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Using a prospective, observational cohort study during the post-"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5-vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks.
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Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Estudos Prospectivos , Eficácia de Vacinas , China/epidemiologia , Adenoviridae/genéticaRESUMO
BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.
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Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , Pré-Escolar , COVID-19/prevenção & controle , Estudos Retrospectivos , China/epidemiologia , Infecções AssintomáticasRESUMO
A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.
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Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Estudos Retrospectivos , Neutrófilos , Estudos Prospectivos , Doença Enxerto-Hospedeiro/etiologia , Terapia de Imunossupressão , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-TransplanteRESUMO
OBJECTIVE: Regular retrospective analysis is necessary for potential improvement in clinical practice for the treatment of hard-to-heal wounds. Comorbidities and outcomes have demonstrated spatial and temporal diversity, emphasising the importance of updates in epidemiology. The complexity of healing hard-to-heal wounds has long been known, and so we sought evidence-based improvement on the current principles of treatment. METHOD: Demographic and clinical information of patients from the WoundCareLog database was collected. Patients who met the inclusion criteria and completed follow-up after treatment were included. Comorbidities were diagnosed and classified into eight categories based on ICD-10. We compared the demographic and aetiological characteristics between patients with and without comorbidities by t-test and Chi-squared test. The impact of comorbidities on wound healing were evaluated with a multivariate Cox model. RESULTS: A total of 2163 patients met the inclusion criteria and were enrolled, of whom 37.0% were aged 61-80 years, 36.0% were aged 41-60 years and 60.8% were male. The lower extremities and buttocks were the most commonly affected areas with hard-to-heal wounds. Non-traumatic wounds accounted for 66.6% of cases, and infection, pressure and diabetes were the most common causes. Paralysis and diabetes were the most important factors which led to a prolonged healing process and inferior clinical outcomes. CONCLUSION: Comorbidities of hard-to-heal wounds were treated as separate contributors and their weighted effect on outcome was calculated through correlation analysis. Paralysis and diabetes were the most unfavourable comorbidities affecting the treatment of non-traumatic hard-to-heal wounds. Our study highlighted the priority of comorbidity treatment through data-driven approaches. It provides potential value in developing better public health strategies and preventive medicine.
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Paralisia , Cicatrização , China/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Prevalência , Prognóstico , Estudos RetrospectivosRESUMO
ß-Thalassemia (ß-thal), one of the most common form of single-gene inheritable blood diseases in the world, is highly prevalent in southern China, especially in the Guangxi Zhuang Autonomous Region. To update the ß-thal mutation spectrum in this region, we performed hematological and genetic analyses on 888 ß-thal major (ß-TM), ß-thal intermedia (ß-TI) and ß-thal carrier patients, aged 0-15 years old, from different parts of Guangxi Province. We identified 55 genotypes and 18 ß-thal mutations. The codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (43.97%), codon 17 (A>T) (HBB: c.52A>T) (25.43%), -28(A>G) (HBB: c.-78A>G) (8.18%), IVS-II-654 (C>T) (HBB: c.316-197C>T) (7.85%) and codon 26 (G>A) (HBB: c.79G>A) (5.02%) were the five most common, accounting for more than 90.0%. The results of our study are providing an up-to-date ß-thal mutation spectrum in the 0-15-year-old pediatric population, which will help genetic counseling and prevention of ß-TM in mainland China's most endemic region, Guangxi Zhuang Autonomous Region.
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Talassemia beta , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Códon , Frequência do Gene , Genótipo , Humanos , Lactente , Recém-Nascido , Mutação , Globinas beta/genética , Talassemia beta/epidemiologia , Talassemia beta/genéticaRESUMO
BACKGROUND Symptom distress is very common in patients with nasopharyngeal carcinoma (NPC) during radiotherapy, seriously affecting their quality of life and impeding the process of rehabilitation. Resourcefulness training can enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation. However, the effects of resourcefulness training on local complications and benefit-finding in NPC patients during radiotherapy remains poorly understood. MATERIAL AND METHODS Questionnaires and resourcefulness training intervention were used in this study. The relationships among resourcefulness, benefit-finding, and symptom distress of 304 NPC patients were analyzed and the effects of resourcefulness training on NPC patients (N=80) were evaluated during radiotherapy. RESULTS Among the 304 NPC patients, age, educational level, occupation, family monthly income, method of payment of medical expenses, and histological types were significant factors influencing resourcefulness and benefit-finding. The patients' resourcefulness was positively correlated to their benefit-finding; and their distress was negatively correlated to their resourcefulness. After resourcefulness training for 2 months, average scores of the resourcefulness and benefit-finding were significantly increased in the intervention group (N=40) compared to those in the control group (N=40). Average scores of symptom distress were significantly reduced in the 2 groups, but they were reduced more significantly in the intervention group than in the control group. CONCLUSIONS The patients' benefit-finding and symptom distress were correlated with their resourcefulness. Resourcefulness training could enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation in NPC patients during radiotherapy.
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Carcinoma/psicologia , Neoplasias Nasofaríngeas/psicologia , Participação do Paciente/psicologia , Adulto , Idoso , China , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Educação de Pacientes como Assunto/métodos , Participação do Paciente/métodos , Qualidade de Vida , Inquéritos e Questionários , Avaliação de Sintomas/métodos , Avaliação de Sintomas/psicologiaRESUMO
Circadian rhythms of gene expression are generated by the combinatorial action of transcriptional and translational feedback loops as well as chromatin remodelling events. Recently, long noncoding RNAs (lncRNAs) that are natural antisense transcripts (NATs) to transcripts encoding central oscillator components were proposed as modulators of core clock function in mammals (Per) and fungi (frq/qrf). Although oscillating lncRNAs exist in plants, their functional characterization is at an initial stage. By screening an Arabidopsis thaliana lncRNA custom-made array we identified CDF5 LONG NONCODING RNA (FLORE), a circadian-regulated lncRNA that is a NAT of CDF5. Quantitative real-time RT-PCR confirmed the circadian regulation of FLORE, whereas GUS-staining and flowering time evaluation were used to determine its biological function. FLORE and CDF5 antiphasic expression reflects mutual inhibition in a similar way to frq/qrf. Moreover, whereas the CDF5 protein delays flowering by directly repressing FT transcription, FLORE promotes it by repressing several CDFs (CDF1, CDF3, CDF5) and increasing FT transcript levels, indicating both cis and trans function. We propose that the CDF5/FLORE NAT pair constitutes an additional circadian regulatory module with conserved (mutual inhibition) and unique (function in trans) features, able to fine-tune its own circadian oscillation, and consequently, adjust the onset of flowering to favourable environmental conditions.
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Arabidopsis/fisiologia , Relógios Circadianos/genética , Flores/genética , RNA Longo não Codificante , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Fotoperíodo , Plantas Geneticamente Modificadas , RNA Antissenso , RNA Interferente PequenoRESUMO
BACKGROUND AND AIMS: To explore the relationship between habitual tea consumption and arterial stiffness. METHODS: This is a cross-sectional, epidemiological survey of 6589 male and female residents aged 40-75 in Wuyishan, Fujian Province, China. Tea consumption and other lifestyle characteristics were obtained by structured questionnaires. Pulse wave velocity (PWV) and ankle-brachial pressure index (ABI) were measured using an automated analyzer. RESULTS: Among the 5006 analyzed subjects, 1564 adults (31.2%) consumed tea once or more per week for at least one year. The levels of brachial-ankle pulse wave velocity (ba-PWV) were lowest among subjects who consumed tea habitually for more than 10 years compared with the other 3 subgroups (nonhabitual, 1 to 5 years, and 6 to 10 years habitual tea drinkers), and the levels of ba-PWV were lower with subjects who consumed 10-20 and >20 g/d tea habitually compared to nonhabitual tea drinkers. As the duration and the daily amount of habitual tea consumption increased the average ba-PWV decreased. Multiple logistic regression models revealed that habitual tea consumption was a positive predictor for ba-PWV (odds ratio [OR] = 0.63, 95% confidence interval [CI], 0.57-0.70). CONCLUSIONS: Habitual tea consumption may have a protective effect against arterial stiffness, especially for subjects who have habitually consumed tea for more than 6 years and >10 g daily.
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Chá , Rigidez Vascular/fisiologia , Adulto , Idoso , Índice Tornozelo-Braço , China , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Onda de Pulso , Inquéritos e QuestionáriosRESUMO
BACKGROUND: We found that selenium-binding protein 1 (SBP1) was progressively decreased in the human bronchial epithelial carcinogenic processes. Knockdown of SBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. However, the relationship between SBP1 expression and clinicopathological factors of patients has not been defined completely. The specific role of SBP1 in prognosis of lung squamous cell carcinoma (LSCC) is still unknown. METHODS: Tissue samples from 82 patients treated by pulmonary lobectomy for LSCC were used. Immunohistochemistry and western blotting were used to detect the expressions of SBP1 protein. The relationships between the expression level of SBP1 and the clinicopathological features of patients were analyzed. Cox proportional hazard regression analysis and Kaplan-Meier method were used to perform survival analysis. RESULTS: Expressions of SBP1 proteins were significantly lower in LSCC tissues than that in the corresponding normal bronchial epithelium (NBE) tissues (P = 0.000). In LSCC, The expression levels of SBP1 had not correlated with patients' age, gender, smoking state, primary tumor stages (T), TNM clinical stages, and distant metastasis (M) (P > 0.05). However, downregulation of SBP1 was significantly associated with higher lymph node metastasis and lower overall survival rate (P < 0.05). Cox regression analysis indicated low expressions of SBP1 can be an independent prognostic factor for poor overall survival in LSCC patients (P = 0.002). CONCLUSIONS: Downregulation of SBP1 may play a key role in the tumorigenic process of LSCC. SBP1 may be a novel potential prognostic factor of LSCC.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/secundário , Neoplasias Pulmonares/patologia , Proteínas de Ligação a Selênio/metabolismo , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Regulação para Baixo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Acute closed midsubstance Achilles tendon rupture(ACMATR) is common, with various treatment methods developed over time. We retrospectively compared the two mini transverse-incision repair (2MTIR) with percutaneous repair (PR) to determine which method yields better results. METHODS: All cases meeting criteria from 2018 to 2021 in our hospital were included and followed up for 1 to 5 years. A final questionnaire with multiple indexes was conducted via phone call. Comparative analysis of these indexes between the two groups was performed using IBM SPSS Statistics (V.26). Continuous variables that passed tests for normality and equal variance were compared using the Student's t-test. Ranked data were compared using the Mann-Whitney U test. Categorical variables were tested with the chi-square test or Fisher's exact test. A p-value of less than 0.05 was considered statistically significant. RESULTS: There was one rerupture in the PR group. The final indexes for "Tightness Feeling", "Heel Rising Strength", and "Foot Numbness" were statistically different (P < 0.05) between the two groups. The "Re-rupture" and "Return to Sports" indexes showed no statistical difference (P > 0.05). CONCLUSIONS: The 2MTIR technique provided a technically straightforward, minimally invasive procedure with well-preserved paratenon and direct end-to-end firm fixation in cases of ACMATR. It resulted in very low complications, easy rehabilitation, and full weight-bearing as early as 5-6 weeks postoperatively, yielding better functional outcomes compared to the PR technique in the 1-5 year follow-up. TRIAL REGISTRATION: The study was preliminarily registered and approved by the University of Hong Kong-Shenzhen Hospital Ethical Board with Project number: hkuszh2023074 on May 4, 2023.
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Tendão do Calcâneo , Humanos , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Estudos Retrospectivos , Masculino , Feminino , Adulto , Ruptura/cirurgia , Estudos de Casos e Controles , Resultado do Tratamento , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Traumatismos dos Tendões/cirurgia , Seguimentos , Procedimentos Ortopédicos/métodosRESUMO
The increased dose of hepatitis B vaccine has been adopted for newborns since 2013 in Fujian, China. However, little is known about the impact of this measure on hepatitis B virus (HBV) prevention. We used the seroepidemiological surveys conducted in 2014 and 2020 to address the concern. Compared with subjects who received a 5 µg hepatitis B vaccine, participants who took a 10 µg hepatitis B vaccine were associated with a lower risk of HBV infection (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI]: 0.10-0.68) and a marginal reduction risk of anti-HBc positive (OR, 0.37; 95% CI: 0.13-1.08; P = .07), but not for HBsAg carrier risk. The relation between vaccine dose and risk of anti-HBc positive (OR, 0.20; 95% CI: 0.05-0.81) became slightly stronger and significant among children investigated in 2020 who probably received universal vaccination. No significant association was found for subjects whose mothers were positive for HBsAg. The current 10 µg hepatitis B vaccines for universal vaccination for newborns are reasonable and effective in HBV prevention. More measures should be taken to reduce the risk of HBsAg carriers for infants whose mothers are positive for HBsAg.
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Vírus da Hepatite B , Hepatite B , Criança , Lactente , Feminino , Recém-Nascido , Humanos , Vacinas contra Hepatite B , Antígenos de Superfície da Hepatite B , Anticorpos Anti-Hepatite B/uso terapêutico , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vacinação , China/epidemiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controleRESUMO
Culture in temporary immersion systems (TIS) is a valuable tool for the semi-automation of high frequency somatic embryogenesis of coffee. This system allows the intermittent exposure of explants to liquid medium in cycles of specific frequency and duration of immersion with renewal of the culture atmosphere in each cycle. TIS have revolutionized somatic embryogenesis of coffee plants as an alternative for scaling up and reducing costs associated with labor-intensive solid media culture. In Central America, somatic embryogenesis is employed on a commercial scale to produce F1 Coffea arabica hybrids. In Asia and Africa, somatic embryogenesis is used for the multiplication of selected genotypes of C. arabica and C.canephora. Somatic embryogenesis of coffee plants is considered a model system for woody species due to its biological versatility and low frequency of somaclonal variation. Nevertheless, the success of somatic embryogenesis for mass propagation of coffee plants depends on the development, optimization, and transfer of complementary technologies. Temporary immersion using the RITA® bioreactor is, so far, the best complementary tool for somatic embryogenesis of Arabica coffee for a single recipient with simple changes in liquid media. Likewise, high volume bioreactors, such as 10-L glass BIT® and 10-L flexible disposable plastic bags, have been successfully used for somatic embryogenesis of other coffee species. These bioreactors allow the manipulation of thousands of embryos under semi-automated conditions. The protocols, advantages, and benefits of this technology have been well documented for organogenesis and somatic embryogenesis pathways. However, adaptation in commercial laboratories requires technical and logistical adjustments based on the biological response of the cultures as well as the costs of implementation and production. This review presents the historical and present background of TIS and its commercial application and, in particular, pertinent information regarding temporary immersion culture for C. arabica somatic embryogenesis. The main limitations of this technology, such as hyperhydricity, asynchrony, and developmental abnormalities, are examined, and a critical analysis of current knowledge regarding physiological, biochemical, and molecular aspects of the plant response to temporary immersion is offered. Further, perspectives are provided for understanding and solving the morpho-physiological problems associated with temporary immersion culture of coffee plants. Systematic Review Registration.
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Objective: To introduce a new surgical method for the repair of a large inner canthus combined with tissue loss at the inner canthal angle of the eye by using a bird-beak-type z-shaped asymmetrical flap and to summarize its clinical effect. Method: A total of 56 patients with a large inner canthus were randomly selected, and a bird-beak-type z-shaped asymmetrical flap was used on the nasal side of the lower eyelid to repair and reconstruct the inner canthal folds. The inner canthal point was located according to physiological aesthetics. The short and long arms of the z-shaped asymmetrical flap were separated, replaced, fixed, and shaped to reconstruct the skin folds of the inner canthus and restore its aesthetic morphology. Results: All incisions after surgery achieved primary healing, and all 56 cases were followed up for 6-20 months (average 8.6 months). The caruncula lacrimalis was moderately exposed, the inner canthal angles possessed a natural appearance, and the results of the surgery were satisfactory. Five patients developed scar hyperplasia within one month after surgery, and arnica gel was applied topically for 3-6 months until the scar faded or disappeared, but no obvious scars were seen in the surgical area of the remaining patients. In two patients, the internal canthi were asymmetrical, but this improved after adjustment. Conclusion: Repair of a large inner canthus and tissue loss at the inner canthal angle of the eye using a bird-beak-type z-shaped asymmetrical flap is a simple operation, resulting in minimal trauma. Postoperatively, the inner canthal angle possessed a natural appearance with no obvious scarring.
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China has regulated its hepatitis B vaccination policy. However, data on the prevalence of hepatitis B virus (HBV) infection have not been updated since 2014. In addition, the impact of the policy on awareness of hepatitis B is limited, especially in Fujian Province where HBV infection is highly prevalent. We conducted a sero-epidemiological survey in five national monitoring counties to address these concerns. A total of 5,873 subjects were included and classified into four birth cohorts according to the policy time nodes (1981, 1992, and 2002). The HBsAg carrier rate for the general population was 8.6% (95% confidence interval [CI]: 7.9-9.3). Compared with those born before 1981, adjusted odds ratios (OR) for HBV infection were 0.51 (95% CI: 0.43-0.62), 0.10 (0.08-0.12), and 0.015 (0.01-0.023) among the 1981-1991, 1992-2001, and ≥2002 birth cohorts, respectively; while the OR was 1.26 (1.00-1.57), 0.39 (0.26-0.58), and 0.019 (0.006-0.06) for HBsAg carriage, respectively. Among the 4865 residents aged ≥15 years, hepatitis B awareness has been declining since the introduction of the hepatitis B vaccine into the immunization program (ß = -0.25, SE = 0.08, P = .001, and ß = -0.20, SE = 0.08, P = .017 for 1992-2001 and ≥2002 birth cohort, respectively). This decline was obvious for the initiation time of the first dose of the hepatitis B vaccine. Although the hepatitis B vaccination policies have helped reduce the infection, the awareness has declined. More measures on the target population are warranted to improve the public's awareness of hepatitis B vaccination in the context of great achievements.
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Antígenos de Superfície da Hepatite B , Hepatite B , Humanos , Vacinas contra Hepatite B , Hepatite B/prevenção & controle , Vírus da Hepatite B , Anticorpos Anti-Hepatite B , Vacinação , Políticas , China/epidemiologiaRESUMO
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporine plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (Pâ¯=â¯.97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), Pâ¯=â¯.04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% versus 85.7%, Pâ¯=â¯.04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% versus 15.7%, P < .001; OR: 97.9% versus 72.6%, Pâ¯=â¯.001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA.
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Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Animais , Benzoatos , Humanos , Hidrazinas , Terapia de Imunossupressão , Pirazóis , Irmãos , SuínosRESUMO
OBJECTIVE: To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation. METHODS: Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed. RESULTS: Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning. CONCLUSION: Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.
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Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística , Anemia Aplástica/terapia , Hemoglobinúria Paroxística/terapia , Humanos , Condicionamento Pré-TransplanteRESUMO
Sleep disturbance is generally common in populations as a chronic disease or a complained event. Chronic sleep disturbance is proposed to be closely linked to the pathogenesis of diseases, especially neurodegenerative diseases. We recently found that 2 months of sleep fragmentation initiated Alzheimer's disease (AD)-like behavioral and pathological changes in young wild-type mice. Herein, we present a standardized protocol to achieve chronic sleep fragmentation (CSF). Briefly, CSF was induced by an orbital rotor vibrating at 110 rpm and operating with a repetitive cycle of 10 s-on, 110 s-off, during light-ON phase (8:00 AM-8:00 PM) continuously for up to 2 months. Impairments of spatial learning and memory, anxiety-like but not depression-like behavior in mice as consequences of CSF modeling, were evaluated with Morris water maze (MWM), Novel object recognition (NOR), Open field test (OFT) and Forced swimming test (FST). In comparison with other sleep manipulations, this protocol minimizes the handling labors and maximizes the modeling efficiency. It produces stable phenotypes in young wild-type mice and can be potentially generated for a variety of research purposes.
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Ansiedade/etiologia , Comportamento Animal , Transtornos Cognitivos/etiologia , Modelos Biológicos , Privação do Sono/complicações , Vibração , Animais , Ansiedade/fisiopatologia , Doença Crônica , Transtornos Cognitivos/fisiopatologia , Depressão/etiologia , Depressão/fisiopatologia , Masculino , Memória , Camundongos Endogâmicos C57BL , Teste do Labirinto Aquático de Morris , Teste de Campo Aberto , Privação do Sono/fisiopatologia , Aprendizagem Espacial , NataçãoRESUMO
AIMS: Insufficient sleep has been found to result in varying degrees of cognitive impairment and emotional changes. Sleep was reported probably responsible for cleaning metabolic wastes in brain by increasing extracellular bulk flow. Herein, we propose that chronic sleep insufficiency in young adult wild-type mice is also linked with dysfunction of intracellular protein degradation pathways and microglia-mediated neuroinflammation, which are potentially important mechanisms in the initiation of neurodegeneration. METHODS: We applied the chronic sleep fragmentation (CSF) model to induce chronic sleep insufficiency in wild-type mice. After 2 months of CSF, cognitive function, amyloid-ß accumulation, dysfunction of endosome-autophagosome-lysosome pathway, and microglia activation were evaluated. RESULTS: Following CSF, impairment of spatial learning and memory, and aggravated anxiety-like behavior in mice were identified by behavioral experiments. Increased intracellular amyloid-ß accumulation was observed in cortex and hippocampus. Mechanistically, CSF could significantly enhance the expression of Rab5 (early endosome marker), Rab7 (late endosome marker), as well as LC3B (autophagosome marker), and autophagy-positive regulatory factors in brain detected by immunofluorescent staining and Western blot. In addition, activation of microglia was evident by enhanced CD68, CD16/32, and CD206 levels after CSF treatment. CONCLUSIONS: Chronic sleep fragmentation could initiate pathogenetic processes similar to the early stage of neurodegeneration, including dysfunction of endosome-autophagosome-lysosome pathway and microglia-mediated neuroinflammation. Our findings further strengthen the link between chronic sleep insufficiency and the initiation of neurodegeneration even if lack of genetic predisposition.
Assuntos
Autofagossomos/patologia , Encefalite/patologia , Endossomos/patologia , Lisossomos/patologia , Microglia/patologia , Doenças Neurodegenerativas/patologia , Transdução de Sinais , Privação do Sono/patologia , Animais , Ansiedade/psicologia , Doença Crônica , Cognição , Aprendizagem em Labirinto , Memória , Camundongos , Camundongos Endogâmicos C57BL , Reconhecimento Psicológico , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo , proteínas de unión al GTP Rab7RESUMO
The aim of the present paper is to better understand the mechanism of hematopoietic development through studying the biological characteristics of hematopoietic progenitor cells at different stages of development. Firstly, the c-kit expression levels of the mononuclear cells from murine embryonic aorta-gonad-mesonephros (AGM) region at embryonic day (E)10.5 and E11.5, fetal liver (FL) at E12.5, E14.5, E16.5, E18 and bone marrow (BM) were assayed with fluorescence activated cell sorting (FACS). Secondly, hematopoietic progenitor cells derived from AGM at E10.5, FL at E14.5 and BM were isolated by using c-kit microbeads. Isolated c-kit(+) population cells from AGM, FL and BM were then co-cultured with E14.5 FL-derived stromal cells in transwell co-culture system in vitro. After 3, 7, 10 days of co-culture, numerous floating cells were generated. The floating cells generated in transwell inserts were collected for FACS cell count, migration activity detection and colony forming unit (CFU) formation assay. The results showed that the c-kit was highly expressed in E10.5 AGM, with the percentage of c-kit(+) cells declining during AGM development. c-kit expression was highly expressed again in E12.5 FL, declining along with the progressive development of the FL region. Co-cultured with FL-derived stromal cells, E10.5 AGM-derived c-kit(+) cells produced the highest number of hematopoietic cells, while BM-derived c-kit(+) cells produced the lowest number of hematopoietic cells. Compared with E10.5 AGM-derived c-kit(+) cells, E14.5 FL- and BM- derived c-kit(+) cells inclined to differentiate after 7 to 10 days of culture in vitro. E10.5 AGM and E14.5 FL-derived c-kit(+) cells exhibited a higher migration activity than BM-derived c-kit(+) cells. Moreover, E10.5 AGM-derived c-kit(+) cells showed a higher ability to form mixed colony-forming unit (CFU-Mix) colony. In conclusion, compared with FL- and BM-derived c-kit(+) cells, E10.5 AGM-derived c-kit(+) hematopoietic progenitor cells exhibit better proliferation, migration potential, and have a higher ability to maintain the undifferentiation state in vitro, providing an insight into their clinical manipulation.
Assuntos
Hematopoese , Células-Tronco Hematopoéticas/citologia , Animais , Aorta/embriologia , Técnicas de Cocultura , Ensaio de Unidades Formadoras de Colônias , Gônadas/embriologia , Mesonefro/embriologia , Camundongos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Células Estromais/citologiaRESUMO
For the ubiquitous phenomenon of strand symmetry, it has been shown that it may persist for higher-order oligonucleotides. However, there is no consensus about to what extent (order of oligonucleotides or length of words) strand symmetry still persists. To determine the extent of strand symmetry in genomic sequences is critically important for the further understanding of the phenomenon. Based on previous studies, we have developed an algorithm for the novel word symmetry distance analysis. We applied it to evaluate the higher-order strand symmetry for 206 archaeal genomes and 2,659 bacterial genomes. Our results show that the new approach could provide a clear-cut criterion to determine the extent of strand symmetry for a group of genomes or individual genomes. According to the new measure, strand symmetry would tend to persist for up to 8-mers in archaeal genomes, and up to 9-mers in bacterial genomes. And the persistence may vary from 6- to 9-mers in individual genomes. Moreover, higher-order strand symmetry would tend to positively correlate with GC content and mononucleotide symmetry levels of genomic sequences. The variations of higher-order strand symmetry among genomes would indicate that strand symmetry itself may not be strictly relevant to biological functions, which would provide some insights into the origin and evolution of the phenomenon.