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1.
Proc Natl Acad Sci U S A ; 120(40): e2305125120, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748051

RESUMO

Conductive metal-organic frameworks (cMOFs) manifest great potential in modern electrical devices due to their porous nature and the ability to conduct charges in a regular network. cMOFs applied in electrical devices normally hybridize with other materials, especially a substrate. Therefore, the precise control of the interface between cMOF and a substrate is particularly crucial. However, the unexplored interface chemistry of cMOFs makes the controlled synthesis and advanced characterization of high-quality thin films, particularly challenging. Herein, we report the development of a simplified synthesis method to grow "face-on" and "edge-on" cMOF nanofilms on substrates, and the establishment of operando characterization methodology using atomic force microscopy and X-ray, thereby demonstrating the relationship between the soft structure of surface-mounted oriented networks and their characteristic conductive functions. As a result, crystallinity of cMOF nanofilms with a thickness down to a few nanometers is obtained, the possible growth mechanisms are proposed, and the interesting anisotropic softness-dependent conducting properties (over 2 orders of magnitude change) of the cMOF are also illustrated.

2.
Mol Cell Proteomics ; 22(12): 100672, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37866481

RESUMO

Talaroconvolutin-A (TalaA) is a compound from the endophytic fungus T. convolutispora of the Chinese herbal medicine Panax notoginseng. Whether TalaA exerts anticancer activity in bladder cancer remains unknown. Using CCK8 assay, EdU staining, crystal violet staining, flow cytometry, living/dead cell staining, and Western blotting, we studied the anticancer activity of TalaA in vitro. Moreover, we performed xenograft tumor implantation. The antitumor effects were evaluated through H&E and immunohistochemistry staining. Proteomics was conducted to detect changes in the protein profile; transcriptomics was performed to detect changes in mRNA abundance; phosphoproteomics was used to detect changes in protein phosphorylation. TalaA inhibited tumor cell proliferation, DNA replication, and colony formation in a dose-dependent manner in bladder cancer cells. The IC50 values of TalaA on SW780 and UM-UC-3 cells were 5.7 and 8.2 µM, respectively. TalaA (6.0 mg/kg) significantly repressed the growth of xenografted tumors and did not affect the body weight nor cause obvious hepatorenal toxicity. TalaA arrested the cell cycle by downregulating cyclinA2, cyclinB1, and AURKB and upregulating p21/CIP. TalaA also elevated intracellular reactive oxygen species and upregulated transferrin and heme oxygenase 1 to induce ferroptosis. Moreover, TalaA was able to bind to MAPKs (MAPK1, MAPK8, and MAPK14) to inhibit the phosphorylation of ∗SP∗ motif of transcription regulators. This study revealed that TalaA inhibited bladder cancer by arresting cell cycle to suppress proliferation and triggering ferroptosis to cause cell death. Conclusively, TalaA would be a potential candidate for treating bladder cancer by targeting MAPKs, suppressing the cell cycle, and inducing ferroptosis.


Assuntos
Antineoplásicos , Ferroptose , Neoplasias da Bexiga Urinária , Humanos , Antineoplásicos/farmacologia , Proteômica , Apoptose , Linhagem Celular Tumoral , Ciclo Celular , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Proliferação de Células , Perfilação da Expressão Gênica
3.
Nucleic Acids Res ; 51(7): 3166-3184, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-36881772

RESUMO

The eukaryotic exon junction complex component Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. Using immunoprecipitation-RNA-seq, we identified a set of Y14-associated long non-coding RNAs (lncRNAs). The lncRNA HOTAIRM1 serves as a strong candidate that mediates the interaction between Y14 and the NHEJ complex. HOTAIRM1 localized to near ultraviolet laser-induced DNA damage sites. Depletion of HOTAIRM1 delayed the recruitment of DNA damage response and repair factors to DNA lesions and compromised the efficiency of NHEJ-mediated DSB repair. Identification of the HOTAIRM1 interactome revealed a large set of RNA processing factors including mRNA surveillance factors. The surveillance factors Upf1 and SMG6 localized to DNA damage sites in a HOTAIRM1-dependent manner. Depletion of Upf1 or SMG6 increased the level of DSB-induced non-coding transcripts at damaged sites, indicating a pivotal role for Upf1/SMG6-mediated RNA degradation in DNA repair. We conclude that HOTAIRM1 serves as an assembly scaffold for both DNA repair and mRNA surveillance factors that act in concert to repair DSBs.


Assuntos
Quebras de DNA de Cadeia Dupla , RNA Longo não Codificante , DNA , Reparo do DNA por Junção de Extremidades , Reparo do DNA/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Humanos , Linhagem Celular
4.
Mol Pain ; 20: 17448069241240692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38443317

RESUMO

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.


Assuntos
Dor do Câncer , Eletroacupuntura , Neoplasias , Neuropeptídeos , Ratos , Humanos , Camundongos , Animais , Dor do Câncer/etiologia , Dor do Câncer/terapia , Dor do Câncer/metabolismo , Nociceptividade , Camundongos Nus , Ratos Sprague-Dawley , Dor/metabolismo , Hiperalgesia/complicações , Hiperalgesia/terapia , Hiperalgesia/induzido quimicamente , Analgésicos/metabolismo , Inflamação/metabolismo , Medula Espinal/metabolismo
5.
Am J Transplant ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723867

RESUMO

Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3448 cases (1724 donor-recipient pairs) from January 2011 to March 2023 (NCT06062706). Among donors, 520 (30%) were female. Adult-to-adult LDLT comprised 1061 (62%) cases. A total of 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. Primary outcomes: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (P < .001) procedures. Pediatric and adult recipient mortality was similar among the 3 donor hepatectomy approaches: robotic 1.5% and 7.0%, compared with 2.3% and 8.3% laparoscopic, and 1.6% and 5.5% for open donor surgery, respectively (P = .802, P = .564). Secondary outcomes: pediatric and adult recipients major morbidity after robotic hepatectomy was 15% and 23%, compared with 25% and 44% for laparoscopic surgery and 19% and 31% for open surgery, respectively (P = .033, P < .001). Graft and recipient 5-year survival were 90% and 93% for pediatrics and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared with the laparoscopic and open approaches. Both donors and, for the first time reported, recipients benefitted from lower morbidity rates in robotic surgery, emphasizing its potential for further advancing this field.

6.
Liver Transpl ; 30(5): 484-492, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38015444

RESUMO

Due to the success of minimally invasive liver surgery, laparoscopic and robotic minimally invasive donor hepatectomies (MIDH) are increasingly performed worldwide. We conducted a retrospective, multicentre, propensity score-matched analysis on right lobe MIDH by comparing the robotic, laparoscopic, and open approaches to assess the feasibility, safety, and early outcomes of MIDHs. From January 2016 until December 2020, 1194 donors underwent a right donor hepatectomy performed with a robotic (n = 92), laparoscopic (n = 306), and open approach (n = 796) at 6 high-volume centers. Donor and recipients were matched for different variables using propensity score matching (1:1:2). Donor outcomes were recorded, and postoperative pain was measured through a visual analog scale. Recipients' outcomes were also analyzed. Ninety-two donors undergoing robotic surgery were matched and compared to 92 and 184 donors undergoing laparoscopic and open surgery, respectively. Conversions to open surgery occurred during 1 (1.1%) robotic and 2 (2.2%) laparoscopic procedures. Robotic procedures had a longer operative time (493 ± 96 min) compared to laparoscopic and open procedures (347 ± 120 and 358 ± 95 min; p < 0.001) but were associated with reduced donor blood losses ( p < 0.001). No differences were observed in overall and major complications (≥ IIIa). Robotic hepatectomy donors had significantly less pain compared to the 2 other groups ( p < 0.001). Fifty recipients of robotic-procured grafts were matched to 50 and 100 recipients of laparoscopic and open surgery procured grafts, respectively. No differences were observed in terms of postoperative complications, and recipients' survival was similar ( p =0.455). In very few high-volume centers, robotic right lobe procurement has shown to be a safe procedure. Despite an increased operative and the first warm ischemia times, this approach is associated with reduced intraoperative blood losses and pain compared to the laparoscopic and open approaches. Further data are needed to confirm it as a valuable option for the laparoscopic approach in MIDH.


Assuntos
Laparoscopia , Transplante de Fígado , Procedimentos Cirúrgicos Robóticos , Humanos , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doadores Vivos , Fígado , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Tempo de Internação
7.
Annu Rev Biomed Eng ; 25: 281-309, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37068764

RESUMO

Lipids are essential cellular components forming membranes, serving as energy reserves, and acting as chemical messengers. Dysfunction in lipid metabolism and signaling is associated with a wide range of diseases including cancer and autoimmunity. Heterogeneity in cell behavior including lipid signaling is increasingly recognized as a driver of disease and drug resistance. This diversity in cellular responses as well as the roles of lipids in health and disease drive the need to quantify lipids within single cells. Single-cell lipid assays are challenging due to the small size of cells (∼1 pL) and the large numbers of lipid species present at concentrations spanning orders of magnitude. A growing number of methodologies enable assay of large numbers of lipid analytes, perform high-resolution spatial measurements, or permit highly sensitive lipid assays in single cells. Covered in this review are mass spectrometry, Raman imaging, and fluorescence-based assays including microscopy and microseparations.


Assuntos
Lipídeos , Transdução de Sinais , Humanos , Lipídeos/análise , Lipídeos/química , Espectrometria de Massas/métodos , Metabolismo dos Lipídeos
8.
Hepatology ; 78(1): 136-149, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631003

RESUMO

BACKGROUND AND AIMS: The liver has the unique ability of regeneration, which is extremely important for restoring homeostasis after liver injury. Although clinical observations have revealed an association between psychological stress and the liver, whether stress has a causal influence on the liver regeneration remains markedly less defined. APPROACH AND RESULTS: Rearing rodents in an enriched environment (EE) can induce eustress or positive psychological stress. Herein, EE-induced eustress was found to significantly enhance the ability of liver regeneration after partial hepatectomy or carbon tetrachloride-induced liver injury based on the more rapid restoration of liver/body weight ratio and the significantly increased number of proliferating hepatocytes in EE mice. Mechanistically, the cytokine array revealed that IL-22 was markedly increased in the regenerating liver in response to EE. Blockade of IL-22 signaling abrogated the enhanced liver regeneration induced by EE. Group 1 innate lymphoid cells (ILCs), including type 1 ILCs (ILC1s), have been identified as the major sources of IL-22 in the regenerating liver. EE housing led to a rapid accumulation of hepatic ILC1s after partial hepatectomy and the EE-induced enhancement of liver regeneration and elevation of IL-22 was nearly eliminated in ILC1-deficient Tbx21-/- mice. Chemical sympathectomy or blockade of ß-adrenergic signaling also abolished the effect of EE on ILC1s and attenuated the enhanced liver regeneration of EE-housed mice. CONCLUSION: The study findings support the brain-liver axis and suggest that environment-induced eustress promotes liver regeneration through the sympathetic nerve/ILC1/IL-22 axis.


Assuntos
Imunidade Inata , Regeneração Hepática , Camundongos , Animais , Regeneração Hepática/fisiologia , Linfócitos , Interleucinas , Hepatectomia , Fígado , Hepatócitos/fisiologia , Camundongos Endogâmicos C57BL , Interleucina 22
9.
J Biomed Sci ; 31(1): 69, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992696

RESUMO

BACKGROUND: Local translation at synapses is important for rapidly remodeling the synaptic proteome to sustain long-term plasticity and memory. While the regulatory mechanisms underlying memory-associated local translation have been widely elucidated in the postsynaptic/dendritic region, there is no direct evidence for which RNA-binding protein (RBP) in axons controls target-specific mRNA translation to promote long-term potentiation (LTP) and memory. We previously reported that translation controlled by cytoplasmic polyadenylation element binding protein 2 (CPEB2) is important for postsynaptic plasticity and memory. Here, we investigated whether CPEB2 regulates axonal translation to support presynaptic plasticity. METHODS: Behavioral and electrophysiological assessments were conducted in mice with pan neuron/glia- or glutamatergic neuron-specific knockout of CPEB2. Hippocampal Schaffer collateral (SC)-CA1 and temporoammonic (TA)-CA1 pathways were electro-recorded to monitor synaptic transmission and LTP evoked by 4 trains of high-frequency stimulation. RNA immunoprecipitation, coupled with bioinformatics analysis, were used to unveil CPEB2-binding axonal RNA candidates associated with learning, which were further validated by Western blotting and luciferase reporter assays. Adeno-associated viruses expressing Cre recombinase were stereotaxically delivered to the pre- or post-synaptic region of the TA circuit to ablate Cpeb2 for further electrophysiological investigation. Biochemically isolated synaptosomes and axotomized neurons cultured on a microfluidic platform were applied to measure axonal protein synthesis and FM4-64FX-loaded synaptic vesicles. RESULTS: Electrophysiological analysis of hippocampal CA1 neurons detected abnormal excitability and vesicle release probability in CPEB2-depleted SC and TA afferents, so we cross-compared the CPEB2-immunoprecipitated transcriptome with a learning-induced axonal translatome in the adult cortex to identify axonal targets possibly regulated by CPEB2. We validated that Slc17a6, encoding vesicular glutamate transporter 2 (VGLUT2), is translationally upregulated by CPEB2. Conditional knockout of CPEB2 in VGLUT2-expressing glutamatergic neurons impaired consolidation of hippocampus-dependent memory in mice. Presynaptic-specific ablation of Cpeb2 in VGLUT2-dominated TA afferents was sufficient to attenuate protein synthesis-dependent LTP. Moreover, blocking activity-induced axonal Slc17a6 translation by CPEB2 deficiency or cycloheximide diminished the releasable pool of VGLUT2-containing synaptic vesicles. CONCLUSIONS: We identified 272 CPEB2-binding transcripts with altered axonal translation post-learning and established a causal link between CPEB2-driven axonal synthesis of VGLUT2 and presynaptic translation-dependent LTP. These findings extend our understanding of memory-related translational control mechanisms in the presynaptic compartment.


Assuntos
Plasticidade Neuronal , Proteínas de Ligação a RNA , Transmissão Sináptica , Proteína Vesicular 2 de Transporte de Glutamato , Animais , Camundongos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Plasticidade Neuronal/fisiologia , Transmissão Sináptica/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/genética , Camundongos Knockout , Axônios/metabolismo , Axônios/fisiologia , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Masculino , Biossíntese de Proteínas
10.
Ann Hematol ; 103(6): 1989-2001, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38233570

RESUMO

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.


Assuntos
Anticorpos Monoclonais , Linfoma Extranodal de Células T-NK , Humanos , Anticorpos Monoclonais/uso terapêutico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/imunologia , Masculino , Feminino , ADP-Ribosil Ciclase 1 , Pessoa de Meia-Idade , Idoso , Adulto , Glicoproteínas de Membrana
11.
Anesthesiology ; 140(3): 409-416, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039392

RESUMO

BACKGROUND: Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. METHODS: This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. RESULTS: The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, -0.64%; 97.5% CI, -2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, -10.8%; 97.5% CI, -14.0% to -8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. CONCLUSIONS: This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.


Assuntos
Gastroscopia , Propofol , Humanos , Método Simples-Cego , Benzodiazepinas , Peso Corporal , Hipnóticos e Sedativos
12.
BMC Neurol ; 24(1): 182, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822265

RESUMO

OBJECTIVES: To investigate the risk factors and underlying causes of pregnancy-related cerebral venous thrombosis (PCVT). METHODS: A retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT. RESULTS: PCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (P < 0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one was diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G > A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.677C > T (p. Ala222Val). CONCLUSIONS: The occurrence of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.


Assuntos
Trombose Intracraniana , Trombose Venosa , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Trombose Intracraniana/epidemiologia , Fatores de Risco , Trombose Venosa/epidemiologia , China/epidemiologia , Adulto Jovem , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/diagnóstico , Deficiência de Proteína S/epidemiologia , Deficiência de Proteína S/complicações , Deficiência de Proteína S/diagnóstico , Deficiência de Proteína S/genética
13.
Thromb J ; 22(1): 50, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886735

RESUMO

BACKGROUND: About 13-25% of cerebral venous thrombosis (CVT) cases lack clear etiology, which may be associated with underlying genetic factors. This study aims to investigate genetic factors in CVT patients using whole exome sequencing (WES). METHODS: Thirty-eight CVT patients hospitalized underwent WES. 977 subjects with WES data from a community cohort study --the Shunyi cohort were as the control group. Using bioinformatics analysis, differential genes with rare damaging variants between two groups were filtered (P < 0.05). KEGG enrichment analysis was performed on the screened genes to identify pathways associated with CVT. RESULTS: Through analysis of medical history, routine tests, and imaging examinations, the etiology of 38 patients: 8 cases of antiphospholipid syndrome, 6 cases with hematologic diseases, 3 cases of protein C deficiency, and 2 cases of protein S deficiency. Five cases occurred during pregnancy or puerperium, and 3 cases had a history of oral contraceptive use, and so on. The etiology was unknown in 12 cases (31.6%), and the etiology of 4 patients were further clarified through WES: F9 c.838 + 1_838 + 16del, Hemizygote: F9 EX1-EX7 Dup; CBS c.430G > A, CBS c.949 A > G; F2 c.1787G > A; SERPINC1 c.409-11G > T. Comparing the WES data of two groups, a total of 179 different genes with rare damaging variants were screened (P < 0.05), with 5 genes of interest (JAK2, C3, PROC, PROZ, SERPIND1). Enrichment analysis of the 179 different genes revealed the complement and coagulation pathway and the mitogen activated protein kinases (MAPK) pathway were associated with CVT. CONCLUSION: For CVT patients with unknown etiology, WES could help identify the cause of CVT early, which is of great significance for treatment decisions and prognosis. In addition to the complement and coagulation pathway, MAPK pathway is associated with CVT, potentially related to platelet regulation and inflammatory response.

14.
Neuroradiology ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844696

RESUMO

This retrospective study examined the clinical outcomes and complications in 6 cases of compound Meige's syndrome, presenting with blepharospasm and masticatory muscle spasm, following treatment with CT-guided radiofrequency ablation targeting bilateral facial nerves and mandibular branches of the trigeminal nerve. After the operation, the symptoms of eyelid spasm and masticatory muscle spasm resolved, but mild facial paralysis and numbness of mandibular nerve innervation persisted. Follow-up for 4-28 months showed that the symptoms of facial paralysis resolved within 2-5 (3.17 ± 0.94) months after the operation, whereas the numbness in the mandibular region persisted, accompanied by a decrease in masticatory function. During the follow-up period, none of the 6 patients experienced a recurrence of Meige's syndrome. These findings suggest that CT-guided radiofrequency ablation of the bilateral facial nerve and mandibular branches of the trigeminal nerve may offer a promising approach to treating compound Meige's syndrome.

15.
Surg Endosc ; 38(4): 2050-2061, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429573

RESUMO

BACKGROUND: Choledochoscopy is a highly effective approach for managing intrahepatic bile duct stones (IHDs). However, postoperative infection is a common complication that significantly impacts treatment outcomes. Despite its clinical relevance, the risk factors associated with this procedure remain largely unexplored. METHODS: This study focused on a consecutive cohort of patients who underwent choledochoscopy for IHDs at our institution between January 2016 and December 2022. The primary objective was to analyze the relationship between various clinical factors and postoperative infection, and to compare the postoperative infection of different choledochoscopic procedures. RESULTS: The study cohort consisted of 126 patients, with 60 individuals (47.6%) experiencing postoperative infection. Notably, preoperative biliary obstruction (odds ratio [OR] 1.861; 95% confidence interval [CI] 1.314-8.699; p = 0.010) and operation time (OR 4.414; 95% CI 1.635-12.376; p = 0.004) were identified as risk factors for postoperative infection. Additionally, biliary tract infections (60.00%) were primarily responsible for postoperative infection, with Escherichia coli (47.22%) being the predominant bacterial strain identified in bile cultures. Furthermore, biliary tract obstruction (OR 4.563; 95% CI 1.554-13.401; p = 0.006) and body mass index (BMI) (OR 1.186; 95% CI 1.015-1.386; p = 0.031) were determined to be independent risk factors for postoperative biliary tract infection. CONCLUSIONS: The occurrence of postoperative infection in patients undergoing choledochoscopy was primarily associated with the duration of the operation and the presence of preoperative biliary obstruction.


Assuntos
Colestase , Laparoscopia , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Ductos Biliares Intra-Hepáticos , Fatores de Risco
16.
Langenbecks Arch Surg ; 409(1): 143, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683375

RESUMO

BACKGROUND: Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors. RESULTS: Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2 years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33). CONCLUSION: Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Listas de Espera , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Feminino , Listas de Espera/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Longitudinais , Idoso , Adulto , Taxa de Sobrevida
17.
J Asian Nat Prod Res ; 26(3): 320-327, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37455565

RESUMO

Two new quinazoline alkaloids versicomides G-H (1 and 2), together with seven known compounds, were isolated from Aspergillus versicolor HYQZ-215 obtained from the sediment of Qarhan Salt Lake. Their structures were elucidated by NMR, HRESIMS, and quantum chemical ECD calculations data. The antimicrobial activities of these compounds were evaluated against seven agricultural pathogenic fungi and eight clinically drug-resistant bacteria.


Assuntos
Alcaloides , Anti-Infecciosos , Aspergillus , Estrutura Molecular , Quinazolinas/farmacologia , Quinazolinas/química , Alcaloides/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química
18.
Int J Nurs Pract ; : e13256, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570821

RESUMO

AIMS: This study describes the incidence of fatigue in kidney transplant recipients and analyses the relationship between physiological factors, psychological factors, situational factors and fatigue in kidney transplant recipients. BACKGROUND: Fatigue, as a common symptom after kidney transplantation, is affected by many factors, but the influence of some factors on the fatigue of kidney transplant recipients is still controversial. DESIGN: This cross-sectional study was designed based on the theory of unpleasant symptoms. METHODS: Our survey involved 307 participants attending the kidney transplant outpatient clinic of a tertiary Class A hospital (Changsha, Hunan, China). Data were collected between February and April 2021 using a structured questionnaire and electronic medical records. Data were analysed using IBM SPSS 25.0 (SPSS Inc.) RESULTS: It was found that the incidence of fatigue in kidney transplant recipients was 53.1%. According to the binary logistic regression analysis, sleep quality, hypokalemia, anxiety, depression and education level were independent risk factors for fatigue in kidney transplant recipients. CONCLUSION: The incidence of fatigue in kidney transplant recipients was high and was influenced by physical, psychological and situational factors. Clinical nurses should assess fatigue levels in a timely and multidimensional manner in clinical practice and provide effective and scientific guidance about fatigue self-coping and symptom management for kidney transplant recipients.

19.
Angew Chem Int Ed Engl ; 63(16): e202401679, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38389160

RESUMO

Electrically conductive metal-organic frameworks (cMOFs) have garnered significant attention in materials science due to their potential applications in modern electrical devices. However, achieving effective modulation of their conductivity has proven to be a major challenge. In this study, we have successfully prepared cMOFs with high conductivity by incorporating electron-donating fused thiophen rings in the frameworks and extending their π-conjugated systems through ring-closing reactions. The conductivity of cMOFs can be precisely modulated ranging from 10-3 to 102 S m-1 by regulating their dimensions and topologies. Furthermore, leveraging the inherent tunable electrical properties based on topology, we successfully demonstrated the potential of these materials as chemiresistive gas sensors with an outstanding response toward 100 ppm NH3 at room temperature. This work not only provides valuable insights into the design of functional cMOFs with different topologies but also enriches the cMOF family with exceptional conductivity properties.

20.
Angew Chem Int Ed Engl ; 63(21): e202401005, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38584128

RESUMO

Developing highly stable porous coordination polymers (PCPs) with integrated electrical conductivity is crucial for advancing our understanding of electrocatalytic mechanisms and the structure-activity relationship of electrocatalysts. However, achieving this goal remains a formidable challenge because of the electrochemical instability observed in most PCPs. Herein, we develop a "modular design" strategy to construct electrochemically stable semiconducting PCP, namely, Fe-pyNDI, which incorporates a chain-type Fe-pyrazole metal cluster and π-stacking column with effective synergistic effects. The three-dimensional electron diffraction (3D ED) technique resolves the precise structure. Both theoretical and experimental investigation confirms that the π-stacking column in Fe-pyNDI can provide an efficient electron transport path and enhance the structural stability of the material. As a result, Fe-pyNDI can serve as an efficient model electrocatalyst for nitrate reduction reaction (NO3RR) to ammonia with a superior ammonia yield of 339.2 µmol h-1 cm-2 (14677 µg h-1 mgcat. -1) and a faradaic efficiency of 87 % at neutral electrolyte, which is comparable to state-of-the-art electrocatalysts. The in-situ X-ray absorption spectroscopy (XAS) reveals that during the reaction, the structure of Fe-pyNDI can be kept, while part of the Fe3+ in Fe-pyNDI was reduced in situ to Fe2+, which serves as the potential active species for NO3RR.

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