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Traditional Chinese medicine (TCM) is a combination of raw herbs and herbal extracts with a plethora of documented beneficial bioactivities, which has unique advantages in anti-tumor therapy, and many of its major bioactive molecules have been identified in recent years due to advances in chemical separation and structural analysis. However, the major chemical classes of plant-derived bioactive compounds frequently possess chemical properties, including poor water solubility, stability, and bioavailability, that limit their therapeutic application. Alternatively, natural small molecules (NSMs) containing these components possess modifiable groups, multiple action sites, hydrophobic side chains, and a rigid skeleton with self-assembly properties that can be exploited to construct self-assembled nanoparticles with therapeutic effects superior to their individual constituents. For instance, the construction of a self-assembled nanodrug delivery system can effectively overcome the strong hydrophobicity and poor in vivo stability of NSMs, thereby greatly improving their bioavailability and enhancing their anti-tumor efficacy. This review summarizes the self-assembly methods, mechanisms, and applications of a variety of NSMs, including terpenoids, flavonoids, alkaloids, polyphenols, and saponins, providing a theoretical basis for the subsequent research on NSMs and the development of SANDDS.
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Antineoplastic Agents , Drugs, Chinese Herbal , Medicine, Chinese Traditional/methods , Drugs, Chinese Herbal/chemistry , PolyphenolsABSTRACT
Objective To investigate the clinical manifestations of nodo-paranodopathy(NPP)with anti-neurofascin 186(NF186)antibody positive.Methods The clinical data of a NPP patient with cranial nerve damage caused by anti-NF186 antibody positive was retrospectively analyzed.Results The patient was a 70-year-old male with sudden speech disorder and dysphagia one month ago.Glucocorticoid therapy was discontinued after improvement.The patient's speech,swallowing,chewing,bristling,turning and head-up movements were laborious and progressively aggravated 5 days ago.The EMG examination of the limbs was normal,and the serum and CSF anti-NF186 antibody were positive.The curative effect of glucocorticoid treatment was not obvious,and the symptoms were significantly improved after plasma exchange treatment.Conclusions Anti-NF186 antibody-positive NPP has late onset age,severe illness and accompanied with cranial nerves damage.Conventional hormone therapy is not effective,but plasma exchange therapy is effective.
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The Choledochal cyst is an extremely rare congenital anomaly of the bile duct. Early cyst resection and Roux-en-Y hepatojejunostomy are the primary surgical methods for treating choledochal cyst. With the emergence of enhanced recovery after surgery, laparoscopic surgery has effectively reduced the incidence of biliary complications and wound infections, but it still does not meet people's requirements for minimally invasive surgery. Robotic surgery system has the potential to enhance surgical precision and the maneuverability of surgeons due to clear surgical visualization and flexible mechanical arms. The authors review the relevant literatures and conduct a Meta-analysis to evaluate the efficacy of robot-assisted surgery and laparoscopic surgery for choledochal cyst.
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Polycystic ovary syndrome(PCOS)is characterized by high heterogeneity and heredity,and its exact pathogenesis is still not clear.Some studies have shown that epigenetic disorders,such as hyperandrogen-induced methyla-tion or acetylation of lysine at different sites(K4,K9,and K27)in histone H3,methylation and demethylation modifica-tion of genes related to steroids,hormone receptors and follicular development,and transcriptional control of microRNA or long noncoding RNA,play a central role in the occurrence and development of PCOS.This article reviews the research ad-vances in epigenetic mechanisms(histone modifications,DNA methylation,and noncoding RNA)of PCOS,in order to provide a reference for the prediction and early prevention of PCOS.
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Insulin resistance(IR)is an abnormal pathological and physiological process characterized by a decrease in the ability of target tissues and organs to utilize insulin.There are many factors related to IR.Epigenetic modification is one of the important regulatory mechanisms that cause IR.N6-methyladenosine(m6A)is an epigenetic modification with high abundance in Eukaryote mRNA.Its dynamic changes can regulate the expression of related enzymes,affect IR process and exert different biological effects in target organs.This article reviews the research progress of dynamic modification and regulation of m6A methylation in IR.
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ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.
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By integrating plant metabonomics and target quantitative analysis methods, this study systematically analyzed the differences of chemical constituents in Scutellaria baicalensis leaves from different producing areas in Shanxi, so as to provide theoretical basis for rational and effective utilization of Scutellaria baicalensis leaves. Based on the idea of plant metabonomics, the liquid quality of 53 batches of Scutellaria baicalensis leaves from 8 different producing areas in Shanxi was analyzed by UPLC-QTOF-MS, and the collected data were imported into SIMCA 14.1 software for multivariate statistical analysis to screen the different chemical constituents among different habitats in Shanxi. Meanwhile, a method for simultaneous determination of 7 flavonoids and 3 organic acids in Scutellaria baicalensis leaves was optimized and established to quantitatively analyze the differences of chemical components in Scutellaria baicalensis leaves from different producing areas in Shanxi. The results of plant metabonomics showed that there were differences in the chemical composition of Scutellaria baicalensis leaves in northern Shanxi (Datong, Xinzhou), Jinzhong (Yangquan, Luliang) and southern Shanxi (Changzhi, Yuncheng, Jincheng, Linfen): there were 14 significant differences in chemical composition between northern Shanxi and Jinzhong; there were 18 significant differences in chemical constituents between southern Shanxi and central Shanxi. There were 15 significant differences in chemical constituents between northern Shanxi and southern Shanxi. Among them, scutellarin and isocarthamidin-7-O-glucuronide were the common differences among the three regions, and the content of scutellarin was the highest in southern Shanxi and the lowest in northern Shanxi. The content of isocarthamidin-7-O-glucuronide was the highest in Jinzhong area and the lowest in northern Shanxi area. Quantitative analysis further confirmed that the average contents of apigenin, naringenin and citric acid were the highest in northern Shanxi, scutellarin, caffeic acid, apigenin-7-O-glucuronide, malic acid and wogonoside were the highest in southern Shanxi, and wogonoside and baicalin were the highest in central Shanxi. This study is of great significance to the quality control of Scutellaria baicalensis leaf resources, and provides theoretical basis for rational and effective utilization of Scutellaria baicalensis leaf resources.
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OBJECTIVE@#To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.@*METHODS@#Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).@*RESULTS@#This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).@*CONCLUSION@#We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
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Humans , Escherichia coli/genetics , Escherichia coli Infections/epidemiology , Multilocus Sequence Typing , Genotype , Beijing , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Diarrhea , Microbial Sensitivity TestsABSTRACT
@#Apoptosis is an important means to regulate cell proliferation and maintain homeostasis. Recent researches have shown that the B-cell lymphoma-2 (BCL-2) family not only plays a dominant role in the regulation of normal cell apoptosis, but also plays a crucial role in the formation of tumor genesis, progression and subsequent drug resistance mediated by the escape mode of apoptosis. The phenomenon that BCL-2 family antagonized the apoptosis induced by antitumor drugs and then acquired drug resistance has been reported in the clinical treatment of hematologic lymphatic system tumors, breast cancer, lung cancer, gastric cancer and other diseases. Thus, specific inhibitors targeting anti-apoptotic members of the BCL-2 family have emerged with the development of research. In this paper, we systematically reviewed the regulation of apoptosis mediated by BCL-2 family and the drug resistance mediated by BCL-2 family. Meanwhile, we summarized the research advances of BCL-2 family specific inhibitors to provide new strategy for solving the problems on tumor therapeutic resistance and for finding new therapeutic targets in the future.
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Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury (MIRI). Moderate mitophagy can remove damaged mitochondria, inhibit excessive reactive oxygen species accumulation, and protect mitochondria from damage. However, excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival, and aggravates cell death. How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane, which mainly include phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced kinase 1/Parkin, hypoxia-inducible factor-1 α/Bcl-2 and adenovirus e1b19k Da interacting protein 3, FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on. In this review, the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI, and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine, thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.
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Humans , Mitochondria/metabolism , Mitophagy/genetics , Myocardial Reperfusion Injury , Protein Kinases/metabolismABSTRACT
OBJECTIVE To determine the roles of phosphorylated ubiquitin(pUb)on ubiquitin-dependent proteasomal(UPS)degradation activity,and the roles of pUb on neurodegeneration.METHODS We use PTEN induced kinase 1(PINK1)to phosphorylate ubiquitin.The Ub/S65A cannot be phosphorylated by PINK1,and was used to antagonize the roles of pUb.The Ub/S65E was used to mimic the roles of pUb.The roles of pUb on UPS degradation activity were determined by immunoflu-orescence,Western blot and TIRF microscope at cellular and protein level.The roles of pUb on neurodegeneration were determined by behavior tests,immunofluorescence,Golgi staining,TEM,Western blot and proteomics sacle in mouse.RESULTS The level of soluble PINK1(sPINK1)and pUb increased in the neurons of aged mouse brain,and in the cells upon the administration of MG132,a proteasome inhibitor.The elevation of sPINK1 and pUb was accompanied by protein aggregation upon aging or the proteasomal inhibition.The pink1 knockout alleviated proteasomal inhibition induced protein aggregation and association of ubiquitinated proteins with proteasome.The over-expression of sPINK1 increased pUb level in hippocampal neuron,which chronically induced protein aggregation,mitochondrial damage and damage the structure of neuronal spines.Such neuronal injury lead to cognitive impairment of mice.The roles of sPINK1 was reversed by co-expression with Ub/S65A,and was mimic by over-expression with Ub/S65E.CONCLUSION The phosphorylation of ubiquitin aggravates UPS degrada-tion,and accelerates neuronal degeneration upon the decline of proteasomal degradation in aging and age-related neuronal diseases.
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Objective:To observe the safety and efficacy of Keluoxin capsules in the treatment of moderate to severe non-proliferative diabetic retinopathy (NPDR).Methods:An open-label, multi-center, single-arm, phase Ⅱa clinical trial. From May 2014 to December 2016, the patients diagnosed with moderate to severe NPDR who received Keroxin treatment in General Hospital of Central Theater Command, Affiliated Eye Hospital to Nanchang University, Xiyuan Hospital of China Academy of Chinese Medical Sciences, and Eye Hospital China Academy of Chinese Medical Sciences were divided into moderate NPDR group and severe NPDR group. The baseline data of the patients were obtained, best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography and fundus photography were performed. On the basis of maintaining the original diabetes treatment, all patients took Keluoxin capsules orally for 24 weeks; 24 weeks after treatment was used as the time point for evaluating the efficacy. BCVA letters, central macular thickness (CMT) and 6 mm diameter total macular volume (TMV), retinal vascular leakage area, and retinal non-perfusion (RNP) area within an average diameter of 6 mm were compared between the two groups at baseline and 24 weeks after treatment. Independent sample Mann-Whitney U test was used to compare continuous variables between groups. Categorical data were compared by χ2 test. Results:A total of 60 NPDR patients and 60 eyes were included, 9 cases were lost to follow-up, and 51 cases and 51 eyes were finally included, including 37 eyes in the moderate NPDR group and 14 eyes in the severe NPDR group, respectively. At baseline, BCVA in moderate NPDR group and severe NPDR group were (80.1±6.8), (81.4±6.3) letters, respectively. CMT were (249.5±32.1), (258.9±22.2) μm, respectively. TMV were (8.79±1.09), (8.95±1.31) mm 3, respectively. Retinal vascular leakage areas were (7.69±10.63), (10.45±7.65) mm 2, respectively. RNP area were (2.48±5.74), (10.63±20.06) mm 2, respectively. There were 11 (29.7%, 11/37) and 4 (28.6%, 4/14) eyes with diabetic macular edema (DME), respectively; 24 weeks after treatment, BCVA in moderate NPDR group and severe NPDR group increased by (1.3±5.2), (3.2±3.0) letters, respectively. Compared with baseline, there was a statistically significant difference in the severe NPDR group ( t=-3.986, P=0.033). CMT were (252.1±45.6), (269.8± 57.2) μm, respectively. There were no significant differences compared with baseline ( t=-0.567, -0.925; P>0.05). TMV were (9.96±1.16), (10.09±1.32) mm 3, respectively. There were no significant differences compared with baseline ( t=-0.996, -1.304; P>0.05). Retinal vascular leakage area decreased (0.19±6.90), (1.98±7.52) mm 2, respectively. There were no significant differences compared with baseline ( t=0.168, 0.983; P>0.05). RNP area were (3.01±6.47), (10.36±19.57) mm 2, respectively. Compared with baseline, the differences were statistically significant ( t=-1.267, 0.553; P>0.05). There were 8 (21.6%, 8/37) and 3 (21.4%, 3/14) eyes with DME, respectively. Compared with baseline, the difference was statistically significant ( χ2=11.919, 4.571; P=0.001, 0.033). Conclusion:Keluoxin capsules can stabilize or improve BCVA, CMT, TMV and RNP area in patients with moderate and severe NPDR, and reduce the area of retinal vascular leakage.
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Objective To analyze the control status and influencing factors of glycosylated hemoglobin (HbA1c) in children with type 1 diabetes mellitus (T1DM) in Tianjin from 2020 to 2021, and to provide a theoretical basis for controlling blood glucose in children with type 1 diabetes mellitus. Methods A total of 538 children with type 1 diabetes, including 275 males and 263 females, were selected from our hospital from January 2020 to June 2021. All the children were determined according to the level of HbA1c and divided into well-controlled group (HbA1c<7.0%, n=469) and poorly controlled group (HbA1c≥7.0%, n=69), 3ml fasting elbow venous blood was extracted from the two groups, and the levels of HbA1c, FPG, 2hPG, TC and LDL-C were compared between the two groups. Clinical data of the children were collected from the medical record system. The factors affecting the control of HbA1c in children with type 1 diabetes were analyzed by univariate analysis and logistic regression. Results The comparison of general data between the two groups showed no significant difference in age, sex and course of type 1 diabetes mellitus (P<0.05). The levels of HbA1c, FPG, 2hPG, TC and LDL-C in poorly controlled group were significantly higher than those in well controlled group (P<0.05). The blood glucose monitoring <60 times/month (OR=3.017), uncontrolled diet (OR=2.871), obesity (OR=2.623) were independent risk factors for poor control of HbA1c in children with type 1 diabetes (P<0.05). Conclusions Children with type 1 diabetes mellitus have a greater risk of poor control of HbA1c. It is necessary to strengthen publicity and education for parents of children with diabetes, regularly monitor blood glucose and control diet to effectively improve blood glucose control in children.
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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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OBJECTIVE: To investigate use of multidata analysis based on an artificial neural network (ANN) to predict long-term pain outcomes after microvascular decompression (MVD) in patients with trigeminal neuralgia (TN) and to explore key predictors. METHODS: Perioperative and long-term follow-up multidata of 1041 patients with TN who received MVD surgery at Hangzhou First People's Hospital from March 2013 to May 2018 were collected to construct an ANN model for prediction. The prediction results were compared with the actual follow-up outcomes, and the variables in each input layer were changed to test the effectiveness of ANN and explore the factors that had the greatest impact on prediction accuracy. RESULTS: The ANN model could predict the long-term pain outcomes after MVD in patients with TN with an accuracy rate of 95.2% and area under the curve of 0.862. Four factors contributed the most to the predictive performance of the ANN: whether the neurovascular offending site of the trigeminal nerve corresponded the region of facial pain, immediate postoperative pain remission after MVD, degree of nerve compression by culprit vessels, and the type of culprit vessels. After these factors were sequentially removed, the accuracy of the ANN model decreased to 74.5%, 78.6%, 87.2%, and 90.1%, while the area under the curve was 0.705, 0.761, 0.793, and 0.810. CONCLUSIONS: The ANN model, constructed using multiple data, predicted long-term pain prognosis after MVD in patients with TN objectively and accurately. The model was able to assess the importance of each factor in the prediction of pain outcome.
Subject(s)
Microvascular Decompression Surgery , Trigeminal Neuralgia , Facial Pain/etiology , Facial Pain/surgery , Humans , Microvascular Decompression Surgery/methods , Neural Networks, Computer , Retrospective Studies , Treatment Outcome , Trigeminal Neuralgia/surgeryABSTRACT
ObjectiveIn September 2020, records of 15,861 SARS-CoV-2 cases failed to upload from the Second Generation Laboratory Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, resulting in a delay in the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on health outcomes: transmission events, hospitalisations, and mortality. Previously, a modelling study had suggested a substantial impact. DesignObservational study SettingEngland. PopulationIndividuals testing positive for SARS-CoV-2 and their reported contacts. Main outcome measuresSecondary attack rates (SARs), hospitalisations, and deaths amongst primary and secondary contacts were calculated, compared to all other concurrent, unaffected cases. SGSS records affected by the event were matched to CTAS records and successive contacts and cases were identified. ResultsThe initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared to the control group (3 days). This was associated with lower completion of contact tracing of primary cases in the delay group: 80% (95%CI: 79-81%) in the delay group and 83% (95%CI: 83-84%) in the control group. There was some evidence to suggest an increase in transmission to non-household contacts amongst those affected by the delay. The SAR for non-household contacts was higher amongst secondary contacts in the delay group than the control group (delay group: 7.9%, 95%CI:6.4% to 9.2%; control group: 5.9%, 95%CI: 5.3% to 6.6%). There was no evidence of a difference between the delay and control groups in the odds of hospitalisation (crude odds ratio: 1.1 (95%CI: 0.9 to 1.2) or death (crude odds ratio: 0.7 (0.1 to 4.0)) amongst secondary contacts. ConclusionsThe delay in contact tracing had a limited impact on population health outcomes. Strengths and limitations of the studyO_LIShows empirical data on the health impact of an event leading to a delay in contact tracing so can test hypotheses generated by models of the potential impact of a delay in contact tracing C_LIO_LIEstimates the extent of further transmission and odds of increased mortality or hospitalisation in up to the third generation of cases affected by the event C_LIO_LIThe event acts as a natural experiment to describe the possible impact of contact tracing, comparing a group affected by chance by delayed contact tracing to a control group who experienced no delay C_LIO_LIContact tracing was not completed for all individuals, so the study might not capture all affected contacts or transmissions C_LI
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BackgroundThe SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources. MethodsOmicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. We used multivariable logistic regression was used to control for factors associated with transmission. FindingsAnalysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16). InterpretationOur study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron. FundingStudy funded by the UK Health Security Agency.
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Objective:To investigate the diagnostic value of chest enhanced computed tomography (CT) for mediastinal lymph node metastasis of esophageal cancer and the influencing factors for its accuracy.Methods:The retrospective case-control study was conducted. The clinico- pathological data of 463 patients with esophageal cancer who underwent surgical treatment in the First Affiliated Hospital of Army Medical University from July 2016 to June 2021 were collected. There were 385 males and 78 females, aged (61±8)years. Observation indicators: (1) results of pre-operative chest enhanced CT and postoperative pathological examination; (2) diagnostic value of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer; (3) influencing factors analysis of the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer. Measurement data with normal distribution were represented as Mean± SD, and count data were represented as absolute numbers and (or) percentages. Sensitivity, specificity, positive predictive value, negative predictive value and Youden index were used for authenticity evaluation of diagnostic value of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer, and accuracy and Kappa value were used for reliability evaluation. The higher the value of above indicators, the higher the authenticity and (or) reliability. The univariate analysis was conducted using the chi-square test, and multivariate analysis was conducted using the binary Logistic regression model after including indicators with P<0.20 of univariate analysis. Results:(1) Results of preoperative chest enhanced CT and postoperative pathological examination. Of the 463 patients with esophageal cancer, mediastinal lymph node metastasis were diagnosed in 90 cases (including 35 cases of true positive and 55 cases of false positive) and no mediastinal lymph node metastasis were diagnosed in 373 cases (including 300 cases of true negative and 73 cases of false negative) by preoperative chest enhanced CT. Mediastinal lymph node metastasis were diagnosed in 108 cases and no mediastinal lymph node metastasis were diagnosed in 355 cases by postoperative patholo-gical examination. (2) Diagnostic value of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer. Authenticity evaluation of diagnostic value of chest enhanced CT for medias-tinal lymph node metastasis of esophageal cancer showed that sensitivity, specificity, positive predic-tive value, negative predictive value and Youden indexes were 32.41%(35/108), 84.51%(300/355), 38.89%(35/90), 80.43%(300/373), 0.169, respectively. Reliability evaluation showed that accuracy and Kappa value were 72.35%(335/463) and 0.180 ( P<0.05), respectively. (3) Influencing factors analysis of the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer. Results of univariate analysis showed that the tumor diameter and the depth of tumor invasion were related factors affecting the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer ( χ2=7.65, 6.07, P<0.05). Results of multi-variate analysis showed that the tumor diameter ≥2.1 cm was an independent risk factor affecting the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer ( odds ratio=2.05, 95% confidence interval as 1.23?3.43, P<0.05). Conclusions:The clinical value of chest enhanced CT for diagnosing mediastinal lymph node metastasis of esophageal cancer is limited, and the consistency with pathological results is quite different. The tumor diameter ≥2.1 cm is an independent risk factor affecting the diagnostic accuracy of chest enhanced CT for mediastinal lymph node metastasis of esophageal cancer
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The gross specimens and tissue slices used for traditional experimental pathology curriculum are fragile, and some specimens or slices are difficult to be supplemented. Besides, the classroom and schedule for experimental pathology teaching are inflexible. Therefore, the teaching effects for experimental pathology course are limited. The development of digital technology has promoted the teaching reform of medical experimental curriculum. We have digitalized the gross specimens and tissue slices to preserve and expand the samples, and constructed pathological sample repository containing both physical samples and digital samples. Furthermore, we have established a platform for remote access, and thus improved the flexibility and autonomy of study for experimental pathology curriculum. Additionally, we have integrated clinical information of the teaching samples, and interpreted the specimens with the assistance of two-dimensional code technology and voice broadcast technology, to realize human-computer interactive learning. The questionnaire shows that the application of pathological sample repository in experimental teaching has improved student learning effect and recognition.
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Objective:To analyze and compare the X-ray procedures and radiation dose composition of ophthalmic inpatients, and to explore the changes of the X-ray examination mode in recent years and the effect of optimization in imaging technology on the radiation dose level of the patients.Methods:The simple random sampling method was used to retrospectively select the imaging data of the ophthalmic inpatients in the Second Affiliated Hospital of Zhejiang University School of Medicine from July 1st to November 31st in 2019 and from July 1st to November 31st in 2020. A total of 516 cases were selected according to the imaging time, including 258 cases in 2019 and 258 cases in 2020. Based on our previous research and the related documents of low-dose CT screening, a series of optimizations on CT scanning parameters and process were carried out in 2020, including the frequency of DR and CT scanning, the number of examinations per capita, the composition ratio of CT and DR, and X-ray dose per capita.Results:In 2020, the average effective doses of chest CT and orbital CT for ophthalmic inpatients were (2.587±1.586) mSv and (0.877±0.733) mSv, significantly lower than those in 2019 ( F=0.52, 0.72, P<0.05), and decreased by 34.82% and 37.13%, respectively. There was no significant difference in the average effective dose of chest DR and head CT between 2020 and 2019 ( F=6.01, 1.81, P>0.05). The number of X-ray examination per capita increased by 0.15 times, and the effective dose increased by 1.44 times (1.589 mSv). Chest DR was the main type of X-ray examination, accounting for 68.79% of all examinations in 2019, while chest CT was the main type, accounting for 71.05% in 2020. The composition of chest CT in 2020 increased by 63.17% compared with 2019, and the compositions of chest DR, orbital CT and cranial CT were decreased by 53.88%, 5.79% and 2.89%, respectively. Conclusions:With dose optimization measures, the single CT dose of ophthalmic inpatients in 2020 was lower than that in 2019. Chest CT increased significantly in frequency, and became main X-ray examination instead of chest DR which made the effective dose of ophthalmic inpatients increasing significantly.