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ObjectiveTo summarize the clinical features and prognosis of pulmonary mucormycosis （PM） in southern China， and to explore the diagnostic value of metagenomic next generation sequencing （mNGS） in PM. MethodsThe clinical manifestations， diagnosis， treatment and prognosis of patients diagnosed with PM in The First Affiliated Hospital of Sun Yat-sen University from January 1， 2019 to January 31， 2022 who had undergone mNGS detection in lung tissue or alveolar lavage fluid were collected retrospectively. A total of 14 patients with PM were included， including 4 patients with confirmed diagnosis and 10 patients with clinical diagnosis. ResultsAll patients had underlying medical conditions， with hematological malignancies and diabetes being the most common. The most common symptoms were fever （n = 10）， cough （n = 9） and shortness of breath （n = 9）. Consolidation was the most common sign of chest CT， followed by mass， mostly with cavity. On laboratory tests， decreased CD4+T lymphocytes， elevated CD8+T lymphocytes， and decreased CD4+/CD8+ ratio， and presentation with pleural effusion indicate poor prognosis. The positive rate of mNGS diagnosis was 78.5%， which was significantly higher than that of histopathology （50%）， fungus rapid fluorescence staining （61.5%） and fungal culture （23.1%） of bronchoalveolar lavage fluid. ConclusionsPulmonary mucormycosis is more likely to occur in patients with underlying diseases or who are immunocompromised. The clinical manifestations lack specificity. The low CD4/CD8 ratio and presentation of pleural effusion on CT imaging indicate poor prognosis of patients. mNGS is a rapid， convenient and sensitive method for the diagnosis of PM， which has advantages in the diagnosis of pulmonary mucormycosis.
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Glutamate excitotoxicity mediated by metabotropic glutamate receptor 1 (mGluR1) overexpression or overactivation plays an important role in the development of Parkinson's disease (PD). Although clinical trials support the therapeutic potential of certain mGluR negative allosteric modulators (NAMs), there are still some limitations of precise modulation of mGluR using NAMs. Thus, the identification of small molecules or endogenous genes that facilitate mGluR1 modulation might be potentially beneficial for PD treatment. We determined the role of interacting partner cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in overactivated mGluR1-mediated cell apoptosis and signaling pathway in vitro and in vivo. HEK293 cells were used as an experimental tool to directly examine the interaction between CAL and mGluR1. We found that agonist of mGluR1 significantly enhanced the interaction between CAL and mGluR1 (P< 0. 05). Furthermore, CAL suppressed overactivated mGluR1-induced cell apoptosis and the activation of mGluR1 downstream signaling pathways. CAL overexpression relieved rotenone-induced neuron death (P< 0. 001) by inhibiting the activation of mGluR1-mediated signaling pathways in rotenone-induced rat model of PD. This study may reveal a new mechanism of mGluR1 activity regulation, and hopefully provide a novel molecular mechanism for the nervous system related diseases.
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To evaluate the clinical efficacy and safety of berberine in the treatment of dyslipidemia. In this review, CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library, EMbase, and Medline(OVID) were retrieved from database establishment to January, 2019 in any language. Randomized controlled trials(RCTs) of berberine with or without lipid-lowering drugs vs placebo, without drugs or lipid-lowering drugs only in treatment of dyslipidemia were collected. Data extraction and paper quality assessment were conducted according to the Cochrane Handbook. Then RevMan 5.3 software was used for Meta-analysis. A total of 25 trials were included, covering 3 042 cases, including 1 552 cases in the experimental group and 1 490 cases in the control group. The clinical heterogeneity of the included trials was relatively high, and the methodological quality of most trials was generally low, with bias in terms of random sequence generation, allocation hiding, blind method and result data. Interventions were divided into different subgroups for analysis. Meta-analysis suggested that use berberine alone or along with lipid lowing drugs could reduce TC, TG, LDL-C levels and increased HDL-C levels with statistically significant difference as compared with control group. As compared with control group, there was no statistically significant difference in the incidence of adverse events. No severe adverse effects were reported in all trials. Berberine has good efficacy and safety in the treatment of dyslipidemia. Due to the quality limitations of the included trials, the above conclusions need to be further verified by high-quality, large sample size and multi-center clinical trials.
Subject(s)
Humans , Berberine/therapeutic use , Dyslipidemias/drug therapy , Hypolipidemic Agents/therapeutic use , Lipids , Randomized Controlled Trials as TopicABSTRACT
To qualitatively characterize the chemical composition of Guizhi Fuling Capsules using UPLC-ESI-Q-TOF-MS/MS. The analysis was performed on Agilent ZORBAX RRHD Eclipes Plus C_(18)(2.1 mm×100 mm, 1.8 μm) column,that was eluted with mobile phase consisting of acetonitrile and 0.1% formic acid in a gradient mode. The flow rate was 0.4 mL·min~(-1), and column temperature was 30 ℃. Tandem mass spectrometry was acquired in both negative and positive ESI modes. These components were further analyzed based on high-resolution mass-to-charge ratios, fragment ion species, reference substances and literature data. In conclusion, a total of 200 compounds were identified, in which 40 were verified with reference substances. The current study laid a foundation for in-depth studies of its mass balance and pharmacodynamics.
Subject(s)
Capsules , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Tandem Mass SpectrometryABSTRACT
Objective To investigate the relationship between albumin/globulin ratio (AGR) and postoperative survival among patients with esophageal squamous cell carcinoma(ESCC) undergoing radical oesophagectomy, to establish an effective prognostic nomogram for ESCC and to provide a reference for prognosis prediction of ESCC. Methods From February 2014 to September 2017, 390 ESCC patients who underwent surgery were retrospectively enrolled from the tumor hospital in Fujian Province. The receiver operating characteristic curves(ROC) were applied to establish optimal cutoff points. Chi-square test was used to estimate the relationship between the AGR and the clinical features. Cox proportional hazards model was used to estimate the HR and 95% CI for the associations between AGR and Prognosis of ESCC patients. A nomogram model was established to predict the outcome of ESCC patients. Results The ROC demonstrated the best cutoff value for AGR was 1.16. A total of 356 patients were recruited in the final analysis, who were divided into the high AGR group (≥1.16) and the low AGR group (<1.16) by the best cutoff value. Both 1-year and 3-year survival rates in the high AGR group were higher than those detected in the low AGR group(all P<0.05). Multivariate analysis showed that the T stage, N stage, and AGR were independent prognostic factors of overall survival(all P<0.05). The HR of T stage was 1.87 (T3-T4 vs T1-T2, 95% CI: 1.04-3.35); The HR of N stage was1.89 (N+ vs N0, 95% CI: 1.13-3.17); The HR of AGR was 0.57(the high AGR group vs the low AGR group, 95%CI: 0.36-0.90). The concordance index(C-index) of the nomogram to predict overall survival was 0.68 (95% CI: 0.62-0.73，P<0. 001)．Conclusions The AGR was an independent prognosis factor for operated ESCC patients. The prognosis of ESCC in the high AGR group was better than that in the low AGR group and the prognostic nomogram provides individualized risk estimate of survival in ESCC patients after surgery.
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Objective To explore the effects of preoperative serum cancer antigen 19-9 (CA19-9) and neuron-specific enolase (NSE) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods This prospective study enrolled 176 patients with ESCC. 2 test was used to analyze the relationship between CA19-9, NSE and general clinical features. Survival curves were estimated using Kaplan-Meier method and comparisons were performed using the log-rank test. The Cox proportional hazards model was performed for multivariate analyses of overall survival (OS) and disease free survival (DFS). Results The patients with both high CA19-9 and NSE had the poor prognosis compared with those had both low CA19-9 and NSE (OS: HR=2.310, 95% CI: 1.208-4.418; DFS:HR=2.354, 95% CI：1.265-4.381). Compared to the separate detection of the two markers, the combined detection of CA19-9 and NSE was more accurate in the prognosis prediction of patients with ESCC (OS:C-index=0.686; DFS:C-index=0.684). Conclusions Preoperative serum CA19-9 and NSE were risk factors for the prognosis of patients with ESCC. Combined detection had higher accuracy of prediction of prognosis in patients with ESCC.
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The post-marketing re-evaluation of traditional Chinese medicine (TCM) is a crucial stage for drug evaluation. Due to the particularity of TCM, it is necessary to re-evaluate the effectiveness of certain Chinese medicines by studying and collecting the studies on safety of long-term/extensive populations under actual clinical application, in order to verify the effectiveness of post-marketing TCM. However, there is an absence in technical specifications for relevant clinical trials on re-evaluation of effectiveness at present. As a consequence, the preliminary technical specifications were drafted in this article, focusing on several perspectives related to the re-evaluation of post-marketing clinical effectiveness of TCM, including ethical protection, research plan formulation, real-world research methods, randomized controlled trial methods, research methods of clinical pharmacological mechanism, sublimation method of TCM theory and so on. The objective of writing this article is to provide general methodological guidance for the re-evaluation of TCM post-marketing effectiveness, so that the process and results of post-marketing re-evaluation of TCM can be more scientific and reasonable.
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<p><b>OBJECTIVE</b>To observe the effects of Huannao Yicong Formula (, HYF) on learning and memory and it's regulating effect on γ-secretase related anterior pharynx defective 1 (APH-1), presenilin enhancer-2 (PEN-2) signaling pathway, so as to discuss and further clarify the mechanism of HYF on Alzheimer's disease.</p><p><b>METHODS</b>Sixty APP/PS1 transgenic mice, randomly allocated into 4 groups, the model group, the donepezil group (0.65 mg/kg), HYF low-dose group (HYF-L, 5.46 g/kg) and HYF high-dose group (HYF-H, 10.92 g/kg), 15 for each group. Another 15 C57BL/6J mice with the same age and same genetic background were allocated into the control group, proper dosage of drugs or distilled water were given by intragastric administration once daily for 12 weeks. After 12 weeks of administration, the learning and memory abilities of mice in each group was evaluated by the morris water maze test, amyloid precursor protein (APP), Aβand Aβlevels in hippocampus were detected by enzyme-linked immunosorbent assay, γ-secretase was detected by dual luciferase assaying, the levels of APH-1a, hypoxia-inducible factor 1α (HIF-1α), cAMP response element-binding protein (CREB) and PEN-2 and their mRNA expression was measured by Western blot and real-time polymerase chain reaction.</p><p><b>RESULTS</b>HYF can ameliorate learning and memory deficits in APP/PS1 transgenic mice by decreasing the escape latency, improving the number of platform crossing and swimming speed (P<0.01, P<0.05). HYF can decrease the levels of APP, Aβ, Aβand the activity of γ-secretase in hippocampus of Alzheimer's disease model mice. HYF can down-regulate the levels of CREB and PEN-2 and the expression of their mRNA.</p><p><b>CONCLUSION</b>HYF can improve the learning and memory ability by inhibiting the activity of γ-secretase through the CREB/PEN-2 signaling pathway, and this may be one of the therapeutic mechanisms of HYF in Alzheimer's disease.</p>
Subject(s)
Animals , Female , Male , Amyloid Precursor Protein Secretases , Metabolism , Amyloid beta-Protein Precursor , Metabolism , Cyclic AMP Response Element-Binding Protein , Genetics , Metabolism , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Endopeptidases , Genetics , Metabolism , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation , Hippocampus , Metabolism , Pathology , Hypoxia-Inducible Factor 1, alpha Subunit , Genetics , Metabolism , Immunohistochemistry , Learning , Memory Disorders , Drug Therapy , Genetics , Mice, Inbred C57BL , Mice, Transgenic , Presenilin-1 , Metabolism , Presenilin-2 , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Signal TransductionABSTRACT
<p><b>BACKGROUND</b>Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.</p><p><b>METHODS</b>A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.</p><p><b>RESULTS</b>A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.</p><p><b>CONCLUSION</b>Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Dermatitis, Atopic , Diagnosis , Allergy and Immunology , Eczema , Diagnosis , Immunoglobulin E , Blood , Retrospective Studies , Surveys and QuestionnairesABSTRACT
<p><b>OBJECTIVE</b>To investigate the temperature change of scrotum caused by varicocele(VC) and its significance.</p><p><b>METHODS</b>One hundred and sixty-six VC patients were examined by infrared ray imaging and colored ultrasonic scanning, and the results were analyzed. Comparisons of the infrared ray images and the routine semen analysis of 106 of the patients were made between before and after the operation.</p><p><b>RESULTS</b>The difference in the infrared ray images between before and after the operation on the VC patients was significant (P < 0.01), and so was the difference in the results of semen analysis(P < 0.01; some of the items P < 0.05).</p><p><b>CONCLUSIONS</b>The infrared ray imaging, together with the semen analysis and colored ultrasonic scanning, had a directive value for the diagnosis and treatment of VC patients.</p>