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Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: ⢠Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.
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OBJECTIVE: To investigate the correlation between oxidative stress in the bronchoalveolar lavage fluid (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and the clinical characteristics of severe MPP (SMPP) and refractory MPP (RMPP). METHODS: Clinical and BALF-related data were collected from 83 patients with MPP, of which 29 had SMPP and 54 had general MPP (GMPP); 37 patients were in the RMPP group and 46 in the non-RMPP group. The levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPP) as well as the activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in BALF were detected. Logistic regression analyses were performed on MDA, AOPP, SOD, GSH-PX, gender, heat peak, neutrophil percentage, C-reactive protein, lactate dehydrogenase, d-dimer, lung consolidation, sputum embolus, and pleural effusion. RESULTS: The levels of MDA and AOPP in the BALF of the MPP group were significantly higher than those in the control group (p < .05), whereas SOD and GSH-PX levels were lower than those in the control group (p < .05). The BALF AOPP levels in the RMPP group were higher than those in the non-RMPP group, and the SOD and GSH-PX levels in the BALF were lower than those in the non-RMPP group; the difference was statistically significant (p < .05). The levels of MDA and AOPP in the BALF of children in the SMPP group were higher than those in the GMPP group, and the levels of SOD and GSH-PX were lower than those in the GMPP group, with statistically significant differences (p < .05). The C-index of the logistic regression model was 0.960 (95% confidence interval 0.958-0.963), which indicates that the model has good predictive ability. CONCLUSION: Advanced oxidation protein products may be a marker for predicting the conditions of SMPP and RMPP, and the prediction model can assess the risk of progression in children to RMPP, which is conducive to clinical diagnosis and treatment.
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INTRODUCTION: Mycoplasma pneumoniae pneumonia (MPP) is prevalent in paediatric patients and can progress to refractory mycoplasma pneumoniae pneumonia (RMPP). OBJECTIVE: To assess the predictive value of bronchoscopy combined with computed tomography (CT) score in identifying RMPP in children. METHODS: A retrospective analysis was conducted on 244 paediatric patients with MP, categorising them into RMPP and general mycoplasma pneumoniae pneumonia (GMPP) groups. A paired t-test compared the bronchitis score (BS) and CT score before and after treatment, supplemented by receiver operating characteristic (ROC) analysis. RESULTS: The RMPP group showed higher incidences of extrapulmonary complications and pleural effusion (58.10% and 40%, respectively) compared with the GMPP group (44.60%, p = 0.037 and 18.71%, p < 0.001, respectively). The CT scores for each lung lobe were statistically significant between the groups, except for the right upper lobe (p < 0.05). Correlation analysis between the total CT score and total BS yielded r = 0.346 and p < 0.001. The ROC for BS combined with CT score, including area under the curve, sensitivity, specificity, and cut-off values, were 0.82, 0.89, 0.64, and 0.53, respectively. CONCLUSION: The combined BS and CT score method is highly valuable in identifying RMPP in children.
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Broncoscopia , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Valor Preditivo dos Testes , Curva ROC , Tomografia Computadorizada por Raios X , Humanos , Pneumonia por Mycoplasma/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Criança , Pré-Escolar , Mycoplasma pneumoniae/isolamento & purificação , Antibacterianos/uso terapêutico , Adolescente , Sensibilidade e Especificidade , Pulmão/diagnóstico por imagem , Bronquite/diagnóstico por imagem , Bronquite/microbiologia , Bronquite/diagnósticoRESUMO
OBJECTIVES: To assess the value of carbon dioxide transoral laser microsurgery (CO2 TOLMS) for early-stage glottic cancer with special regard to involvement of the anterior commissure (AC). STUDY DESIGN: Single-center retrospective cohort study. SETTING: Grade-A tertiary hospital. METHODS: A retrospective analysis of patients with early-stage (Tis-T2) glottic cancer who underwent CO2 TOLMS. All patients had at least 2 years of follow-up. The univariate and multivariate survival analyses were used to identify the risk factors for recurrence and the Kaplan-Meier method was used to analyze OS and DSS rates. RESULTS: A total of 102 patients were included in the study. Eleven patients (10.78%) had recurrence. The univariate analysis showed that the recurrence was associated with the AC classification, T staging, tumor size, and tobacco use (P < .05). However, on multivariate analysis, the AC classification was the only independent risk factor for recurrence (P < .001, HR = 3.179). AC classification were distributed as follows: 59 (57.84%) AC0, 29 (28.43%) AC1, 8 (7.84%) AC2, and 6 (5.88%) AC3, 2-year/5-year OS and DSS rates were progressively reduced in the AC0, AC1, AC2, and AC3 groups (P < .001). At the same T staging, the OS rates incrementally decreased as the level of involvement of the AC became higher (P = .004). CONCLUSION: CO2 TOLMS is an effective treatment for early-stage glottic cancer. AC involvement is an independent risk factors for recurrence and poor prognosis. The AC classification system may be better at grading the prognosis of patients with early-stage glottic cancer and has prognostic value independent of T staging.
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Glote , Neoplasias Laríngeas , Terapia a Laser , Microcirurgia , Estadiamento de Neoplasias , Humanos , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/mortalidade , Masculino , Glote/cirurgia , Glote/patologia , Estudos Retrospectivos , Feminino , Microcirurgia/métodos , Pessoa de Meia-Idade , Terapia a Laser/métodos , Idoso , Resultado do Tratamento , Recidiva Local de Neoplasia , Adulto , Lasers de Gás/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
Two undescribed sesquiterpenoids, including one nor-eudesmane type (1) and one guaiane type (2), together with two known analogues (3-4) have been isolated and identified from the fruits of Alpinia oxyphylla. The structures of these new compounds were elucidated by extensive spectroscopic analyses (1D-, 2D-NMR, HRESIMS, IR, UV) and NMR calculations with DP4+ analysis. The anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on PGE2 production in LPS stimulated RAW 264.7 macrophages.
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BACKGROUND: Early evaluation of severe mycoplasma pneumoniae pneumonia (SMPP) and the prompt utilization of fiberoptic bronchoscopic manipulation can effectively alleviate complications and restrict the progression of sequelae. This study aim to establish a nomogram forecasting model for SMPP in children and explore an optimal early therapeutic bronchoalveolar lavage (TBAL) treatment strategy. METHODS: This retrospective study included children with mycoplasma pneumoniae pneumonia (MPP) from January 2019 to December 2021. Multivariate logistic regression analysis was used to screen independent risk factors for SMPP and establish a nomogram model. The bootstrap method was employed and a receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy and robustness of the model. Kaplan-Meier analysis was used to assess the effect of lavage and hospitalization times. RESULTS: A total of 244 cases were enrolled in the study, among whom 68 with SMPP and 176 with non-SMPP (NSMPP). A prediction model with five independent risk factors: left upper lobe computed tomography (CT) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health assessment (APACHE) II score, bronchitis score (BS), and c-reactive protein (CRP) was established based on the multivariate logistic regression analysis. The ROC curve of the prediction model showed the area under ROC curve (AUC) was 0.985 (95% confidence interval (CI) 0.972-0.997). The Hosmer-Lemeshow goodness-of-fit test results showed that the nomogram model predicted the risk of SMPP well (χ2 = 2.127, P = 0.977). The log-rank result suggested that an early BAL treatment could shorten MPP hospitalization time (P = 0.0057). CONCLUSION: This nomogram model, based on the left upper lobe CT score, SOFA score, APACHE II score, BS, and CRP level, represents a valuable tool to predict the risk of SMPP in children and optimize the timing of TBAL.
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Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Criança , Humanos , Estudos Retrospectivos , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/terapia , Lavagem Broncoalveolar , Nomogramas , PrognósticoRESUMO
Clostridium septicum alpha toxin (CSA) plays significant roles in ruminant's braxy. Genetically engineered CSA has been shown to function as a potential vaccine candidate in the prevention of the disease caused by Clostridium septicum. In the present study, we synthesized a non-toxic recombinant, rCSAm4/TMD by introducing four amino acid substitutions (C86L/N296A/H301A/W342A) and 11-amino-acid deletion (residues 212 to 222). Compared to recombinant CSA, rCSAm4/TMD showed no cytotoxicity to MDCK cells and was not fatal to mice. Moreover, rCSAm4/TMD could protect immunized mice against 5 × mouse LD100 (100% lethal dose) of crude CSA without obvious pathological change. Most importantly, rabbits immunized with rCSAm4/TMD produced high titers of neutralizing antibodies which protected the rabbits against crude CSA challenge. These data suggest that genetically detoxified rCSAm4/TMD is a potential subunit vaccine candidate against braxy.
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Infecções por Clostridium , Clostridium septicum , Coelhos , Animais , Camundongos , Infecções por Clostridium/prevenção & controle , Anticorpos Neutralizantes , Vacinas BacterianasRESUMO
Calcium sulfoaluminate cement concrete (CSAC) reinforced by fiber-reinforced polymer (FRP) bars, termed bars for brevity, is a good alternative to steel-reinforced concrete in marine environments due to the corrosion resistance of FRP and the lower pH of CSAC. For the first time, multi-mechanical tests are conducted to compare the durability of glass FRP (GFRP) to that of carbon FRP (CFRP) after exposure to CSAC pore solution. The bars were immersed in a simulated pore solution of CSAC made with either fresh water and river sand or with seawater and sea sand. Solution temperature was held constant at 30 °C, 45 °C or 60 °C for 30, 60, 90 and 180 days of immersion. Tensile, horizontal and transverse shear tests, as well as detailed microstructural analyses, were conducted to determine the level and mechanisms of degradation for each type of bar. Sea salt increases the degradation of both bars, but it degrades GFRP more than CFRP. The bars' retained tensile strength is a reliable indicator of their durability, while their post-exposure horizontal and transverse shear strengths are found inconsistent and counter intuitive. In the GFRP, the fiber, the epoxy matrix and their interface suffered damage, but in the CFRP, the carbon fiber was not damaged. Under the test conditions in this study, the maximum reduction in the tensile strength of the GFRP was 56.9% while that of CFRP was 15.1%. Based on the relevant ASTM standard, the CFRP bar satisfies the alkaline resistance requirement of the standard in the CSAC pore solution with and without salt, whereas the GFRP bar does not meet the same requirement in the above pore solution with salt.
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This study aims to develop a rapid and non-destructive method to identify counterfeit and substandard drugs, addressing the critical need for better quality control in drug production. According to the reasons for counterfeit products in actual production, the commonly used solid preparation excipients such as HPMC, MCC, Mg-St and Pregelatinized Starch, as well as three chemical drugs with similar efficacy to Guizhi-Fuling (GZFL) Capsule as adulterants, including Aspirin, Ibuprofen and Sinomenine Hydrochloride were selected and designed as adulteration samples with different levels of adulteration. NIR spectra were collected in a non-invasive mode and analyzed by one-class classification methods. The feasibility of using Near-infrared (NIR) spectroscopy as a detection method to qualitatively identify adulterated samples was explored at three packaging levels of powder, intact capsules and capsules in PVC. The differences between the samples were analyzed by NIR spectra comparison, cluster analysis and principal component analysis. The performance of SVM, OCPLS and DD-SIMCA models in dealing with the authentication of genuine and counterfeit products was established and compared. The results show that the spectra contain sample information and the adulterated samples could be discriminated correctly by established models. Moreover, applying appropriate spectral preprocessing methods can further improve the model's performance. In addition, a PLS regression model was developed to predict the adulteration levels of the three packing level samples, which yielded satisfactory results. This study highlights the potential of NIR spectroscopy combined with Chemometrics as a rapid and non-destructive testing analysis method to accurately identify counterfeit and substandard drugs, thereby ensuring drug quality.
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Espectroscopia de Luz Próxima ao Infravermelho , Medicamentos Fora do Padrão , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Quimiometria , Cápsulas , Análise por Conglomerados , Contaminação de Alimentos/análise , Análise dos Mínimos QuadradosRESUMO
Epsilon toxin (ETX) is secreted by Clostridium perfringens (C. perfringens)as a relatively inactive prototoxin (pETX), which is enzymatically activated to ETX by removing carboxy-terminal and amino-terminal peptides. Genetically engineered ETX mutants have been shown to function as potential vaccine candidates in the prevention of the enterotoxemia caused by C. perfringens. In the present study, two recombinant site-directed mutants of pETX, rpETXY30A/Y71A/H106P/Y196A (rpETXm41) and rpETXY30A/H106P/Y196A/F199E (rpETXm42), were synthesized by mutating four essential amino acid residues (Tyr30, Tyr71, His106, Tyr196 or Phe199). Compared to recombinant pETX (rpETX), both rpETXm41 and rpETXm42 lacked the detectable toxicity in MDCK cells and mice, which suggested that both rpETXm41 and rpETXm42 are sufficiently safe to be vaccine candidates. Despite the fact that rpETXm41 and rpETXm42 were reactogenic with polyclonal antibodies against crude ETX, both single- and double-dose vaccination (Vs and Vd, respectively) of rpETXm41 induced a higher level of IgG titer and protection in mice than that of rpETXm42. Therefore, we selected rpETXm41 for the further study. Sheep received Vs of 150 µg rpETXm41 developed significant levels of toxin-neutralizing antibodies persisting for at least 6 months, which conferred protection against crude ETX challenge without microscopic lesions. These data suggest that genetically detoxified rpETXY30A/Y71A/H106P/Y196A could form the basis of a next-generation enterotoxemia vaccine.
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Enterotoxemia , Vacinas , Cães , Animais , Camundongos , Ovinos , Enterotoxemia/prevenção & controle , Enterotoxemia/patologia , Clostridium perfringens/genética , Células Madin Darby de Rim Canino , PeptídeosRESUMO
In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.
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Inteligência Artificial , Medicina Tradicional Chinesa , Reprodutibilidade dos Testes , Controle de Qualidade , Inteligência , Preparações FarmacêuticasRESUMO
Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.
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Excessive illumination is one of the most severe environmental factors that impacts the organism. There is growing evidence that obesity significantly contributes to the onset of chronic kidney disease. However, the effect of continuous light on the kidney and which color can produce an apparent phenomenon remains elusive. In this study, C57BL/6 mice given either a normal diet (LD-WN) or a high-fat diet (LD-WF) were subjected to a light cycle of 12 h of illumination followed by 12 h of darkness for 12 weeks. Meanwhile, 48 high-fat diet mice were given a 24 h monochromatic light exposure of varying colors (white, LL-WF; blue, LL-BF; green, LL-GF) for 12 weeks. As expected, the LD-WF mice showed significant obesity, kidney injury, and renal dysfunction compared with the LD-WN group. LL-BF mice had worse kidney injury than LD-WF mice, including higher Kim-1 and Lcn2. The kidney of the LL-BF group showed marked glomerular and tubular injury, with decreased levels of Nephrin, Podocin, Cd2ap, and α-Actinin-4 compared to LD-WF. LL-BF also reduced the antioxidant capacity, including GSH-Px, CAT, and T-AOC, increased the production of MDA, and inhibited the activation of the NRF2/HO-1 signaling pathway. Furthermore, LL-BF upregulated the mRNA levels of the pro-inflammatory factors Tnf-α, Il-6, and Mcp-1, decreasing the inhibitory inflammatory Il-4 expression. We observed increased plasma corticosterone (CORT), renal glucocorticoid receptors (GR) expression, Hsp90, Hsp70, and P23 mRNA levels. These findings suggested that LL-BF increased CORT secretion and affected glucocorticoid receptors (GR) in comparison to the LD-WF group. Moreover, in vitro research demonstrated that CORT treatment increased oxidative stress and inflammation, which was counteracted by adding a GR inhibitor. Thus, the sustained blue light worsened kidney damage, possibly by inducing elevated CORT and increasing oxidative stress and inflammation via GR.
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BACKGROUND: There is still a lack of effective scoring criteria for assessing the severity of pulmonary infection associated with changes in the endobronchial lining of the bronchus in children. This study aimed to ascertain the timing and value of endoscopic scoring of fibreoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) in children with severe pneumonia. METHOD: The clinical data of 229 children with severe pneumonia treated with BAL in the Pediatric Intensive Care Unit of the First Affiliated Hospital of Xinxiang Medical University between November 2018 and December 2021 were collected. According to the severity of the disease, patients were divided into an invasive ventilation group and a non-invasive ventilation group, as well as an early BAL group (receiving BAL within 1 day of admission) and a late BAL group (receiving BAL 2 days after admission). A Student's t-test, Chi-square test, receiver operating characteristic (ROC) curve and survival curve were used to analyse the bronchitis score, aetiology of BAL fluid and survival data. RESULTS: The scores of endoscopic mucosal oedema, erythema and pallor and the total score in the invasive ventilation group were higher than those in the non-invasive ventilation group (P < 0.05), and they were consistent with the Sequential Organ Failure Assessment (SOFA) scores. The secretion colour score was lower in the early BAL group than in the late BAL group (P < 0.05). On the bronchitis scores, which were evaluated using a ROC curve, the difference in the mucosal erythema, pallor, oedema and total score of the invasive and non-invasive groups was statistically significant (P < 0.05), which was consistent with the area under the ROC of the SOFA scores. Acute Physiology and Chronic Health Assessment II and SOFA scores after FOB were lower than those before treatment (P < 0.05). In terms of ICU hospitalisation days and total hospitalisation days, the time of the early FOB patients was shorter than that of the late FOB patients (P < 0.05). A total of 22 patients (9.61%) died. The Kaplan-Meier analysis and log-rank test showed that the survival rate of the non-invasive ventilation group was higher than that of the invasive ventilation group (P < 0.05). CONCLUSION: This study found that FOB combined with BAL is an important method for the diagnosis and treatment of severe pneumonia. Early BAL can reduce hospitalisation and ICU time; however, it cannot improve the survival rate. The endoscopic score has a certain role to play in assessing the severity of pulmonary inflammation, but studies with a large sample are still needed to confirm this.
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Bronquite , Pneumonia , Humanos , Criança , Broncoscopia/métodos , Palidez , Pneumonia/diagnóstico , Líquido da Lavagem Broncoalveolar , Curva ROC , Prognóstico , Estudos RetrospectivosRESUMO
Clostridium perfringens epsilon toxin (ETX) and Clostridium septicum alpha toxin (CSA) are lethal and necrotizing toxins, which play key roles in enterotoxemia and braxy of ruminants, respectively. In the present study, we synthesized a bivalent chimeric protein rETXm3CSAm4/TMD comprising ETXm3 (Y30A/H106P/Y196A) and CSAm4/TMD (C86L/N296A/H301A/W342A and a deletion of residues 212 to 222). Compared with recombinant ETX and recombinant CSA, rETXm3CSAm4/TMD showed no cytotoxicity in Madin-Darby Canine Kidney cells and was not fatal to mice. Moreover, rETXm3CSAm4/TMD could protect immunized mice against 10 × mouse LD100 of crude ETX or 3 × mouse LD100 of crude CSA without obvious histopathologic difference. Most importantly, both rabbits and sheep immunized with rETXm3CSAm4/TMD produced high titers of neutralizing antibody which protected the animals against the challenge with crude ETX or crude CSA. These data suggest that genetically detoxified rETXm3CSAm4/TMD is a potential subunit vaccine candidate against enterotoxemia and braxy.
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Infecções por Clostridium , Enterotoxemia , Animais , Cães , Coelhos , Ovinos , Camundongos , Enterotoxemia/prevenção & controle , Enterotoxemia/patologia , Proteínas Recombinantes de Fusão/genética , Clostridium perfringens , Infecções por Clostridium/prevenção & controle , Vacinas BacterianasRESUMO
The research aimed to study an Avian polyomavirus strain that was isolated in Shandong, China. To study the pathogenicity of APV in SPF chickens, and provide references for epidemiological research and disease prevention and control of APV. The genetic characterization of APV strain (termed APV-20) was analyzed and the pathogenicity of APV was investigated from two aspects: different age SPF chickens, and different infection doses. The results revealed that the APV-20 exhibits a nucleotide homology of 99% with the other three APV strains, and the evolution of APV In China was slow. In addition, the APV-20 infection in chickens caused depression, drowsiness, clustering, and fluffy feathers, but no deaths occurred in the infected chickens. The main manifestations of necropsy, and Hematoxylin and Eosin staining (HE) showed that one-day-old SPF chickens were the most susceptible, and there was a positive correlation between viral load and infection dose in the same tissue. This study showed that SPF chickens were susceptible to APV, and an experimental animal model was established. This study can provide a reference for the pathogenic mechanism of immune prevention and control of APV.
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Because of the complex components, simple content determination can hardly reflect the overall quality of Guizhi Fuling Capsules. Therefore, it is necessary to carry out a multi-component dissolution test. The variability of quality among different batches of products from different manufacturers is a common problem of Chinese medicine solid preparations. To comprehensively control the quality of Guizhi Fuling Capsules, we studied the dissolution behaviors of 7 index components in the capsules under different conditions, and investigated the consistency of dissolution behaviors among different batches of products from the same manufacturer. The basket method of general rule 0931 in Chinese Pharmacopoeia was adopted, and the rotating speeds were set at 50, 75, and 100 r·min~(-1), respectively. The hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.0), pure water, and phosphate buffer solution(pH 6.8) were used as the dissolution media. Automatic sampling was carried out at the time points of 5, 10, 20, 30, 45, and 60 min, respectively. The cumulative dissolution of 7 index components was measured through ultra-performance liquid chromatography(UPLC). The difference factor f_1 and similarity factor f_2 were calculated to comprehensively evaluate the similarity of the dissolution curves among 8 batches of Guizhi Fuling Capsules, and a variety of dissolution and release equations were fitted. The results showed that multiple components had faster dissolution rates at higher rotating speed and in hydrochloric acid medium. The 8 batches of Guizhi Fuling capsules showed the average f_1 value lower than 15 and the average f_2 value higher than 50, which indicated that different batches of products had similar dissolution behaviors. Most components had synchronous dissolution behaviors and similar release cha-racteristics. This study provides a reference for the quality consistency evaluation among batches, processing optimization, and dosage form improvement of Guizhi Fuling Capsules.
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Medicamentos de Ervas Chinesas , Wolfiporia , Cápsulas , Solubilidade , Ácido Clorídrico , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta PressãoRESUMO
BACKGROUND: The limited therapeutic outcomes of atherosclerosis (AS) have allowed, traditional Chinese medicine has been well established as an alternative approach in ameliorating AS and associated clinical syndromes. Clinically, Tongsaimai tablet (TSMT), a commercial Chinese patent medicine approved by CFDA, shows an obvious therapeutic effect on AS treatment. However, its effective mechanism and quality control still need thorough and urgent exploration. METHODS: The mice were orally administered with TSMT and their serum was investigated for the absorbed compounds using serum pharmacochemistry via the UPLC-Q-Exactive Orbitrap/MS analysis was employed to investigate these absorbed compounds in serum of mice orally administrated with TSMT. Based on these absorbed prototype compounds in serum derived from TSMT, a component-target-disease network was constructed using network pharmacology strategy, which elucidated the potential bioactive components, effective targets, and molecular mechanisms of TSMT against AS. Further, the screened compounds from the component-target network were utilized as the quality control (QC) markers, determining multi-component content determination and HPLC fingerprint to assess quality of nine batches of TSMT samples. RESULTS: A total of 164 individual components were identified in TSMT. Among them, 29 prototype compounds were found in serum of mice administrated with TSMT. Based on these candidate prototype components, 34 protein targets and 151 pathways related to AS were predicted, and they might significantly exhibit potential anti-AS mechanisms via synergistic regulations of lipid regulation, shear stress, and anti-inflammation, etc. Five potentially bioactive ingredients in TSMT, including Ferulic acid, Liquiritin, Senkyunolide I, Luteolin and Glycyrrhizic acid in quantity not less than 1.2798, 0.4716, 0.5419, 0.1349, 4.0386 mg/g, respectively, screened from the component-target-pathway network. Thereby, these indicated that these five compounds of TMST which played vital roles in the attenuation of AS could serve as crucial marker compounds for quality control. CONCLUSIONS: Overall, based on the combination of serum pharmacochemistry and network pharmacology, the present study firstly provided a useful strategy to establish a quality assessment approach for TSMT by screening out the potential anti-AS mechanisms and chemical quality markers.
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Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.