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BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.
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Antígenos CD19 , Febre , Imunoterapia Adotiva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Imunoterapia Adotiva/métodos , Adulto , Antígenos CD19/metabolismo , Infecções/sangue , Idoso , Curva ROC , Adulto Jovem , Estudos RetrospectivosRESUMO
Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.
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Linfoma não Hodgkin , Células Supressoras Mieloides , Humanos , Células Supressoras Mieloides/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/diagnóstico , Prognóstico , Adulto , Linfócitos T/imunologia , Idoso , Animais , Camundongos , Arginase/metabolismoRESUMO
BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder, and female patients may develop gynecologic tumours. The prognosis for such patients is poor and the specific pathogenesis remains uncertain. Therefore, there are currently no uniform treatment options. CASE SUMMARY: Herein, we introduce the case of a 45-year-old female who was diagnosed with PJS for 45 years and cervical cancer for 3 years. Postoperative pathological examination showed metastases in the right external iliac lymph nodes. The patient was initially treated with a combination of doxorubicin and carboplatin chemotherapy and pelvic magnetic resonance showed that the metastases had grown. Subsequently, we performed whole exome sequencing in this patient and identified the relevant causative gene. In addition to the chemotherapy regimen, sindilizumab was administered and the patient was followed up. After 4 cycles of treatment, the metastases were substantially reduced and were not enlarged after six months of follow-up. This case report suggests that patients with PJS combined with cervical cancer may have a sustained response to immune-combination chemotherapy regimens. CONCLUSION: Clinicians should be aware of the importance of immunotherapy in patients with PJS combined with advanced cervical cancer.
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Objective: Long-term acupoint stimulation (LAS), also called embedding acupuncture, is a modified acupuncture technique. The preliminary results have demonstrated its efficacy in body-weight control. However, the low quality of available trials limited its application. This study aimed to evaluate the efficacy and safety of LAS in body-weight control by using a randomized, parallel, sham-controlled clinical trial design. Methods: This was a randomized, single-blind, sham-controlled clinical trial including 84 adult participants (18-60 years) with a body mass index (BMI) of ≥ 24 kg/m2 conducted in three general hospitals in Shanghai, China. Participants were equally assigned to receive LAS or sham LAS (SLAS) once per 10 days, eight times in total. After completion, an additional intervention with a 3-month follow-up period was set to examine the continued effect of LAS. The primary outcome was the change in body weight from baseline to treatment endpoint within the intention-to-treat (ITT) analysis. Secondary outcomes contained changes in waist-to-hip ratio (WHR), lipid metabolism, and visceral and subcutaneous adipose tissues. Results: From 14 May 2018 to 03 November 2019, 84 participants out of 201 screened individuals met the eligibility criteria, were randomized, and were analyzed (42 participants in each group). From baseline to treatment endpoint, the body-weight reduction in the LAS group was significantly larger than in the sham control (net difference: 1.57 kg, 95% CI: 0.29-2.86, p = 0.012). The superior weight reduction effect persisted in the follow-up period (net difference: 3.20 kg, 95% CI: 1.17-5.21, p = 0.001). LAS therapy also showed improvement in triglyceride and subcutaneous adipose tissue (SAT) compared with sham control. One participant in the LAS group reported a slightly uncomfortable and tingling sensation after the additional intervention. No other adverse events (AEs) were documented. Conclusion: LAS, a modified acupuncture technique, is safe and effective in body-weight control. It could be used as an alternative choice to classical acupuncture for obesity management. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR1800015498].
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Pontos de Acupuntura , Terapia por Acupuntura , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Adulto , China , Humanos , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Redução de PesoRESUMO
Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world with a five-year survival rate of less than 20%. Nonetheless, selecting an appropriate therapeutic agent to inhibit the development of hepatoma cells is still a challenge. Bufalin, a component of the traditional Chinese medicine Chansu, has been shown to inhibit the proliferation, invasion and metastasis of HCC through various signaling pathways. In addition, bufalin and sorafenib demonstrate a synergistic effect in cancer therapeutics. This review highlighted on several focal signaling pathways involved in the inhibitory effects of bufalin on HCC and its synergistic mechanisms with sorafenib. The immunotherapy effect of bufalin has also been discussed as a novel property.
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Oscillospira is a common yet rarely cultivated gut bacterial genus. Recently human gut microbiota studies have demonstrated its underlying significance for host health. However, little is known about Oscillospira-related host information and the links between Oscillospira and other members of the gut microbial community. To study the ecology of Oscillospira and gain insights into Oscillospira-related host physiological conditions, we analyzed data from the Guangdong Gut Microbiome Project, one of the largest gut microbiota database currently. Data of 6376 participants were analyzed. We studied the prevalence and relative abundance of Oscillospira as well as the profiles of associated microbial communities. We found that Oscillospira is closely related to human health because its abundance was positively correlated with microbial diversity, high density lipoprotein, and sleep time, and was inversely correlated with diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, uric acid and Bristol stool type. Moreover, random forest analysis with five-fold cross validation showed Oscillospira could be a predictor of low BMI and constipation in the subset. Overall, in this study, we provide a basic understanding of Oscillospira-related microbiota profile and physiological parameters of the host. Our results indicate Oscillospira may play a role in aggravating constipation.
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Índice de Massa Corporal , Clostridiales/isolamento & purificação , Constipação Intestinal/microbiologia , Microbioma Gastrointestinal , China , Clostridiales/fisiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status. RESULTS: At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population. CONCLUSIONS: The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence.
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Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Síndrome Metabólica/economia , Síndrome Metabólica/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , Status Econômico , Fezes/microbiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , FilogeniaRESUMO
In the version of this article originally published, in the sentence "Applying the same approach to obesity (Fig. 2b), MetS (Fig. 2c) and fatty liver (Fig. 2d) yielded similar results," two figure panels were cited incorrectly. The data for obesity are in Fig. 2c, and the data for MetS are in Fig. 2b. The sentence has been updated with the correct citations in the print, PDF and HTML versions of the article.
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Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression1-3. Diagnostic applications have been proposed for inflammatory bowel disease diagnosis and prognosis4, colorectal cancer prescreening5 and therapeutic choices in melanoma6. Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic7 and cardiovascular diseases8. To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks.
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Microbioma Gastrointestinal/genética , Interações Hospedeiro-Patógeno/genética , Doenças Metabólicas/microbiologia , Filogeografia , China/epidemiologia , Feminino , Humanos , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/genética , PrognósticoRESUMO
OBJECTIVE: To establish a machine learning model based on gut microbiota for predicting the level of trimethylamine N-oxide (TMAO) metabolism in vivo after choline intake to provide guidance of individualized precision diet and evidence for screening population at high risks of cardiovascular disease. METHODS: We quantified plasma levels of TMAO in 18 healthy volunteers before and 8 h after a choline challenge (ingestion of two boiled eggs). The volunteers were divided into two groups with increased or decreased TMAO level following choline challenge. Fresh fecal samples were collected before taking fasting blood samples for amplifying 16S rRNA V4 tags, and the PCR products were sequenced using the platform of Illumina HiSeq 2000. The differences in gut microbiata between subjects with increased and decreased plasma TMAO were analyzed using QIIME. Based on the gut microbiota data and TMAO levels in the two groups, the prediction model was established using the machine learning random forest algorithm, and the validity of the model was tested using a verified dataset. RESULTS: An obvious difference was found in beta diversity of the gut microbota between the subjects with increased and decreased plasma TMAO level following choline challenge. The area under the curve (AUC) of the model was 86.39% (95% CI: 72.7%-100%). Using the verified dataset, the model showed a much higher probability for correctly predicting TMAO variation following choline challenge. CONCLUSION: The model is feasible and reliable for predicting the level of TMAO metabolism in vivo based on gut microbiota.
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Colina/administração & dosagem , Microbioma Gastrointestinal , Aprendizado de Máquina , Metilaminas/metabolismo , Algoritmos , Ovos , Voluntários Saudáveis , Humanos , Óxidos , RNA Ribossômico 16SRESUMO
BACKGROUND: Oral mucositis is probably the most debilitating complication that can arise in treating a patient with head and neck cancer. Little is known about the impacts of oral microbiota on the initiation and progression of mucositis. METHODS: Based on 16S rRNA gene sequencing, dynamic changes in oral bacterial profile as well as correlations between the severity of mucositis and bacterial shifts during radiotherapy were investigated. FINDINGS: Our results revealed that bacterial community structure altered progressively during radiation therapy, in parallel with a marked increase in the relative abundance of some Gram-negative bacteria. Patients who eventually developed severe mucositis harbored a significantly lower bacterial alpha diversity and higher abundance of Actinobacillus during the phase of erythema - patchy mucositis. Accordingly, a random forest model for predicting exacerbation of mucositis was generated, which achieved a high predictive accuracy (AUC) of 0.89. INTERPRETATION: Oral microbiota changes correlate with the progression and aggravation of radiotherapy-induced mucositis in patients with nasopharyngeal carcinoma. Microbiota-based strategies can be used for the early prediction and prevention of the incidence of severe mucositis during radiotherapy.
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Carcinoma/radioterapia , Microbiota , Neoplasias Nasofaríngeas/radioterapia , Estomatite/microbiologia , Actinobacillus/genética , Actinobacillus/isolamento & purificação , Adulto , Idoso , Carcinoma/complicações , Carcinoma/patologia , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , Feminino , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/patologia , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Doses de Radiação , Radiação Ionizante , Análise de Sequência de DNA , Índice de Gravidade de Doença , Estomatite/diagnóstico , Estomatite/etiologia , Estomatite/patologia , Adulto JovemRESUMO
OBJECTIVES: To perform an in vitro experimental study of the possible damage effects on Bacille Calmette-Guérin (BCG) by low-frequency (42-kHz) ultrasound (US) irradiation at low spatially and temporally averaged intensities and different exposure times. METHODS: A 2-mL BCG suspension was added to the wells of a 24-well cell culture plate. Then the samples were randomly divided into 4 groups, each group including 3 wells, with group 1 as a control group and groups 2, 3, and 4, as US treatment groups. The samples for groups 2, 3, and 4 were irradiated with US at 0.13 W/cm(2) for 5 minutes, 0.13 W/cm(2) for 15 minutes, and 1.53 W/cm(2) for 15 minutes, respectively. After irradiation, the temperature, ratio of damage, and structure of the bacteria were examined. The cavitation effect of the device was detected by the passive cavitation detection method. RESULTS: After US irradiation at the different doses (intensity and exposure time), no significant temperature change was found in all sample suspensions. The ratio of bacterial damage tested by flow cytometry and the optical density of the suspensions as assayed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric method showed that the US-irradiated groups were significantly different from the control group. The BCG damage ratio reached 28% at the intensity of 1.53 W/cm(2). Transmission electron microscopic results showed that the bacterial structure of BCG could be destroyed by low-frequency, low-intensity US. CONCLUSIONS: Low-frequency, low-intensity US can cause acute injury to BCG, and the degree of injury is closely correlated with the US dose applied.
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Mycobacterium bovis/fisiologia , Mycobacterium bovis/ultraestrutura , Terapia por Ultrassom/métodos , Ondas Ultrassônicas , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Mycobacterium bovis/efeitos da radiação , Projetos Piloto , Doses de Radiação , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the vaginal flora in patients with recurrent vulvovaginal candidiasis (RVVC). METHODS: Vaginal swabs were collected at different time points from 6 RVVC patients and 5 healthy women of child-bearing age. The dynamic changes, microbiota composition, alpha diversity and beta diversity in the two groups were assessed by analyzing the 16S rRNA V4 hypervariable region amplified from the total genomic DNA from the swabs. RESULTS: Lactobacillus was the predominant species in healthy women with similar proportions of L.iners and L.crispatus; small proportions of Gardnerella, Prevotella and other genus were also detected. In some healthy women, the vaginal flora showed a high relative abundance of anaerobic bacteria such as Gardnerella, Prevotella, Atopobium, Sneathia. Compared with the healthy women, patients with RVVC showed a significantly reduced diversity of vaginal flora, where L.iners was the predominant species and the content of L.crispatus decreased significantly. In healthy women, the vaginal flora fluctuated with the menstrual cycle, and the fluctuation was the most prominent during menstruation; the dominant species either alternated regularly or maintain an absolute superiority in the menstrual cycle. The vaginal flora showed attenuated fluctuation in women with RVVC, were highly conserved within the menstrual cycle, and maintained a similar composition in the episodes and intermittent periods. CONCLUSION: The vaginal flora of RVVC patients do not undergo regular variations with the menstrual cycle and shows a similar composition between the episodes and intermittent periods. Promoting the production of L.iners or inhibiting the colonization of L.crispatus to restore the composition of the vaginal flora may help in the treatment of RVVC.
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Candidíase Vulvovaginal/microbiologia , Lactobacillus/isolamento & purificação , Microbiota , Vagina/microbiologia , Estudos de Casos e Controles , Feminino , Humanos , Lactobacillus/classificação , Estudos Longitudinais , Ciclo Menstrual , RNA Ribossômico 16S/isolamento & purificaçãoAssuntos
Encefalopatias/complicações , Encefalopatias/diagnóstico , Coreia/complicações , Coreia/diagnóstico , Doença de Hashimoto/complicações , Doença de Hashimoto/diagnóstico , Idoso , Encefalopatias/fisiopatologia , Coreia/fisiopatologia , Eletroencefalografia , Encefalite , Doença de Hashimoto/fisiopatologia , Humanos , MasculinoAssuntos
Cefaleia/etiologia , Trombose dos Seios Intracranianos/complicações , Idoso , Anticoagulantes/uso terapêutico , Angiografia Cerebral , Doença Crônica , Circulação Colateral/fisiologia , Feminino , Cefaleia/diagnóstico , Humanos , Hipertensão/complicações , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Papiledema/complicações , Recidiva , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
Worldwide schistosomiasis continues to be a serious public health problem. Over the past five decades, China has made remarkable progress in reducing Schistosoma japonicum infections in humans to a relatively low level. Endemic regions are currently circumscribed in certain core areas where re-infection and repeated chemotherapy are frequent. At present, selective chemotherapy with praziquantel is one of the main strategies in China's National Schistosomiasis Control Program, and thus diagnosis of infected individuals is a key step for such control. In this paper we review the current status of our knowledge about diagnostic tools for schistosomiasis japonica. A simple, affordable, sensitive, and specific assay for field diagnosis of schistosomiasis japonica is not yet available, and this poses great barriers towards full control of schistosomiasis. Hence, a search for a diagnostic approach, which delivers these characteristics, is essential and should be given high priority.
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Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/tendências , Praziquantel/uso terapêutico , Esquistossomose Japônica/diagnóstico , Esquistossomose Japônica/tratamento farmacológico , Animais , China , Testes Diagnósticos de Rotina/instrumentação , Humanos , Morbidade , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/mortalidadeRESUMO
PURPOSE: To obtain mimic peptides that specifically bind with the first and second extracellular loops (ECL1, ECL2) of the CC chemokine receptor 5 (CCR5) and to study their treatment effects on experimental autoimmune encephalomyelitis (EAE) mice. METHODS: A phage display peptide library was applied to screen peptides that bond with ECL1 and ECL2. ELISA and DNA sequence analysis were used to identify positive clones. EAE mice were treated with synthesized peptides by intraperitoneal injection. RESULTS: Eighteen positive clones were obtained and four peptides with sequences STFTTTL, TPIPQLL, SLPLPKP and QTSSAAL were identified. These peptides could significantly protect against and reduce the severity of EAE. The infiltration of monocytes and lymphocytes into the spinal cord decreased significantly in treated mice, while abundant inflammatory cells and demyelination were observed in spinal cords of EAE mice. CONCLUSION: CCR5 mimic peptides provided a significant protective effect to EAE mice. These potent inhibitory mimic peptides could be useful in the clinical treatment of multiple sclerosis.
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Encefalomielite Autoimune Experimental/prevenção & controle , Peptídeos/metabolismo , Peptídeos/uso terapêutico , Receptores CCR5/química , Receptores CCR5/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Encefalomielite Autoimune Experimental/patologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Biblioteca de Peptídeos , Peptídeos/genética , Ligação Proteica , Medula Espinal/metabolismo , Medula Espinal/patologiaRESUMO
OBJECTIVE: To analyze the spatial characteristic on the distribution of Oncomelania hupensis in mountainous regions. METHODS: Based on the geographic database of snail distribution in Puge county, Sichuan province, spatial autocorrelation analysis and spatial scan statistics were applied to analyze the spatial characteristic of snail distribution. RESULTS: With regard to the rate of frame with snails, the global Moran's I indicator was 0.095 (P < 0.05), which indicated the spatial autocorrelation of snail distribution in Puge county. Data from the local spatial autocorrelation analysis showed that there were 28 snail habitats with statistically significant differences on local indicators of spatial autocorrelation (LISA) value (P < 0.05), among which existed high-high, low-low, low-high and high-low four types of correlation model. The Spatial Scan Statistics had in total identified 24 snail habitat clusters (P < 0.05), including 14 high rate clusters and 10 low rate clusters, and the result was similar to that of LISA analysis. CONCLUSION: There were spatial autocorrelation and spatial aggregation of snail distribution in mountainous regions, meanwhile spatial heterogeneity of snail distribution also existed. This law could be explored for better control of snails.
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Sistemas de Informação Geográfica , Caramujos , Animais , Meio AmbienteRESUMO
BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is known as an autosomal dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7 have increased rapidly in recent years. However, SCA7 is a rare subtype of SCA, and most data available about SCA7 are those of white people. The aim of the present study was to systematically review the prevalence and clinical and genetic aspects of SCA7 patients in East Asian population. METHODS: A search for publications on SCA7 was performed by using the "PubMed" database with the published language limited in English. Publications mainly focusing on the prevalence of SCA7 in patients with SCA and the clinical and genetic features of SCA7 patients were fully reviewed and analyzed. RESULTS: The prevalence of SCA7 in SCA patients ranged from 0 to 7.7%, which was similar to those reported previously. The clinical manifestations were typically present at the 30's of its victims (median, 29 years; interquartile range (IQR), 19.5-36.5 years), and the symptoms appeared 15 years ((15.17+/-4.22) years) earlier on average in the offspring than in the parents. Gait ataxia and visual impairment were both found in all patients of whom the clinical features were described. Mutant SCA7 alleles contained 40-100 CAG repeats, with a median of 47 repeats (IQR, 44.5-50.0); and the offspring had 13 more repeats on average compared with their parents (12.62+/-19.03). A strong negative correlation was found between CAG repeat size and the onset age of patients (r=-0.739, P=0.000). In addition, no significant difference was found in CAG repeat sizes between patients with visual impairment as the initial symptom and those with gait disturbance as their initial symptom (P=0.476). CONCLUSIONS: The prevalence of SCA7 in SCA patients, the age at onset and CAG repeats of SCA7 patients in East Asia are consistent with those of white people. However, larger population study is needed to assess the correlation between the CAG repeat size and initial symptoms of SCA7 patients in East Asia.