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Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals.
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Ceramidas , Proteínas de Ligação ao GTP , Animais , Humanos , Longevidade/genética , Células Endoteliais/metabolismo , Mamíferos/metabolismoRESUMO
Apoptosis is a genetically regulated program of cell death that plays a key role in immune disease processes. We identified EBF4, a little-studied member of the early B cell factor (EBF) family of transcription factors, in a whole-genome CRISPR screen for regulators of Fas/APO-1/CD95-mediated T cell death. Loss of EBF4 increases the half-life of the c-FLIP protein, and its presence in the Fas signaling complex impairs caspase-8 cleavage and apoptosis. Transcriptome analysis revealed that EBF4 regulates molecules such as TBX21, EOMES, granzyme, and perforin that are important for human natural killer (NK) and CD8+ T cell functions. Proximity-dependent biotin identification (Bio-ID) mass spectrometry analyses showed EBF4 binding to STAT3, STAT5, and MAP kinase 3 and a strong pathway relationship to interleukin-2 regulated genes, which are known to govern cytotoxicity pathways. Chromatin immunoprecipitation and DNA sequencing analysis defined a canonical EBF4 binding motif, 5'-CCCNNGG/AG-3', closely related to the EBF1 binding site; using a luciferase-based reporter, we found a dose-dependent transcriptional response of this motif to EBF4. We also conducted assay for transposase-accessible chromatin sequencing in EBF4-overexpressing cells and found increased chromatin accessibility upstream of granzyme and perforin and in topologically associated domains in human lymphocytes. Finally, we discovered that the EBF4 has basal expression in human but not mouse NK cells and CD8+ T cells and vanishes following activating stimulation. Together, our data reveal key features of a previously unknown transcriptional regulator of human cytotoxic immune function.
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Apoptose , Linfócitos T CD8-Positivos , Citotoxicidade Imunológica , Proteína Ligante Fas , Linfócitos T Citotóxicos , Fatores de Transcrição , Animais , Apoptose/fisiologia , Cromatina/metabolismo , Citotoxicidade Imunológica/genética , Proteína Ligante Fas/metabolismo , Granzimas/genética , Humanos , Camundongos , Perforina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Objectives To screen high active volatile organic compounds (VOCs)-producing Trichoderma isolates against strawberry gray mold caused by Botrytis cinerea, and to explore their antagonistic mode of action against the pathogen. VOCs produced by nine Trichoderma isolates (Trichoderma atroviride T1 and T3; Trichoderma harzianum T2, T4 and T5; T6, T7, T8 and T9 identified as Trichoderma asperellum in this work) significantly inhibited the mycelial growth (13.9-63.0% reduction) and conidial germination (17.6-96.3% reduction) of B. cinerea, the highest inhibition percentage belonged to VOCs of T7; in a closed space, VOCs of T7 shared 76.9% and 100% biocontrol efficacy against gray mold on strawberry fruits and detached leaves, respectively, prolonged the fruit shelf-life by 3 days in presence of B. cinerea, completely protected the leaves from B. cinerea infecting; volatile metabolites of T7 damaged the cell membrane permeability and integrity of B. cinerea, thereby inhibiting the mycelial growth and conidial germination. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the VOCs contain 23 potential compounds, and the majority of these compounds were categorised as alkenes, alcohols, and esters, including PEA and 6PP, which have been reported as substances produced by Trichoderma spp. T. asperellum T7 showed high biofumigant activity against mycelial growth especially conidial germination of B. cinerea and thus protected strawberry fruits and leaves from gray mold, which acted by damaging the pathogen's plasma membrane and resulting in cytoplasm leakage, was a potential biofumigant for controlling pre- and post-harvest strawberry gray mold.
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BACKGROUND: Interscalene catheters (ISC) are considered as the gold standard for perioperative pain control after total shoulder arthroplasty (TSA). Liposomal bupivacaine (LB) for interscalene blocks (ISB) or the addition of dexamethasone to ISBs have both presented as additional options for extended analgesia. We aimed to compare the efficacy of LB to a single shot ISB (SISB) with added dexamethasone to an ISC. We hypothesized that a single injection of LB or an ISB with a dexamethasone will provide non-inferior duration and quality of analgesia compared to ISC. METHODS: A single centered triple blinded randomized controlled trial evaluated patients undergoing elective primary TSA. Patients were randomized to 3 groups, Group A (control): 0.5% bupivacaine 15 ml with a rescue catheter left in situ (0.125% bupivacaine infusion), Group B: 0.5% bupivacaine 14 ml with 4mg (1 ml) dexamethasone with a catheter left in situ (saline infusion), Group C: 10 ml of liposomal bupivacaine (133 mg) with 0.5% bupivacaine 5 ml, with a catheter left in situ (saline infusion). The primary outcome was the worst NRS (numeric rating scale) measured on arrival to PACU, 6 hours, 12 hours, 24 hours, and 36 hours postoperatively. Secondary outcomes recorded were time to first analgesic request, intraoperative opioid consumption, total inpatient opioid consumption, arm weakness, arm numbness, time of analgesia duration, time of motor recovery, sensory testing using pinprick on POD1, Q36, Q48, hand strength assessment using dynamometer POD1, Q36, Q48, PACU and hospital length of stay. RESULTS: We analyzed 72 patients in 3 groups (Group A 24, group B 24, Group C 24). The pre-surgery physical function scores were similar between groups. The change in postoperative pain was not different among the three groups. All 3 groups demonstrated an increase in the postoperative values, a change that was not statistically significant between groups. Likewise, no difference in the mental function score was seen within or between groups. No differences in sleep quality or satisfaction were seen among groups (P values 0.405 and 1.00, respectively). No adverse events were reported in all groups. CONCLUSIONS: No significant difference was demonstrated between a single injection ISB with dexamethasone, a LB injection and an ISC. Given the equivalence in analgesia provided with these three modalities, providers should carefully consider the option that best fits each patient. Thus, a single injection of LB or single injection of bupivacaine with dexamethasone provides similar analgesic efficacy compared to ISC.
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Understanding rhinoplasty characteristics important to patients, physicians, and society is essential for evaluating outcomes and designing optimal treatment plans. The authors aimed to elucidate specific rhinoplasty-related outcomes that are most important to patients, surgeons, and the general population. A cross-sectional survey comprising 11 rhinoplasty-specific characteristics, was distributed to patients, facial plastic surgeons, and the general population. Adult patients presenting for rhinoplasty consideration or follow-up after undergoing rhinoplasty were recruited. Characteristics rankings were compared between the 3 respondent groups using Spearman's rank correlation coefficient (ρ). Responses from 150 surgeons, 111 patients, and 102 lay individuals from the general population were included for analysis. When ranking rhinoplasty-specific characteristics in order of importance, patients and the general population ranked "ability to breathe through nose while awake" first and "overall appearance of nose" as second. Surgeons ranked "overall appearance of nose" first and "ability to breathe through nose while awake" second. There were strong correlations between patients' and surgeons' rankings (Spearman's ρ=0.836, P =0.002), between patients' and the general population's rankings (Spearman's ρ=0.773, P =0.007), and between surgeons' and the general population's rankings (Spearman's ρ=0.782, P =0.006). Our results highlight a significant correlation between characteristics of the "ideal" nose as determined by patients, surgeons, and the general population.
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Rinoplastia , Humanos , Feminino , Masculino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários , Resultado do Tratamento , Satisfação do Paciente , EstéticaRESUMO
Objective: To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. Methods: A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage â ¢B to â £ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared. Results: In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05). Conclusions: The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.
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Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Objective: To establish a method for the determination of n-butylamine in the air of the workplace by ion chromatography. Methods: In February 2022, on-site sampling was carried out using an atmospheric sampler. N-butylamine was adsorbed by a neutral silica gel tube and then performed for qualitative and quantitative determination by ion chromatography after ultrasonic desorption with 10 mmol/L sulfuric acid solution. Results: The linear range of the method was 0.0375-100.0 µg/ml, the linear equation of the standard curve was y=0.0713x-0.0327, the correlation coefficient was 0.9992. The detection limit of the method was 11.25 µg/L, and the lower limit of quantification was 37.50 µg/L, the lowest quantitative concentration was 0.025 mg/m(3) (in term of sampling 7.5 L). The average desorption efficiency of the method was 91.50%-95.38%, the precision was 1.10%-2.30%, the standard recovery was 83.83%-100.02%, sampling efficiency was 100.00%. Conclusion: This method is fast, sensitive and accurate, and can be used for the determination of n-butylamine in the air of workplace.
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Poluentes Ocupacionais do Ar , Butilaminas , Poluentes Ocupacionais do Ar/análise , Cromatografia/métodos , Local de TrabalhoRESUMO
Exotic spin-dependent interactions involving new light particles address key questions in modern physics. Interactions between polarized neutrons (n) and unpolarized nucleons (N) occur in three forms: g_{S}^{N}g_{P}^{n}σ·r, g_{V}^{N}g_{A}^{n}σ·v, and g_{A}^{N}g_{A}^{n}σ·v×r, where σ is the spin and g's are the corresponding coupling constants for scalar, pseudoscalar, vector, and axial-vector vertexes. If such interactions exist, the Sun and Moon could induce sidereal variations of effective fields in laboratories. By analyzing existing data from laboratory measurements on Lorentz and CPT violation, we derive new experimental upper limits on these exotic spin-dependent interactions at astronomical ranges. Our limits on g_{S}^{N}g_{P}^{n} surpass the previous combined astrophysical-laboratory limits, setting the most stringent experimental constraints to date. We also report new constraints on vector-axial-vector and axial-axial-vector interactions at astronomical scales, with vector-axial-vector limits improved by â¼12 orders of magnitude. We extend our analysis to Hari Dass interactions and obtain new constraints.
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Objective: To explore the safety and effectiveness of early stent implantation in patients with acute anterior circulation large artery disease. Methods: Patients were recruited from the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). Patients who were diagnosed with acute ischemic stroke within 24 hours of onset and given endovascular treatment after consultation from July 2018 to May 2019 from 18 sub-centers nationwide were retrospectively enrolled. According to whether the stents were placed during the operation, the patients were divided into two groups: stenting group and non-stenting group. The baseline between the two groups was matched by propensity score. The matching variables included age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Glasgow Coma Scale (GCS) score, history of stroke, smoking and onset to hospital time. The primary clinical outcome was 90-day good neurological outcome [defined as modified Rankin score (mRS) 0-2]. Secondary outcomes include 90-day mortality, 24-hour re-occlusion of the responsible artery, and symptomatic intracranial hemorrhage. The differences in clinical endpoints between the two groups were compared. Result: A total of 899 patients with acute anterior circulation artery stenosis or occlusion were included in the study, with a mean age of(66±12)years,and 532(59.18%) were male. There were 193 patients in the stenting group and 706 patients in the non-stenting group. After the baseline data between the two groups were matched by propensity score, 169 patients were enrolled in each of two groups respectively. After matching, the proportion of patients in the stenting group with etiological diagnosis of large atherosclerosis [82.53% (137/166) vs 55.69% (93/167)] and the proportion of patients with previous history of hypertension [63.31% (107/169) vs 47.93% (81/169)] in the stenting group were higher than those in the non-stenting group (both P<0.05). While the proportion of patients in the non-stenting group with cardiogenic embolism [37.73%(63/167) vs 11.45%(19/166)]and the proportion of patients with atrial fibrillation [18.93% (32/169) vs 10.65%(18/169)]was higher(all P<0.05). In the stenting group, the time from onset to recanalization was longer[519 (408, 620)min vs 469 (365, 690)min], and the proportion of general anesthesia [50.89% (86/169) vs 35.50% (60/169)] was higher in the stenting group(both P<0.05). In addition, in the stenting group, the proportion of patients receiving mechanical thrombectomy[67.46% (114/169) vs 88.76% (150/169)] and arterial thrombolysis [2.37% (4/169) vs 18.93% (32/169)] was lower than non-stenting group during the operation, while the proportion of patients receiving balloon dilation [53.85% (91/169) vs 13.61% (23/169)]was higher(both P<0.05). The proportion of patients in stent group receiving antiplatelet drugs before operation was higher [13.46% (21/169) vs 8.70% (14/169)](both P<0.05). In terms of clinical outcome, compared with the non-stenting group, the proportion of patients in the stenting group with good neurological function in 90 days was lower [44.79% (73/169) vs 56.36% (93/169)], and the proportion of death at 90 days was higher[15.98% (27/169) vs 8.88% (15/169)] (both P<0.05). There was no significant difference between the two groups in 24-hour re-occlusion[8.88% (15/169) vs 9.47% (16/169)] and symptomatic intracranial hemorrhage[5.92% (10/169) vs 4.76% (8/169)](both P>0.05). Conclusion: For patients with acute anterior circulation artery disease, early stent therapy may increase the proportion of patients with adverse neurological outcomes.
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Doenças Cardiovasculares , Hipertensão , AVC Isquêmico , Estados Unidos , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Retrospectivos , Artérias , Doença Aguda , Hemorragias IntracranianasRESUMO
Scarring, naturally induced by fibroblasts(Fb) during wound healing, is an essential process in response to repair damaged tissue. Excessive Fb proliferation which produces the excessive collagen deposition, including increased extracellular matrix synthesis or insufficient decomposition, typically contributes to hypertrophic scar(HS) formation. Although exact mechanisms of HS are not yet fully understood, it is generally believed that dysfunction of Fb and regulation of signal pathways play an important role in HS formation. Biologically, Fb function is affected by various factors such as cytokines, extracellular matrix and itself. In addition, modifications of miRNA, ceRNA, lncRNA, peptides and histones participate in HS formation by affecting the biological function of Fb. Despite the clinical importance, very few therapeutic modalities are available to prevent HS. To achieve this, a deeper characterization of Fb is required to identify mechanisms of HS. To the aspect of HS prevention and treatment, we review recent findings, concentrating on Fb function and collagen secretion. The objective of this article is to frame the current understanding, gain the deeper insights into Fb function, and provide the more comprehensive cognition and perspective for prevention and treatment of HS.
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Cicatriz Hipertrófica , Humanos , Cicatriz Hipertrófica/prevenção & controle , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/metabolismo , Colágeno/metabolismo , Colágeno/uso terapêutico , Fibroblastos , Transdução de Sinais , Matriz Extracelular/metabolismoRESUMO
Circular RNAs are implicated in the pathogenesis of ischemic stroke. In this work, we explored the modulation and potential mechanisms of action of circ_0005585 in ischemic stroke. Expression of circ_0005585 and miR-16-5p was assessed by quantitative real-time reverse transcription PCR. Ischemic stroke was modeled in mice by middle cerebral artery occlusion (MCAO). The infarct volume was assessed by triphenyl tetrazolium chloride staining. Neurological deficits were evaluated according to Neurological Severity Score. The permeability of the blood-brain barrier was assessed by Evan's blue leakage and brain water content. Apoptosis in brain tissues was measured by the TUNEL test. Relative expression of apoptosis-related proteins was evaluated by Western blotting. The direct interaction between circ_0005585 and miR-16-5p was verified by dual-luciferase reporter assay. The expression of circ_0005585 was lower in mice with MCAO. Lentivirus-mediated overexpression of circ_0005585 ameliorated the neurological deficits and decreased the infarction volume in MCAO mice. The brain water content and Evan's blue leakage through the blood-brain barrier were reduced. In addition, overexpression of circ_0005585 inhibited apoptosis in the cerebral tissues. Our results revealed direct interaction between circ_0005585 and miR-16-5p. Hence, circ_0005585 protects mouse brain during ischemic stroke by targeting miR-16-5p, which uncovers the pathogenesis of this pathology and opens new vitas for its therapy.
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Isquemia Encefálica , AVC Isquêmico , MicroRNAs , Traumatismo por Reperfusão , Camundongos , Animais , Isquemia Encefálica/metabolismo , Azul Evans , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Apoptose/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismoRESUMO
Acute-on-chronic liver failure (ACLF) is a potentially reversible entity that occurs in patients with chronic liver disease accompanied with or without cirrhosis and is characterized by extrahepatic organ failure and high short-term mortality. Currently, the most effective treatment method for patients with ACLF is liver transplantation; therefore, admission timing and contraindications must be emphasized. The function of vital organs such as the heart, brain, lungs, and kidneys should be actively supported and protected during the liver transplantation perioperative period in patients with ACLF. Focusing on the anesthesia management level during anesthesia selection, intraoperative monitoring, three-stage management, prevention and treatment of post-perfusion syndrome, monitoring and management of coagulation function, volume monitoring and management, and body temperature monitoring management for liver transplantation should strengthen anesthesia management. Additionally, standard postoperative intensive care treatment should be recommended, and grafts and other vital organ functions should be monitored throughout the perioperative period to promote early postoperative recovery in patients with ACLF.
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Insuficiência Hepática Crônica Agudizada , Transplante de Fígado , Humanos , Insuficiência Hepática Crônica Agudizada/cirurgia , Cirrose Hepática/complicações , Período Perioperatório , PrognósticoRESUMO
Objective: To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer. Methods: 393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests. Results: 367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant (χ (2) = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant (χ (2) = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant (χ (2) = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion: In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.
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Biomarcadores Tumorais , Neoplasias Hepáticas , Septinas , Humanos , alfa-Fetoproteínas/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Cirrose Hepática/sangue , Cirrose Hepática/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Septinas/sangue , Septinas/genética , Septinas/metabolismo , Metilação de DNA , Sensibilidade e Especificidade , Análise Química do SangueRESUMO
The development of ocular organoids, which closely mimic the tissue structure and functionality of the human eye, has emerged as a prominent area of research in the field of ophthalmology. These organoids serve as valuable models for investigating the mechanisms and interventions of eye-related diseases. However, the establishment of in vitro models that accurately represent the tissue structure and functionality of the human eye has long been a challenge in ophthalmic research. Numerous efforts have been made to enhance the fidelity of ocular organoid models, aiming to improve their suitability for studying disease pathogenesis and drug efficacy. With advancements in technology, it has become possible to construct individual components of the eye, such as the cornea and retina, in vitro. This review summarizes the recent advancements in ocular organoid research, with a focus on corneal and retinal organoids.
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Oftalmopatias , Organoides , Humanos , Retina , Córnea , FaceRESUMO
Proliferative vitreoretinopathy (PVR) is an avascular fibroproliferative disease that occurs in the retina. The main pathological changes are the proliferation and traction of retinal pigment epithelial cells (RPE) and glial cells on the vitreous and retina. Basic research has confirmed that the formation of PVR is related to multiple signaling pathways, including NK-κB signaling pathway, MAPK and its downstream signaling pathways, JAK/STAT signaling pathway, PI3K/Akt signaling pathway, thrombin and its receptor pathway, TGF-ß and downstream signaling pathway, North signaling pathway and Wnt/ß-catenin signaling pathway, etc. This review summarizes the research progress of the main signaling pathways in the formation mechanism of PVR, and provides the basis and support for the research of PVR drug therapy.
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Vitreorretinopatia Proliferativa , Humanos , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Retina , NeurôniosRESUMO
Objective: To investigate the characteristics of initial ocular symptoms in children with optic pathway glioma (OPG) at different age stages. Methods: A retrospective case series study was conducted. Clinical data of 16 children with OPG who were diagnosed and treated in the Department of Ophthalmology, Beijing Children's Hospital, Capital Medical University from April 2017 to July 2021 were collected. The initial ocular symptoms, clinical manifestations of the eyes and nervous system, imaging and histopathological features were analyzed, and the differences in initial ocular symptoms between infants and young children aged≤36 months and older children aged>36 months were compared. Results: Of all 16 children included, 9 were male and 7 were female. The onset age was 15.0 (6.3, 56.5) months, and the diagnosis age was 48.0 (11.3, 78.0) months. There were 11 infants and young children, and 5 older children. Eye symptoms were the initial manifestation in 11 cases, including 8 cases of infants and young children (5 cases presented with irregular nystagmus, 2 cases with strabismus, and 1 case with failure to chase visual target), and 3 cases of older children (2 cases presented with decreased vision and 1 case with optic disc edema). The imaging findings showed that optic chiasm-involved OPG accounted for the highest proportion, with 3 cases in older children and 8 cases in infants and young children. Among the 8 children with optic chiasm-involved OPG who underwent surgical treatment, 5 were diagnosed with pilocytic astrocytoma according to histopathological results. Seven children had useful vision saved after treatment, and 1 child had visual loss accompanied by cognitive impairment due to surgery after 4 years of nystagmus. Conclusion: OPG in children often manifests as initial ocular symptoms, with irregular nystagmus being more common in infants and young children, and vision loss being the main symptom in older children.
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Nistagmo Patológico , Glioma do Nervo Óptico , Lactente , Criança , Humanos , Masculino , Feminino , Adolescente , Pré-Escolar , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Glioma do Nervo Óptico/complicações , Glioma do Nervo Óptico/diagnóstico , Glioma do Nervo Óptico/patologia , Transtornos da VisãoRESUMO
Objective: To establish a high performance liquid chromatography method for the determination of misoprostol in workplace air. Methods: From February to August 2021, the misoprostol in the workplace air was collected by glass fiber filter membrane, and theeluent was separated by C18 liquid chromatography column, determined by UV detector, and quantified by external standard method. Results: The quantitative lower limit of misoprostol determination method was 0.05 µg/ml, and the lowest quantitative concentration was 1.4 µg/m(3) (calculated by collecting 75 L air sample). The concentration of misoprostol has a good linear relationship between 0.05 to 10.00 µg/ml. The relative coefficient was 0.9998. The regression equation of the standard working curve was y=495759x-45257. The range of average recovery rates were from 95.5% to 102.8%. The intra-assay precision of the method was 1.2%-4.6%, and the inter-assay precision was 2.0%-5.9%. The samples could be stored stably for 7 days at 4 â. Conclusion: The high performance liquid chromatography method for the determination of misoprostol has high sensitivity, good specificity and simple procedure of sample pretreatment. It is suitable for the detection of misoprostol in the workplace air.
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Poluentes Ocupacionais do Ar , Misoprostol , Cromatografia Líquida de Alta Pressão/métodos , Misoprostol/análise , Poluentes Ocupacionais do Ar/análise , Local de Trabalho , Cromatografia LíquidaRESUMO
This paper reported 3 cases of poisoning caused by chlorfenagyr. Chlorfenapyr poisoning has gradually increased in clinical practice. The early stage after poisoning is digestive tract symptoms, followed by sweating, high fever, changes in consciousness, changes in myocardial enzymology, etc. Its main mechanism of intoxication is uncoupling oxidative phosphorylation. Since there is no specific antidote after poisoning, the fatality rate of chlorfenapyr poisoning remains high. The therapeutic measures are early gastrointestinal decontamination, symptomatic and supportive treatments, and early blood purification may be an effective treatment.
Assuntos
Inseticidas , Intoxicação , Piretrinas , Humanos , Trato Gastrointestinal , Intoxicação/diagnósticoRESUMO
Objective: To evaluate the accuracy and applicability of detection tube method for quantitative detection of hydrogen sulfide in workplace air. Methods: In September 2021, the lower limit of quantification, accuracy, precision, environmental factors, interfering gases and other performance indicators of the method for determining hydrogen sulfide in the air of workplace were verified by the detection tube, and the results were compared with those of GB 11742-89 "Standard method for hygienic examination of hydrogen sulfide in air of residential areas-methylene blue spectrophotometric method" to evaluate the application effect of the detection tube method for quantitative detection of hydrogen sulfide in workplace air. Results: There was no significant difference in the results of 2.83 mg/m(3), 4.25 mg/m(3) and 17.00 mg/m(3) hydrogen sulfide concentration between the two methods (P>0.05) , but there was significant difference in the results of 8.50 mg/m(3) concentration (P<0.05) . The lower limit of quantification of hydrogen sulfide in workplace air was 2.83 mg/m(3), the accuracy was 96.0%-111.0%, and the precision was 0.70%-6.64%. Under the condition of 4 â, the measured results decreased by 3.39%-13.10%. When the humidity was 50%-80%, the relative error of the average measured value was -1.67%-4.44%. Interference gases that may exist in the workplace (including carbon dioxide, carbon monoxide, mercaptans, nitrogen oxides, sulfur dioxide, etc.) did not interfere with the results of the test tube. Conclusion: The accuracy and precision of the detection tube method meet the detection requirements. The method is simple, rapid and easy to be popularized, and can be used for the rapid detection of hydrogen sulfide gas concentration in the workplace.