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Objective To establish a mouse model of type Ⅰ tricho-hepato-enteric syndrome(THES)induced by Ttc37 deficiency.Methods Ttc37 flox strain was established by site-specifically inserted loxP sites into Ttc37 gene via CRISPR/CAS9 technology.Ubiquitously expressed CAG-Cre was introduced for all-tissue removal of Ttc37 in Ttc37flox/flox;CAG-Cre mice.The knock-out effect was confirmed by fluorescence quantitative PCR and Western blot.Phenotypic evaluations were conducted in 8-week-old mice including hematoxylin-eosin staining of skin,spleen,liver,bladder,and gastrointestinal tract(GI),serum enzyme activity assay of aspartate aminotransferase(AST)and alanine aminotransferase(ALT),measurement of serum hemoglobin level,and ELISA for IgG and IgM level upon antigen immunization.Results Similar to type Ⅰ THES patients,Ttc37flox/flox;CAG-Cre mice exhibited impaired development of hair shaft,epidermis,B cell and eyes,while liver,GI,bladder and serum hemoglobin level seemed normal under unstressed condition.Conclusion A novel mouse model of typeⅠ THES was constructed successfully,which was applicable for pathological study.
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ObjectiveTo construct 131Ⅰ-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma. MethodsThree short nucleic acid chains self-assembled to a long nucleic acid chain after being annealed， and 131Ⅰ-NT was obtained by radioiodine labeling using chloramine T method. The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography. The stability of the labeled products in vitro at different temperatures and different storage solvents was detected. The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy， and the radioactive uptake ratio of 131Ⅰ-NT combined with human hepatocellular carcinoma cell HepG2 and normal hepatocyte L02 was measured. The biodistribution of 131Ⅰ-NT was obtained through injecting 131Ⅰ-NT into HepG2 tumor-bearing mice via tail vein. ResultsThe labeling rate of 131Ⅰ-NT was （93.05±0.74） %， and the radiochemical purity post purification was （98.35±0.32） %. Its radiochemical purity in PBS and pure serum at 4℃ for 24 h was （92.77±0.04） % and （89.43±0.2） %， respectively. The radioactivity uptake rate of HepG2 cells was higher than that of L02 cells after 131Ⅰ-NT was incubated with two kinds of cells for 2 h significantly. After injection of 131Ⅰ-NT through tail vein， the radioactive uptake per gram of tumor tissue were （4.9±0.55）%ID/g， （10.12±0.32）%ID/g and （4.25±0.31）%ID/g at 30 min， 1 h and 2 h， respectively. The T/M ratio was 7.33±2.04， 36.54±12.72 and 44.93±7.90 respectively. ConclusionsThe 131Ⅰ-labeled long chain nucleic acid nanotrain was constructed successfully， which possesses relatively high stability in vitro ， and high targeting ability to HepG2 cells in vitro and HepG2 tumor-bearing mouse model. Our study demonstrated that 131Ⅰ-NT may be a potential radionuclide carrier targeting human liver cancer， which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinoma.
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【Objective】 To evaluate the interference of anti-CD47 monoclonal antibody on transfusion compatibility detection, in order to establish methods for removing interference and evaluate its efficacy. 【Methods】 Blood samples from 8 patients in our clinical trial who were treated with anti-CD47 monoclonal antibody from Tianjing and Xinda were collected. ABO and Rh blood group antigen identification, direct anti-human globulin test, unexpected antibody screening test and cross-matching test were performed by ZZAP, Gamma-clone(an anti-globulin reagent lacking IgG4) and Immucor Capture-R solid phase agglutination kit. 【Results】 ABO blood group identification of 5 subjects were interfered after treatment with anti-CD47 monoclonal antibody. All 8 subjects showed 2+ to 4+ agglutination intensity on direct anti-human globulin test and 3+ to 4+ on unexpected antibody screening. The results of unexpected antibody screening by Gamma-clone and Immucor Capture-R solid phase agglutination kit were all negative, while the cross-matching test were compatible. Patients with anemia caused by CD47 monoclonal antibody treatment were transfused with 2 U suspension red blood cells, and the evaluation showed that the transfusion was effective. 【Conclusion】 The CD47 monoclonal antibody can interfere with transfusion compatibility detection, and the use of antiglobulin reagents lacking IgG4 and Immucor Capture-R solid phase agglutination kit can remove the interference, with good transfusion efficacy in patients.
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Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.
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Adolescent , Child , Female , Humans , Male , Cardiomyopathies/etiology , Glycogen Storage Disease Type IIb/complications , Hypertrophy, Left Ventricular/etiology , Lysosomal-Associated Membrane Protein 2/genetics , Pre-Excitation Syndromes/geneticsABSTRACT
Extracellular signal-regulated kinase 1/2 (ERK1/2) is a serine/threoninekinase involved in the signal transduction cascade of Ras-Raf-mitogen-activated protein kinase (MEK)-ERK.It participates in the cell growth,proliferation and even invasion by regulating gene transcription and expression.The occurrence of a variety of diseases such as lung cancer,liver cancer,ovarian cancer,cervical cancer,endometriosis,and preeclampsia,as well the metastasis and disease progression,is closely associated with the regulation of cell invasion by ERK1/2 signaling pathway.Therefore,exploring the regulation of ERK1/2 signaling on cell invasion and its role in pathogenesis of diseases may help to develop more effective treatment schemes.This article introduces recent progress in the regulation of ERK1/2 signaling on cell invasion and the role of such regulation in diseases,with a view to give new insights into the clinical treatment of ERK 1/2-related diseases.
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Female , Pregnancy , Humans , Mitogen-Activated Protein Kinase 3 , Signal Transduction , Mitogen-Activated Protein Kinases , Cell Cycle , Cell ProliferationABSTRACT
The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.
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Humans , Orphan Nuclear Receptors/metabolism , Receptors, Steroid/physiology , Ligands , Liver , Liver Diseases , Intercellular Signaling Peptides and ProteinsABSTRACT
Myocardial infarction caused by myocardial ischemia can lead to the loss of cardiomyocytes, resulting in the replacement of the myocardial infarction area with scar tissue and ultimately leading to heart failure. However, the treatment options are currently very limited. Currently, myocardial patch therapy is a promising strategy for treating severe myocardial infarction. This approach is based on engineering principles and involves combining seed cells or biological active substances with suitable scaffold materials to construct biomaterials that can be used for transplantation, repair, or replacement of autologous myocardium. The biomaterial scaffolds for engineered myocardial patches are usually prepared by means of acellular matrix, electrospinning technology, 3D biological printing, hydrogel, cell patch and other methods. In this paper, the preparation methods of myocardial patches and their application progress in myocardial infarction treatment are reviewed.
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@#Abstract: Objective To understand the contamination status, drug resistance, virulence gene carrying status, and molecular typing characteristics of Vibrio parahaemolyticus (VP) in aquatic products sold in Nanchang City. Methods A total of 170 commercial crayfishes, freshwater fish frogs and related smears samples were collected from various farmers' markets in Nanchang from March to September 2021. The strains of V. parahaemolyticus were detected and isolated from the samples. Antibiotic resistance test, virulence gene test, and pulsed-field gel electrophoresis (PFGE) molecular typing analysis were carried out. Results Among the collected samples, V.parahaemolyticus was only isolated from crayfish and crayfish smear samples, with a total of 35 strains of VP isolated. No V.parahaemolyticus strain was isolated from other freshwater fish, frogs, and their smear samples. Among the 17 common antibiotics tested, only two trains showed resistance to ampicillin, and one strain to streptomycin, , and all were sensitive to other antibiotics; all 35 strains of V. parahaemolyticus carried the gene, but only one strain carried the heat-resistant related hemolysin gene trh, and no direct heat-resistant hemolysin gene tdh positive strain was found; PFGE pattern clustering showed that there was no strain with the same PFGE pattern, and there was no obvious dominant cluster among these strains, and their genetic relationship was relatively distant. Conclusions The contamination of V. parahaemolyticus in small and medium-sized crayfish sold in the market in Nanchang City is relatively serious. The V. parahaemolyticus isolates in these polluted crayfish generally do not carry key virulence genes such as tdh, are sensitive to common antibiotics, and only have low-level resistance to ampicillin and streptomycin. PFGE pattern clustering showed that V. parahaemolyticus does not have no obvious dominant cluster, and these strains have rich genetic diversity, indicating that they may have different sources.
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Objective To evaluate the effect of targeted monitoring and multi-modular improvement strategy on the prevention and control of catheter-associated urinary tract infection(CAUTI).Methods Patients with indwe-lling urinary catheter in a tertiary first-class hospital from January 2018 to December 2022 were selected as the re-search subjects.Targeted monitoring results and distribution of pathogenic bacteria in 5 consecutive years were ana-lyzed,and a multi-modular improvement strategy based on the targeted monitoring results was implemented.The occurrence of CAUTI before and after implementation,status and effectiveness of training in prevention and control measures were compared respectively.Results Before and after the implementation of the multi-modular improve-ment strategy,health care workers'compliance rate of hand hygiene,awareness rate of prevention and control measures,and implementation rate of prevention and control measures all increased significantly(all P＜0.001).Targeted monitoring results showed that daily test rates of urine culture and routine urine from patients with in-dwelling catheters have been on the rise in 5 consecutive years(P＜0.05).A total of 397 cases of CAUTI occurred in the past 5 years.Incidences of CAUTI in general intensive care unit(ICU)and surgical ICU showed decreasing trends in 5 consecutive years(all P＜0.05).Incidence of CAUTI in general wards showed no statistically significant difference in 5 years(P=0.088).A total of 431 strains of pathogenic bacteria were detected,mainly Gram-negative bacteria.Daily incidence of multidrug-resistant organism infection in patients with indwelling catheters was 0.12‰.After the implementation of the multi-modular improvement strategy,incidence of CAUTI in all departments re-duced significantly(P＜0.05).Conclusion Targeted monitoring can help identify departments with high-risk of CAUTI,multi-modular improvement strategy can raise the quality of prevention and control of CAUTI in all occa-sions,reduce the incidence of CAUTI,and is worthy of clinical promotion and application.
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The quality evaluation of traditional Chinese medicine is one of the key issues related to the modernization of traditional Chinese medicine. The quality evaluation technology system of traditional Chinese medicine mainly includes traditional evaluation (traits, microscopic and physicochemical identification), chemical evaluation and biological evaluation. Due to the complex composition of traditional Chinese medicine, the single detection method in the above evaluation technology system usually cannot obtain sufficient quality information. The multi-source information fusion strategy can organically integrate data from multiple analysis and detection technologies to obtain more comprehensive information of samples and improve the quality evaluation effect. At present, multi-source information fusion strategy has been widely used in the fields of military, industrial and food, and it is still in its infancy in the field of quality evaluation of traditional Chinese medicine. This research introduces the definition, structure, method (algorithm) and fusion level of multi-source information fusion, summarizes its research progress in the origin traceability, variety identification and pharmaceutical analysis of traditional Chinese medicine, and sorts out the specific methods of data fusion in each literature. Finally, we summarized, prospected and discussed the application, development and existing problems of information fusion technology and its application in the quality evaluation of traditional Chinese medicine, in order to provide reference for broadening the application of this technology in the field of traditional Chinese medicine.
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To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.
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Objective: To investigate the effects of glucose-6-phosphatase catalytic subunit (G6PC) recombinant adenovirus on proliferation and cell cycle regulation of liver cancer cells. Methods: Recombinant adenovirus AdG6PC was constructed. Huh7 cells and SK-Hep1 cells were set as Mock, AdGFP and AdG6PC group. Cell proliferation and clone formation assay were used to observe the proliferation of liver cancer cells. Transwell and scratch assay were used to observe the invasion and migration of liver cancer cells. Cell cycle flow cytometry assay was used to analyze the effect of G6PC overexpression on the proliferation cycle of liver cancer cells. Western blot was used to detect the effect of G6PC overexpression on the cell-cycle protein expression in liver cancer cells. Results: The recombinant adenovirus AdG6PC was successfully constructed. Huh7 and SK-Hep1 cells proliferation assay showed that the number of proliferating cells in the AdG6PC group was significantly lower than the other two groups (P < 0.05). Clone formation assay showed that the number of clones was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression could significantly inhibit the proliferation of liver cancer cells. Transwell assay showed that the number of cell migration was significantly lower in AdG6PC than the other two groups (P < 0.05). Scratch repair rate was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression can significantly inhibit the invasion and migration of liver cancer cells. Cell cycle flow cytometry showed that G6PC overexpression had significantly inhibited the Huh7 cells G(1)/S phase transition. Western blot result showed that G6PC overexpression had down-regulated the proliferation in cell-cycle related proteins expression. Conclusion: G6PC inhibits the proliferation, cell-cycle related expression, and migration of liver cancer cells by inhibiting the G(1)/S phase transition.
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Humans , Catalytic Domain , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glucose-6-Phosphatase/metabolism , Liver Neoplasms/geneticsABSTRACT
The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24+) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.
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Humans , Abdominal Cavity , Acupuncture Points , Acupuncture Therapy/methods , Tic Disorders/therapyABSTRACT
ObjectiveTo investigate the effect of Shaoyaotang on diarrhea， inflammation， and intestinal flora in rats with dampness-heat diarrhea and explore the mechanism of therapeutic principle "treating incontinent syndrome with dredging method" of Shaoyaotang. MethodThe dampness-heat diarrhea model was induced by high temperature， high humidity， high sugar and fat diet， and pathogenic factors. The rats were divided into normal group， model group （normal saline）， Shaoyaotang group （5.62 g·kg-1）， Rhei Radix et Rhizoma （RRER）-free Shaoyaotang group （5.15 g·kg-1）， and RRER group （0.01 g·kg-1）. The rats were treated correspondingly for five days， twice a day in the morning and evening. The diarrhea index was used to evaluate the antidiarrheal effect of each group three hours after the administration in the evening. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-2， and IL-6 in the serum were detected by enzyme-linked immunosorbent assay （ELISA） three hours after the last administration. The structure of intestinal flora in feces was characterized by 16sDNA. ResultCompared with the model group， the Shaoyaotang group， the RRER-free Shaoyaotang group， and the RRER group showed reduced diarrhea index （P<0.01）， with the onset rates ranking as the Shaoyaotang group>the RRER-free Shaoyaotang group>the RRER group. Those three groups with drug intervention all showed decreased levels of inflammatory factors （P<0.01）， especially the Shaoyaotang group， and no significant difference was observed between the RRER group and the RRER-free Shaoyaotang group. The abundance of pathogenic bacteria and conditioned pathogens （e.g. Escherichia-Shigella， Prevotella， Enterorhabdus， and Bacteroides） was reduced and the proliferation of probiotics （such as Ruminococcus， Turicibacter， and Lachnospiraceae） was increased in the groups with drug intervention （P<0.01）. For the structure of intestinal flora， the RRER group and the Shaoyaotang group were close to the normal group， and the RRER-free Shaoyaotang group was different from the other three groups （P<0.01）. ConclusionShaoyaotang can improve the outcome of rats with dampness-heat diarrhea through anti-inflammation and regulation of intestinal flora disorders. RRER in the prescription plays a key role in reducing the abundance of harmful bacteria and promoting the proliferation of probiotics， which is the key of Shaoyaotang in promoting the re-balance of intestinal flora. It also confirms the scientificity of treating dampness-heat diarrhea with RRER following the therapeutic principle "treating incontinent syndrome with dredging method".
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Chinese medicine dispensing granules, the result of the efforts to transform Chinese medicinal decoction pieces in China, features portability and ease of storage. Thus, it is destined to be an indispensible dosage form in the modernization drive of Chinese medicine. The Announcement on Ending the Pilot Project of Chinese Medicine Dispensing Granules was released in February 2021 and relevant regulations went into force in November 2021, which marks the a new journey for the development of Chinese medicine dispensing granules and the beginning of the "post-pilot era". However, it faces the challenges in quality and standard. This study reviewed the history of Chinese medicine dispensing granules, analyzed the technical progress, market, and main problems in development, and proposed suggestions and prospects for its development in the "post-pilot era", which is expected to serve as a reference for its industry development and rational use.
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China , Drugs, Chinese Herbal/therapeutic use , Industrial Development , Medicine, Chinese Traditional , Pilot ProjectsABSTRACT
Objective:To establish a new fast and accurate method for identifying the authenticity and specifications of Fritillariae Cirrhosae Bulbus based on electronic nose technology， and to discuss the feasibility of this technology in the identification of decoction pieces. Method:Fritillariae Cirrhosae Bulbus was used as the research object， 80 batches of samples to be tested were collected， and the olfactory sensory data of the electronic nose were taken as independent variables （<italic>X</italic>）， the results of the method contained in the 2020 edition of <italic>Chinese Pharmacopoeia</italic> were taken as the focus， and the traditional empirical identification results were used as benchmarking information （<italic>Y</italic>）. Four chemometric methods， including discriminant analysis （DA）， least square support vector machine （LS-SVM）， principal component analysis-DA （PCA-DA） and partial least squares-DA （PLS-DA）， were used to establish the identification model ［<italic>Y</italic>=<italic>F</italic>（<italic>X</italic>）］ of authenticity and commodity specifications of Fritillariae Cirrhosae Bulbus， respectively. Wherein， the identification accuracy and time-consuming was taken as indicators to discuss the results. Result:After cross-verification by leave-one-out method， the correct rates of the above four models were 93.75%， 91.25%， 95.00% and 95.00%， respectively， and the PCA-DA and PLS-DA identification models were the best in terms of authenticity identification. In specification identification， the correct rates of these four models were 86.67%， 88.00%， 89.33% and 68.00%， respectively， and the PCA-DA identification model was the best. The electronic nose had a high accuracy in the identification of authenticity and specification model， and the time consuming was relatively short. Conclusion:Electronic nose technology can identify Fritillariae Cirrhosae Bulbus accurately and quickly， and has significant advantages in terms of timeliness and correct judgment rate.
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Sudden sensorineural hearing loss (SSNHL) refers to the sudden and unexplained sensorineural hearing loss within 72 h and a decrease in hearing of ≥30 dB affecting at least 3 consecutive frequencies. It is one of the common emergencies in neurology and otolaryngology. Early etiological evaluation and systematic and targeted treatment are very important for delaying the progression of SSNHL and restoring hearing. Recent studies have shown that SSNHL overlaps with vascular risk factors of ischemic stroke, and may predict the risk of ischemic stroke. SSNHL may be one of the clinical manifestation and even the prodromal symptoms of ischemic stroke, especially the infarction of the blood supply area of the anterior inferior cerebellar artery or its branch internal auditory artery. Although these factors can not fully reveal the relationship between SSNHL and ischemic stroke, they are enough to warn clinicians that they should consider the possibility of ischemic stroke when receiving patients with SSNHL. Screening of vascular risk factors for patients with SSNHL as early as possible is helpful to avoid the risk of recurrence of ischemic stroke.
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Salidroside (SAL), a major bioactive compound of Rhodiola crenulata, has significant anti-hypoxia effect, however, its underlying molecular mechanism has not been elucidated. In order to explore the protective mechanism of SAL, the lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD) and hypoxia-induced factor 1α (HIF-1α) were measured to establish the PC12 cell hypoxic model. Cell staining and cell viability analyses were performed to evaluate the protective effects of SAL. The metabolomics and bioinformatics methods were used to explore the protective effects of salidroside under hypoxia condition. The metabolite-protein interaction networks were further established and the protein expression level was examined by Western blotting. The results showed that 59 endogenous metabolites changed and the expression of the hub proteins of CK2, p-PTEN/PTEN, PI3K, p-Akt/Akt, NF-κB p65 and Bcl-2 were increased, suggesting that SAL could increase the expression of CK2, which induced the phosphorylation and inactivation of PTEN, reduced the inhibitory effect on PI3K signaling pathways and activated the PI3K/Akt/NF-κB survival signaling pathway. Our study provided an important insight to reveal the protective molecular mechanism of SAL as a novel drug candidate.
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Objective:To investigate the occurrence of carotid artery abnormalities in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and the related risk factors affecting the occurrence of carotid artery abnormalities.Methods:A total of 169 regular follow-up outpatients with HIV/AIDS from April 2003 to December 2019 in Peking Union Medical College Hospital, whose carotid artery ultrasound examination were performed from July 2015 to December 2019 were included. The patients were divided into young (≤44 years old), middle-aged and elderly (≥45 years old) according to their ages, and the physical examination data of the included patients were collected.The statistical methods were logistic regression analysis and single sample t test. Results:Among the 169 HIV/AIDS patients, 40(23.7%) had abnormal carotid artery and 129(76.3%) had no abnormal carotid artery. Middle-aged and elderly people (odds ratio ( OR)=3.85, 95%confidence interval (95% CI) 1.54-9.65, P<0.01), hypertension ( OR=6.24, 95% CI 1.95-20.00, P<0.01), hyperlipidemia ( OR=2.44, 95% CI 1.00-5.93, P<0.05), and elevated human leucocyte antigen (HLA)-DR + CD8 + /CD8 + ( OR=1.03, 95% CI 1.01-1.06, P<0.05) were the risk factors for carotid artery abnormality. The common carotid artery inner medium film thickness (IMT) of patients in HIV/AIDS group Ⅰ (20 to 30 years old), group Ⅱ (31 to 40 years old), group Ⅲ (41 to 50 years old) were (0.061 0±0.001 2), (0.062 9±0.001 4) and (0.065 6±0.002 6) cm, respectively, which were thicker than the control groups ((0.051±0.003), (0.056±0.004) and (0.063±0.002) cm, respectively). The differences were all statistically significant ( t=5.119, 4.775 and 1.739, respectively, all P<0.05). The common carotid artery IMT of patients in HIV/AIDS group A (30 to 44 years old) and group B (45 to 59 years old) were (0.062 6±0.001 1) and (0.072 3±0.003 4) cm, respectively, which were thicker than the control groups ((0.052±0.011) and (0.064±0.015) cm, respectively), the differences were both statistically significant ( t=9.520 and 3.012, respectively, both P<0.01). Conclusion:Younger HIV-positive people have a higher probability of abnormal carotid arteries and may be at greater risk of cardiovascular disease than HIV-negative people of the same age, suggesting that HIV-positive people, especially young people, should be examined early with ultrasound of the neck arteries to detect abnormalities and intervene as soon as possible.
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This study aimed to establish nomograms to preoperatively predict the possibility of testicular salvage (TS) in patients with testicular torsion. The clinical data of 204 patients with testicular torsion diagnosed at Xijing Hospital and Tangdu Hospital (Xi'an, China) between August 2008 and November 2019 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of TS. Based on multivariate regression coefficients, nomograms to predict possibility of TS were established. The predictive ability of the nomograms was internally validated by receiver operating characteristic (ROC) curves and calibration plots. The duration of symptoms ranged from 2 h to 1 month, with a median of 3.5 days. Thirty (14.7%) patients underwent surgical reduction and contralateral orchiopexy, while the remaining 174 (85.3%) underwent orchiectomy and contralateral orchiopexy. Finally, long symptom duration was an independent risk predictor for TS, while visible intratesticular blood flow and homogeneous testicular echotexture under color Doppler ultrasound were independent protective predictors. Internal validation showed that the nomograms, which were established by integrating these three predictive factors, had good discrimination ability in predicting the possibility of TS (areas under the ROC curves were 0.851 and 0.828, respectively). The calibration plots showed good agreement between the nomogram-predicted possibility of TS and the actual situation. In conclusion, this brief preoperative prediction tool will help clinicians to quickly determine the urgency of surgical exploration.