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1.
Int Immunopharmacol ; 131: 111885, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38503015

RESUMO

Cinobufagin (CBG) is a natural active substance. Although its various pharmacological activities have been explored, the immunomodulatory activity of CBG remains unexplored. Therefore, this study aimed to investigate the anti-inflammatory and immunomodulatory activities of CBG ex vivo and in vivo. The immunomodulatory activity of CBG was investigated in RAW 264.7 cells. CBG showed no significant toxicity to cells. Additionally, 0.5-8 µg/mL CBG significantly increased the phagocytosis ability of macrophages and the secretion levels of IL-1ß and TNF-α. Thus, it exerted immunomodulatory effects. We established the immunosuppressive model induced by cyclophosphamide (CTX) in mice and studied the immunomodulatory activity of CBG in vivo. The experimental results showed that the intervention of CBG alleviated the CTX-induced weight loss, restored the lymphocyte nuclear cell number, and promoted the secretion and mRNA expression of cytokines IFN-γ, IL-4, IL-6, and IL-12. Moreover, CBG increased the immune organ index, protected the growth of the spleen and thymus, and improved the pathological changes in immunosuppressed mice. Western blot results showed that different concentrations of CBG upregulated the phosphorylation level of PI3K/Akt/mTOR in the spleen of CTX-induced immunosuppressed mice. This suggests that the immunomodulatory effect of CBG may be related to the regulation of PI3K/Akt/mTOR signaling pathway. This study provides a theoretical basis for developing CBG immune enhancers and opens up new ideas for the comprehensive utilization and development of CBG in factories.


Assuntos
Bufanolídeos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Fosfatidilinositol 3-Quinases/farmacologia , Ciclofosfamida/farmacologia , Terapia de Imunossupressão , Macrófagos , Serina-Treonina Quinases TOR
2.
iScience ; 27(3): 109223, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439978

RESUMO

In recent years, significant advancements have been made in the synthesis and application of 1,3-dienes. This specific structural motif has garnered significant attention from researchers in materials science and biology due to its unique aggregation-induced emission (AIE) properties and extensive conjugation systems. The luminescent characteristics of these compounds are notably influenced by the geometry of the two double bonds. Therefore, it is essential to consolidate stereoselective synthetic strategies for 1,3-dienes. This comprehensive review seeks to elucidate the diverse techniques employed to attain stereo-control in the synthesis of 1,3-diene-based AIE luminogens (AIEgens). Particular emphasis is placed on comprehending the determinants of stereoselectivity and exploring the array of substrates amenable to these methods. Furthermore, the review underscores the AIE properties exhibited by these compounds and their extensive utility in organic light-emitting diodes (OLEDs), stimuli-responsive materials, sensors, bioimaging, and photodynamic therapy (PDT).

3.
BMC Pulm Med ; 24(1): 130, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491484

RESUMO

Bronchopulmonary dysplasia (BPD) is characterized by alveolar dysplasia, and evidence indicates that interferon regulatory factor 4 (IRF4) is involved in the pathogenesis of various inflammatory lung diseases. Nonetheless, the significance and mechanism of IRF4 in BPD remain unelucidated. Consequently, we established a mouse model of BPD through hyperoxia exposure, and ELISA was employed to measure interleukin-17 A (IL-17 A) and interleukin-6 (IL-6) expression levels in lung tissues. Western blotting was adopted to determine the expression of IRF4, surfactant protein C (SP-C), and podoplanin (T1α) in lung tissues. Flow cytometry was utilized for analyzing the percentages of FOXP3+ regulatory T cells (Tregs) and FOXP3+RORγt+ Tregs in CD4+ T cells in lung tissues to clarify the underlying mechanism. Our findings revealed that BPD mice exhibited disordered lung tissue structure, elevated IRF4 expression, decreased SP-C and T1α expression, increased IL-17 A and IL-6 levels, reduced proportion of FOXP3+ Tregs, and increased proportion of FOXP3+RORγt+ Tregs. For the purpose of further elucidating the effect of IRF4 on Treg phenotype switching induced by hyperoxia in lung tissues, we exposed neonatal mice with IRF4 knockout to hyperoxia. These mice exhibited regular lung tissue structure, increased proportion of FOXP3+ Tregs, reduced proportion of FOXP3+RORγt+ Tregs, elevated SP-C and T1α expression, and decreased IL-17 A and IL-6 levels. In conclusion, our findings demonstrate that IRF4-mediated Treg phenotype switching in lung tissues exacerbates alveolar epithelial cell injury under hyperoxia exposure.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Animais , Camundongos , Células Epiteliais Alveolares/patologia , Linfócitos T Reguladores/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Hiperóxia/complicações , Displasia Broncopulmonar/metabolismo , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Fenótipo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo
4.
Mol Omics ; 20(4): 220-233, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38414408

RESUMO

Pancreatic cancer (PC) is a highly malignant cancer characterized by poor prognosis, high heterogeneity, and intricate heterocellular systems. Selecting an appropriate experimental model for studying its progression and treatment is crucial. Patient-derived models provide a more accurate representation of tumor heterogeneity and complexity compared to cell line-derived models. This review initially presents relevant patient-derived models, including patient-derived xenografts (PDXs), patient-derived organoids (PDOs), and patient-derived explants (PDEs), which are essential for studying cell communication and pancreatic cancer progression. We have emphasized the utilization of these models in comprehending intricate intercellular communication, drug responsiveness, mechanisms underlying tumor growth, expediting drug discovery, and enabling personalized medical approaches. Additionally, we have comprehensively summarized single-cell analyses of these models to enhance comprehension of intercellular communication among tumor cells, drug response mechanisms, and individual patient sensitivities.


Assuntos
Organoides , Neoplasias Pancreáticas , Análise de Célula Única , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Análise de Célula Única/métodos , Animais , Organoides/metabolismo , Microambiente Tumoral/genética , Comunicação Celular/genética , Medicina de Precisão
5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010332

RESUMO

OBJECTIVE@#To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway.@*METHODS@#Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR.@*RESULTS@#The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01).@*CONCLUSIONS@#EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.


Assuntos
Ratos , Masculino , Animais , Ratos Sprague-Dawley , Eletroacupuntura , Fosfatidilinositol 3-Quinase/metabolismo , Traumatismos do Nervo Facial/terapia , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Beclina-1 , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Mamíferos/metabolismo
6.
Chem Rec ; 23(12): e202300293, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38010365

RESUMO

Cancer stands as a serious malady, posing substantial risks to human well-being and survival. This underscores the paramount necessity to explore and investigate novel antitumor medications. Nitrogen-containing compounds, especially those derived from natural sources, form a highly significant category of antitumor agents. Among these, antitumor agents with six-membered aromatic nitrogen heterocycles have consistently attracted the attention of chemists and pharmacologists. Accordingly, we present a comprehensive summary of synthetic strategies and clinical implications of these compounds in this review. This entails an in-depth analysis of synthesis pathways for pyridine, quinoline, pyrimidine, and quinazoline. Additionally, we explore the historical progression, targets, mechanisms of action, and clinical effectiveness of small molecule inhibitors possessing these structural features.


Assuntos
Antineoplásicos , Compostos Heterocíclicos , Humanos , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Nitrogênio/química , Antineoplásicos/farmacologia , Antineoplásicos/química
7.
Nucleic Acids Res ; 51(W1): W520-W527, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37194711

RESUMO

Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.


Assuntos
Elementos Facilitadores Genéticos , Redes Reguladoras de Genes , Software , Fatores de Transcrição , Animais , Humanos , Camundongos , Regulação da Expressão Gênica , Genômica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
8.
Am Surg ; 89(5): 1673-1681, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35099329

RESUMO

OBJECTIVE: The present study conducted a meta-analysis to forecast the risk factors associated with level-VII lymph node metastases in case of thyroid neoplasms, intending to assist in determining the requirement for level-VII lymph node lymphadenectomy during the surgery. METHODS: Electronic databases, PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, VIP, and CBM electronic databases were searched for studies focused on level-VII lymph node metastases in thyroid neoplasms, published up to April 2021. Stata 13.1 software was used for analyses. RESULTS: The literature search identified a total of 997 studies. Among these, 8 studies, involving 1813 patients, were included in the present case. All these studies were case-control studies. Results for meta-analysis showed that male (OR = 1.340, 95% CI: 1.018-1.764, P = .037), age < 45 years (OR = 4.178, 95% CI: 1.601-10.908, P = .003), tumor size ≥ 2.0 cm (OR = 1.960, 95% CI: 1.079-3.562, P = .027), extrathyroidal extension (OR = 2.037, 95% CI: 1.578-2.630, P < .001), distant metastasis (OR = 2.775, 95% CI: 2.005-3.840, P < .001), central lymph node metastasis (OR = 3.500, 95% CI: 1.127-10.874, P = .03), contralateral cervicolateral metastasis (OR = 2.119, 95% CI: 1.514-2.965, P < .001), and bilateral nodal metastasis (OR = 4.651, 95% CI: 2.697-8.020, P < .001) acted as risk factors for level-VII lymph node metastases. In addition to this, sensitivity analyses and bias test showed that the results of meta-analysis were reliable and stable and involved no publication bias. CONCLUSION: In the present study, male gender, age < 45 years, tumor size ≥ 2.0 cm, extrathyroidal extension, distant metastasis, central lymph node metastasis, contralateral cervicolateral metastasis, and bilateral nodal metastasis were identified as risk factors for level-VII lymph node metastases in case of thyroid neoplasms.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Papilar/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia
9.
Chinese Journal of Trauma ; (12): 299-308, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-992602

RESUMO

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

10.
Chinese Journal of Trauma ; (12): 204-213, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-992589

RESUMO

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

11.
Journal of Medical Biomechanics ; (6): E324-E330, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-987954

RESUMO

Objective Aiming at the problems of lacking initiative in upper limb rehabilitation training equipment, single training mode, and low active participation of patients, an upper limb continuous motion estimation algorithm model based on multi-modal information fusion was proposed, so to realize accurate estimation of elbow joint torque. Methods Firstly, the surface electromyography (sEMG) signal and posture signal of participants were collected at four angular velocities, and the time domain characteristics of the signal were extracted. The principal component analysis was adopted to multi-feature fusion. The back propagation neural network (BPNN) was optimized through the additional momentum and the adaptive learning rate method. The particle swarm optimization (PSO) algorithm was used to optimize the neural network and a continuous motion estimation model based on PSO-BPNN was constructed. Finally, the joint torque calculated by the second type of Lagrangian equation was used as the accurate value to train the model. The performance of the model was compared with the traditional BP neural network model. Results The root mean square error (RMSE) of the traditional BP neural network model was 558.9 N·m, and the R2 coefficient was 77.19%, Whereas the RMSE and the R2 coefficient of the optimized model were 113.6 mN·m and 99.12%, respectively.Thereby, the accuracy of torque estimation was improved apparently. Conclusions The method for continuous motion estimation of the elbow joint proposed in this study can estimate the motion intention accurately, and provide a practical scheme for the active control of upper exoskeleton rehabilitation robot.

12.
Chinese Medical Ethics ; (6): 130-135, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005521

RESUMO

By reviewing the necessity, current status of cognitive attitudes, influencing factors, and improvement strategies of inpatients’ living wills, this paper proposed to strengthen the publicity and promotion of living wills to advance the development of death with dignity, improve relevant influencing factors, and provide feasible solutions for living wills, and actively develop tools to assess the cognition and attitude of living wills, with a view to providing reference for further promoting the application of living wills in inpatients and improving related research.

13.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1003134

RESUMO

METHODS@#Rat BMSCs were isolated, cultured and identified. The time-dependent expressions of TSP-2 and Sox9 in BMSCs under a dynamic mechanical pressure of 0–120 kPa at 0.1 Hz for 1 h were tested by qPCR and Western blotting. The role of TSP-2 in chondrogenic differentiation of BMSCs under mechanical pressure was validated by using small interfering RNA. The impact of TSP-2 and mechanical pressure on chondrogenesis were detected and the downstream signaling molecules were explored using Western blotting. @*RESULTS@#Mechanical pressure stimulation of 0–120 kPa for 1 h significantly upregulated the expression of TSP-2 in BMSCs. The expression of the chondrogenesis markers Sox9, Aggrecan, and Col-II were all upregulated under dynamic mechanical pressure or TSP-2 stimulation. Additional exogenous TSP-2 may potentiate the chondrogenic effect of mechanical stimulation. After knock down TSP-2, the upregulation of Sox9, Aggrecan and Col-II under mechanical pressure was inhibited. The NF-jB signaling pathway responded to both dynamic pressure and TSP-2 stimulation, and the cartilage-promoting effect was blocked by an NF-jB signaling inhibitor. @*CONCLUSION@#TSP-2 plays an essential role in the chondrogenic differentiation of BMSCs under mechanical pressure. NF-jB signaling is involved in the mechano-chemical coupling of TSP-2 and mechanical pressure for the chondrogenic differentiation of BMSCs.

14.
Acta Pharmaceutica Sinica ; (12): 127-138, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-964293

RESUMO

Juvenile zebrafish were used to screen the active components of Lycii Fructus for improving osteoporosis. The screening results were further verified by zebrafish adult osteoporosis model and the action mechanism was explored. Prednisolone was used as the inducer to build osteoporosis models of juvenile and adult zebrafish, and 9 groups of samples of different extracts and chemical parts of Lycii Fructus were given. Alizarin red staining was applied for observing the scale matrix mineralization and bone resorption. The activities of osteoblasts and osteoclasts were detected using alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP/TRACP) staining. The expressions of bone metabolism-related genes alp, osteoprotectin (opn), osteoblast specific transcription factor (sp7), cathepsin K (ctsk), tracp, and Runt family transcription factor 2b (runx2b) in each group were determined using quantitative polymerase chain reaction. The results showed that all components of Lycii Fructus improved the formation area of the first vertebrae, the staining light density value, and the number of vertebrae joints in juvenile zebrafish and the Lycium barbarum polysaccharide (LBP) treatment group exerted the best effect. In addition, LBP prevented the formation of bone resorption lacunae in zebrafish scales, increased ALP activity, decreased TRAP activity, up-regulated the alp, sp7, and opn genes, and lowered the expressions of ctsk and tracp genes. In conclusion, LBP regulated the activity of osteoblasts and osteoclasts, reduced bone resorption, promoted bone formation and enhanced bone density, which might be the main anti-osteoporosis active fraction of Lycii Fructus. This study provided modern scientific evidence for the scientific connotation of the traditional effect of "strengthening bones and muscles" of Lycii Fructus, provided the reference for the evaluation of the anti-osteoporosis activity of traditional Chinese medicine based on zebrafish adult model, and provided beneficial enlightenment for the bone health needs of the aging society population.

15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981373

RESUMO

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.


Assuntos
Medicina Tradicional Chinesa , Padrões de Referência , Controle de Qualidade , Fermentação
16.
Neuroscience Bulletin ; (6): 245-260, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971567

RESUMO

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.


Assuntos
Camundongos , Animais , Zona Incerta/metabolismo , Neurônios/metabolismo , Medo/fisiologia , Somatostatina/metabolismo
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-971057

RESUMO

OBJECTIVES@#To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD).@*METHODS@#A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth.@*RESULTS@#The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05).@*CONCLUSIONS@#Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.


Assuntos
Criança , Humanos , Lactente , Recém-Nascido , Peso ao Nascer , Displasia Broncopulmonar/patologia , Citocinas , Imunidade Inata , Recém-Nascido Prematuro , Interleucina-13 , Interleucina-33 , Interleucina-5 , Linfócitos/patologia , Linfopoietina do Estroma do Timo
18.
Journal of Geriatric Cardiology ; (12): 330-340, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-982203

RESUMO

BACKGROUND@#The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients.@*METHODS@#A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared.@*RESULTS@#During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar.@*CONCLUSIONS@#The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

19.
Chinese Journal of Cardiology ; (12): 521-525, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984684

RESUMO

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Volume Sistólico , Gânglio Estrelado/cirurgia , Função Ventricular Esquerda , Cardiomiopatias/complicações , Taquicardia Ventricular/terapia , Resultado do Tratamento , Ablação por Cateter
20.
J Pak Med Assoc ; 72(6): 1133-1136, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35751323

RESUMO

OBJECTIVE: To explore correlation of serum markers human neutrophil lipocalin and C-reactive protein with acute cholecystitis associated with bacterial infection, and to evaluate the diagnostic value of the markers. METHODS: The cross-sectional study was conducted from January 2018 to April 2020 at the Beijing Luhe Hospital, Capital Medical University, Beijing, China, and comprised acute cholecystitis patients who were divided into bacterial infection group A and non-bacterial infection group B. Serum human neutrophil lipocalin and C-reactive protein were measured for both the groups. Receiver operating characteristic curve was used to evaluate the diagnostic value of the two markers in acute cholecystitis associated with bacterial infection. Data was analysed using SPSS 25. RESULTS: Of the 145 patients, 65(45%) were in group A; 36(55.38%) males and 29(44.62%) females with a mean age of 45.79±2.50 years. In group B there were 80(55%) subjects; 45(56.25%) males and 35(43.75%) females with a mean age of 46.16±2.52 years (p>0.05). In group A, there were 60(92.31%) cases of acute calculous cholecystitis, and 5(7.69%) had acute acalculous cholecystitis compared to 73(91.25%) and 7(8.75%), respectively, in group B (p>0.05). Serum human neutrophil lipocalin and C-reactive protein levels in group A were higher than group B (p<0.001). Serum human neutrophil lipocalin showed a high positive correlation with C-reactive protein in group A (r=0.800, p<0.001), and a moderate positive correlation in group B (r=0.683, p<0.001). Area under the curve of serum human neutrophil lipocalin associated with C-reactive protein was 0.901 (95% confidence interval: 0.850-0.953), which was higher than that of serum human neutrophil lipocalin and C-reactive protein alone, with sensitivity 95.40% and specificity 80%. CONCLUSIONS: The combined use of serum human neutrophil lipocalin and C-reactive protein may be used as an effective indicator for early diagnosis, identification and monitoring of acute cholecystitis with bacterial infection.


Assuntos
Infecções Bacterianas , Colecistite Aguda , Adulto , Infecções Bacterianas/diagnóstico , Biomarcadores , Proteína C-Reativa/análise , Colecistite Aguda/diagnóstico , Estudos Transversais , Feminino , Humanos , Lipocalina-2/análise , Lipocalinas , Masculino , Pessoa de Meia-Idade , Curva ROC
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