RESUMEN
Staphylococcus xylosus has emerged as a bovine mastitis pathogen with increasing drug resistance, resulting in substantial economic impacts. This study utilized iTRAQ analysis to investigate the mechanisms driving resistance evolution in S. xylosus under ceftiofur sodium stress. Findings revealed notable variations in the expression of 143 proteins, particularly glycolysis-related proteins (TpiA, Eno, GlpD, Ldh) and peptidoglycan (PG) hydrolase Atl. Following the induction of ceftiofur sodium resistance in S. xylosus, the emergence of resistant strains displaying characteristics of small colony variants (SCVs) was observed. The transcript levels of TpiA, Eno, GlpD and Ldh were up-regulated, TCA cycle proteins (ICDH, MDH) and Atl were down-regulated, lactate content was increased, and NADH concentration was decreased in SCV compared to the wild strain. That indicates a potential role of carbon metabolism, specifically PG hydrolysis, glycolysis, and the TCA cycle, in the development of resistance to ceftiofur sodium in S. xylosus.
Asunto(s)
Antibacterianos , Carbono , Cefalosporinas , Farmacorresistencia Bacteriana , Staphylococcus , Cefalosporinas/farmacología , Cefalosporinas/metabolismo , Antibacterianos/farmacología , Staphylococcus/efectos de los fármacos , Staphylococcus/genética , Staphylococcus/metabolismo , Carbono/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Animales , Bovinos , Glucólisis/efectos de los fármacos , Ciclo del Ácido Cítrico , Mastitis Bovina/microbiología , Infecciones Estafilocócicas/microbiología , Pruebas de Sensibilidad Microbiana , FemeninoRESUMEN
Objective: To evaluate and explore the feasibility of using quality control indicators for nutritional therapy in critically ill patients as quality evaluation criteria. Methods: This study focused on intensive care unit (ICU) critically ill patients and conducted a cross-sectional investigation of nutritional therapy quality control indicators (the proportion of patients with application of enteral nutrition pump, nutritional risk assessment rate, the proportion of patients start enteral nutrition within 48 hours, and caloric and protein target achievement rate on 7th day) in 13 hospitals in Jilin Province. After training according to the critical patients nutrition related guidelines and the latest literatures, a second cross-sectional investigation was conducted. Then, analyze the improvement of quality control indicators of the nutritional therapy before and after the training, thus evaluating the feasibility of using these quality control indicators as nutritional therapy quality evaluation criteria in critical patients. Results: (1) A total of 631 patients were included before and after training, with a data acquisition rate of 97.3% for enteral nutrition pumps usage and complete data collection for the remaining nutritional risk assessment rate, start enteral nutrition proportion of patients within 48 h, and caloric and protein target achievement rate on 7th day. (2) The nutritional risk assessment rate before and after training was 88.2% vs. 94.8%, with a P-value of 0.003. The proportion of patients start enteral nutrition within 48 h before and after training was 65.1% vs. 75.4%, with a P-value of 0.039; and protein target achievement rate on 7th day before and after training was 64.6% vs. 79.6%, with a p-value of 0.015. These five indicators as quality evaluation criteria are relevant to the current developments in nutritional therapy and consistent with the national conditions of China. The proportion of patients with application of enteral nutrition pump before and after training was 70.1% vs. 79.4%, with a p-value of 0.065, and the caloric target achievement rate on 7th day before and after training was 73.4% vs. 83.9%, with a p-value of 0.062, and there was no statistical difference between the two groups. Conclusion: The five quality control indicators for nutritional therapy in critically ill patients are clinically feasible and can be used as quality evaluation criteria for nutritional therapy in critically ill patients.
RESUMEN
The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to â¼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.
RESUMEN
China has the largest pig herd in the world which accounts for more than 50% of the global pig population. Over the past three decades, the porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic loss to the Chinese swine industry. Currently, the prevalent PRRSV strains in the field are extremely complicated, and the NADC30-like strains, NADC34-like strains, and novel recombinant viruses have become a great concern to PRRS control in China. In this study, a novel NADC30-like PRRSV, named GS2022, was isolated from the lung of a dead pig collected from a farm that experienced a PRRS outbreak. The complete genome of GS2022 shares the highest identity with the NADC30 strain and contains a discontinuous deletion of 131 aa in nsp2. Novel deletion and insertion have been identified in ORF7 and 3'UTR. Recombination analysis revealed that the GS2022 is a potential recombinant of NADC30-like and JXA1-like strains. Both inter-lineage and intra-lineage recombination events were predicted to be involved in the generation of the GS2022. An infectious cDNA clone of GS2022 was assembled to generate the isogenic GS2022 (rGS2022). The growth kinetics of rGS2022 were almost identical to those of GS2022. The pathogenicity of the GS2022 and rGS2022 was evaluated using a nursery piglet model. In the infection groups, the piglets exhibited mild clinical symptoms, including short periods of fever and respiratory diseases. Both gross lesions and histopathological lesions were observed in the lungs and lymph nodes of the infected piglets. Therefore, we reported a novel recombinant NADC30-like PRRSV strain with moderate pathogenicity in piglets. These results provide new information on the genomic characteristics and pathogenicity of the NADC30-like PRRSV in China.
RESUMEN
Destruction of subcellular organelles can cause dysfunction and even death of cells to elicit immune responses. In this review, the characteristics and functions of important organelles are mainly summarized. Then, the intelligent immunotherapeutic strategies and suggestions based on influencing the organelles are further highlighted. This review will provide ideas for developing novel and effective immunotherapy strategies and advance the development of cancer immunotherapy.
Asunto(s)
Inmunoterapia , Neoplasias , Orgánulos , Humanos , Neoplasias/terapia , Neoplasias/inmunología , AnimalesRESUMEN
A nano-immunomodulator modified with N-acetylgalactosamine (GalNAc) on calcium carbonate (CaCO3) was prepared for targeted and responsive immunotherapy. And the immunologic adjuvant (CpG ODNs) and doxorubicin (DOX) were released to synergistically improve immune response for treating orthotopic liver cancer.
Asunto(s)
Acetilgalactosamina , Carbonato de Calcio , Doxorrubicina , Inmunoterapia , Neoplasias Hepáticas , Carbonato de Calcio/química , Doxorrubicina/química , Doxorrubicina/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Acetilgalactosamina/química , Animales , Humanos , Ratones , Nanopartículas/química , Factores Inmunológicos/química , Factores Inmunológicos/farmacologíaRESUMEN
Current evidence suggests that porcine circovirus type 2 (PCV2) infection induces immunosuppression in piglets. Sophora subprostrate polysaccharide (SSP) exhibits various pharmacological activities, including immunoregulatory, anti-inflammatory, antiviral, and antioxidant properties. However, the acts of lncRNAs in regulating the therapeutic effects of SSP on PCV2-infected RAW264.7 cells remains poorly understood. This study aimed to investigate the molecular mechanisms by which lncRNAs regulate PCV2-induced immunosuppression during SSP treatment. Our findings revealed that 1699 mRNAs, 373 lncRNAs, and 129 miRNAs were differentially expressed in PCV2-infected RAW264.7 cells. Additionally, 359 mRNAs, 271 lncRNAs, and 79 miRNAs exhibited differential expression in SSP-treated PCV2-infected RAW264.7 cells. GO and KEGG analyses indicated that the candidate genes were enriched in the TNF/NF-κB signaling pathway. Furthermore, based on GO and KEGG pathway analysis, a ceRNA network involving chemokine (C-X-C motif) ligand 2 (CXCL2), miR-217-x, and MSTRG.5823.1 was constructed. We demonstrated that lncRNA MSTRG.5823.1 localized to the cytoplasm. Moreover, we found that silencing or overexpressing lncRNA MSTRG.5823.1 significantly modulated PCV2-induced immunosuppression by regulating the activation of the TNF/NF-κB signaling pathway. Specifically, lncRNA MSTRG.5823.1 overexpression increased the expression of TNF/NF-κB signaling pathway-related genes and proteins in PCV2-infected RAW264.7 cells. Conversely, silencing lncRNA MSTRG.5823.1 decreased their expression. Rescue assays further revealed that the suppressive effects of miR-217-x overexpression on TNF/NF-κB signaling pathway-related genes and proteins could be reversed by MSTRG.5823.1 overexpression. These findings highlight the critical role of lncRNA MSTRG.5823.1 in PCV2 infection progression and suggest a new strategy for the prevention and treatment of PCV2 infection.
Asunto(s)
Infecciones por Circoviridae , Circovirus , FN-kappa B , Polisacáridos , ARN Largo no Codificante , Transducción de Señal , Sophora , Animales , Ratones , Circovirus/inmunología , FN-kappa B/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Infecciones por Circoviridae/inmunología , Polisacáridos/farmacología , Porcinos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , MicroARNs/genética , MicroARNs/metabolismo , Tolerancia Inmunológica/efectos de los fármacosRESUMEN
Tumor-associated macrophages (TAMs), as the most prevalent immune cells in the tumor microenvironment, play a pivotal role in promoting tumor development through various signaling pathways. Herein, we have engineered a Se@ZIF-8 core-satellite nanoassembly to reprogram TAMs, thereby enhancing immunotherapy outcomes. When the nanoassembly reaches the tumor tissue, selenium nanoparticles and Zn2+ are released in response to the acidic tumor microenvironment, resulting in a collaborative effort to promote the production of reactive oxygen species (ROS). The generated ROS, in turn, activate the nuclear factor κB (NF-κB) signaling pathway, driving the repolarization of TAMs from M2-type to M1-type, effectively eliminating cancer cells. Moreover, the nanoassembly can induce the immunogenic death of cancer cells through excess ROS to expose calreticulin and boost macrophage phagocytosis. The Se@ZIF-8 core-satellite nanoassembly provides a potential paradigm for cancer immunotherapy by reversing the immunosuppressive microenvironment.
Asunto(s)
Inmunoterapia , Especies Reactivas de Oxígeno , Selenio , Microambiente Tumoral , Macrófagos Asociados a Tumores , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Especies Reactivas de Oxígeno/metabolismo , Ratones , Animales , Humanos , Selenio/química , Selenio/farmacología , Neoplasias/terapia , Neoplasias/inmunología , FN-kappa B/metabolismo , Nanopartículas/química , Nanopartículas/uso terapéutico , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Reprogramación Celular/efectos de los fármacos , Fagocitosis/efectos de los fármacosRESUMEN
Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti-inflammatory, antioxidant, and anti-apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF-κB, ROS/TXNIP/NLRP3, HO-1/Nrf2, Wnt/ß-catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.
RESUMEN
With the proposal of the 2030 Agenda for Sustainable Development, the Chinese medicine extraction technology has been innovatively improved to prioritize low energy consumption, sustainability, and minimized organic solvent utilization. Forsythia suspensa (FS) possesses favorable pharmacological properties and is extensively utilized in traditional Chinese medicine. However, due to the limitations of the composition and extraction methods, its potential has not been fully developed. Thus, a combination of ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), and ß-cyclodextrin extraction (ß-CDE) was employed to isolate and purify rutin, phillyrin, and forsythoside A from FS. The results demonstrated that the efficiency of extracting enzymatic and ultrasound assisted ß-cyclodextrin extraction (EUA-ß-CDE) was highly influenced by the temperature and duration of hydrolysis, as well as the duration of the extraction process. According to the results of the single-factor experiment, Box-Behnken design (BBD) in Response surface method (RSM) was used to optimize the experimental parameters to achieve the maximum comprehensive evaluation value (CEV) value. The EUA-ß-CDE compared with other extraction methods, has good extraction effect and low energy consumption by high performance liquid chromatography (HPLC), scanning electron microscopy (SEM), calculation of power consumption and CO2 emission The EUA-ß-CDE compared with other extraction methods, has good extraction effect and low energy consumption by HPLC, SEM, calculation of power consumption and CO2 emission. Then, the structural characteristics of EUA-ß-CDE of FS extract had significant interaction with ß-CD by Fourier infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In addition, EUA-ß-CDE extract has good antioxidant and anti-inflammatory activities. The establishment of EUA-ß-CDE of FS provides a new idea for the development and application of other sustainable extraction methods of traditional Chinese medicine.
Asunto(s)
Antiinflamatorios , Antioxidantes , Forsythia , Ondas Ultrasónicas , beta-Ciclodextrinas , Forsythia/química , beta-Ciclodextrinas/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Fraccionamiento Químico/métodos , Enzimas/metabolismo , Temperatura , Glucósidos/aislamiento & purificación , Glucósidos/química , Glucósidos/farmacología , Hidrólisis , Rutina/aislamiento & purificación , Rutina/química , Rutina/farmacologíaRESUMEN
BACKGROUND: Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues. METHODS: To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids. RESULTS: The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation. CONCLUSIONS: These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos , Células Madre Hematopoyéticas , Organoides , Humanos , Organoides/metabolismo , Organoides/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/citología , Factor Estimulante de Colonias de Granulocitos/farmacología , Células Madre Embrionarias Humanas/citología , Células Madre Embrionarias Humanas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Regeneración/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Antígenos CD34/metabolismoRESUMEN
Objective: Although the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methods: Twenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. Results: After the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. Conclusion: Parietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal-parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.
RESUMEN
BACKGROUND: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC. METHODS: This review summarized the advances in noninvasive neuromodulation in the treatment of pDoC in the last 5 years. RESULTS: Variable techniques of neuromodulation are used in pDoC. Transcranial ultrasonic stimulation (TUS) and transcutaneous auricular vagus nerve stimulation (taVNS) are very new techniques, while transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are still the hotspots in pDoC. Median nerve electrical stimulation (MNS) has received little attention in the last 5 years. CONCLUSIONS: Noninvasive neuromodulation is a valuable and promising technique to treat pDoC. Further studies are needed to determine a unified stimulus protocol to achieve optimal effects as well as safety.
Asunto(s)
Trastornos de la Conciencia , Estimulación Transcraneal de Corriente Directa , Estimulación Magnética Transcraneal , Estimulación del Nervio Vago , Humanos , Trastornos de la Conciencia/terapia , Estimulación Magnética Transcraneal/métodos , Estimulación Magnética Transcraneal/tendencias , Estimulación Transcraneal de Corriente Directa/métodos , Estimulación del Nervio Vago/métodos , Estimulación del Nervio Vago/tendencias , Estimulación Eléctrica Transcutánea del Nervio/métodos , Estimulación Eléctrica Transcutánea del Nervio/tendenciasRESUMEN
PURPOSE: This comprehensive investigation delved into the intricate causal interplay existing between cardiovascular-related plasma proteins and the susceptibility to colorectal cancer, leveraging the robust framework of Mendelian randomization, and employed expression profiling and survival analysis to unravel the latent clinical worth embedded within pertinent gene expressions. METHODS: Protein quantitative trait loci (pQTLs) of 85 cardiovascular proteins were employed as instrumental variables to investigate the causal relationship between proteins and CRC risk using a Mendelian randomization approach. Causal inferences were graded as strong, intermediate or weak based on statistical checks. Drug-target MR examined VEGF receptors for their potential as therapeutic targets for colorectal cancer. Differential expression analysis, diagnostic ROC curves, and survival analyses were performed for identified proteins using RNA-seq data from The Cancer Genome Atlas (TCGA) colorectal cancer cohort. RESULTS: Using cis-pQTLs, LOX-1, VEGF-A and OPG were associated with increased CRC risk (strong evidence), while PTX3, TNF-R2 and MMP-7 were protective (strong evidence). Pan-pQTL analysis found MMP-10 increased risk (intermediate evidence) and ADM increased risk (weak evidence). Drug-target MR found VEGF R1 may be promising therapeutic targets. Differential expression analysis revealed seven genes encoding the identified proteins were dysregulated in tumors. ROC analysis showed five gene expression had high diagnostic accuracy. KM analysis showed four genes had prognostic value. CONCLUSIONS: This large-scale MR study implicates several cardiovascular proteins in CRC susceptibility and progression. Findings highlight roles for VEGF signaling and extracellular matrix regulation. Results nominate specific proteins as potential diagnostic biomarkers or therapeutic targets warranting further investigation.
Asunto(s)
Neoplasias Colorrectales , Perfilación de la Expresión Génica , Análisis de la Aleatorización Mendeliana , Humanos , Neoplasias Colorrectales/genética , Sitios de Carácter Cuantitativo , Análisis de Supervivencia , Biomarcadores de Tumor/genética , Factores de Riesgo , Receptores Depuradores de Clase E/genética , Femenino , Predisposición Genética a la Enfermedad , MasculinoRESUMEN
This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.
Asunto(s)
Antibacterianos , Meropenem , Pruebas de Sensibilidad Microbiana , Choque Séptico , Humanos , Meropenem/farmacocinética , Meropenem/administración & dosificación , Meropenem/uso terapéutico , Choque Séptico/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Adulto , Perforación Intestinal , Anciano de 80 o más AñosRESUMEN
Purpose: Despite increased attention to the positive development of left-behind adolescents, research findings remain inconclusive. Utilizing latent profile analysis, we identified various positive development profiles among the left-behind adolescents and explored the association between resilience and positive development profiles, alongside the mediating role of making sense of adversity. Methods: A multi-stage cluster sampling procedure was employed, randomly selecting four provinces-Zhejiang, Guangdong, Henan, and Jiangxi-from the central and coastal regions. The sample comprised 718 left-behind adolescents recruited from primary and junior high schools across grades 4, 5, 7, and 8. Three scales were utilized, and analyses included latent profile analysis and mediation analysis. Results: Three latent subgroups of positive development among left-behind adolescents were identified: low, moderate, and high. Those with higher resilience and positive perceptions of adversity tended to belong to the high group rather than the low (ß = -0.45, p < 0.001; ß = -0.09, p < 0.001) or moderate group (ß = -0.23, p < 0.001; ß = -0.04, p < 0.05). Left-behind adolescents with higher negative perceptions of adversity tended to belong to the high group rather than the moderate group (ß = -0.07, p < 0.01). Mediation analysis revealed that resilience facilitated the development of positive appraisals of adversity, subsequently increasing the likelihood of being categorized into the high (95% CI of -0.09 to -0.03) or moderate group (95% CI of -0.05 to -0.01) rather than the low group. Conclusion: These findings hold significant implications for intervention formulation. Educators should focus on strengthening resilience and fostering positive perceptions of adversity among the low group. For the moderate group, maintaining moderate negative perceptions of adversity may stimulate the intrinsic potential for positive development more effectively.
RESUMEN
Research on the association between maternal PM2.5 exposure and hypospadias risk in male offspring, particularly in highly polluted areas, has been limited and inconsistent. This study leveraged data from China's National Population-based Birth Defects Surveillance System spanning the years 2013 to 2019, and employed sophisticated machine learning models to estimate daily PM2.5 levels and other pollutants for mothers at a 1-km resolution and a 6-km buffer surrounding maternal residences. Multivariate logistic regression analyses were performed to evaluate the relationship between PM2.5 exposure and hypospadias risk. For sensitivity analyses, stratification analysis was conducted, and models for one-pollutant and two-pollutants, as well as distributed lag nonlinear models, were constructed. Of the 1194,431 boys studied, 1153 cases of hypospadias were identified. A 10 µg/m3 increase in maternal PM2.5 exposure during preconception and the first trimester was associated with an elevated risk of isolated hypospadias, with Odds Ratios (ORs) of 1.102 (95% CI: 1.023-1.188) and 1.089 (95% CI: 1.007-1.177) at the 1-km grid, and 1.122 (95% CI: 1.034-1.218) and 1.143 (95% CI: 1.048-1.246) within the 6-km buffer. Higher quartiles of PM2.5 exposure were associated with increased odds ratios compared to the lowest quartile. These findings highlight a significant association between PM2.5 exposure during the critical conception period and an elevated risk of isolated hypospadias in children, emphasizing the need for targeted interventions to reduce PM2.5 exposure among expectant mothers.
Asunto(s)
Contaminantes Atmosféricos , Hipospadias , Exposición Materna , Material Particulado , Hipospadias/epidemiología , Humanos , Material Particulado/análisis , Femenino , Masculino , Exposición Materna/efectos adversos , China/epidemiología , Embarazo , Adulto , Contaminantes Atmosféricos/análisis , Efectos Tardíos de la Exposición Prenatal/epidemiología , Recién Nacido , Pueblos del Este de AsiaRESUMEN
AIMS: The aim of this study was to reveal the hepatic cell landscape and function in the progression of NAFLD to NASH. BACKGROUND: Non-alcoholic steatohepatitis (NASH) is the progressive form and turning point of nonalcoholic fatty liver disease (NAFLD), which severely causes irreversible cirrhosis as well as hepatocellular carcinoma. The mechanism underlying the progression of NAFLD to NASH has not been revealed. Unraveling the mechanism of action of NAFLD-NASH is an important goal in improving the survival of patients with liver disease. OBJECTIVE: The aim of this study is to discover heterogeneous hepatic cells during the progression of NAFLD to NASH. METHODS: Single-nucleus RNA-seq (snRNA-seq) data containing NASH in NAFLD samples were obtained from the Gene Expression Omnibus (GEO) database. Cell types in liver tissues from NASH and NAFLD were identified after dimensionality reduction analysis, cluster analysis, and cell annotation. The cell pathways in which differences existed were identified by analyzing metabolic pathways in Hepatic cells. We also identified cell subpopulations in Hepatic cells. The developmental trajectories of Hepatic cells were characterized by pseudotime trajectory analysis. Single-cell regulatory network inference and clustering analysis identified key transcription factors and gene regulatory networks in Hepatic cells. Moreover, cell communication analysis determined the potential interactions between Hepatic cells and immune cells, and heapatic stellate cells. RESULTS: Seven cell types were identified in NAFLD and NASH. The proportion of Hepatic cells was lower in NASH and showed greater energy metabolism and glucose metabolism activity. Hepatic cells exhibited heterogeneity, showing two cell subpopulations, Hepatic cells 1 and Hepatic cells 2. Dysregulation of lipid metabolism in Hepatic Cell 2 resulted in lipid accumulation in the liver, which might be involved in the progression of NAFLD. Four key transcription factors, BHLHE40, NFEL2L, RUNX1, and INF4A, were primarily found in Hepatic cells 2. The transcription factors within the hepatic cells 2 subpopulation mainly regulated genes related to lipid metabolism, energy metabolism, and inflammatory response. The cell communication analysis showed that hepatocyte interactions with immune cells were associated with inflammatory responses, while interactions with hepatic astrocytes were associated with liver injury and hepatocyte fibrosis. CONCLUSION: The hepatic cells 2 might promote the progression of NAFLD to NASH by regulating metabolic activity, which might contribute to liver injury through inflammation.
RESUMEN
BACKGROUND: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. STUDY DESIGN AND METHODS: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. RESULTS: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. CONCLUSION: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.
Asunto(s)
Eliminación de Componentes Sanguíneos , COVID-19 , Médicos , Humanos , Pandemias , Eliminación de Componentes Sanguíneos/métodos , Encuestas y CuestionariosRESUMEN
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo. Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.