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Background: The combination of three-dimensional printing (3DP) technology and near-infrared fluorescence (NIF) technology using indocyanine green (ICG) has demonstrated significant potential in enhancing surgical margin and safety, as well as simplifying segmental resection. However, there is limited literature available on the integrated use of these techniques. The current study assessed the effectiveness and value of integrating 3DP-NIF technologies in the perioperative outcomes of thoracoscopic segmental lung resection. Methods: This single-center, retrospective study recruited 165 patients with pulmonary nodules who underwent thoracoscopic segmentectomy. Eligible patients were categorized into two groups: the 3DP-NIF group (71 patients) treated with a combination of 3DP-NIF technology, and the three-dimensional computed tomography bronchography and angiography with modified inflation-deflation (3D-CTBA-ID) group (94 patients). Following rigorous propensity-score matching (PSM) analysis (1:1 ratio), perioperative outcomes between these two approaches were compared. Results: Sixty-six patients were successfully matched in each group. In the 3D-CTBA-ID group, inadequate visualization of segmental planes was noted in 14 cases, compared to only five cases in the 3DP-NIF group (P=0.03). In addition, the 3DP-NIF group demonstrated a shorter time for clear intersegmental boundary line (IBL) presentation {9 [8, 10] vs. 1,860 [1,380, 1,920] s} (P<0.001), and shorter operative time (134.09±34.9 vs. 163.47±49.4 min) (P<0.001), postoperative drainage time (P<0.001), and postoperative hospital stay (P=0.002) compared to the 3D-CTBA-ID group. Furthermore, the incidence of postoperative air leak was higher in the 3D-CTBA-ID group than in the 3DP-NIF group (33.3% vs. 7.6%, P<0.001). Conclusions: The combination of 3DP-NIF technologies served as a reliable technical safeguard, ensuring the safe and efficient execution of thoracoscopic pulmonary segmentectomy.
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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with sporadic occurrence and high mortality. Herein, we report an example of the in-hospital transmission of SFTS virus (SFTSV) infections with familial and nosocomial clustering in Zhejiang Province, eastern China, from March to April 2023. The epidemiological investigation and genomic analysis revealed that at least eight suspected cases of SFTS occurred in this cluster, including one death and one asymptomatic case. Our report reemphasizes the risk of familial and nosocomial SFTSV infections in healthcare settings and the urgent need for the long-term systematic surveillance of SFTSV evolution in humans and animals in the eastern coastal regions of China.
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This paper presents a novel bio-inspired edge-oriented approach to perceptual contour extraction. Our method does not rely on segmentation and can unsupervised learn to identify edge points that are readily grouped, without invoking any connecting mechanism, into object boundaries as perceived by human. This goal is achieved by using a dynamic mask to statistically assess the inter-edge relations and probe the principal direction that acts as an edge-grouping cue. The novelty of this work is that the mask, centered at a target pixel and driven by EM algorithm, can iteratively deform and rotate until it covers pixels that best fit the Bayesian likelihood of the binary class w.r.t a target pixel. By creating an effect of enlarging receptive field, contiguous edges of the same object can be identified while suppressing noise and textures, the resulting contour is in good agreement with gestalt laws of continuity, similarity and proximity. All theoretical derivations and parameters updates are conducted under the framework of EM-based Bayesian inference. Issues of stability and parameter uncertainty are addressed. Both qualitative and quantitative comparison with existing approaches proves the superiority of the proposed method in terms of tracking curved contours, noises/texture resilience, and detection of low-contrast contours.
Subject(s)
Form Perception , Algorithms , Bayes Theorem , HumansABSTRACT
The ecological security pattern is an important way to coordinate the contradiction between regional economic development and ecological protection and is conducive to promoting regional sustainable development. This study examines Guangxi, a karst region in China. The ecosystem service function and ecological environment sensitivity were both selected to evaluate the ecological conservation importance, and based on the results of the ecological conservation importance evaluation, suitable patches were selected as ecological sources. Meanwhile, resistance factors were selected from both natural factors and human activities to construct a comprehensive resistance surface, circuit theory was used to identify ecological corridors, ecological pinch points, and ecological barrier points, and ecological protection suggestions were then proposed. The results show that there are 50 patches of ecological sources in Guangxi, with a total area of 60,556.99 km2; 115 ecological corridors, with the longest corridor reaching 194.97 km; 301 ecological pinch points, whose spatial distribution is fragmented; and 286 ecological barrier points, most of which are concentrated in the central part of Guangxi. The results of this study provide a reference for the construction of ecological security patterns and ecological conservation in developing countries and karst areas.
Subject(s)
Ecology , Ecosystem , China , Conservation of Natural Resources , Economic Development , HumansABSTRACT
A novel tyrosine hyperoxidation enabling selective peptide cleavage is reported. The scission of the N-terminal amide bond of tyrosine was achieved with Dess-Martin periodinane under mild conditions, generating a C-terminal peptide fragment bearing the unprecedented hyperoxidized tyrosine motif, 4,5,6,7-tetraoxo-1H-indole-2-carboxamide, along with an intact N-terminal peptide fragment. This reaction proceeds with high site-selectivity for tyrosine and exhibits broad substrate scope for various peptides, including those containing post-translational modifications. More importantly, this oxidative cleavage was successfully applied to enable sequencing of three naturally occurring cyclic peptides, including one depsipeptide and one lipopeptide. The linearized peptides generated from the cleavage reaction significantly simplify cyclic peptide sequencing by MS/MS, thus providing a robust tool to facilitate rapid sequence determination of diverse cyclic peptides containing tyrosine. Furthermore, the highly electrophilic nature of the hyperoxidized tyrosine unit disclosed in this work renders it an important electrophilic target for the selective bioconjugation or synthetic manipulation of peptides containing this unit.
ABSTRACT
BACKGROUND: Cochlear implant technology is a well-known approach to help deaf individuals hear speech again and can improve speech intelligibility in quiet conditions; however, it still has room for improvement in noisy conditions. More recently, it has been proven that deep learning-based noise reduction, such as noise classification and deep denoising autoencoder (NC+DDAE), can benefit the intelligibility performance of patients with cochlear implants compared to classical noise reduction algorithms. OBJECTIVE: Following the successful implementation of the NC+DDAE model in our previous study, this study aimed to propose an advanced noise reduction system using knowledge transfer technology, called NC+DDAE_T; examine the proposed NC+DDAE_T noise reduction system using objective evaluations and subjective listening tests; and investigate which layer substitution of the knowledge transfer technology in the NC+DDAE_T noise reduction system provides the best outcome. METHODS: The knowledge transfer technology was adopted to reduce the number of parameters of the NC+DDAE_T compared with the NC+DDAE. We investigated which layer should be substituted using short-time objective intelligibility and perceptual evaluation of speech quality scores as well as t-distributed stochastic neighbor embedding to visualize the features in each model layer. Moreover, we enrolled 10 cochlear implant users for listening tests to evaluate the benefits of the newly developed NC+DDAE_T. RESULTS: The experimental results showed that substituting the middle layer (ie, the second layer in this study) of the noise-independent DDAE (NI-DDAE) model achieved the best performance gain regarding short-time objective intelligibility and perceptual evaluation of speech quality scores. Therefore, the parameters of layer 3 in the NI-DDAE were chosen to be replaced, thereby establishing the NC+DDAE_T. Both objective and listening test results showed that the proposed NC+DDAE_T noise reduction system achieved similar performances compared with the previous NC+DDAE in several noisy test conditions. However, the proposed NC+DDAE_T only required a quarter of the number of parameters compared to the NC+DDAE. CONCLUSIONS: This study demonstrated that knowledge transfer technology can help reduce the number of parameters in an NC+DDAE while keeping similar performance rates. This suggests that the proposed NC+DDAE_T model may reduce the implementation costs of this noise reduction system and provide more benefits for cochlear implant users.
Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Humans , Noise , Speech IntelligibilityABSTRACT
Conventional image entropy merely involves the overall pixel intensity statistics which cannot respond to intensity patterns over spatial domain. However, spatial distribution of pixel intensity is definitely crucial to any biological or computer vision system, and that is why gestalt grouping rules involve using features of both aspects. Recently, the increasing integration of knowledge from gestalt research into visualization-related techniques has fundamentally altered both fields, offering not only new research questions, but also new ways of solving existing issues. This paper presents a Bayesian edge detector called GestEdge, which is effective in detecting gestalt edges, especially useful for forming object boundaries as perceived by human eyes. GestEdge is characterized by employing a directivity-aware sampling window or mask that iteratively deforms to probe or explore the existence of principal direction of sampling pixels; when convergence is reached, the window covers pixels best representing the directivity in compliance with the similarity and proximity laws in gestalt theory. During the iterative process based on the unsupervised Expectation-Minimization (EM) algorithm, the shape of the sampling window is optimally adjusted. Such a deformable window allows us to exploit the similarity and proximity among the sampled pixels. Comparisons between GestEdge and other edge detectors are shown to justify the effectiveness of GestEdge in extracting the gestalt edges.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) has been prescribed by TCM doctors for treating psychiatric diseases with the core symptoms of anhedonia, amnesia, and dizziness. According to the symptoms of patients, KXS series formulae are created by varying the compatible ratio of herbs. Today, these formulae are still used in the clinic to treat major depressive disorders. AIM OF THE STUDY: We hoped to evaluate the antidepressant-like effect of Kai-Xin-San via regulation of the gut-brain axis. MATERIALS AND METHODS: Standardized extracts of three representative compatible ratios of KXS had been prepared, and quality control of the extracts was performed by HPLC-MS/MS. Chronic unpredictable mild stress (CUMS)-induced depression-like mice were used as the depression animal model. After KXS treatment, the antidepressant-like effects of KXS were assessed by behavioural tests. The gut microbiota compositions in the faeces were determined by 16S rRNA sequencing technology. The levels of LPS, pro-inflammatory cytokines and HPA-axis-related hormones were measured by ELISA kits, and the expression of barrier proteins in the small intestines and prefrontal cortex were determined by Western blot analysis. Furthermore, antibiotics were used to determine the correlation between KXS exerting an antidepressant-like effect and regulating the gut-brain axis. RESULTS: KXS alleviated depression-like behaviours in CUMS-exposed mice. Furthermore, these parameters were also found to be changed after KXS treatment. Alteration of the gut microbiota composition were found in the small intestines. A decrease in the LPS and the pro-inflammatory cytokines were found in both the small intestine and brain. An increase in the tight junction proteins was found in the gut epithelium barrier and the blood-brain barrier. A decrease in the stress-related hormones was found in the central nervous system. Furthermore, antibiotic treatment attenuated the antidepressant-like effect of KXS in CUMS-exposed mice. CONCLUSIONS: KXS exerted an antidepressant-like effect regulating the gut-brain axis, which included gut micro-environment modification, suppression of neuronal inflammation in the brain and inhibition of HPA axis activation in CUMS-induced depression-like mice.
Subject(s)
Antidepressive Agents/pharmacology , Behavior, Animal/drug effects , Brain/drug effects , Cytokines/metabolism , Depression/drug therapy , Drugs, Chinese Herbal/pharmacology , Gastrointestinal Microbiome/drug effects , Inflammation Mediators/metabolism , Intestine, Small/microbiology , Stress, Psychological/drug therapy , Animals , Brain/metabolism , Chronic Disease , Depression/metabolism , Depression/microbiology , Depression/psychology , Disease Models, Animal , Dysbiosis , Fluoxetine/pharmacology , Host-Pathogen Interactions , Intestine, Small/metabolism , Male , Mice, Inbred ICR , Stress, Psychological/metabolism , Stress, Psychological/microbiology , Stress, Psychological/psychologyABSTRACT
Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer's disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on ß amyloid protein 1-42 (Aß1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Aß1-42 injection mice. JWKXS granules significantly decreased Aß level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Aß production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Aß and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Aß levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.
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WaterLOGSY is a ligand-observed NMR method that is widely used for the studies of protein-small molecule interactions. The basis of waterLOGSY relies on the transfer of magnetization between water molecules, proteins, and small molecules via the nuclear Overhauser effect and chemical exchange. WaterLOGSY is used extensively for the screening of protein ligands, as it is a robust, relatively high-throughput, and reliable method to identify small molecules that bind proteins with a binding affinity (KD) in the µM to mM region. WaterLOGSY also enables the determination of KD via ligand titration, although careful optimization of the experimental setup is required to avoid overestimation of binding constants. Finally, waterLOGSY allows the water-accessible ligand protons of protein-bound ligands to be identified, thus providing structural information of the ligand binding orientation. In this chapter, we introduce and describe the waterLOGSY method, and provide a practical guide for ligand screening and KD determination. The use of waterLOGSY to study water accessibility is also discussed.
Subject(s)
Ligands , Magnetic Resonance Spectroscopy/methods , Proteins/metabolism , Humans , Kinetics , Protein Binding , Serum Albumin, Human/metabolism , Tryptophan/metabolismABSTRACT
The spread of a novel mobile colistin resistance gene (mcr1) has jeopardised the use of polymyxins, last-resort antibiotics that are used increasingly to treat infections caused by multidrug-resistant (MDR) Gram-negative pathogens. In early 2017, the WHO reported the global spread of mcr1 within a few years after its initial discovery in China. The protein encoded by mcr1 is a putative 60-kDa phosphoethanolamine (pEtN) transferase, MCR-1, and has been studied extensively since its discovery. Herein, we present a comprehensive review of MCR-1 covering its structure, function, and mechanism, to call for the rational drug design of molecular inhibitors of MCR-1 to use in colistin-based combination therapies.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/physiology , Escherichia coli Proteins/physiology , Polymyxins/pharmacology , Transferases/physiology , Bacteria/drug effects , Escherichia coli Proteins/chemistry , Microbial Sensitivity Tests , Protein Conformation , Transferases/chemistryABSTRACT
Recently, an upsurge of deep learning has provided a new direction for the field of computer vision and visual tracking. However, expensive offline training time and the large number of images required by deep learning have greatly hindered progress. This paper aims to further improve the computational performance of CNT which is reported to deliver 5 fps performance in visual tracking, we propose a method called Fast-CNT which differs from CNT in three aspects: firstly, an adaptive k value (rather than a constant 100) is determined for an input video; secondly, background filters used in CNT are omitted in this work to save computation time without affecting performance; thirdly, SURF feature points are used in conjunction with the particle filter to address the drift problem in CNT. Extensive experimental results on land and undersea video sequences show that Fast-CNT outperforms CNT by 2~10 times in terms of computational efficiency.
ABSTRACT
The proposed structure of talarolide A, a cycloheptapeptide featuring a hydroxamate moiety within the peptide backbone, was successfully synthesized. An initial attempt to synthesize a linear peptide precursor containing a C-terminal N-benzyloxy glycine residue was problematic due to an unreported on-resin reduction of N-benzyloxy glycine to glycine. After repositioning the peptide cyclization point, a new linear peptide sequence was successfully prepared using Fmoc-solid-phase peptide synthesis. Subsequent solution-phase cyclization and removal of protecting groups furnished the synthetic talarolide A in good yield. Despite the mismatch of the NMR data between the synthetic talarolide A and the natural product, a detailed structural analysis using 2D NMR spectroscopy, together with re-synthesis of the same synthetic material using two additional cyclization sites, confirmed that our synthetic product has the reported structure of talarolide A.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS), an ancient formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, was frequently applied for Alzheimer's disease and major depression disorders for thousands of years. However, its active components and molecular mechanism have not clearly been investigated. AIM OF THE STUDY: We aimed to reveal the active components of KXS on regulating neurotrophic factor NGF and BDNF expressions and its mechanisms on mouse astrocyte primary cultures. MATERIALS AND METHODS: Extracts of KXS had been prepared by water reflux and chemical standardization was carried out by HPLC-MS/MS. Various ethanol elution components were prepared by eluting ethanol on macro pore resin column and compound identification was carried out by high-resolution mass spectrometry. KXS extract, elution components and identified chemicals were applied on mouse astrocytes and expressions of NGF and BDNF and related metabolic enzymes were analyzed by qPCR and western blotting analysis. RESULTS: One compatible ratio of KXS named D-652 exerted the best effect on stimulation of NGF and BDNF expressions on mouse astrocytes. 70% ethanol elution fraction of D-652 exerted the highest increase tendency on expressions of NGF and BDNF by activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis. Combined with compound identification by high-resolution mass spectrometry, ginsenoside Rg1 and Rb1 might be the active compounds of this fraction on increasing NGF and BDNF expressions. CONCLUSIONS: The active compounds of KXS on increasing NGF and BDNF expressions might be the ginsenosides via activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis, which partly reveal the target of this formulae supported the clinically usage of this decoction.
Subject(s)
Astrocytes/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Drugs, Chinese Herbal/chemistry , Nerve Growth Factor/metabolism , Phytochemicals/pharmacology , Animals , Astrocytes/metabolism , Cells, Cultured , Cyclic AMP/metabolism , Mice, Inbred ICR , Phytochemicals/isolation & purification , Signal Transduction/drug effectsABSTRACT
A fast, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry method has been developed and validated for simultaneous quantification of geniposide, polygalaxanthone III, 3,6'-disinapoyl sucrose, α-asarone, ß-asarone, poricoic acid A, poricoic acid B, dehydrotumulosic acid, deoxyschizandrin, schizandrin B, and kaempferide in plasma after oral administration of extracts of Jia-Wei-Kai-Xin-San in normal and vascular dementia rats. The developed method was precise and accurate within the linearity range of the analytes. The lower limits of quantification were 1.04-2.68 ng/mL for all the analytes. Both intra- and inter day precision and accuracy of the analytes were all within accepted criteria. The mean extraction recoveries of the analytes and the internal standard from rat plasma were all >60.0%. The validated method had been successfully applied to compare pharmacokinetic profiles of the analytes in plasma of normal and vascular dementia rat treated with herbal extracts. Results indicated that differences existed between normal and vascular dementia model rats except dehydrotumulosic acid and kaempferide, which might be due to the pathology of vascular dementia and pharmacological effect of the analytes. These pharmacokinetic studies might benefit for the mechanism exploration and clinical use of traditional Chinese medicine formulae.
Subject(s)
Chromatography, High Pressure Liquid/methods , Dementia, Vascular/blood , Dementia, Vascular/drug therapy , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacokinetics , Tandem Mass Spectrometry/methods , Administration, Oral , Animals , Drugs, Chinese Herbal/administration & dosage , Humans , Male , Plasma/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
WaterLOGSY is a popular ligand-observed NMR technique to screen for protein-ligand interactions, yet when applied to measure dissociation constants (KD) through ligand titration, the results were found to be strongly dependent on sample conditions. Herein, we show that accurate KDs can be obtained by waterLOGSY with optimised experimental setup.
Subject(s)
Ligands , Nuclear Magnetic Resonance, Biomolecular/methods , Proteins/chemistry , Caffeine/chemistry , Humans , Kinetics , Protein Binding , Proteins/metabolism , Serum Albumin/chemistry , Serum Albumin/metabolism , Tryptophan/chemistryABSTRACT
Heat shock protein 90 (HSP90) is a molecular chaperone that plays important functional roles in cells. The chaperone activity of HSP90 is regulated by the hydrolysis of ATP at the protein's N-terminal domain. HSP90, in particular the N-terminal domain, is a current inhibition target for therapeutic treatments of cancers. This paper describes an application of virtual screening, thermal shift assaying and protein NMR spectroscopy leading to the discovery of HSP90 inhibitors that contain the resorcinol structure. The resorcinol scaffold can be found in a class of HSP90 inhibitors that are currently undergoing clinical trials. The proved success of the resorcinol moiety in HSP90 inhibitors validates this combined virtual screen and biophysical technique approach, which may be applied for future inhibitor discovery work for HSP90 as well as other targets.
Subject(s)
HSP90 Heat-Shock Proteins/antagonists & inhibitors , High-Throughput Screening Assays , Dose-Response Relationship, Drug , Humans , Molecular Structure , Structure-Activity Relationship , TemperatureABSTRACT
Protein-directed dynamic combinatorial chemistry is an emerging technique for efficient discovery of novel chemical structures for binding to a target protein. Typically, this method relies on a library of small molecules that react reversibly with each other to generate a combinatorial library. The components in the combinatorial library are at equilibrium with each other under thermodynamic control. When a protein is added to the equilibrium mixture, and if the protein interacts with any components of the combinatorial library, the position of the equilibrium will shift and those components that interact with the protein will be amplified, which can then be identified by a suitable biophysical technique. Such information is useful as a starting point to guide further organic synthesis of novel protein ligands and enzyme inhibitors. This review uses literature examples to discuss the practicalities of applying this method to inhibitor discovery, in particular, the set-up of the combinatorial library, the reversible reactions that may be employed, and the choice of detection methods to screen protein ligands from a mixture of reversibly forming molecules.
Subject(s)
Combinatorial Chemistry Techniques , Ligands , Proteins/chemistry , Binding Sites , Catalytic Domain , Drug Discovery/methods , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Protein Binding , Proteins/antagonists & inhibitors , Proteins/metabolism , Small Molecule LibrariesABSTRACT
To improve the solubility and antitumor activity of ampelopsin, ampelopsin-loaded nanomicelles from the mixture of pluronic F127 and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) were prepared by film-thin hydration method, in order to optimize the process conditions and physicochemical properties. The antitumor activities against MCF-7 cells between ampelopsin and nanomicelles were compared by MTT method, respectively. The results showed that the optimal nanomicelles were round with the nanometric size of (22.6±0.5) nm, encapsulation efficiency rate of (80.42±1.13)%, and drug-loading rate of (4.41±0.26)%. The solubility of ampelopsin in mixed nanomicelles significantly increased by 16 times. In different release media, the mixed nanomicelles could release more than 90% of drug in 8 h, and showed stronger cytotoxicity and inhibition against MCF-7 cells (P<0.01). The mixed nanomicelles can be used as new drug delivery system of ampelopsin.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Delivery Systems/methods , Flavonoids/chemistry , Flavonoids/pharmacology , Drug Carriers/chemistry , Drug Delivery Systems/instrumentation , Humans , MCF-7 Cells , Nanostructures/chemistry , Particle Size , Poloxamer/chemistry , Solubility , Vitamin E/chemistryABSTRACT
BACKGROUND: The influenza A(H7N9) virus causes a serious disease that threatens human health. Fatalities associated with human infections caused by this virus are of great public health concern; however, the possible risk factors are not yet fully known. METHODS: A stratified sampling method, incorporating household income levels and a random number table method, was used to select laboratory-confirmed A(H7N9) cases for this study. Eighty-five patients were selected randomly from 139 laboratory-confirmed A(H7N9) cases occurring in Zhejiang Province between March 1, 2013 and June 30, 2014. Data were collected using a standard method. To test the statistical significance among discrete variables, univariate analyses were used to compare two groups. The Kaplan-Meier product-limit method was used to analyze the patient survival fraction. The Cox proportional hazards regression model was used to analyze all variables with p ≤ 0.05 in the univariate analysis. Lastly, a stepwise procedure was used to construct a final model with a significance level of p > 0.10 for removal and p<0.05 for re-entry. RESULTS: A total of 85 patients with H7N9 virus infection were identified. Among these, 30 (35.29%) died. In the univariate analysis, the following factors were associated with a high risk of influenza A(H7N9) case fatality: age ≥ 60 years (p=0.008), low education level (p=0.030), chronic diseases (p=0.029), poor hand hygiene (p=0.010), time from illness onset to the first medical visit (p=0.029) and to intensive care unit admission (p=0.008), an incubation period of ≤ 5 days (p=0.039), a peak C-reactive protein ≥ 120 mg/l (p=0.012), increased initial neutrophil count (p=0.020), decreased initial lymphocyte count (p=0.021), and initial infection of both lungs (p=0.003). Multivariate analysis confirmed that the independent predictors of H7N9 virus infection mortality in Zhejiang, China were hand hygiene (hazard ratio (HR) 5.163, 95% confidence interval (CI) 1.164-22.661), age (HR 1.042, 95% CI 1.007-1.076), and peak CRP (HR 1.009, 95% CI 1.002-1.016). CONCLUSIONS: Improvements in immunity, early case identification and treatment, and personal protection measures are key to addressing the high human avian influenza A(H7N9) case fatality rate.