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Objective@#Morphometric and morphological evaluation of the mandibular condyle in adults and to identify its correlation with skeletal malocclusion patterns. @*Methods@#Cone-beam computed tomography scans of 135 adult patients were used in this study and classified into groups according to four criteria: (1) sex (male and female); (2) sagittal skeletal discrepancy (Class I, Class II, and Class III); (3) vertical skeletal discrepancy (hyperdivergent, normodivergent, and hypodivergent); and age (group 1 ≤ 20 years, 21 ≤ group 2 < 30, and group 3 ≥ 30 years). The morphometrical variables were mandibular condyle height and width, and the morphological variable was the mandibular condyle shape in coronal and sagittal sections. Three-dimensional standard tessellation language files were created using itk-snap (open-source software), and measurements were performed using Meshmixer (open-source software). @*Results@#The mandibular condyle height was significantly greater (p < 0.05) in patients with class III malocclusion than in those with class I or II malocclusion;the mandibular condyle width was not significantly different among different sexes, age groups, and sagittal and vertical malocclusions. There were no statistical associations between various mandibular condyle shapes and the sexes, age groups, and skeletal malocclusions. @*Conclusions@#The condylar height was greatest in patients with class III malocclusion. The condylar height and width were greater among males than in females. The mandibular condyle shapes observed in sagittal and coronal sections did not affect the skeletal malocclusion patterns.
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ObjectiveTo assess the prognostic value of 18F-FDG PET/CT parameters for predicting therapeutic response in diffuse large B-cell lymphoma (DLBCL). MethodsWe retrospectively analyzed the clinical data and 18F-FDG PET/CT radiomics features of 81 DLBCL patients enrolled between June 2015 and October 2020. Multivariate logistic regression analysis was used to identify the predictive factors for therapeutic response of DLBCL, based on which a predictive model was developed accordingly. The performance of the model was evaluated by receiver operating characteristic (ROC) curves and calibration plots. ResultsDuring the two years after first chemotherapy, 23 patients (28.3%) developed relapse and 58 patients (71.7%) had progression-free survival (PFS). The analysis for the predictive capability of the binary logistic regression model incorporating the PET/CT features revealed that the imaging features of 18F-FDG PET/CT after chemotherapy were independent prognostic factors for PFS. Among them, SUVTHR-mean2 was the most important factor for predicting therapeutic response in DLBCL patients after chemotherapy, with a cutoff value of 2.00 (AUC=0.81). Conclusions18F-FDG PET/CT showed a valuable prognostic performance for PFS in DLBCL patients after chemotherapy, with the imaging feature after chemotherapy SUVTLR-mean2 being the optimal independent predictor. Our predictive model of imaging features might have an important prognostic value in assessing the risk of disease progression, guiding the treatment and follow-up protocol, improving therapeutic efficiency and cutting down the medical cost.
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In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.
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Background Changes in cognitive function exist before the onset of clinical Parkinson's disease. However, studies on association between cognitive function and prodromal Parkinson's disease (pPD) are limited. Objective To estimate probability of pPD and assess its association with global and domain cognitive function in Chinese elders. Methods Data were drawn from the Community-based Cohort Study on Nervous System Disease 2018 (baseline) and 2020 (follow-up). We selected 3911 residents aged 55 and above who participated the two waves, without Alzheimer's disease and Parkinson's disease, and with completed information on demographics, disease history, cognitive function test, and risk factors of Parkinson's disease. Cognitive function was assessed using the Chinese version of Montreal Cognitive Assessment Scale. Calculation of probability of pPD and assessment of possible (probability between 30% and <80%) or probable (probability ≥80%) pPD were performed according to the criteria published by the International Parkinson and Movement Disorder Society. Multiple linear regression model was employed to analyze the association between baseline cognitive function and follow-up probability of pPD. Results The medians of scores of baseline global cognitive function and cognitive domains in terms of memory, execution, visuospatial function, language, attention, and orientation were 23, 12, 9, 6, 5, 14, and 6, respectively. The median of follow-up probability of pPD was 0.87%, and the proportion of participants with possible or probable pPD was 0.4%. The differences in the distribution of follow-up probability of pPD were significant in groups by baseline global cognitive score quartiles (χ2=21.68, P<0.001). A higher baseline global cognitive score was considerably related to a lower follow-up probability of pPD, b(95%CI)=0.994(0.988~0.999), P=0.040. After adjusting for selected confounders, the results of multiple linear regression analyses showed that the probability of pPD in the highest quartile group was decreased by 10.7% (b=0.893, 95%CI: 0.794-0.992, P=0.034) relative to the lowest quartile group, and the trend was significant (trend P=0.031). Higher baseline index scores of execution, attention, and orientation were highly related to a lower follow-up probability of pPD (all P<0.05). Conclusion Declines in global cognitive function and cognitive domains of execution, attention, and orientation may associate with a higher probability of pPD in middle-aged and elderly population, which suggests the significance of cognitive intervention in early stage for pPD prevention.
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Background It has been reported that a high intake of dairy products might be associated with an increased risk of Parkinson's disease (PD) in foreign studies, but no such study has yet been conducted on prodromal Parkinson's disease (pPD) and the Chinese population. Objective To investigate the prospective relationship between the intake of dairy products and pPD among people aged 55 and above in four provinces of China. Methods The research data were obtained from the baseline 2018 and follow-up 2020 surveys of Community-based Cohort Study on Nervous System Disease. A total of 9984 residents were selected who participated in both waves of surveys and had complete data on demographics, dietary products intake, and risk factors for PD. We evaluated the risk level and the numbers of related risk/prodromal markers of pPD in the participants based on a criteria recommended by the International Parkinson and Movement Disorder Society (MDS). Food Frequency Questionnaire was used to obtain food consumption data in the past 12 months, and the intake of dairy products was calculated and divided into non-consumption and tertiles of consumption (T1, T2, and T3 from low to high). Multiple linear regression was used to analyze the association between baseline dairy intake and risk level of follow-up pPD. Poisson regression and multinomial logit regression models were used to analyze the relationship of baseline dairy products and the number of risk/prodromal markers of follow-up pPD in the population, and multiple logistic regression was used to analyze each risk/prodromal marker of follow-up pPD according to baseline levels of dairy products intake. Results The percentage of residents without dairy products consumption was 58.02% in 2018, and the dairy products intakes were relatively high among residents being female, aged 55 to 74 years, with an education level of middle school and above, with a per capita monthly household income ≥ 1000 yuan, living in urban areas, and without active employment (P<0.05). The median risk level of pPD was 0.74% in 2020, and the proportion of residents with 3 to 5 markers was 66.74%. The multiple linear regression analysis results suggested no association between baseline dairy intake and follow-up risk level of pPD. The Poisson regression model showed that the high dairy products intake group at baseline (T3, median=250.00 g·d−1) was found to be 1.159 (95%CI: 1.065~1.261, Ptrend<0.001) times more likely to have the risk/prodromal markers of pPD at follow-up than non-consumers. When the number of markers was grouped, no statistically significant association was found by multiple logistic regression analysis. Conclusion Although high dairy products intake levels might be associated with pPD risk/prodromal markers among people aged 55 and above in four provinces of China, no direct association is found between dairy products intake and pPD risk levels in this study.
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Background Gastrointestinal microbiota plays an important role in the development of Parkinson's disease (PD), and dietary factors have a great impact on intestinal micro ecology. At present, few studies focus on red meat and PD, especially prodromal PD (pPD). Objective To understand the relationships of the intake of red meat and processed meat products with pPD and the number of risk/prodromal markers, and to explore the association of dietary factors with pPD. Methods Based on the data of Community-based Cohort Study on Nervous System Disease in 2018 and 2020, adults aged 55 years and older with complete demographic information, dietary survey information, and information on risk factors related to PD were selected from four provinces of China. After excluding those reporting abnormal total energy intake or those reporting alcohol drinking or abused drugs for a long period of time, and confirmed mental diseases with prescribed drugs, a total of 10003 subjects were included. Food frequency questionnaire was used to calculate the intake of red meat and processed meat products. The pPD-related risk/prodromal markers were selected following the International Parkinson and Movement Disorder Society criteria for pPD, and the risk level and the number of markers of pPD were then calculated. The relationship between the intake of red meat and processed meat and the risk level of pPD was analyzed by multiple linear regression. The relationship between the intake of red meat and processed meat and the pPD marker number groups was analyzed by multinomial logit regression model. Results In 2018, the intake of red meat and processed meat was 28.57 g·d−1 in the target population. In 2020, the median of the number of risk/prodromal markers was 3, and the median M (P25, P75) of the posterior probability of pPD was 0.74% (0.42%, 1.49%). The multiple linear regression analysis showed that the higher the intake of red meat and processed meat, the higher the risk level of pPD in follow-up (b=0.021, P<0.05). The multiple logit regression model showed that compared with the lowest quartile (Q1), the highest quartile (Q4) group of red meat and processed meat intake were more likely reporting 3−5 risk/prodromal markers than ≤ 2 risk/prodromal markers (OR=1.185, 95%CI: 1.015−1.382). Conclusion The intake level of red meat and processed meat is related to the risk level of pPD, and a higher intake of red meat and processed meat may be a potential risk factor of pPD.
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Background China is witnessing an accelerated aging process and an increasingly serious situation of Parkinson's disease. Research on the pre-disease stage and its related influencing factors has gained more and more attention. Objective To analyze the current situation of prodromal Parkinson's disease (pPD) of people aged 55 years and above in four provinces of China, and to explore its influencing demographic and socio-economic characteristics. Methods Using the data of Community-based Cohort Study on Nervous System Disease in 2020, a total of 10724 participants with complete data on demographic and socio-economic factors and risk factors on Parkinson's disease were selected. Based on the criteria recommended by the International Parkinson and Movement Disorder Society (MDS), we evaluated risk level (i.e., post-test probability) of pPd, prevalence of possible or probable pPD, and number of pPD-related risk/prodromal markers in the participants. Multiple linear regression and multiple logistic regression models were used to analyze the influencing socio-demographic factors of risk level of pPd and prevalence of possible or probable pPD, and Poisson regression and multinomial logit regression models were used to analyze the influencing socio-demographic factors of the number of pPD-related risk/prodromal markers in the total sample, men, and women, respectively. Results The median (P25, P75) of post-test probability of pPD in 2020 was 0.78% (0.42%, 1.66%), the prevalence rate of possible or probable pPD was 0.34%, and 69.03% of the participants reported 3-5 pPD-related risk/prodromal markers. The post-test probabilities of men, those with older age, lower education level, per capita monthly household income < 1000 yuan, urban residency, or without active employment were higher (P<0.05). Men and being aged ≥ 75 years had a higher prevalence of possible or probable pPD (P<0.05). The OR of possible or probable pPD was 8.404 (95%CI: 2.839−24.879) in subjects aged ≥ 75 years versus those aged 55−64 years. Males, those without active employment, being less educated, with older age, and urban residents were more likely to report pPD-related risk/prodromal markers than those of the opposite groups (P<0.05). Conclusion Men, subjects aged ≥75 years, those with lower education level, urban residents, and those without active employment have higher risk levels of pPD and are more likely to report pPD-related risk/prodromal markers among people aged 55 years and above in the four provinces of China, poor economic situation is also associated with higher risk levels of pPD.
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Parkinson's disease (PD) is a chronic neurodegenerative disease commonly seen in middle-aged and elderly people, and aging is the largest risk factor for PD. With acceleration of the aging process in China, the wellbeing and life quality of the elderly are expected to be disturbed by increasing prevalence of PD. The Community-based Cohort Study on Nervous System Diseases (CCSNSD) has established community population-based cohorts of epilepsy, Alzheimer's disease, and PD, respectively; baseline survey and one round of follow-up have finished so far. The CCSNSD collected data on demographics, community environment, diet, lifestyle, cognition, history of chronic diseases, and PD-related risk factors and facilitated exploration of the relationship between dietary nutrition and PD-related outcomes. This special column described status on prodromal Parkinson's disease (pPD) risk and its demographic & economic differences among people aged 55 and above in four provinces of China, and investigated the associations of red meat and processed meat products intake , dairy products intake, and cognitive function with pPD risk, respectively. Furthermore, one paper reviewed previous studies on dietary nutrition, lifestyle, and PD risks. However, the follow-up time of CCSNSD was relatively short as of the publishing of this column, longer follow-ups are required to allow studying potential factors and risk of incident PD combined with clinical examination and diagnosis of PD.
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Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.
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Objective:To investigate the clinical value of virtual monoenergetic images (VMI) and electron density map (EDM) derived from the dual-layer spectral detector CT (DLCT) in the differential diagnosis of benign and malignant pulmonary ground glass nodules (GGN).Methods:From July 2019 to August 2020, a total of 65 patients with lung GGN (27 benign GGNs and 38 malignant GGNs) confirmed by pathology were retrospectively enrolled in Gulou Clinical Medical College of Nanjing Medical University. All the patients underwent DLCT plain scanning within two weeks before the surgery. The conventional 120 kVp polyenergetic image (PI), EDM and 40-80 keV VMI were reconstructed. The differences of CT and electron density (ED) values between benign and malignant lesions on different images were compared by Mann-Whitney U test. Independent t-test was used to compare the lesion size and χ 2 test was used to analyze the CT features (including lesion location, shape, edge, internal structure, adjacent structure, nodule type) between benign and malignant lesions. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of different energy spectrum quantitative parameters in the differential diagnosis of benign and malignant GGN. The statistically significant CT signs and energy spectrum quantitative parameters were analyzed by logistic regression analysis to find out the independent risk factors of malignant GGN, and then ROC curve analysis was performed for each independent risk factor alone or in combination. Results:There were significant differences in lesion shape, spiculation, lobulation, location and size between benign and malignant groups ( P<0.05). The CT value of pulmonary GGN in PI, 40-80 keV VMI and the ED value in EDM were statistically different between benign and malignant lesions ( P<0.05). The area under ROC curve (AUC) were 0.680, 0.682, 0.683, 0.686, 0.694, 0.676 and 0.722, respectively, among which the ED value had the highest AUC. Binary logistic regression analysis was carried out with GGN shape, spiculation, lobulation, location, size, ED value and CT value in PI, 40-80 keV VMI as independent variables, and malignant GGN as dependent variables. The results showed that ED value (OR=1.045, 95%CI 1.001-1.090, P=0.044), lesion size (OR=1.582, 95%CI 1.159-2.158, P=0.004), spiculation sign (OR=11.352, 95%CI 2.379-54.172, P=0.002) were independent risk factors for malignant GGN. ROC curve analysis showed the AUC of ED value, lesion size, spiculation sign and combination of the three for differential diagnosis of benign and malignant GGN were 0.722, 0.772, 0.698 and 0.885. The AUC for the combined parameters was the largest, with sensitivity of 92.1% and specificity of 74.1%. Conclusion:The diagnostic efficacy of EDM is higher than that of other VMI in the differential diagnosis of pulmonary GGN by DLCT images; The efficacy is further improved when EDM is combined with lesion size and spiculation sign for comprehensive diagnosis.
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Objective:To evaluate the clinical application of three dimensional artificial intelligence(3D-AI) localization technology in chest CT scan.Methods:A total of 100 patients who underwent chest CT for COVID-19 screening in Nanjing University Medical School Affiliated Drum Tower Hospital were collected from September 2020 to October 2020 were analyzed retrospectively. The patients were divided into manual positioning group ( n=50) and 3D-AI automatic positioning group ( n=50) with block randomization method. All patients were scanned with the same CT scanning protocol. The off-center distance, CT dose index (CTDI), dose length product (DLP) and CT examination time were measured and recorded. Quantitative image evaluation of mediastinal window images and qualitative image evaluation of chest window images were assessed by two radiologists. The off-center distance, CTDI, DLP, CT examination time and objective indexes of image quality of two groups were compared by independent sample t test. The quantitative image quality scores were compared with χ 2 test. Results:Compared with manual positioning group, the overall off-center distance of 3D-AI automatic positioning group was reduced by 42.86% [(15.4±9.7) vs. (8.8±7.2)mm, t=3.65, P<0.01], CTDI was reduced by 10.67%[(7.5±2.5) vs. (6.7±2.6)mGy, t=0.59, P=0.04], DLP was reduced by 13.33%[(270±95) vs. (234±86)mGy·cm, t=1.98, P=0.02], the average examination time was reduced by 29.91% [(214±26) vs. (150±14)s, t=15.79, P<0.01]. There were no significant differences in the background noise, signal to noise ratio of descending aorta and erecting spinal muscle, and subjective score between two groups ( P>0.05). Conclusion:The 3D-AI automatic positioning technology can greatly improve the accuracy of patient positioning and reduce the radiation dose for chest CT imaging, and improve work efficiency with qualified chest CT image quality.
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Qingjin Huatan Decoction is a classic prescription with the effects of clearing heat, moistening lung, resolving phlegm, and relieving cough. In order to explore the critical quality attributes of Qingjin Huatan Decoction, we identified the blood components of Qingjin Huatan Decoction by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) under the following conditions, chromatographic column: Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm); mobile phase: 0.1% formic acid acetonitrile(A)-0.1% formic acid in water(B); gradient elution; flow rate: 0.2 mL·min~(-1); column temperature: 30 ℃; injection volume: 5 μL. The electrospray ionization(ESI) source was used to collect data in both positive and negative ion modes under the following conditions, capillary voltage: 3 kV for the positive ion mode and 2 kV for the negative ion mode; ion source temperature: 110 ℃; cone voltage: 30 V; cone gas flow rate: 50 L·h~(-1); nitrogen degassing temperature: 350 ℃; degassing volume flow rate: 800 L·h~(-1); scanning range: m/z 50-2 000. In this experiment, a total of 66 related components of Qingjin Huatan Decoction were identified, including 22 prototype components and 44 metabolites. The results of this study preliminarily revealed the pharmacodynamic material basis of Qingjin Huatan Decoction in vivo, which has provided an experimental basis for the determination of quality markers of Qingjin Huatan Decoction and the development of new drugs.
Subject(s)
Chromatography, High Pressure Liquid/methods , Chromatography, Liquid , Drugs, Chinese Herbal/chemistry , Tandem Mass Spectrometry/methodsABSTRACT
Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.
Subject(s)
Humans , China , Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal/adverse effects , Medicine, Chinese Traditional , Nonprescription Drugs/adverse effects , PharmacovigilanceABSTRACT
Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".
Subject(s)
Humans , China , Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal/adverse effects , Medicine, Chinese Traditional , Nonprescription Drugs/adverse effects , Reference StandardsABSTRACT
Cilium, an organelle with a unique proteome and organization, protruding from the cell surface, generally serves as a force generator and signaling compartment. During ciliogenesis, ciliary proteins are synthesized in cytoplasm and transported into cilia by intraflagellar transport (IFT) particles, where the inner counterparts undergo reverse trafficking. The homeostasis of IFT plays a key role in cilial structure assembly and signaling transduction. Much progress has been made on the mechanisms and functions of IFT; however, recent studies have revealed the involvement of IFT particle subunits in organogenesis and spermatogenesis. In this review, we discuss new concepts concerning the molecular functions of IFT protein IFT25 and how its interactions with other IFT particle subunits are involved in mammalian development and fertility.
Subject(s)
Animals , Male , Biological Transport , Carrier Proteins/metabolism , Cilia/metabolism , Flagella/metabolism , Mammals/metabolism , Organogenesis , Proteins/metabolism , Signal TransductionABSTRACT
OBJECTIVE@#To analyze the clinical features and genetic variant in a patient with Usher syndrome.@*METHODS@#Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus.@*RESULTS@#The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year.@*CONCLUSION@#The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.
Subject(s)
Child , Female , Humans , Infant, Newborn , Pregnancy , Cadherin Related Proteins , Cadherins/genetics , China , Genetic Testing , Pedigree , Prenatal Diagnosis , Usher Syndromes/geneticsABSTRACT
OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree.@*RESULTS@#The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual.@*CONCLUSION@#The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Subject(s)
Female , Humans , Adenosine Deaminase/genetics , China , Mutation , Pedigree , Pigmentation Disorders/congenital , RNA-Binding Proteins/geneticsABSTRACT
As an important exercise and energy metabolism organ of the human body, the normal maintenance of skeletal muscle mass is essential for the body to perform normal physiological functions. The autophagy-lysosome (AL) pathway is a physiological or pathological mechanism that is ubiquitous in normal and diseased cells. It plays a key role in the maintaining of protein balance, removing damaged organelles, and the stability of internal environment. The smooth progress of the autophagy process needs to go through multiple steps, which are completed under the coordinated action of multiple factors. Autophagy maintains the muscle homeostasis of a healthy body by removing cell components such as damaged myofibrils and isolated cytoplasmic proteins. Autophagy could also provide the initial energy required for cell proliferation, promote muscle regeneration and remodeling after injury. At the same time, autophagy disorder is also an important cause of age-related skeletal muscle atrophy. Autophagy could affect the response of skeletal muscle to exercise, and increasing the level of basic autophagy is beneficial to improve the adaptive response of skeletal muscle to exercise. This article summarizes the role and pathways of autophagy in the maintenance of skeletal muscle quality, in order to provide effective rehabilitation strategies for clinical prevention and treatment of muscle atrophy.
Subject(s)
Humans , Autophagy/physiology , Exercise/physiology , Muscle, Skeletal/pathology , Muscular Atrophy/pathology , Signal TransductionABSTRACT
Lonicerae Japonicae Flos, as common Chinese medicine, has been used for thousands of years in the treatment of inflammation and infectious diseases with definite efficacies. The complex composition of Lonicerae Japonicae Flos results in its extensive pharmacological effects, so the assessment of its quality by only a few index components is not comprehensive. Guided by the quality marker(Q-marker), the present study comprehensively analyzed and predicted the quality connotation of Lonicerae Japonicae Flos based on the chemical composition and component transfer, the phylogenetic relationship, chemical composition effectiveness, measurability, and specificity. Chlorogenic acid, isochlorogenic acids A, B, and C, luteoloside, rutin, sweroside, and secoxyloganin were predicted as candidate Q-markers of Lonicerae Japonicae Flos.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Flowers/chemistry , Lonicera/chemistry , Phylogeny , Quality ControlABSTRACT
A high-throughput screening machine learning model for mitochondrial function was constructed, and compounds of Aco-niti Lateralis Radix Praeparata were predicted. Deoxyaconitine with the highest score and benzoylmesaconine with the lowest score among the compounds screened by the model were selected for mitochondrial mechanism analysis. Mitochondrial function data were collected from PubChem and Tox21 databases. Random forest and gradient boosted decision tree algorithms were separately used for mo-deling, and ECFP4(extended connectivity fingerprint, up to four bonds) and Mordred descriptors were employed for training, respectively. Cross-validation test was carried out, and balanced accuracy(BA) and overall accuracy were determined to evaluate the performance of different combinations of models and obtain the optimal algorithm and hyperparameters for modeling. The data of Aconiti Lateralis Radix Praeparata compounds in TCMSP database were collected, and after prediction and screening by the constructed high-throughput screening machine learning model, deoxyaconitine and benzoylmesaconine were selected to measure mitochondrial membrane potential, reactive oxygen species(ROS) level and protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax) and peroxisome proliferator-activated receptor-γ-coactivator 1α(PGC-1α). The results showed that the model constructed using gradient boosted decision tree+Mordred algorithm performed better, with a cross-validation BA of 0.825 and a test set accuracy of 0.811. Deoxyaconitine and benzoylmesaconine changed the ROS level(P<0.001), mitochondrial membrane potential(P<0.001), and protein expression of Bcl-2(P<0.001, P<0.01) and Bax(P<0.001), and deoxyaconitine increased the expression of PGC-1α protein(P<0.01). The high-throughput screening model for mitochondrial function constructed by gradient boosted decision tree+Mordred algorithm was more accurate than that by random forest+ECFP4 algorithm, which could be used to build an algorithm model for subsequent research. Deoxyaconitine and benzoylmesaconine affected mitochondrial function. However, deoxyaconitine with higher score also affected mitochondrial biosynthesis by regulating PGC-1α protein.