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1.
Antimicrob Agents Chemother ; : e0008024, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709007

RESUMO

This study was conducted to compare the effectiveness of ceftriaxone with that of aqueous crystalline penicillin G in treating ocular syphilis. We conducted a retrospective study from 2010 to 2021. Syphilis patients were administered either ceftriaxone (2 g intravenously daily for 14 days) or aqueous crystalline penicillin G [4 million units (MU) intravenously every 4 h for 14 days] as therapeutic interventions. Subsequently, we utilized these two groups to assess the serological results, cerebrospinal fluid analysis, and visual acuity at time intervals spanning 3 to 6 months post-treatment. A total of 205 patients were included, with 34 assigned to the ceftriaxone group and 171 to the penicillin group. The median age of patients was 56 years, with an interquartile range of 49-62 years, and 137 of them (66.8%) were male. Between 3 and 6 months after treatment, 13 patients (38.2%) in the ceftriaxone group and 82 patients (48.0%) in the penicillin group demonstrated effective treatment based on the clinical and laboratory parameters. The crude odds ratio (OR) was 0.672 (95% confidence interval [CI]: 0.316-1.428, P = 0.301), indicating no significant difference in effectiveness between the two groups. Thirty patients (17.5%) in the penicillin group and six patients (17.6%) in the ceftriaxone group did not experience successful outcomes. Notably, no serious adverse effects were reported in both the groups. There was no significant difference in the effectiveness of ceftriaxone and aqueous crystalline penicillin G in treating ocular syphilis. The administration of ceftriaxone without requiring hospitalization presents a convenient and safe alternative treatment option for ocular syphilis.

2.
Sex Transm Infect ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902025

RESUMO

OBJECTIVES: This study aimed to describe the clinical features of neurosyphilis in Chinese patients in an attempt to find clinical features that are helpful for the early identification of neurosyphilis. METHODS: This retrospective study included people with syphilis who visited Shanghai Skin Disease Hospital between January 2010 and December 2020. Lumbar puncture was performed on those who met the inclusion and exclusion criteria. The diagnosis of neurosyphilis was based on clinical and laboratory findings. The parameters were analysed statistically. RESULTS: Of the 3524 patients with neurosyphilis, 2111 (59.9%) and 1413 (40.1%) were asymptomatic and symptomatic neurosyphilis, respectively. General paresis was the most common type of symptomatic neurosyphilis (46.8%). The clinical manifestations of symptomatic neurosyphilis include psychiatric and neurotic symptoms, among which general paresis predominantly presented as psychiatric symptoms such as affective (66.7%) and memory disorder (72.9%). Tabes dorsalis is often presented as neurotic symptoms. One hundred fifty patients (10.6%) with symptomatic neurosyphilis presented candy signs, a rare and specific neurosyphilis symptom that is common in general paresis. Girdle sensation was presented in 13 patients, mainly with tabes dorsalis, which had not been reported in previous studies. CONCLUSIONS: Notably, the candy sign is identified as a specific symptom of general paresis, while girdle sensations are highlighted as a particular symptom of tabes dorsalis. This is the largest study describing the clinical spectrum of neurosyphilis since the onset of the penicillin era and could help doctors learn more about the disease. A comprehensive description of the possible clinical manifestations of late symptomatic neurosyphilis, particularly highlighting rare symptoms, can identify suspicious patients and prevent diagnostic delays.

3.
Epidemiol Infect ; 152: e21, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224151

RESUMO

Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83-0.85) and 0.82 (95% CI, 0.78-0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP.


Assuntos
Infecções por HIV , Neurossífilis , Sífilis , Humanos , Masculino , Neurossífilis/diagnóstico , Neurossífilis/epidemiologia , Punção Espinal , Medição de Risco
4.
Postepy Dermatol Alergol ; 41(1): 91-99, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38533366

RESUMO

Introduction: Secondary syphilis is well-known for its protean cutaneous manifestations and therefore very easy to be misdiagnosed. Aim: The current study was to observe the frequency of histopathological features characterizing secondary syphilis, and summarize the diseases most likely to be misdiagnosed. Material and methods: In this study a total of 129 pathological specimens from 114 patients with biopsy-proven secondary syphilis were retrospectively analysed and categorized according to clinicopathologic characteristics. The frequency of histopathological features characterizing secondary syphilis were analysed by comparison with clinical features. Results: We found that in a single sample there is at least one feature or at most 13 features exist concurrently, and most demonstrated between 5 and 9 diagnostic features. Plasma cells (97.6% overall vs. 94.0% ≤ 6 features), endothelial swelling (86.8% vs. 74.0%), epidermis hyperplasia (73.6% vs. 62.0%) especially irregular acanthosis, lymphocytes infiltration (71.3% vs. 52.0%) and interstitial patterns (69% vs. 72.0%) were the most common findings in all cases as well as in cases with ≤ 6 features. Granulomatous inflammation is an uncommon histopathologic pattern in secondary syphilis (12.4%). The rash morphologies of our biopsies mainly manifesting as macules and maculopapules were more likely to have 6 or fewer features, which were not only easily misdiagnosed for pityriasis rosea, tinea and erythema multiforme, but also mostly taken from the trunk and genitalia. Atypical morphologies can be combined with plasma cell infiltration and T. pallidum immunohistochemical stain to confirm the diagnosis. Conclusions: In this study plasma cells from superficial and deep perivascular distribution to nodular infiltration were a crucial clue for diagnosis of secondary syphilis.

5.
Eur Spine J ; 28(5): 1053-1063, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30604297

RESUMO

PURPOSE: Surgical procedures on atlantoaxial dislocation remain controversial. The aim of this observational retrospective study was to investigate the treatment algorithm of surgical procedures. METHODS: According to CT and intraoperative evaluation during direct posterior reduction, 135 AAD cases were categorized into three groups: Group I: reducible dislocation; Group II: irreducible dislocation (Group IIa: effective decompression achieved after posterior reduction; Group IIb: no effective decompression after posterior reduction); and Group III: fixed dislocation. Group III presented with extensive bony fusions. Group I and Group IIa were treated with direct posterior reduction and fixation. Group IIb underwent posterior fixation and transoral odontoidectomy. Group III underwent transoral odontoidectomy alone. Japanese Orthopedic Association scores (JOA) were assessed to evaluate clinical status before and 6, 12 months after surgery. RESULTS: Our study included 118 Group I cases, 16 Group II cases (Group IIa: 11 cases; Group IIb: 5 cases), and one Group III case. Follow-up ranged from 12 to 36 months. PRIMARY OUTCOME: Anatomic atlantoaxial reduction was achieved in 118 of 135 patients (87.4%). Clinical improvements were seen in 96.3% (130/135) all the patients. Solid atlantoaxial fusion was shown in 134 patients. Secondary outcome: The overall complication rate was 3.7% (5/135). For Group I, the mean postoperative 6-month JOA was 14.5 versus 12.2 in preoperative patients (paired Student's t test, P < 0.01). CONCLUSIONS: This article proposes a clinical procedure that assists with therapeutic decision making and indicates the severity and difficulty of reduction of the atlantoaxial joint. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Articulação Atlantoaxial , Descompressão Cirúrgica , Luxações Articulares/cirurgia , Procedimentos Ortopédicos , Traumatismos da Coluna Vertebral/cirurgia , Algoritmos , Articulação Atlantoaxial/lesões , Articulação Atlantoaxial/cirurgia , Humanos , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Procedimentos Ortopédicos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
6.
Eur Spine J ; 27(6): 1234-1248, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29663144

RESUMO

PURPOSE: To compare the clinical and radiographic outcomes of irreducible atlantoaxial dislocation (IAAD) treated with posterior fusion after anterior release and direct posterior reduction of the dislocation. METHODS: Online databases were searched for articles describing IAAD published from 1999 to 2015. Five studies (105 patients) described treatment with posterior fusion after periodontoid tissue release, and five studies (113 patients) described treatment with direct posterior reduction of the dislocation. The primary outcomes in this study were the complete reduction rate, Japanese Orthopedic Association score, perioperative morbidity, perioperative mortality, complications, vascular injury, and infection. Standard meta-analysis techniques were used to compare the outcomes. RESULTS: Of 319 citations examined, 10 articles involving 218 participants were eligible. Overall, there were no significant differences between the anterior release and posterior fixation (ARPF) group and direct posterior reduction and fixation (DPRF) group in the complete reduction rate, neurologic recovery rate, perioperative morbidity, perioperative mortality, vascular injury, or infection. However, the complication rate in the DPRF group was much lower than that in the ARPF group. CONCLUSIONS: Compared with posterior fusion after anterior release, direct posterior reduction of the dislocation showed no significant differences in terms of the complete reduction rate, neurologic recovery rate, or fusion rate; however, it was a simpler process associated with less surgical trauma and a shorter operation time. Because of the limitations of the small sample in this study, whether direct posterior reduction of the dislocation is more effective and safer than posterior fusion after anterior release remains unclear. LEVEL OF EVIDENCE: III. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Articulação Atlantoaxial/cirurgia , Luxações Articulares/cirurgia , Fusão Vertebral/métodos , Tração/métodos , Feminino , Humanos , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Fusão Vertebral/efeitos adversos , Taxa de Sobrevida , Tração/efeitos adversos , Resultado do Tratamento
7.
Infect Drug Resist ; 17: 2463-2466, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912217

RESUMO

Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Secondary syphilitic lesions typically manifest within 3 months following initial exposure to T. pallidum. The predominant cutaneous manifestations of secondary syphilis are macula and papule. Certain individuals with syphilis may present with an atypical rash during the secondary stage owing to immunosuppression and other factors. Herein, we report a rare case of atypical recurrent secondary syphilis around the anus in a 65-year-old woman. Based on cerebrospinal fluid findings and skin biopsy results, the patient was ultimately diagnosed as neurosyphilis and recurrent secondary syphilis. Following intravenous antibiotic therapy, the patient's rash improved significantly. This case underscores the importance for physicians to remain vigilant regarding the possibility of syphilis when encountering cases exhibiting unusual clinical manifestations, as a definitive diagnosis necessitates a comprehensive evaluation.

8.
Front Immunol ; 15: 1393851, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919626

RESUMO

Tendinitis, characterized by the inflammation of tendons, poses significant challenges in both diagnosis and treatment due to its multifaceted etiology and complex pathophysiology. This study aimed to dissect the molecular mechanisms underlying tendinitis, with a particular focus on inflammasome-related genes and their interactions with the immune system. Through comprehensive gene expression analysis and bioinformatics approaches, we identified distinct expression profiles of inflammasome genes, such as NLRP6, NLRP1, and MEFV, which showed significant correlations with immune checkpoint molecules, indicating a pivotal role in the inflammatory cascade of tendinitis. Additionally, MYD88 and CD36 were found to be closely associated with HLA family molecules, underscoring their involvement in immune response modulation. Contrary to expectations, chemokines exhibited minimal correlation with inflammasome genes, suggesting an unconventional inflammatory pathway in tendinitis. Transcription factors like SP110 and CREB5 emerged as key regulators of inflammasome genes, providing insight into the transcriptional control mechanisms in tendinitis. Furthermore, potential therapeutic targets were identified through the DGidb database, highlighting drugs that could modulate the activity of inflammasome genes, offering new avenues for targeted tendinitis therapy. Our findings elucidate the complex molecular landscape of tendinitis, emphasizing the significant role of inflammasomes and immune interactions, and pave the way for the development of novel diagnostic and therapeutic strategies.


Assuntos
Inflamassomos , Tendinopatia , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamassomos/imunologia , Humanos , Tendinopatia/genética , Tendinopatia/imunologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Pirina/genética , Proteínas NLR/genética , Regulação da Expressão Gênica , Transcriptoma , Redes Reguladoras de Genes
9.
Mol Neurobiol ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38789894

RESUMO

After spinal cord injury, astrocytes undergo a reactive process and form an astroglial scar, which impedes the regeneration of axons. The role of Runx2 in promoting the transformation of astrocytes in the central nervous system is well-established. However, it remains unclear whether Runx2 also plays a role in the development of astroglial scar, and the precise underlying mechanism has yet to be identified. Recently, our study using cell culture and animal models has demonstrated that Runx2 actually suppresses astrocyte activation and the formation of astroglial scar following injury. The initial results demonstrated an increase in the expression of Runx2 in astrocytes following in vivo injury. Subsequently, the overexpression of Runx2 resulted in the inhibition of astrocyte activation, reduction in the total area of astroglial scar, and restoration of neural function after 14 days of injury. However, these effects were reversed by CADD522. These findings indicate that Runx2 could potentially serve as a therapeutic intervention for spinal cord injury (SCI). Furthermore, our findings suggest that the Nuclear-matrix-targeting signal (NMTS) of Runx2 is associated with its effect. In summary, the study's results propose that targeting Runx2 may be a promising treatment approach for reactive astrocytes and astroglial scar in the recovery of SCI.

10.
BMC Psychol ; 11(1): 344, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853423

RESUMO

The importance of psychological detachment during nonwork time has been emphasized, and its effect on depressive symptoms has been identified. However, the mechanism underlying this association remains to be elucidated. This study was conducted to identify the indirect role of emotional exhaustion in the association between psychological detachment and depressive symptoms and the moderating role of self-compassion in the relationship between emotional exhaustion and depressive symptoms on the basis of the recovery-engagement-exhaustion model and emotion regulation theory. Through an online survey, relevant data were collected from 727 university teachers (mean age, 37.65 ± 7.77 years; 38.5% men). Indirect and moderation effect were analyzed through structural equation modeling (Mplus). Psychological detachment was found to be associated with depressive symptoms through emotional exhaustion. Self-compassion moderated the association between emotional exhaustion and depressive symptoms. The association between emotional exhaustion and depressive symptoms was weaker among university teachers with high levels of self-compassion than among those with low levels of self-compassion. This study improves our understanding of the association between psychological detachment and depressive symptoms by identifying the emotional pathway and protective function of self-compassion. Interventions for improving mental health in work context should be designed considering psychological detachment and self-compassion to deal with work-induced emotional strain.


Assuntos
Depressão , Autocompaixão , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Depressão/psicologia , Empatia , Emoções , Inquéritos e Questionários
11.
Obes Surg ; 33(10): 3163-3176, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37635165

RESUMO

BACKGROUND: Current bariatric surgery models primarily utilize mice with obesity, overlooking those with type 2 diabetes (T2DM). These models have limitations in replicating clinical procedures accurately and achieving broad applicability. This study aimed to develop novel mouse models of Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) surgeries specifically designed for T2DM research, utilizing simplified surgical techniques closely resembling clinical procedures. METHODS: Eight-week-old C57/Bl6 mice, except for the Blank-Control group, were induced with T2DM by combining a high-fat diet and streptozotocin injection. RYGB involved creating a 10% gastric pouch, a 4-cm biliopancreatic limb (BL), and a 4-cm Roux limb (RL). Similarly, OAGB maintained a 10% gastric pouch and a 4-cm BL. To assess the efficacy of these models, we measured the body weight and fasting blood glucose (FBG) and conducted intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), and liver B-ultrasound, as well as a histopathological analysis of multiple organs 12 weeks post-operation. RESULTS: The survival rates in the Blank-Control, T2DM-Sham, T2DM-RYGB, and T2DM-OAGB groups were 100% (6/6), 100% (6/6), 85.7% (6/7), and 100% (6/6), respectively. Both RYGB and OAGB surgeries similarly led to sustained weight loss, reduced the FBG levels, improved the IPGTT and ITT results, and alleviated the histopathological manifestations in multiple organs. CONCLUSION: The innovative mouse models of RYGB and OAGB surgeries effectively improve T2DM. Both surgeries demonstrate comparable efficacy in ameliorating T2DM, even when utilizing a gastric pouch of the same size and the same length of BL in OAGB.


Assuntos
Parede Abdominal , Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Animais , Camundongos , Diabetes Mellitus Tipo 2/cirurgia , Obesidade Mórbida/cirurgia , Modelos Animais de Doenças
12.
Infect Drug Resist ; 15: 6603-6612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406865

RESUMO

Background: The gut microbiota plays an important role in the development of neurological disorders such as Parkinson's disease and Alzheimer's disease. However, studies on the gut microbiota of patients with neurosyphilis (NS) were rarely reported. Methods: In this study, we collected fecal samples from 62 syphilis patients, including 39 with NS and 23 with non-NS. Among the NS patients, 18 were general paresis (GP). The white blood cell counts, protein concentrations, and Venereal Disease Research Laboratory test positive rates of cerebrospinal fluid from patients in NS or GP group were significantly higher than those from patients in non-NS group. 16S ribosomal RNA sequencing results revealed that the alpha and beta diversities of the gut microbiota were similar between NS and non-NS patients or GP and non-NS patients. Results: Linear discriminant analysis with effect size (LEfSe) analysis showed that some taxa, such as Coprobacter, were increased in both NS group and GP group, compared with non-NS group. Besides, the clade of Akkermansia was also overrepresented in GP Patients. Meanwhile, some taxa such as Clostridia_UCG-014 and SC-I-84 were underrepresented in NS patients. The abundances of class Bacilli and genus Alloprevotella were decreased in GP patients. Among them, the abundances of some taxa such as Coprobacter and Akkermansia have been reported to be associated with other neuropsychiatric disorders. Conclusion: Our findings suggest that the alternation of the gut microbiota in NS patients may contribute to the course of NS, which will deepen our understanding of NS.

13.
Int J Infect Dis ; 118: 230-235, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35301100

RESUMO

OBJECTIVES: To uncover the role of the platelet indices in patients with syphilis. METHODS: A total of 2061 patients with syphilis and 528 healthy controls were enrolled in this retrospective cohort study. The data of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and indicators of syphilis activities were collected. The correlations between the platelet indices and disease activities were analyzed. RESULTS: A total of 425 (20.6%) of the 2061 patients were of primary and secondary syphilis, 433 (21.0%) latent, 463 (22.5%) serofast, 350 (17.0%) asymptomatic neurosyphilis, and 390 (18.9%) symptomatic neurosyphilis. Compared with the healthy controls, PLT was significantly increased in the primary and secondary syphilis group; whereas, MPV and PDW were significantly decreased in all stages of syphilis. These changes of platelet indices were reversed after anti-treponemal therapy. Further correlation analysis showed that PLT was positively associated with the syphilis activity indicators [rapid plasma reagin (RPR) titer, cerebrospinal fluid white blood cell (CSF-WBC), CSF-protein, and CSF-VDRL (venereal disease research laboratory)] and inflammatory markers [WBC, C-reaction protein (CRP), and erythrocyte sedimentation rate (ESR)]. Conversely, PDW was negatively correlated with all of these parameters. MPV had an inverse relationship with RPR, ESR, and CRP. CONCLUSIONS: Platelet indices are associated with syphilis activities.


Assuntos
Neurossífilis , Sífilis , Biomarcadores , Humanos , Volume Plaquetário Médio , Neurossífilis/líquido cefalorraquidiano , Estudos Retrospectivos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico
14.
Front Oncol ; 11: 595259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816228

RESUMO

Introduction: Proneural and mesenchymal subtypes are the most distinct demarcated categories in classification scheme, and there is often a shift from proneural type to mesenchymal subtype in the progression of glioblastoma (GBM). The molecular characters are determined by specific genomic methods, however, the application of radiography in clinical practice remains to be further studied. Here, we studied the topography features of GBM in proneural subtype, and further demonstrated the survival characteristics and proneural-mesenchymal transition (PMT) progression of samples by combining with the imaging variables. Methods: Data were acquired from The Cancer Imaging Archive (TCIA, http://cancerimagingarchive.net). The radiography image, clinical variables and transcriptome subtype from 223 samples were used in this study. Proneural and mesenchymal subtype on GBM topography based on overlay and Voxel-based lesion-symptom mapping (VLSM) analysis were revealed. Besides, we carried out the comparison of survival analysis and PMT progression in and outside the VLSM-determined area. Results: The overlay of total GBM and separated image of proneural and mesenchymal subtype revealed a correlation of the two subtypes. By VLSM analysis, proneural subtype was confirmed to be related to left inferior temporal medulla, and no significant voxel was found for mesenchymal subtype. The subsequent comparison between samples in and outside the VLSM-determined area showed difference in overall survival (OS) time, tumor purity, epithelial-mesenchymal transition (EMT) score and clinical variables. Conclusions: PMT progression was determined by radiography approach. GBM samples in the VLSM-determined area tended to harbor the signature of proneural subtype. This study provides a valuable VLSM-determined area related to the predilection site, prognosis and PMT progression by the association between GBM topography and molecular characters.

15.
Cancer Immunol Res ; 9(12): 1383-1399, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34667108

RESUMO

Glioblastoma (GBM), the most common malignant primary brain cancer in adults, nearly always becomes resistant to current treatments, including the chemotherapeutic temozolomide (TMZ). The long noncoding RNA (lncRNA) TMZ-associated lncRNA in GBM recurrence (lnc-TALC) promotes GBM resistance to TMZ. Exosomes can release biochemical cargo into the tumor microenvironment (TME) or transfer their contents, including lncRNAs, to other cells as a form of intercellular communication. In this study, we found that lnc-TALC could be incorporated into exosomes and transmitted to tumor-associated macrophages (TAM) and could promote M2 polarization of the microglia. This M2 polarization correlated with secretion of the complement components C5/C5a, which occurred downstream of lnc-TALC binding to ENO1 to promote the phosphorylation of p38 MAPK. In addition, C5 promoted the repair of TMZ-induced DNA damage, leading to chemotherapy resistance, and C5a-targeted immunotherapy showed improved efficacy that limited lnc-TALC-mediated TMZ resistance. Our results reveal that exosome-transmitted lnc-TALC could remodel the GBM microenvironment and reduce tumor sensitivity to TMZ chemotherapy, indicating that the lnc-TALC-mediated cross-talk between GBM cells and microglia could attenuate chemotherapy efficacy and pointing to potential combination therapy strategies to overcome TMZ resistance in GBM.See related Spotlight by Zhao and Xie, p. 1372.


Assuntos
Complemento C5/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Exossomos/genética , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Microglia/metabolismo , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Camundongos , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Hematol Oncol ; 13(1): 15, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111231

RESUMO

NoncoRNA (http://www.ncdtcdb.cn:8080/NoncoRNA/) is a manually curated database of experimentally supported non-coding RNAs (ncRNAs) and drug target associations that aim to potentially provide a high-quality data resource for exploring drug sensitivity/resistance-related ncRNAs in various human cancers. ncRNA are RNA molecular that do not encode proteins, but are involved in gene regulation and cellular functions in variety of human diseases, including neurodegenerative diseases and cancers. Here, we developed NoncoRNA which contained 8233 entries between 5568 ncRNAs and 154 drugs in 134 cancers. Each entry in the NoncoRNA contains detailed information on the ncRNAs, drugs, and cancers, the ncRNA expression pattern and experimental detection techniques, drug response and other targets, literature references, and other information. NoncoRNA offers a user-friendly, open access web interface to easily browse, search, and download data. NoncoRNA also provides a submission page for researchers to submit newly validated ncRNA-drug-cancer associations. NoncoRNA might serve as an immeasurable resource for understanding the roles of ncRNAs in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Bases de Dados de Ácidos Nucleicos , Neoplasias/tratamento farmacológico , RNA não Traduzido/genética , Descoberta de Drogas , Resistencia a Medicamentos Antineoplásicos , Humanos , Terapia de Alvo Molecular , Neoplasias/genética
17.
Nat Commun ; 11(1): 594, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001707

RESUMO

Activation of receptor tyrosine kinase (RTK) protein is frequently observed in malignant progression of gliomas. In this study, the crosstalk activation of epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) signaling pathways is demonstrated to contribute to temozolomide (TMZ) resistance, resulting in an unfavorable prognosis for patients with glioblastoma. To simultaneously mitigate EGFR and MET activation, a dual functionalized brain-targeting nanoinhibitor, BIP-MPC-NP, is developed by conjugating Inherbin3 and cMBP on the surface of NHS-PEG8-Mal modified MPC-nanoparticles. In the presence of BIP-MPC-NP, DNA damage repair is attenuated and TMZ sensitivity is enhanced via the down-regulation of E2F1 mediated by TTP in TMZ resistant glioma. In vivo magnetic resonance imaging (MRI) shows a significant repression in tumor growth and a prolonged survival of mice after injection of the BIP-MPC-NP and TMZ. These results demonstrate the promise of this nanoinhibitor as a feasible strategy overcoming TMZ resistance in glioma.


Assuntos
Encéfalo/patologia , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Glioma/tratamento farmacológico , Nanopartículas/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Transdução de Sinais , Temozolomida/uso terapêutico , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fator de Transcrição E2F1/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Temozolomida/farmacologia
18.
JMIR Mhealth Uhealth ; 7(10): e12200, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31588914

RESUMO

BACKGROUND: Although there are more than 60 smartphone apps for smoking cessation in China, many of them do not include the content and features that health care professionals and smokers prefer-which may make them impractical, unengaging, and ineffective. Therefore, we investigated both health care providers' and smokers' preferences for features of future smoking cessation apps. OBJECTIVE: This study aimed to investigate Chinese health care providers' and smokers' desired features of a smoking cessation app, with the goal of providing design recommendations for app designers and researchers. METHODS: Both Chinese smokers who own smartphones (n=357) and Chinese health care providers (n=224) responded to a survey collecting data on their sociodemographic characteristics and opinions on the importance of 20 smoking cessation app design features studied in previous US research. RESULTS: Chinese health care providers expressed strong support of smoking cessation apps on a number of attitude indicators (range 153/224, 68.3% to 204/224, 91.1%). They rated nearly all (18/20) features as very or extremely important (range 52.2%-83.4%) and rated nearly all features (17/20) as more important than the smokers did. More than 60% of smokers rated the following 4 features as very or extremely important: allow sharing the process of smoking cessation with family members and friends (216/319, 67.7%), helping smokers track their progress (such as the amount of smoking per day; 213/319, 66.8%), helping with the side effects of medications and nicotine withdrawal symptoms (201/319, 63.0%), and adapting to ongoing needs and interests of smokers (194/319, 60.8%). Contrary to a similar study of US smokers and health care providers, Chinese smokers and providers rated reputation and ability to communicate with family members and friends as important features, whereas Chinese smokers rated privacy and security as less important. CONCLUSIONS: The design of future smoking cessation and health behavior change apps should consider perspectives of both providers and smokers as well as the role of culture.


Assuntos
Pessoal de Saúde/psicologia , Aplicativos Móveis , Fumantes/psicologia , Abandono do Hábito de Fumar/métodos , Adulto , China , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Desenvolvimento de Programas/métodos , Pesquisa Qualitativa , Fumantes/estatística & dados numéricos , Abandono do Hábito de Fumar/psicologia , Design de Software , Inquéritos e Questionários
19.
World Neurosurg ; 132: e324-e332, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476460

RESUMO

OBJECTIVE: To assess the value and limitation of cervical traction in the evaluation of the reducibility of atlantoaxial dislocation (AAD) and basilar invagination (BI) using the intraoperative O-arm. METHODS: A total of 22 patients with hyperextensive, irreducible AAD were included. The cervical traction test under general anesthesia was performed, and the degree of reduction was evaluated using the O-arm before the operation started. The traction effects both vertically and horizontally were evaluated. All cases then underwent modified direct posterior reduction and fixation. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scale. Radiologic measurements included the anterior atlantodental interval, the distance of odontoid tip above Chamberlain line, and the clivus-canal angle. Magnetic resonance imaging signal changes, size of syringomyelia, and the space ventral to medulla also were used to evaluate the postoperative reduction result. RESULTS: After the cervical traction test, 7 patients achieved incomplete reduction, 5 achieved only vertical reduction, 6 achieved only horizontal reduction, and 4 achieved complete reduction in both horizontal and vertical orientations as assessed by the O-arm. All patients underwent a direct reduction technique. The mean JOA score increased from 11.1 to 14.5. Complete reduction of AAD and BI were achieved in 19 patients (86.4%), with partial reduction achieved in 3 (13.6%). Sufficient cerebrospinal fluid space anterior to the medulla with improved JOA score was achieved in the 3 partially reduced patients. CONCLUSIONS: With the innovations of direct posterior reduction techniques, cervical traction under anesthesia may not sufficiently predict the reducibility of BI and AAD. Cervical traction still plays an important role during the direct posterior reduction procedure.


Assuntos
Articulação Atlantoaxial/cirurgia , Imageamento Tridimensional/métodos , Luxações Articulares/cirurgia , Fusão Vertebral/métodos , Tração/métodos , Adolescente , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Luxações Articulares/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cirurgia Assistida por Computador , Insuficiência Vertebrobasilar/diagnóstico , Adulto Jovem
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