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BACKGROUND: Immunoglobulin light-chain amyloidosis is a relatively rare condition with a worldwide incidence of 5.1-12.8 cases per million person-years (Baker, 2022). It is characterized by a clonal population of immunoglobulin-secreting cells that produce a monoclonal light chain of κ or λ type as either an intact molecule or a fragment. CASE PRESENTATION: A 69-year-old East Asian (Chinese) male patient who presented with progressive dysphagia visited multiple hospitals repeatedly for more than 2 years and was finally diagnosed with immunoglobulin light-chain amyloidosis. CONCLUSIONS: Otolaryngologists should consider immunoglobulin light-chain amyloidosis when encountering suspicious clinical manifestations and intervene early to avoid misdiagnosis.
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Transtornos de Deglutição , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Masculino , Transtornos de Deglutição/etiologia , Idoso , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/diagnósticoRESUMO
OBJECTIVE: The purpose of this meta-analysis was to assess the effects of online education for practical skills among nursing students. METHODS: This research was done by searching PubMed, Embase, CINAHL, and Web of Science electronic databases from inception to August 18, 2023, to identify English-language articles. Data extraction, quality assessment, and literature screening were carried out independently by two researchers. The Cochrane risk of bias tool and the Methodological Items for Nonrandomized Studies (MINORS) tool were used to assess the risk of bias of the included studies. Meta-analysis was carried out using Review Manager (RevMan) version 5.3 software. RESULTS: Eighteen studies involving 2274 nursing students met the inclusion criteria. Nursing students' skills (SMD = 0.43, 95â¯% CI [0.33, 0.54], P<0.00001), knowledge (SMD = 0.16, 95â¯% CI (0.02, 0.30], P = 0.02), satisfaction (SMD = 0.29, 95â¯% CI (0.10, 0.47], P < 0.01), and confidence (SMD = 0.56, 95â¯% CI [0.29, 0.83], P < 0.0001) were all significantly improved by the online teaching intervention compared with traditional face-to-face instruction. Self-efficacy (SMD = 0.1, 95â¯% CI [-0.13, 0.33], P = 0.41) was also improved, but the difference was not statistically significant. CONCLUSION: Online learning is a novel and efficient approach to teaching practical skills to nursing students. Online education can enhance students' knowledge, skills, confidence, and learning satisfaction, and it is superior to traditional classroom instruction. The findings of this study can serve as a basis for the development of standardized online teaching techniques and assessment metrics.
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Competência Clínica , Educação a Distância , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Competência Clínica/normas , Bacharelado em Enfermagem/métodosRESUMO
BACKGROUND & AIMS: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. METHODS: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including hepatitis B surface antigen, hepatitis B envelope antigen, hepatitis B core antigen, HBV DNA, and HBV RNA. RESULTS: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. CONCLUSION: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.
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Vírus da Hepatite B , Tolerância Imunológica , Camundongos Knockout , Fatores de Crescimento Neural , Fator de Transcrição STAT3 , Animais , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/genética , Vírus da Hepatite B/imunologia , Camundongos , Fator de Transcrição STAT3/metabolismo , Modelos Animais de Doenças , Humanos , Hepatócitos/metabolismo , Hepatócitos/virologia , Hepatócitos/imunologia , Hepatite B/imunologia , Hepatite B/virologia , Carga Viral , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/imunologia , Fígado/imunologia , Fígado/metabolismo , Fígado/virologia , Camundongos Endogâmicos C57BL , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologiaRESUMO
OBJECTIVE: This study aimed to compare the efficacy of balloon Eustachian tuboplasty (BET) plus tympanostomy tube insertion (TTI) and simple TTI for postirradiation otitis media with effusion (OME) in patients with nasopharyngeal carcinoma. METHOD: This study included 36 patients (51 ears) with OME after the first radiotherapy course for nasopharyngeal carcinoma and categorized them into the BET + TTI and simple TTI groups. Effective rates, pure tone hearing threshold, Eustachian tube function score, and complication incidences were compared. RESULTS: The effective rates of the BET+TTI and TTI groups were 93.75 % and 75 %, respectively, with no statistically significant difference (P = 0.29). The pure tone hearing threshold examination at 9 months postoperatively revealed significantly lower mean air-pure tone and air-bone gap in both the BET + TTI and TTI groups than preoperatively. Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores at every postoperative visit were significantly higher than preoperative scores in the two groups (all P < 0.05); ETDQ-7 score reduction in the BET + TTI group at 3, 9, and 12 months postoperatively was significantly higher than that in the TTI group. Otorrhea and recurrence both occurred in the BET+TTI and TTI groups, but the BET+TTI group demonstrated a lower incidence. CONCLUSION: BET + TTI is an effective treatment method for postirradiation OME.
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Tuba Auditiva , Ventilação da Orelha Média , Neoplasias Nasofaríngeas , Otite Média com Derrame , Humanos , Tuba Auditiva/cirurgia , Otite Média com Derrame/etiologia , Otite Média com Derrame/cirurgia , Masculino , Feminino , Ventilação da Orelha Média/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Adulto , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/cirurgia , Audiometria de Tons Puros , Idoso , Estudos Retrospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/cirurgiaRESUMO
Only few studies have investigated the prevalence of feline coronavirus (FCoV) infection in domestic cats in Fujian, China. This is the first study to report the prevalence rate of FCoV infection in domestic cats in Fujian, China, and to analyse the epidemiological characteristics of FCoV infection in the region. A total of 112 cat faecal samples were collected from animal hospitals and catteries in the Fujian Province. RNA was extracted from faecal material for reverse transcription polymerase chain reaction (RT-PCR). The prevalence rate of FCoV infection was determined, and its epidemiological risk factors were analysed. The overall prevalence of FCoV infection in the cats, was 67.9%. We did not observe a significant association between the age, sex, or breed of the cats included in the study and the prevalence rate of the viral infection. Phylogenetic analysis showed that the four strains from Fujian were all type I FCoV. This is the first study to analyse the prevalence and epidemiological characteristics of FCoV infection in domestic cats in Fujian, China, using faecal samples. The results of this study provide preliminary data regarding the prevalence of FCoV infection in the Fujian Province for epidemiological studies on FCoV in China and worldwide. Future studies should perform systematic and comprehensive epidemiological investigations to determine the prevalence of FCoV infection in the region.
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Infecções por Coronavirus , Coronavirus Felino , Peritonite Infecciosa Felina , Gatos , Animais , Peritonite Infecciosa Felina/epidemiologia , Peritonite Infecciosa Felina/genética , Prevalência , Filogenia , RNA Viral/genética , RNA Viral/análise , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Coronavirus Felino/genética , China/epidemiologiaRESUMO
Modified Chaishao Liujunzi Decoction (MCLD) is a traditional Chinese medicine formula that is used mainly to improve clinical symptoms, alleviate gastric mucosal inflammation, and improve gastric mucosal lesions in patients with gastric intestinal metaplasia (GIM). GIM is considered a precancerous gastric cancer (GC) lesion (PLGC) and exploring effective intervention measures for GIM is of great importance for the prevention of GC. The purpose of this study was to reveal the potential molecular mechanism of MCLD in improving GIM induced by bile acid (BA) using network pharmacology and experimental validation. Through network pharmacology, we speculated that MCLD could act on GIM by driving the epidermal growth factor receptor (EGFR)/PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. After that, we used deoxycholic acid (DCA) to treat GES-1 cells to simulate BA-induced GIM and observed the effects of MCLD treatment. The results indicate that MCLD can significantly inhibit DCA-induced cell proliferation and down-regulate the expression of pro-inflammatory cytokines and intestinal-specific markers. At the same time, MCLD also negatively regulated the expression of genes and proteins of the EGFR/PI3K/AKT/mTOR pathway. Combination with EGFR agonists and inhibitors suggested that MCLD may improve GIM by inhibiting the EGFR/PI3K/AKT/mTOR pathway, which may be related to its inhibition of DCA-induced cell proliferation through this pathway. In conclusion, MCLD may improve BA-induced GIM through the EGFR/PI3K/AKT/mTOR pathway, as predicted by network pharmacology, and is a potential Chinese medicine prescription for the treatment or reversal of GIM.
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Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ácidos e Sais Biliares , Fosfatidilinositol 3-Quinases , Neoplasias Gástricas/genética , Lesões Pré-Cancerosas/genética , Receptores ErbB/metabolismo , Serina-Treonina Quinases TOR , MetaplasiaRESUMO
BACKGROUND: Chronic gastritis (CG) is characterized by inflammation of the gastric mucosa, which can progress to atrophic gastritis, intestinal metaplasia, and dysplasia. Xiangsha Liujunzi Decoction (XSLJZD), a classic traditional Chinese medicine prescription commonly used to treat digestive system diseases, is widely used to treat CG. Therefore, it is necessary to systematically evaluate the efficacy and safety of XSLJZD in the treatment of CG. METHODS: Chinese and English databases were searched, and randomized controlled trials of XSLJZD for the treatment of CG were collected from the establishment of the databases to December 28, 2022. Studies were screened according to inclusion and exclusion criteria. The methodological quality of the included studies was assessed using the risk-of-bias assessment tool in the Cochrane Handbook. Data from the included studies were extracted, and a meta-analysis was performed using Review Manager 5.3 and Stata 15.1. Finally, funnel plots and Egger's tests were used to assess publication bias. RESULTS: Fourteen studies with a sample size of 1434 cases. XSLJZD has more advantages than conventional treatment in the treatment of CG, as it can improve the clinical cure rate, clinical efficacy rate, efficacy rate of endoscopic examination, recurrence rate, and TCM symptom scores, and is relatively safe. Funnel plots and Egger's tests indicated publication bias in the included studies. CONCLUSION: The results of the meta-analysis showed that XSLJZD has advantages in treating CG compared with conventional treatment and is relatively safe. However, owing to the limitations in the quality and quantity of the included studies, caution is recommended when generalizing and applying these results. Further high-quality studies are needed to confirm these findings.
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The low bactericidal activity and poor osteogenic activity of Ti limit the use of this metal in dental implants by increasing the risk of their periimplantitis-induced failure. To address this problem, we herein surface-modify biomedical Ti through the plasma immersion coimplantation of Mg and Cu ions and examine the physicochemical properties and bio-/hemocompatibility of the resulting materials as well as their activity against periimplantitis-causing bacteria, namely Streptococcus mutans and Porphyromonas gingivalis. The reactive oxygen species release (ROS) was assessed via the 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay. The best-performing sample Mg/Cuï¼8/10ï¼-Ti promotes cell proliferation and initial cell adhesion while exhibiting high hydrophilicity, outstanding activity against the aforementioned pathogens, and good bio-/hemocompatibility. Additionally, higher levels of cellular ROS generation in S. mutans and P. gingivalis could provide insight into the antibacterial mechanisms involved in Mg/Cuï¼8/10ï¼-Ti. Thus, Mg/Cu coimplantation is concluded to endow the Ti surface with high bacteriostatic activity and biocompatibility, paving the way to the widespread use of Ti-based dental implants.
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Implantes Dentários , Peri-Implantite , Humanos , Propriedades de Superfície , Titânio/química , Espécies Reativas de Oxigênio , Antibacterianos/farmacologia , Streptococcus mutansRESUMO
Climate warming poses a great threat to ecosystems worldwide, which significantly affects the geographical distribution and suitable growth area of species. Taking Castanopsis hystrix Miq. as the research object, the potentially suitable cultivation regions under present and future climatic emission scenarios in China were predicted based on the MaxEnt model with 360 effective individual distributions and eight environmental variables. The min temperature of coldest month (bio6), precipitation of driest month (bio14), and precipitation of warmest quarter (bio18) are three leading factors affecting the geographical distribution area of C. hystrix Miq. The suitable cultivation regions of C. hystrix Miq. range from 18°-34° N, 89°-122° E in central and southern China and cover an area of 261.95 × 104 km2. The spatial pattern of C. hystrix Miq. will migrate to the southern region of low latitudes with a decreasing suitable area when in ssp1-2.6, and to the southwestern region of low latitudes or expand to the northeast region at high latitudes in ssp5-8.5, with an increasing suitable area; no significant change on the spatial pattern in ssp2-2.4. For ssp1-2.6 or ssp2-4.5 climate scenarios, the southern region of high latitudes will be appropriate for introducing and cultivating C. hystrix Miq., and the cultivation area will increase. For ssp5-8.5, its cultivation will increase and expand to the northeast of high-latitude areas slightly.
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Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a soluble endoplasmic reticulum (ER) luminal protein and its expression and secretion can be induced by ER stress. Despite initially being classified as a neurotrophic factor, MANF has been demonstrated to have restorative and protective effects in many different cell types such as neurons, liver cells, retinal cells, cardiac myocytes, and pancreatic ß cells. However, underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the understanding of the trophic activities of MANF in tissue repair and regeneration as well as underlying molecular mechanisms. The structural motifs and immune modulation of MANF are also described. We therefore propose that MANF might be a promising therapeutic target for tissue repair.
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Astrócitos , Fatores de Crescimento Neural , Astrócitos/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios , Miócitos Cardíacos/metabolismo , Retículo Endoplasmático/metabolismo , Estresse do Retículo EndoplasmáticoRESUMO
Background: Parathyroid carcinoma is an infrequent neoplasm of the endocrine system, constituting roughly 0.5% to 5% of cases of primary hyperparathyroidism. The diagnosis of this condition presents a unique challenge for healthcare professionals. Case report: We present a case of a 77-year-old female patient who presented with a longstanding right-sided neck tumor. The Positron emission tomography-computed tomography (PET-CT) scan detected a substantial tumor situated at the inferior border of the thyroid gland. A surgical procedure was conducted, resulting in the total excision of the tumor. The diagnosis of parathyroid carcinoma was confirmed through pathological investigation. At the six-month follow-up, the patient exhibited favorable post-operative outcomes with no evidence of recurrence. Conclusion: The primary approaches for managing parathyroid carcinoma involve precise diagnosis and surgical removal. This case report provides confirmation that the implementation of rigorous treatment measures can yield a substantial improvement in the prognosis.
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The Chinese government has issued a series of new policies to make it easier to industrialize gene-edited crops. However, whether technological advantages will eventually translate into industrial advantages and whether farmers will soon have access to gene-edited varieties partly depends on seed companies' willingness to produce and sell gene-edited varieties to farmers and to invest in developing their own gene-edited varieties. This study utilizes data from a survey of 111 seed companies collected in 2019 before the implementation of new regulations. This study provides empirical evidence on whether gene-edited crops will be available to farmers. The results show that the number of companies conducting research on gene-edited crops is limited, mostly to large companies. Approximately 55% of seed company managers would consider developing and selling gene-edited crops modified by SDN-1 and SDN-2 site-directed nuclease genome editing without external genetic material, whereas 46% support crops modified by SDN-3, which require gene replacement or foreign deoxyribonucleic acid (DNA) insertion and are regulated as genetically modified organisms (GMOs). The regression results show that large companies and companies with well-educated researchers are more likely to support and develop gene-editing technology. Past GM investment experience and collaboration with public institutions in gene-editing research increases the probability of company investment in gene editing R&D. These results suggest that gene-edited cultivars are more likely to be produced and sold to farmers in the future than GMOs, and that gene-edited agricultural products could have a significant market share of the seed market in the future.
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Produtos Agrícolas , Edição de Genes , Edição de Genes/métodos , Plantas Geneticamente Modificadas/genética , Produtos Agrícolas/genética , Sementes , Tecnologia , Atitude , ChinaRESUMO
To evaluate the adverse reactions associated with the four types of monovalent antivenom currently used in China, we retrospectively analysed the data of all patients admitted for snakebites who received antivenom treatment at the main institution for the treatment of venomous snakebites in Guangzhou from January 2013 to December 2021. A total of 1658 patients were analysed in our study, and 60.7% (n = 1007) of the snakebite patients received antivenom treatment. The incidence rate of adverse reactions that occurred after the administration of all types of monovalent antivenom was 4.9% (n = 49), and the incidence rate of acute adverse reactions was 2.7% (n = 27). The number of adverse reactions that occurred was 38/744 (5.1%) in patients who received prophylactic application of glucocorticoids alone and 10/217 (4.6%) in those who received a combination of antihistamines and glucocorticoids (P = 0.83). The average doses of the antivenoms used in patients exhibiting acute adverse reactions and serum sickness were 3.31 ± 0.75 vials and 2.36 ± 0.26 vials, respectively (P = 0.28). The antivenom skin test showed high specificity (98.3%, 95% CI: 97.24%-99.01%) but low sensitivity (14.3%, 95% CI: 6.41%-27.86%). Our results showed that the four types of monovalent antivenom were safe. No significant difference was observed between the use of glucocorticoids alone and the use of antihistamines combined with glucocorticoids as premedication for the prevention of adverse reactions. Reducing the dose of antivenoms or reducing the combination of antivenoms did not help to reduce the occurrence of adverse reactions. Skin testing should not be recommended due to its low sensitivity.
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Antivenenos , Mordeduras de Serpentes , Humanos , Antivenenos/toxicidade , Mordeduras de Serpentes/epidemiologia , Estudos Retrospectivos , Incidência , HospitalizaçãoRESUMO
Background: Chronic cough is a troublesome clinical problem with long-term impacts at the patient level. However, the burden of chronic cough in China is largely unknown. Thus, we performed a multicenter cross-sectional survey on the current status of chronic cough and its impact on quality of life in Guangdong, south China. Methods: Using a standardized questionnaire, we extracted and analyzed the relevant data on demographics, number of visits to a doctor, previous diagnosis, previous medications used and initial diagnosis. Cough-specific quality of life was measured by the Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC). Results: Of 933 patients from 13 tertiary medical centers in Guangdong, 52.2% were female, the median age was 40.0 [interquartile range (IQR), 31.0-52.0] years, and the median duration of chronic cough was 6.0 (IQR, 3.0-24.0) months. Over half (n=452, 54.0%) of the patients had visited physicians ≥3 times for cough. In terms of previous diagnosis, bronchitis (n=432, 46.5%) had been most frequently diagnosed, followed by pharyngitis (n=246, 26.5%) and asthmatic cough (n=98, 10.5%). A majority of patients with chronic cough had used antitussive agents (n=539, 58.5%), antibiotics (n=374, 40.6%) and traditional Chinese medicine (TCM) (n=294, 31.9%). Among the three subscales of the LCQ-MC, we observed lower scores in the mental health domain than in the physical and social domains (both P<0.001). Additionally, lower LCQ-MC scores were found in females and patients who saw the doctor >3 times for both the total and three subscale scores (all P<0.05). Conclusions: Misdiagnosis and inappropriate treatment are prevalent in patients with chronic cough and lead to considerable antibiotic abuse. Chronic cough markedly affects suffers' quality of life, especially for women.
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BACKGROUND: Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits. METHODS: In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared. RESULTS: CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p < 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p < 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p < 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p < 0.001), and was positively correlated with LCQ scores. CONCLUSIONS: CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort. Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017.
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Asma , Refluxo Gastroesofágico , Rinite , Asma/complicações , Asma/diagnóstico , Asma/epidemiologia , Tosse/diagnóstico , Tosse/epidemiologia , Humanos , Óxido Nítrico , Fenótipo , Estudos Prospectivos , Sons Respiratórios , Rinite/complicações , Inquéritos e QuestionáriosRESUMO
The high-quality development of agriculture requires not only sustainable growth of agricultural productivity but also green agricultural production. Internet technology has played an essential role in agricultural production and marketing in China over the past decades. This paper estimates provincial agricultural green growth in China from 1997 to 2019 and decomposes it into technological progress (TP) and efficiency changes (EC) based on the Luenberger productivity indicator method. Then an econometric model is employed to analyze the impact of the Internet on the growth of agricultural green productivity and each sub-component, and moderating role of farmer education in such effect. The empirical results indicated that annual average growth rate of agricultural green productivity in China is 1.33% from 1997 to 2019, and technological progress dominates its growth. The development of Internet technology has a significant positive impact on agricultural green productivity and its decomposition. Farmer education has strengthened the effect of Internet technology on agricultural green productivity and its decomposition TP and EC.
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Agricultura , Tecnologia , Agricultura/métodos , Eficiência , China , InternetRESUMO
Chronic hepatitis B (CHB) is a contagious disease caused by the hepatitis B virus, which can damage the liver via cirrhosis or cancer. Existing CHB treatments are not completely effective; immune checkpoint inhibitors show potential hope for treating CHB, but their safety and efficacy need to be further validated. In this review, we introduce the mechanisms of CHB virus infection, the expression of immune checkpoints during CHB, and the treatments that are currently available. Finally, we discuss the possibilities for using immune checkpoint inhibitors to treat CHB.
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Hepatite B Crônica , Neoplasias Hepáticas , Vírus da Hepatite B , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Cirrose Hepática , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Calpain-1, a calcium-activated neutral cysteine proteases, has been reported to be involved in the formation of pulmonary hypertension. HIF-1α, an oxygen-sensitive transcription factor, has been reported to activate genes involved in cell proliferation and extracellular matrix recombination. This study was designed to investigate the effect of calpain-1 in hypoxic pulmonary hypertension (HPH) and to explore whether there is a relationship between calpain-1 and HIF-1α in this disease. In the hypoxia-induced model of HPH, we found that hypoxia resulted in increased right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodelling and collagen deposition in lung tissues of mice. The levels of calpain-1 and HIF-1α were up-regulated in the lung tissues of hypoxia-treated mice and pulmonary arterial smooth muscle cells (PASMCs). Knock-out of calpain-1 restrained haemodynamic and histological changes induced by chronic hypoxia in mice, and inhibition of calpain-1 also repressed the abnormal proliferation and migration of PASMCs. Besides, knock-out or inhibition of calpain-1 suppressed hypoxia-induced expression of HIF-1α, VEGF, PCNA, TGF-ß1, MMP2 and collagen I in vivo and in vitro. While inhibition of HIF-1α abolished the above effects of calpain-1. Furthermore, we found that calpain-1 mediates the expression of HIF-1α through NF-κB (P65) under hypoxia conditions. In conclusion, our results suggest that calpain-1 plays a pivotal role in hypoxia-induced pulmonary vascular remodelling and fibrosis through HIF-1α, providing a better understanding of the pathogenesis of HPH.
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Calpaína , Hipertensão Pulmonar , Subunidade alfa do Fator 1 Induzível por Hipóxia , Remodelação Vascular , Animais , Calpaína/genética , Calpaína/metabolismo , Proliferação de Células/fisiologia , Fibrose , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismoRESUMO
Aroma is one of the major inherent quality characteristics in fruits. Understanding the composition of aroma volatiles and their biosynthesis mechanism is crucial to improving fruit quality. However, the biosynthesis mechanism of aroma volatiles has not been characterized yet in white-fleshed pitaya (Hylocereus undatus). This study was performed to investigate aroma volatiles and related gene expression patterns in the pulp of "mild grassy" and "strong grassy" aroma cultivars. Analysis of volatile composition and concentration showed that aldehydes, alcohols, esters, and alkenes were predominant in both cultivars. However, comparative analysis revealed a significant difference in the concentration of several metabolites, particularly hexanal and 1-hexanol. The results of the comparative transcriptome identified a large number of aroma-related differentially expressed genes. The majority of these genes were enriched in fatty acid and isoleucine degradation pathways. According to integrative analyses, changes in the expression of lipoxygenase pathway genes, specifically FAD, LOXs, HPLs, and ADHs, probably lead to the difference in strength of "grassy" aroma between both cultivars. The qRT-PCR of 18 aroma-related genes was performed to validate the transcriptome analysis. Our results identified key genes and pathways connected with the biosynthesis of aroma volatiles in white-fleshed pitaya. These results will be useful to dissect the genetic mechanism of fruit aroma in white-fleshed pitaya.