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Tuberculosis (TB) and human immunodeficiency virus infection / acquired immune deficiency syndrome (HIV/AIDS) are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years, with the promotion and application of new TB and HIV detection technologies worldwide, TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening, summarizes important progress of research and applications, and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.
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OBJECTIVE@#This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.@*METHODS@#We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( n = 113,154) and MDD ( n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.@*RESULTS@#The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.@*CONCLUSION@#This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.
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Humanos , Trastorno Depresivo Mayor/genética , Depresión , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Factores de Riesgo , Proteínas de Transporte de Serotonina en la Membrana PlasmáticaRESUMEN
Screening and preventive treatment for latent tuberculosis infection (LTBI) are important measures to reduce the incidence of active tuberculosis (TB) and its global burden. This paper discusses the current status of LTBI prevalence and preventive treatment, risk of incidence in high-risk groups, screening methods, and other interventions, emphasizing the importance of prevention and control as early as possible in a scientific strategy, so as to lay a solid foundation for eliminating TB by 2030.
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ObjectiveTo obtain the status of latent tuberculosis infection (LTBI) among tuberculosis (TB)-related health-care workers (HCWs) in Shanghai, and to explore the risk factors related to TB infection. MethodsA multi-center cross-sectional study was conducted by recruiting medical workers from multiple designated TB hospitals, centers for disease control and prevention, and community health service centers in Shanghai. Each subject was required to complete a questionnaire and to provide a blood sample for TB infection test. Univariate and multivariate analysis ware made in order to find risk factors relating to TB infection. ResultsA total of 165 medical workers were recruited, and the proportion of TB infection was 16.36% (95%CI: 11.49%‒22.76%). Multivariate logistic analysis showed that clinical doctors and nurses (adjusted OR=9.756, 95%CI: 1.790‒53.188), laboratory staffs (adjusted OR=78.975, 95%CI: 8.749‒712.918), and nursing and cleaning workers (adjusted OR=89.920, 95%CI: 3.111‒2 598.930) had higher risk of TB infection. ConclusionThe overall LTBI prevalence among TB-related HCWs is low. However, working as doctors, nurses, laboratory staffs, nursing workers and cleaning workers are risk factors of TB infection. TB-related HCWs who work at hospitals are at risk of TB infection comparing to medical staffs who work outside hospitals.
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ObjectiveTo evaluate the current screening methods for the students who were in close contact with tuberculosis patients, that could accurately identify the preventive treatment subjects, and to improve the tuberculosis prevention and control in Shanghai schools. MethodsThe freshman/sophomore who were in close contact with active tuberculosis patients in the colleges in 2019 were recruited. All the subjects underwent both tuberculin skin test (TST) and QuantiFERON-TB gold in-tube (QFT) test at the enrollment. After signed the informed consent, all of the participants filled in a questionnaire and determined their baseline tuberculosis infection status. They were followed up for 2 years to monitor the conversion of infection status and the incidence of tuberculosis. ResultsFour of 9 (44.4%) positive participants had conversion to negative results, and 5 of 300 (1.7%) negative participants had conversion to positive during the 2-year follow-up, one of which was diagnosed with active tuberculosis. We assessed diagnostic agreement between QFT and TST at different cut-off values. The highest coincidence rate was 94.0% when choosing 15 mm as the cut-off value, with Kappa coefficient of 0.45 (95%CI: 0.32‒0.59). ConclusionAlthough stricter than the national work requirements, the prevention and control of tuberculosis in Shanghai schools still need to be carried out meticulously. It's necessary to strengthen daily prevention and control measures, and improve the ability of management.
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ObjectiveTo describe the characteristics of treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients enrolled in second-line treatment in Shanghai from 2017 to 2018, and to analyze the influencing factors of treatment outcomes. MethodsTotally 182 MDR-TB patients were analyzed by using data collected from the China tuberculosis management information system, the hospital's electronic medical record information system, whole genome sequencing results and a questionnaire survey, and logistic regression analysis was used to analyze the factors affecting the success of treatment. ResultsIn 182 MDR-TB patients, the success rate of treatment was 65.4%, the loss to follow-up rate was 8.2%, the mortality rate was 4.9%, the unassessable rate was 13.7%, and the drug withdrawal rate was 7.7%. The factors affecting the success of treatment in MDR-TB patients included age (35‒ years old, OR=5.28, 95%CI: 1.58‒17.59, P=0.007; 55‒ years old, OR=16.30, 95%CI: 4.36‒60.92, P<0.001) and compliance to medication (OR=0.55, 95%CI: 0.42‒0.72, P<0.001). ConclusionThe treatment success rate of MDR-TB patients in Shanghai from 2017 to 2018 is significantly higher than the average level in China. Older patients and patients with less compliant are at higher risk of adverse treatment outcomes.
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This study aimed to provide data support for resource utilization of the stems and leaves of Astragalus membranaceus var. mongholicus(SLAM) by analyzing and evaluating the chemical constituents. The crude protein, crude fiber, and soluble saccharide of SLAM were analyzed by Kjeldahl method, filtration method, and UV-Vis spectrophotometry, respectively. The nucleosides, amino acids, flavonoids, and saponins of SLAM were analyzed by ultraperformance liquid chromatography-triple quadrupole mass spectrometry(UPLC-TQ-MS). Combined with principal component analysis(PCA), the quality difference of resource components of SLAM was comprehensively evaluated. The results showed that the average content of crude protein, crude fiber, total polysaccharide, and redu-cing sugar in SLAM was 5.11%, 30.33%, 11.03 mg·g~(-1), and 31.90 mg·g~(-1), respectively. Six nucleosides, 15 amino acids, 22 flavonoids, and one saponin were detected, with an average content of 1.49 mg·g~(-1), 6.00 mg·g~(-1), 1.86 mg·g~(-1), and 35.67 μg·g~(-1), respectively. The content of various types of chemical components in SLAM differed greatly in different harvesting periods and growing years. The results of PCA showed that the quality of SLAM produced in Ningxia was superior. The results can provide references for the utilization of SLAM.
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Astragalus propinquus/química , Cromatografía de Gases y Espectrometría de Masas , Flavonoides/análisis , Hojas de la Planta/química , Aminoácidos , Saponinas/análisisRESUMEN
Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.
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Humanos , Lectinas , Candida , Candidemia , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa , Ácidos Nucleicos , Fenómenos MagnéticosRESUMEN
Standardized clinical assessment and management plans (SCAMPs) are becoming popular as a fast, scientific, feedback based, and modifiable clinical practice execution tool. The authors introduced the background, development overview, the development and implementation process, and application effectiveness of SCAMPs. They also compared the similarities and differences between SCAMPs and clinical practice guidelines, and proposed countermeasures and suggestions for the application and promotion of SCAMPs in China, for reference of medical quality and safety management.
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As a retrovirus with high recombination and mutation rate, HIV targets CD4+ T lymphocytes, causing damage to the body's immune system and eventually leading to severe immune function defects. Different subtypes of the HIV virus exhibit significant sequence differences in their structural and regulatory genes, and this diversity is closely related to etiology, transmission, diagnosis, drug therapy, disease progression, and vaccine development. As a country with the largest number of HIV subtypes, rapid and accurate typing of the HIV virus holds great significance for China's efforts in disease prevention and control. This study provides a comprehensive reveiw of domestic and international HIV genotyping methods, and summarizes the clinical significance of different subtypes in order to provide reference for further research.
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ObjectiveTo compare the efficacy between the Mycob.T scanner system and manual microscopy for detecting acid-fast bacilli in sputum specimens. MethodsBetween January and November 2020, a total of 1 519 sputum samples from suspected primary tuberculosis patients from 5 designated tuberculosis hospitals in Shanghai were examined by Smear and BACTEC MGIT 960 liquid culture (liquid culture) methods. Each specimen was subiected to 2 direct smear slides. One slide was stained by Z-N method and examined with manual microscopic method. Another slide was stained and scanned by the Mycob.T system. The efficacy of manual microscopy and the Mycob.T scanner system for detecting acid-fast bacilli in sputum specimens was compared based on the result of liquid culture. Results of the repetitive scanning by the Mycob.T scanner system and the recheck of the manual microscopy were analyzed. ResultsThe average positive rate by the Mycob.T scanner system was 14.4% (219/1 519) while the average positive rate by manual microscopy was 16.3% (248/1 519). No significant difference was observed (χ2=2.13, P=0.145). Based on liquid culture confirmation results, the sensitivity of manual microscopy (60.36%) was higher than that of the Mycob.T scanner system (52.94%), and the difference is statistically significant (χ2=4.38, P=0.036). Both methods had high specificity (98.94%). The concordance of the Mycob.T scanner system and manual microscopy was 95.46%, with the kappa value of 0.826. The results of repeatability test of the Mycob.T scanner system and the recheck results of the manual microscopy showed that the coincidence rate of scanning by the Mycob.T scanner system was 99.5% (436/438), and the recheck coincidence rate by the manual microscopy was 98.6% (432/438). ConclusionThe Mycob.T scanner system have high specificity for detecting acid-fast bacilli in sputum samples and good consistency with the results of manual microscopy. Compared with manual microscopic examination, the Mycob.T scanner system can greatly alleviate the work intensity.
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ObjectiveTo explore the possible mechanism of Tongdu Xingshen needling method (通督醒神针刺法) on post-stroke cognitive impairment. MethodsSD rats were randomly divided into a normal group (n=12), a sham surgery group (n=12), a model group (n=12), and a electroacupuncture group (n=13). The rats in the model group and electroacupuncture group were subjected to the wire bolus method to establish the rats model with learning memory impairment after cerebral ischaemia-reperfusion. After successful modelling, the rats in the electroacupuncture group were given electroacupuncture interventions at “Shenting (GV 24)” and “Baihui (GV 20)” once a day for 30 minutes for 14 days. The other three groups did not receive other interventions but grasp. A 5-day localisation navigation experiment was conducted on the 9th day of intervention, and a spatial exploration experiment was conducted on the 14th day of intervention to evaluate the learning and memory abilities of the rats. After the spatial exploration experiment, hippocampal tissues were taken from each group of rats, and the changes in the volume of cerebral infarction were observed by TTC staining; the changes in the morphology of pyramidal neurons and the density of dendritic spines in the CA1 area of the hippocampus were observed by Golgi staining; protein immunoblotting was used to detect the relative protein expression of the subunits of the α-amino-3-carboxy-5-methylisoxazole-4-propionic acid (AMPA) receptor including glutamate receptor 1 (GluR1), glutamate receptor 2 (GluR2), glutamate receptor 3 (GluR3) and auxiliary proteins TARPγ2, TARPγ8 in hippocampal tissues of rats in each group; the real-time fluorescence quantitative PCR was used to detect GluR1, GluR2, GluR3 mRNA levels in the hippocampal tissues of rats. ResultsIn the localisation navigation experiment, compared with the normal group and sham surgery group, the escape latency and total distance of rats in the model group were significantly extended (P<0.05) at day 1, 2, 3, 4, and 5; and the escape latency and total distance of rats in the electroacupuncture group tended to be significantly shorter than those in the model group (P<0.05). In the spatial exploration experiment, compared with the normal group and the sham surgery group, the number of rats crossing the platform in the model group was significantly reduced (P<0.05), and the number of crossings of the platform in the electroacupuncture group increased significantly (P<0.05). The results of TTC staining showed that the volume of cerebral infarction increased clearly in the model group compared with the sham surgery group (P<0.05), and apparently decreased in the electroacupuncture group compared with the model group (P<0.05). Golgi staining showed that the number of dendritic branches of pyramidal neurons and dendritic spines in hippocampal CA1 region significantly decreased in the model group compared with the normal group and the sham surgery group (P<0.05). The number of dendritic branches of pyramidal neurons and the density of dendritic spines in hippocampal CA1 region significantly increased in the electroacupuncture group compared with the model group (P<0.05). The protein relative expression levels of GluR1, GluR2, GluR3, TARPγ2 and TARPγ8, and the mRNA levels of GluR1, GluR2 and GluR3 in hippocampus decreased in the model group compared with the normal group and the sham surgery group (P<0.05). The protein relative expression levels of GluR1, GluR2, GluR3, TARPγ2 and TARPγ8, and the mRNA levels of GluR1, GluR2 and GluR3 in hippocampus increased in the electroacupuncture group compared with model group (P<0.05). ConclusionThe Tongdu Xingshen needling method can improve learning memory impairment after cerebral ischaemia-reperfusion, which may be related to up-regulation of the expression of AMPA receptor and their auxiliary protein TARP, and promoting the synaptic plasticity of hippocampal tissues.
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【Objective:】 To analyze and explore the key points of the ethical review of real-world research in pediatric population, and to provide reference for ethical review of real-world research in pediatric population. 【Methods:】 According to the characteristics of real-world research and pediatric clinical trials, the review points of real-world research in pediatric population were analyzed and discussed in comparison with the principles and focus of ethical review in general clinical research. 【Results:】 The ethics committee should pay particular attention to the review of informed consent, privacy protection, risk benefit assessment, cost and compensation, and should also take into account the research design, data governance, research conflicts of interest, research registration and publication, etc., and conduct scientific and reasonable ethical review of real-world research in pediatric population. 【Conclusion:】 Clinical trials in pediatric population should have stricter and scientific ethical review, which can not only protect the interests of vulnerable groups of minors, but also standardize real-world research in pediatric population and promote the healthy development of pediatric clinical research, so as to better protect children and promote their health.
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Asparaginyl endopeptidases (AEPs) in plants belong to the family of cysteine protease that undergo self-activation in the form of zymogen in acidic vacuole and play important physiological roles in maturation of seed storage proteins, protein degradation, programmed cell death and host defense. Bioprocessing enzymes (peptidyl Asx-specific ligases, PALs) that promote the maturation of cyclotides have recently been isolated and identified from several cyclotide-rich plants. PALs derived from AEPs can site-specifically catalyze the formation of asparagine or aspartate peptide bonds. Due to the advantages of relatively traceless peptide bonds and broad substrate spectrum and high catalytic efficiency, they have been playing important roles in the cyclization and modification of peptides and proteins, and are powerful tools for improving the stability of peptide drugs. This review describes the physiological functions of AEPs in plants and summarizes the discoveries, structural characteristics, catalytic mechanism and protein engineering of PALs, as well as the limitation of their applications and future trends. In addition, the applications of PALs in cyclotides biosynthesis and the development of macrocyclic peptides are highlighted, with the aim of providing a new idea for the biocatalytic synthesis of cyclic peptides.
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OBJECTIVE@#To investigate the molecular mechanism by which miR-20a-5p regulates HOXB13 gene expression and inhibits lung cancer cell proliferation.@*METHODS@#The expression levels of HOXB13 mRNA and protein in lung cancer A549 cells transfected with HOXB13 overexpression plasmid or HOXB13 siRNA were detected with real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting. CCK-8 and EdU assays were used to examine the effect of modulation of HOXB13 expression on cell proliferation. We screened possible binding miRNAs of HOXB13 by bioinformatics analysis. In A549 cells transfected with miR-20a-5p mimic or miR-20a-5p inhibitor, the expression level of miR-20a-5p was detected by qRT-PCR and the protein expression of HOXB13 was determined with Western blotting. CCK-8 and EdU assays were used to assess the effect of miR-20a-5p overexpression on the proliferation of A549 cells. miR-20a-5p mimic and HOXB13 overexpression plasmids were co-transfected into A549 cells, and the changes in cell proliferation were evaluated with CCK-8 and EdU assays.@*RESULTS@#HOXB13 overexpression obviously promoted the proliferation of A549 cells (P < 0.05). miR-20a-5p was identified as the potential binding miRNA of HOXB13. Overexpression of miR-20a-5p in A549 cells significantly decreased the expression of HOXB13 protein (P < 0.05), while interference of miR-20a-5p obviously increased HOXB13 expression (P < 0.05). The results of cell proliferation experiment showed that miR-20a-5p and HOXB13 had opposite effects on cell proliferation, and the cells overexpressing both miR-20a-5p and HOXB13 showed a lower proliferation activity than the cells overexpressing HOXB13 but higher than the cells overexpressing miR-20a-5p alone (P < 0.05).@*CONCLUSION@#miR-20a-5p inhibits proliferation of lung cancer cells by down-regulating the expression of HOXB13.
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Humanos , Células A549 , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Proteínas de Homeodominio/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , SincalidaRESUMEN
Nasal spray can treat local diseases such as rhinitis, it also plays an important role in the treatment of systemic diseases including vaccine immunity. As a drug-device combination product, spray pattern is often used as the quality indicator of nasal spray to ensure its quality, plume geometry can not only be combined with the spray pattern to evaluate the performance of the nasal spray, but also can predict the deposition of the nasal spray in the nasal cavity. This article systematically reviews the definition and measurement methods of the spray pattern and plume geometry of nasal spray and their correlation with nasal deposition behavior. The measurement parameters of spray pattern and plume geometry are defined. The influence of formulation, device and trigger parameters on spray pattern and plume geometry is clarified. The correlation between various parameters and nasal deposition is analyzed. The measurement parameters are classified according to the size and shape of the spray. Plume angle is closely related to the deposition of drugs in the nasal cavity. Jet-like plume with a smaller plume angle can increase the navigation ability of the nasal spray in the curved anatomical structure of the nasal cavity, which is conducive to increase drug deposition. This makes it possible to increase deposition of the nasal spray in the nasal cavity via appropriately increasing viscosity and thixotropy of the nasal spray formulation. This review provides the theoretical basis for the high quality nasal spray product development.
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Objective:To investigate the mechanism of PE_PGRS60 protein in the pathogenesis of Mycobacterium tuberculosis infection. Methods:The cloned and purified PE_PGRS60 protein from Mycobacterium tuberculosis was used to stimulate RAW264.7 cells. The expression of cyclooxygenase 2(COX2) mRNA and protein was detected by qRT-PCR and Western blot, respectively. The signal pathways that may regulate the expression of COX2 were screened, and the expression of inflammatory cytokines induced by PE_PGRS60 was detected by ELISA. The level of cell death was measured by lactate dehydrogenase(LDH) release test and flow cytometry PI staining. Western blot was used to detect the expression of COX2 in Peripheral blood mononuclear cell(PBMC) from active tuberculosis patients. Results:PE_PGRS60 protein was found to promote the expression of COX2 in RAW264.7 cells and activate the three major members of the mitogen-activated protein kinase(MAPK) family: extracellular regulated protein kinase(ERK), p38 and c-Jun N-terminal kinase(JNK). Interestingly, only JNK-IN-7, the inhibitor of JNK was observed to suppress the up-regulation expression of COX2 induced by PE_PGRS60. This up-regulated expression of COX2 was also found in PBMCs from active tuberculosis patients. The COX2 inhibitor celecoxib can effectively block the expression of the inflammatory factors IL-1β, TNF-α and IL-6 induced by PE_PGRS60 and promote macrophage death.Conclusions:PE_PGRS60 can promote macrophages to release inflammatory factors by activating JNK/COX2 signal axis. Some macrophages still die under the protection of COX2.
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Epstein-Barr virus (EBV) and cytomegalovirus (CMV), two of the most prevalent human herpesviruses, cause a wide spectrum of diseases and symptoms and are associated with serious health problem. In this study, we developed an internal control reference recombinase-aided amplification (ICR-RAA) assay for the rapid detection of EBV and CMV within 30 min. The assay had a sensitivity of 5 and 1 copies/test for EBV and CMV, respectively, with no cross reaction with other pathogens. In comparison with those of the commercial quantitative polymerase chain reaction (qPCR), the sensitivity of the EBV and CMV ICR-RAAs using extracted DNA was 93.33% and 84.84%, respectively; the specificity was 98.75% and 100.00%, respectively; and the Kappa values were 0.930 and 0.892 (
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Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Adulto Joven , Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , ADN Viral/análisis , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/genética , Técnicas de Amplificación de Ácido Nucleico , Recombinasas/genéticaRESUMEN
OBJECTIVE@#To investigate the biomechanical effects of different bone cement diffusion patterns in the treatment of osteoporotic vertebral compression fractures.@*METHODS@#One volunteer with L1 osteoporotic vertebral compression fracture was selected, male, aged 68 years old, heighed 172 cm, weighted 60 kg, and healthy before. CT scans were used from T@*RESULTS@#After the establishing the finite element model of osteoporotic vertebral compression fracture in the thoracolumbar segment, it was found that the deformation of three different bone cement distribution models above was not significantly different. In L@*CONCLUSION@#The bone cement contact with both upper and lower endplates can effectively absorb and transfer the stress level brought by the load, reduce the stress level of cancellous bone, and reduce the possibility of refracture of the operative vertebral body.
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Anciano , Humanos , Masculino , Cementos para Huesos , Análisis de Elementos Finitos , Fracturas por Compresión/cirugía , Fracturas de la Columna Vertebral/cirugía , VertebroplastiaRESUMEN
Intestinal microbes have an adjuvant therapeutic effect on neurological disorders (such as Parkinson's, depression, and Alzheimer's disease). It affects brain function and host behavior through the neural pathways, the immune pathways and the microbial metabolites, the so-called gut-brain axis. This article summarizes the recent advances in the role of the microbe-gut-brain axis in neurological disorders, in order to provide new ideas for the treatment of neurodegenerative diseases.