deficiency. Rapid and sustained oxygen delivery following MI rescues cardiac cells and restores cardiac function. However, current oxygen-generating materials cannot be administered during acute MI stage without direct injection or suturing methods, both of which risk rupturing weakened heart tissue. Here, we present infarcted heart-targeting, oxygen-releasing nanoparticles capable of being delivered by intravenous injection at acute MI stage, and specifically accumulating in the infarcted heart. The nanoparticles can also be delivered before MI, then gather at the injured area after MI. We demonstrate that the nanoparticles, delivered either pre-MI or post-MI, enhance cardiac cell survival, stimulate angiogenesis, and suppress fibrosis without inducing substantial inflammation and reactive oxygen species overproduction. Our findings demonstrate that oxygen-delivering nanoparticles can provide a nonpharmacological solution to rescue the infarcted heart during acute MI and preserve heart function.

Simultaneous Photo-Induced Magnetic and Dielectric Switching in an Iron(II)-Based Spin-Crossover Hofmann-Type Metal-Organic Framework.

Molecular materials possessing photo-tunable polarization switching is promising for optical switches, smart sensors, and data storage devices. However, it is challenging to devise a molecular material featuring simultaneous switchable magnetic and dielectric properties with regard to non-invasive and convenient light stimulus. Herein, we report a new Hofmann-type metal-organic framework (MOF) {Fe(bpt)[Pt(CN)4 ]} ⋅ 0.5anth (1, bpt=2,5-bis(4-pyridyl)thiophen; anth=anthracene), which displays thermo- and photo-switchable magnetic and dielectric properties. Photo-monitored structural analyses revealed that it was the photo-induced deformation of FeII coordination sphere and relative movement of guest anthracene that resulted in the variation of the local electric dipoles. These findings provide a new strategy to realize polarization switching through the light-induced spin crossover, and would be of fundamental significance for future photo-switchable and multifunctional materials.

Sustained delivery of rhMG53 promotes diabetic wound healing and hair follicle development.

MG53 is an essential component of the cell membrane repair machinery, participating in the healing of dermal wounds. Here we develop a novel delivery system using recombinant human MG53 (rhMG53) protein and a reactive oxygen species (ROS)-scavenging gel to treat diabetic wounds. Mice with ablation of MG53 display defective hair follicle structure, and topical application of rhMG53 can promote hair growth in the mg53 -/- mice. Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells (HFSCs). We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes. The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs. The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice. These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds.

Delivery of VEGF and delta-like 4 to synergistically regenerate capillaries and arterioles in ischemic limbs.

Vascularization of the poorly vascularized limbs affected by critical limb ischemia (CLI) is necessary to salvage the limbs and avoid amputation. Effective vascularization requires forming not only capillaries, but also arterioles and vessel branching. These processes rely on the survival, migration and morphogenesis of endothelial cells in the ischemic limbs. Yet endothelial cell functions are impaired by the upregulated TGFß. Herein, we developed an injectable hydrogel-based drug release system capable of delivering both VEGF and Dll4 to synergistically restore endothelial cellular functions, leading to accelerated formation of capillaries, arterioles and vessel branching. In vitro, the Dll4 and VEGF synergistically promoted the human arterial endothelial cell (HAEC) survival, migration, and formation of filopodial structure, lumens, and branches under the elevated TGFß1 condition mimicking that of the ischemic limbs. The synergistic effect was resulted from activating VEGFR2, Notch-1 and Erk1/2 signaling pathways. After delivering the Dll4 and VEGF via an injectable and thermosensitive hydrogel to the ischemic mouse hindlimbs, 95% of blood perfusion was restored at day 14, significantly higher than delivery of Dll4 or VEGF only. The released Dll4 and VEGF significantly increased density of capillaries and arterioles, vessel branching point density, and proliferating cell density. Besides, the delivery of Dll4 and VEGF stimulated skeletal muscle regeneration and improved muscle function. Overall, the developed hydrogel-based Dll4 and VEGF delivery system promoted ischemic limb vascularization and muscle regeneration. STATEMENT OF SIGNIFICANCE: Effective vascularization of the poorly vascularized limbs affected by critical limb ischemia (CLI) requires forming not only capillaries, but also arterioles and vessel branching. These processes rely on the survival, migration and morphogenesis of endothelial cells. Yet endothelial cell functions are impaired by the upregulated TGFß in the ischemic limbs. Herein, we developed an injectable hydrogel-based drug release system capable of delivering both VEGF and Dll4 to synergistically restore endothelial cell functions, leading to accelerated formation of capillaries, arterioles and vessel branching.

Efficacy of ultra-mini percutaneous nephrolithotomy and retrograde intrarenal surgery in the treatment of 2-3 cm lower calyceal stones / Eficacia de la nefrolitotomía percutánea ultramini y la cirugía intrarrenal retrógrada en el tratamiento de cálculos caliceales inferiores de 2-3 cm

Abstract We aimed to compare the efficacy and safety of ultra-mini percutaneous nephrolithotomy (UMP) and retrograde intrarenal surgery (RIRS) for the management of lower calyceal stones. A group of 136 patients with a single lower calyceal stone (2-3 cm in diameter) was divided into the UMP or RIRS groups. The average operation time in the RIRS group was significantly longer than that in the UMP group, and the intraoperative blood loss in the former was markedly less than that in the latter. Besides, in the RIRS group, the decreased value of postoperative Hb was obviously lower, the postoperative hospital stay was evidently shorter, and the total hospitalization expenses were markedly less than those in UMP group were. Moreover, the success rate of the first-stage lithotripsy in the UMP group was notably higher than that in RIRS group. The RIRS group had an obviously lower VAS score but a markedly higher BCS score than the UMP group six hours after surgery. At 24 h after operation, the levels of serum CRP, TNF-α and IL -6 in patients in both groups were remarkably increased, and they were evidently lower in the RIRS group than those in the UMP group were. Three days after surgery, the levels of serum CRP, TNF-α and IL -6 were notably lower in the UMP group than those in RIRS group were. RIRS and UMP are safe and effective in the treatment of 2-3 cm lower calyceal stones. The first-stage UMP is characterized by a high stone-free rate (SFR), short operation time and low postoperative infection risk, while RIRS is associated with less blood loss and low total expenses.

Resumen Nuestro objetivo fue comparar la eficacia y seguridad de la nefrolitotomía percutánea ultramini (UMP) y la cirugía intrarrenal retrógrada (CRIR) en el manejo quirúrgico de los cálculos caliceales inferiores. Un grupo de 136 pacientes con un solo cálculo calicial inferior (2-3 cm de diámetro) se dividió en un grupo UMP o un grupo CRIR. El tiempo de operación promedio en el grupo CRIR fue significativamente más largo que en el grupo UMP, y la pérdida de sangre intraoperatoria en el primero fue marcadamente menor que en el segundo. Además, en el grupo CRIR, el valor disminuido de la Hb postoperatoria fue obviamente menor, la estancia hospitalaria postoperatoria fue evidentemente más corta y los gastos totales de hospitalización fueron notablemente menores que los del grupo UMP. Además, la tasa de éxito de la litotricia de primera etapa en el grupo UMP fue notablemente más alta que en el grupo CRIR. El grupo CRIR tuvo una puntuación VAS obviamente más baja pero una puntuación BCS marcadamente más alta que el grupo UMP a seos horas después de la operación. A las 24 h después de la operación, los niveles séricos de PCR, TNF-α e IL -6 en los pacientes de ambos grupos aumentaron notablemente y fueron evidentemente más bajos en el grupo CRIR que en el grupo UMP. Tres días después de la operación, los niveles séricos de PCR, TNF-α e IL -6 fueron notablemente más bajos en el grupo UMP que en el grupo CRIR. Los procedimientos CRIR y el UMP son seguros y eficaces en el tratamiento de cálculos caliciales inferiores de 2-3 cm. El UMP de primera etapa se caracteriza por tener una tasa libre de cálculo (SFR) alta, un tiempo de operación corto y un riesgo de infección posoperatorio bajo, y el RIRS se caracteriza por una menor pérdida de sangre y gastos totales bajos.

Single-Cell Transcriptome Analysis Reveals Embryonic Endothelial Heterogeneity at Spatiotemporal Level and Multifunctions of MicroRNA-126 in Mice.

BACKGROUND: Endothelial cells (ECs) play a critical role in angiogenesis and vascular remodeling. The heterogeneity of ECs has been reported at adult stages, yet it has not been fully investigated. This study aims to assess the transcriptional heterogeneity of developmental ECs at spatiotemporal level and to reveal the changes of embryonic ECs clustering when endothelium-enriched microRNA-126 (miR-126) was specifically knocked out. METHODS: C57BL/6J mice embryos at day 14.5 were harvested and digested, followed by fluorescence-activated cell sorting to enrich ECs. Then, single-cell RNA sequencing was applied to enriched embryonic ECs. Tie2 (Tek receptor tyrosine kinase)-cre-mediated ECs-specific miR-126 knockout mice were constructed, and ECs from Tie2-cre-mediated ECs-specific miR-126 knockout embryos were subjected to single-cell RNA sequencing. RESULTS: Embryonic ECs were clustered into 11 groups corresponding to anatomic characteristics. The vascular bed (arteries, capillaries, veins, lymphatics) exhibited transcriptomic similarity across the developmental stage. Embryonic ECs had higher proliferative potential than adult ECs. Integrating analysis showed that 3 ECs populations (hepatic, mesenchymal transition, and pulmonary ECs) were apparently disorganized after miR-126 being knocked out. Gene ontology analysis revealed that disrupted ECs were mainly related to hypoxia, glycometabolism, and vascular calcification. Additionally, in vivo experiment showed that Tie2-cre-mediated ECs-specific miR-126 knockout mice exhibited excessive intussusceptive angiogenesis; reductive glucose and pyruvate tolerance; and excessive accumulation of calcium. Agonist miR-126-3p agomir significantly rescued the phenotype of glucose metabolic dysfunction in Tie2-cre-mediated ECs-specific miR-126 knockout mice. CONCLUSIONS: The heterogeneity of ECs is established as early as the embryonic stage. The deficiency of miR-126 disrupts the differentiation and diversification of embryonic ECs, suggesting that miR-126 plays an essential role in the maintenance of ECs heterogeneity.

Strengthening capacity-building in malaria and schistosomiasis control under China-Africa cooperation: Assessing a case study of Burkina Faso.

Malaria and schistosomiasis are highly prevalent in Burkina Faso, whereas China has successfully eliminated malaria as well as schistosomiasis as a public health problem. To implement the China-Africa health cooperation initiative, a series of activities were launched since 2019 to enhance understanding and cooperation among malaria and schistosomiasis professionals in China and Burkina Faso. This study described the achievements of the First Virtual Symposium of China-Burkina Faso Cooperation on Schistosomiasis and Malaria Control. Pre- and post-test questionnaires were employed to study the knowledge changes of participants regarding malaria and schistosomiasis control and elimination, explore capacity-building priorities, and identify potential challenges. Chi-squared statistics were used to compare the differences between sub-groups, and p value < 0.05 was considered statistically significant. Participants ranked their preferences for challenges and capacity-building priorities in future cooperation. The responses of participants from both China and Burkina Faso indicated effective improvement in their general knowledge about the diseases whereas the improvement in professional knowledge on malaria and schistosomiasis was limited. The total correct response rate increased from 54.08% to 66.78%. Chinese participants had better schistosomiasis knowledge than Burkina Faso participants did, but the same result was not found for malaria. Diseases control strategies, surveillance and response system, and diagnostics techniques were identified as the top three priorities for future capacity building. Participants from China and Burkina Faso shared almost the same views about challenges except with respect to pathogens, which the former saw as a major challenge and the latter did not. The study findings will help policymakers, health managers, and researchers to understand the future cooperation between Burkina Faso and China on malaria and schistosomiasis.

Dynamics of Early Serum Tumour Markers and Neutrophil-to-Lymphocyte Ratio Predict Response to PD-1/PD-L1 Inhibitors in Advanced Non-Small-Cell Lung Cancer.

PURPOSE: To evaluate the dynamics of early serum tumour markers (STMs) and the neutrophil-to-lymphocyte ratio (NLR) to predict clinical efficacy and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who received programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. PATIENTS AND METHODS: We retrospectively reviewed patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors between September 2017 and August 2020. NLR and STMs were routinely measured between immunotherapy initiation and the first radiological evaluation. A combination score based on the leading STM and NLR and their dynamic changes was established. The effects of leading STM change, NLR change, and the combination score on the objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analysed. The accuracy of the combination score was evaluated by receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: Overall, 124 patients were included in this retrospective cohort study. The ORR was 22.8%, DCB was 54.5%, and the median OS and PFS were 21.6 and 14.9 months, respectively. Patients with low combination scores had a significantly improved ORR and DCB compared with those with intermediate or high scores (P = 0.002 for ORR, P < 0.0001 for DCB). In a multivariate model, the combination score was an independent indicator of PFS (P < 0.0001) and OS (P < 0.0001). The AUC demonstrated that the combination score (AUC = 0.706) has greater predictive power than either the posttreatment NLR (AUC = 0.668) or the leading STM change (AUC = 0.648) alone. CONCLUSION: An easy, cost-effective, and novel combination score based on the dynamics of an early STM and the NLR can accurately predict the clinical efficacy of PD-1/PD-L1 inhibitors and prognosis in advanced NSCLC patients.