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BACKGROUND: TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance. METHODS: We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6. RESULTS: WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman. CONCLUSIONS: This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.
Subject(s)
Chromosomes, Human, Pair 17 , Haplotypes , Heterozygote , T-Box Domain Proteins , Humans , T-Box Domain Proteins/genetics , Female , Chromosomes, Human, Pair 17/genetics , Pregnancy , Adult , Chromosome Deletion , Exome Sequencing , Sequence Deletion , Fetus/abnormalities , Ultrasonography, PrenatalABSTRACT
Thinning-a widely used forest management practice-can significantly influence soil nitrogen (N) cycling processes in subtropical forests. However, the effects of different thinning intensities on nitrification, denitrification, and their relationships with soil properties and microbial communities remain poorly understood. Here, we conducted a study in a subtropical forest in China and applied three thinning treatments, i.e., no thinning (0 %), intermediate thinning (10-15 %), and heavy thinning (20-25 %), and investigated the effects of thinning intensity on the potential nitrification rate (PNR), potential denitrification rate (PDR), and microbial communities. Moreover, we explored the relationships among soil physicochemical properties, microbial community structure, and nitrogen transformation rates under different thinning intensities. Our results showed that intermediate and heavy thinning significantly increased the PNR by 87 % and 61 % and decreased the PDR by 31 % and 50 % compared to that of the control, respectively. Although the bacterial community structure was markedly influenced by thinning, the fungal community structure remained stable. Importantly, changes in microbial community composition and diversity had minimal impacts on the nitrogen transformation processes, whereas soil physicochemical properties, such as pH, organic carbon content, and nitrogen forms, were identified as the primary drivers. These findings highlight the critical role of managing soil physicochemical properties to regulate nitrogen transformations in forest soils. Effective forest management should focus on precisely adjusting the thinning intensity to enhance the soil physicochemical conditions, thereby promoting more efficient nitrogen cycling and improving forest ecosystem health in subtropical regions.
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Forests , Nitrification , Nitrogen , Soil Microbiology , Soil , Nitrogen/analysis , Soil/chemistry , China , Forestry/methods , Denitrification , Microbiota , Nitrogen Cycle , Environmental MonitoringABSTRACT
The isolation and identification of plant growth-promoting endophytic bacteria (PGPEB) from Achyranthes bidentata roots have profound theoretical and practical implications in ecological agriculture, particularly as bio-inoculants to address challenges associated with continuous monoculture. Our research revealed a significant increase in the abundance of these beneficial bacteria in A. bidentata rhizosphere soil under prolonged monoculture conditions, as shown by bioinformatics analysis. Subsequently, we isolated 563 strains of endophytic bacteria from A. bidentata roots. Functional characterization highlighted diverse plant growth-promoting traits among these bacteria, including the secretion of indole-3-acetic acid (IAA) ranging from 68.01 to 73.25 mg/L, phosphorus and potassium solubilization capacities, and antagonistic activity against pathogenic fungi (21.54%-50.81%). Through 16S rDNA sequencing, we identified nine strains exhibiting biocontrol and growth-promoting potential. Introduction of a synthetic microbial consortium (SMC) in pot experiments significantly increased root biomass by 48.19% in A. bidentata and 27.01% in replanted Rehmannia glutinosa. These findings provide innovative insights and strategies for addressing continuous cropping challenges, highlighting the practical promise of PGPEB from A. bidentata in ecological agriculture to overcome replanting obstacles for non-host plants like R. glutinosa, thereby promoting robust growth in medicinal plants.
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The differences in chemical components, nutritional value, volatile organic compounds, antioxidant activity and α-glucosidase inhibiting capacity in vitro in coconut waters with different maturities (8, 10, and 12 months after pollination and germination height below 10 cm were named CW-8, CW-10, CW-2, and MCW, respectively) from the tall coconut variety were compared and analyzed. Results showed that as the maturity increased, the ash and reducing sugar in coconut water gradually decreased, while the protein content and fatty acids continued to increase. Potassium, phosphorus, and sodium in four coconut waters showed a trend of first increasing and then decreasing, and CW-12 had the highest content of 2133.85 mg/kg, 239.74 mg/kg, and 310.75 mg/kg, respectively. The volatile organic compounds (VOCs) present in higher amounts are alcohols and esters in coconut waters, among which 2-methylbutyl acetate, ethyl acetate monomer, and 2-methyl-1-propanol dimer were the characteristic volatile substances that distinguish MCW from the other three coconut waters. MCW has the best DPPH-scavenging and ferrous-ion-chelating ability (87.39% and 7.65%), while CW-8 had the highest hydroxyl and ABTS radicals scavenging rate (97.31% and 83.48%) and α-glucosidase inhibitory rate (81.36%). These results can provide support for the differential and high-value utilization of coconut water with different maturities.
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BACKGROUND: Copy number variation sequencing (CNV-seq) is crucial in prenatal diagnosis, but its limitations in detecting polyploidy, maternal cell contamination (MCC), and uniparental disomy (UPD) restrict its application in the analysis of products of conception (POCs). This study aimed to investigate an optimal genetic testing strategy for POCs in the era of CNV-seq. METHODS: CNV-seq and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed in all 4,211 spontaneous miscarriage cases. Different testing strategies were compared and the optimal testing strategies were proposed. RESULTS: Of the 4,211 cases, 2561 (60.82%) exhibited clinically significant chromosomal abnormalities. CNV-seq alone, without QF-PCR, might misdiagnose 311 (7.39%) cases, including 278 polyploidy, 13 UPD, and 20 MCC. In 20 MCC cases identified by QF-PCR, CNV-seq successfully pinpointed the cause of miscarriage in 13 cases. Furthermore, in cases where QF-PCR suggested polyploidy, CNV-seq improved the diagnostic accuracy in 54 (1.28%) hypo/hypertriploidy cases. After comparing four different strategies, the sequential approach (initiating with CNV-seq followed by QF-PCR if necessary) emerged as advantageous, reducing approximately 70% of the cost associated with QF-PCR while maintaining result accuracy. CONCLUSIONS: We propose an initial CNV-seq followed by QF-PCR if needed-an efficient and cost-effective strategy for the genetic analysis of POCs.
Subject(s)
Abortion, Spontaneous , Chromosome Disorders , Pregnancy , Female , Humans , Chromosome Disorders/genetics , DNA Copy Number Variations/genetics , Abortion, Spontaneous/diagnosis , Abortion, Spontaneous/genetics , Karyotyping , Chromosome Aberrations , Prenatal Diagnosis , PolyploidyABSTRACT
Base editors (BEs) introduce base substitutions without double-strand DNA cleavage. Besides precise substitutions, BEs generate low-frequency 'stochastic' byproducts through unclear mechanisms. Here, we performed in-depth outcome profiling and genetic dissection, revealing that C-to-G BEs (CGBEs) generate substantial amounts of intermediate double-strand breaks (DSBs), which are at the centre of several byproducts. Imperfect DSB end-joining leads to small deletions via end-resection, templated insertions or aberrant transversions during end fill-in. Chromosomal translocations were detected between the editing target and off-targets of Cas9/deaminase origin. Genetic screenings of DNA repair factors disclosed a central role of abasic site processing in DSB formation. Shielding of abasic sites by the suicide enzyme HMCES reduced CGBE-initiated DSBs, providing an effective way to minimize DSB-triggered events without affecting substitutions. This work demonstrates that CGBEs can initiate deleterious intermediate DSBs and therefore require careful consideration for therapeutic applications, and that HMCES-aided CGBEs hold promise as safer tools.
Subject(s)
Alkanesulfonic Acids , DNA Breaks, Double-Stranded , Translocation, Genetic , Humans , DNA End-Joining Repair , DNA Repair/genetics , CRISPR-Cas SystemsABSTRACT
BACKGROUND: Pathogenic variants in the centrosome protein (CEP) family have been implicated in primary microcephaly, Seckel syndrome, and classical ciliopathies. However, most CEP genes remain unlinked to specific Mendelian genetic diseases in humans. We sought to explore the roles of CEP295 in human pathology. METHODS: Whole-exome sequencing was performed to screen for pathogenic variants in patients with severe microcephaly. Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying pathomechanisms, including centriole/centrosome development, cell cycle and proliferation changes, and ciliogenesis. Complementary experiments using CEP295 mRNA were performed to determine the pathogenicity of the identified missense variant. FINDINGS: Here, we report bi-allelic variants of CEP295 in four children from two unrelated families, characterized by severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes, suggesting a Seckel-like syndrome. Mechanistically, depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Moreover, loss of CEP295 causes extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts. INTERPRETATION: This study reports CEP295 as a causative gene of the syndromic microcephaly phenotype in humans. Our study also demonstrates that defects in CEP295 result in primary ciliary defects. FUNDING: A full list of funding bodies that contributed to this study can be found under "Acknowledgments."
Subject(s)
Intellectual Disability , Microcephaly , Child , Humans , Cell Cycle/genetics , Centrioles/genetics , Centrioles/metabolism , Intellectual Disability/genetics , Microcephaly/genetics , Proteins/metabolismABSTRACT
Field effect transistor(FET)biochemical sensors show great potential in the fields of environmental monitoring,food safety,disease diagnosis and clinical treatment due to their low noise,low power consumption,label-free,easy integration and miniaturization characteristics.Two-dimensional(2D)materials,as a new generation of channel materials for FET biochemical sensors,have atomic-level thickness,high carrier mobility,high specific surface area and tunable bandgap,which can further improve the performance of FET biochemical sensors,extend their application areas,and promote the rapid development of FET biochemical sensors.This review focused on the development and latest progress of 2D material-based FET biochemical sensors,along with the challenges and prospects of 2D material-based FET biochemical sensors,which aimed to provide new device design conceptions and promote the further development of biochemical sensing technology.
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OBJECTIVE To explore the effect of paeoniflorin on glucose metabolism, inflammation and oxidative stress in rats with gestational diabetes mellitus (GDM) and its potential mechanism based on nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1)/nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 (NQO1) signaling pathway. METHODS The female rats fed with high fat and high sugar diet and the male rats fed with an ordinary diet were caged, the successfully conceived rats were collected, and streptozotocin was injected intraperitoneally once to induce the GDM model. The successfully modeled rats were randomly divided into the model group, metformin hydrochloride group (200 mg/kg metformin by gavage), paeoniflorin low-, high-dose groups (45, 90 mg/kg paeoniflorin by gavage, respectively), paeoniflorin+ML385 group (90 mg/kg paeoniflorin by gavage and intraperitoneal injection of 30 mg/kg Nrf2 inhibitor ML385), with 12 rats in each group; in addition, another 12 conceived rats fed with an ordinary diet were selected as the control group. The rats in each drug group were given the corresponding drug/normal saline, once a day, for 2 consecutive weeks. Glucose metabolism indexes [fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (HOMA-IR)], serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α)] and renal tissue oxidative stress indexes [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px)] were detected; the pathological changes of renal tissue were observed, and the protein expressions of Nrf2, HO-1 and NQO1 in renal tissue were detected. RESULTS Compared with the control group, the renal tissue lesions of the model group were obvious, including glomerular atrophy, edema degeneration of renal tubular epithelial cells and a large number of inflammatory cell infiltration; the levels of FBG and FINS, HOMA-IR, the levels of IL-6 and TNF-α in serum, and the level of MDA in renal tissue were significantly increased (P<0.05), while the levels of SOD and GSH-Px and the protein expressions of Nrf2, HO-1 and NQO1 in renal tissue were significantly decreased (P<0.05). Compared with the model group, the renal tissue lesions of rats in paeoniflorin low-dose and high-dose groups were reduced, the above quantitative indexes were significantly improved, and the improvement effect was better in high-dose group (P<0.05), while ML385 could significantly reverse the improvement effect of paeoniflorin on the above indexes (P<0.05). CONCLUSIONS Paeoniflorin can improve the abnormal glucose metabolism, inflammation and oxidative stress damage of renal tissue in GDM rats, which may be related to the activation of Nrf2/HO-1/NOQ1 signaling pathway.
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OBJECTIVES: To analyze the clinical and genetic characteristics of children with autosomal dominant neurodevelopmental disorders caused by kinesin family member 1A (KIF1A) gene variation. METHODS: Clinical and genetic testing data of 6 children with KIF1A gene de novo heterozygous variation diagnosed in Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from the year 2018 to 2020 were retrospectively analyzed. Pathogenic variants were identified based on whole exome sequencing, and verified by Sanger sequencing. Moreover, the effect of variants on three-dimensional structure and stability of protein was analyzed by bioinformatics. RESULTS: Among 6 patients there were 4 males and 2 females, and the age of consultation varied from 7 months to 18 years. All cases had varying degrees of motor developmental delay since childhood, and 4 of them had gait abnormalities or fell easily. In addition, 2 children were accompanied by delayed mental development, epilepsy and abnormal eye development. Genetic tests showed that all 6 cases had heterozygous de novo variations of KIF1A gene, including 4 missense mutations c.296C>T (p.T99M), c.761G>A (p.R254Q), c.326G>T (p.G109V), c.745C>G (p.L249V) and one splicing mutation c.798+1G>A, among which the last three variants have not been previously reported. Bioinformatics analysis showed that G109V and L249V may impair their interaction with the neighboring amino acid residues, thereby impacting protein function and reducing protein stability, and were assessed as "likely pathogenic". Meanwhile, c.798+1G>A may damage an alpha helix in the motor domain of the KIF1A protein, and was assessed as "likely pathogenic". CONCLUSIONS: KIF1A-associated neurological diseases are clinically heterogeneous, with motor developmental delay and abnormal gait often being the most common clinical features. The clinical symptoms in T99M carriers are more severe, while those in R254Q carriers are relatively mild.
Subject(s)
Epilepsy , Neurodevelopmental Disorders , Male , Female , Humans , Child , Retrospective Studies , China , Mutation , Epilepsy/genetics , Neurodevelopmental Disorders/genetics , Kinesins/geneticsABSTRACT
AIM: To investigate the effects of antitumor drug paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, cell morphology, and related protein expression of Müller cells, and to evaluate its potential toxicity to the retina.METHODS:Müller cells were cultured in vitro and divided into two groups: control group(normal medium)and PTX group. Retinal Müller cells were treated with different concentrations of PTX(0.005, 0.05, 0.5 and 5mg/L)for varying durations(12, 24, 36, 48 and 72h). The CCK8 method was used to assess the effects of different concentrations of PTX and treatment duration on the proliferation Müller cells. Flow cytometry was employed to investigate the impact of different concentrations of PTX on Müller cells apoptosis and cell cycle arrest. Immunofluorescence was used to observe morphological changes in Müller cells. The effects of PTX on the expression of apoptosis-related proteins and aquaporins were analyzed by Western blot and qRT-PCR.RESULTS: PTX exhibits the ability to inhibit the proliferation of Müller cells when cultured in vitro. The efficacy of this inhibition was found to be dependent on both the concentration of the drug and the duration of the stimulation. Higher concentrations of the drug and longer stimulation times resulted in a weaker ability of the cells to proliferate. Additionally, PTX also induces apoptosis in Müller cells, with increased drug concentrations and longer stimulation times leading to higher apoptosis rates. Flow cytometry analysis demonstrates that PTX arrests Müller cells in the G2-M phase of the cell cycle. Moreover, there is a distinct change in cell morphology, with a shift from the typical appearance characterized by clear and slender fibrous structures to a rounder morphology, accompanied by a significant decrease in cell numbers. Further, our findings reveal that there is a transient increase in the expression of cytoinflammatory factors following drug treatment compared to the control group. However, discontinuation of drug stimulation can alleviate this heightened expression. In treated cells, the expression of the CA XIV protein is upregulated compared to the control group, while the expression of vascular endothelial growth factor(VEGF)is downregulated(P<0.05). Additionally, the levels of inflammatory factors in the PTX group are significantly higher than those in the control group(P<0.05), suggesting that PTX has the potential to disrupt the retinal barrier function.CONCLUSION: PTX affects the proliferation and apoptosis of Müller cells, with the effects dependent on stimulation duration and drug concentration. In addition, PTX blocks the Müller cell cycle at the G2-M phase and alters cell morphology, leading to a transient upregulation of inflammatory factors and affecting the integrity of the retinal barrier. These findings indicate the potential toxicity of the antitumor drug PTX to the retina.
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Glycosyltransferases (GTs) catalyze the transfer of sugar moieties from activated donormolecules to acceptors such as sugars, lipids, proteins, and nucleic acids. Protein glycosylation is one ofthe most important post-translational modifications (PTMs). In recent years, increasing studies haveshown that glycosyltransferases are closely related to the virulence of pathogenic bacteria, and play a keyrole in adhesion, immune evasion, and host colonization. According to the features of three-dimensionalstructure, glycosyltransferases are classified into three groups (GT-A, GT-B and GT-C), among whichGT-A and GT-B folds are more common. Glycosyltransferases, which play a role in bacterial adhesion, adopt the GT-B or GT-C fold and glycosylate the surface proteins of pathogenic bacteria (adhesionproteins, autotransporters, etc.). It plays an important role in the adhesion of pathogenic bacteria, theformation of biofilm, and the virulence mechanisms. Glycosyltransferases take part in bacterial adhesionprocess of infection, and glycosyltransferases belonging to GT-A directly glycosylate host proteins andaffect host signal transduction, protein translation, and immune response. This review discusses thestructure of common pathogenic bacteria glycosyltransferases and the pathogenic mechanisms underlyingthese diseases of glycosylation. One kind of glycosyltransferases mainly modify their surface proteins, suchas the glycosyltransferase for specifically glycosylating high-molecular-weight(HMW) adhesion proteins, glycosyltransferases for glycosylation modification of serine-rich repeat proteins (SRRPs), bacterialautotransporter heptosyltransferase (BAHT) family, and N-linked protein system. The other kinds ofglycosyltransferases modulate host responses by directly modifying host proteins, such as Clostridium largecytotoxin, Legionella glycosyltransferase, and the NleB effector from enterobacteria. This review providesa reference for systematically revealing the pathogenic mechanism of glycosyltransferase in pathogenicbacteria, and contributes scientific knowledge in the development of pathogenic bacteria diagnosis, drugdesign, and vaccine development.
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OBJECTIVE@#To compare the clinical effect of wheat grain moxibustion combined with rehabilitation training and simple rehabilitation training on finger spasm after stroke.@*METHODS@#A total of 80 patients with finger spasm after stroke were randomly divided into an observation group and a control group, 40 cases in each group. The control group was given routine rehabilitation training, once a day, 30 min each time. The observation group was given wheat grain moxibustion at Shixuan (EX-UE 11) on the basis of the control group, 8~10 moxibustion cones at each point, once a day. Both groups were treated for 6 days as one course of treatment for 4 courses. The motor function of the affected hand (Fugl-Meyer assessment [FMA] score) and muscle tension (modified Ashworth scale [MAS] grading), surface EMG indexes (wrist dorsiflexor muscle and flexor carpal metacarpal muscle mean square [RMS] value), hand muscle strength (neurological deficit score [NDS]) and daily living ability (modified Barthel index [MBI] score) were compared between the two groups before and after treatment, and clinical efficacy was evaluated.@*RESULTS@#After treatment, FMA and MBI scores in the 2 groups were increased compared with before treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The RMS value of wrist dorsiflexor muscle and flexor carpal metacarpal muscle in relaxation and passive function testsand and NDS in the 2 groups were lower than those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). MAS grading in the 2 groups was improved compared with before treatment (P<0.05), and that in the observation group was better than the control group (P<0.05). The total effective rate of the observation group was 92.5% (37/40), which was higher than that of the control group (80.0%, 32/40, P<0.05).@*CONCLUSION@#Wheat grain moxibustion at Shixuan (EX-UE 11) combined with rehabilitation training can improve the hand motor function and daily living ability of patients with finger spasm after stroke, improve the degree of spasm and the function of wrist dorsiflexor muscle and flexor carpal metacarpal muscle, the clinical effect is better than simple rehabilitation training.
Subject(s)
Humans , Acupuncture Therapy , Moxibustion , Spasm/therapy , Stroke/therapy , Stroke Rehabilitation , Treatment Outcome , TriticumABSTRACT
The treatment of refractory Glaucoma is a difficult problem in clinical ophthalmology. For refractory glaucoma patients with hyphema, shallow anterior chamber, anterior conglutination of peripheral chamber angle, corneal endothelium dystrophy or decompensated, at present, there is no effective treatment. In order to solve this problem, a new type posterior integral glaucoma valve with IOP control device was designed using medical titanium alloy, and the valve model was established by Abaqus software, and the stiffness and preload of the valve were analyzed by finite element method. The results showed that the opening and closing of the valve were controlled automatically by the pressure difference between the front and back of the valve, and the opening and flow rate of the valve increase dynamically with the increase of intraocular pressure, and finally reached the set ideal IOP value of steady state.
Subject(s)
Humans , Finite Element Analysis , Follow-Up Studies , Glaucoma , Glaucoma Drainage Implants , Intraocular Pressure , Treatment OutcomeABSTRACT
Objective: To observe the changes of parameters derived from transthoracic echocardiography (TTE) before and after left ventricular assist device (LVAD) implantation, and to evaluate the clinical value of TTE in the perioperative period of LVAD implantation. Methods: This is a retrospective study. The data of patients who underwent LVAD implantation in Fuwai Hospital from January 2018 to December 2020 were analyzed retrospectively. The TTE parameters, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin (TBil) before and 1 month after LVAD implantation were collected and analyzed. Results: A total of 12 male patients undergoing LVAD implantation were included in this study. The mean age was (43.3±8.6) years. The left atrial volume index ((41.4±12.8)ml/m2 vs. (74.9±30.7)ml/m2, P<0.001), left ventricular end-diastolic volume index ((152.1±35.3)ml/m2 vs. (205.5±35.7)ml/m2, P<0.001), left ventricular end-systolic volume index ((112.5±27.9)ml/m2 vs. (155.1±29.1)ml/m2, P<0.001), right atrial diameter index ((23.7±3.5)mm/m2 vs. (27.2±5.8)mm/m2, P=0.023), right ventricular internal diameter at end-diastole ((24.6±2.7)mm vs. (30.0±4.8)mm, P<0.001), tricuspid annular plane systolic excursion ((11.5±2.9)mm vs. (14.6±2.8)mm, P=0.007), systolic pulmonary arterial pressure ((29.2±4.8) mmHg vs. (55.1±19.3) mmHg, P<0.001, 1 mmHg=0.133 kPa) were significantly reduced at 1 month post LVAD implantation as compared to before LVAD implantation. The aortic sinus diameter ((33.8±4.7)mm vs. (31.6±5.1)mm, P=0.007), left ventricular ejection fraction ((26.3±3.0)% vs. (23.8±4.4)%, P=0.016), right ventricular fractional area change ((31.0±8.6)% vs. (23.8±5.5)%, P=0.004) at 1 month post LVAD implantation were significantly higher than before LVAD implantation. The degree of mitral and tricuspid regurgitation decreased, and the inspiratory collapse rate of inferior vena cava increased (all P<0.05). NT-proBNP ((1 418.4±812.6)ng/L vs. (5 097.5±3 940.4)ng/L, P=0.004) and TBil ((12.4±5.4)μmol/L vs. (27.5±14.0)μmol/L, P=0.001) decreased significantly at 1 month post LVAD implantation. Conclusions: TTE results show that LVAD could effectively relieve left ventricular load and improve right ventricular function. TTE can monitor the cardiac structural and functional changes during the perioperative period of LVAD implantation, and provide the imaging evidence for clinical evaluation of the therapeutic effect of LVAD.
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Adult , Humans , Male , Middle Aged , Echocardiography , Heart Failure/surgery , Heart-Assist Devices , Perioperative Period , Retrospective Studies , Stroke Volume , Ventricular Function, LeftABSTRACT
An appropriate animal model of dysphagia is important for research of the mechanism and treatment. Animal models of dysphagia mainly involve rodents, non-human primates and some other mammals, in which rats and mice are the most commonly used. The diseases mainly reproduced include stroke, amyotrophic lateral sclerosis, Parkinson's disease and oropharyngeal neuromuscular diseases, with dysphagia. The success of modeling mainly depends on the assessment of swallowing function, such as videofluoroscopic swallowing study and electrophysiological examination. No animal model can perfectly represent the clinical and pathological characteristics of dysphagia in humans now. With the development of targeted genetic modification and detection indicators, more reasonable dysphagia models would be reproduced.
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BACKGROUND@#As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis.@*METHODS@#WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC).@*RESULTS@#Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased.@*CONCLUSIONS@#IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.
Subject(s)
Animals , Mice , Chemokine CXCL1 , Metabolism , Cytokines , Metabolism , Disease Models, Animal , Imiquimod , Toxicity , Interleukin-17 , Metabolism , Interleukin-18 , Metabolism , Mice, Knockout , Psoriasis , Genetics , Metabolism , Skin , Allergy and Immunology , MetabolismABSTRACT
Currently, individualized exercise prescription plays a vital role in the cardiac rehabilitation of patients with chronic cardiovascular diseases. Many cardiopulmonary exercise tests proved that individualized exercise prescription can lower blood pressure and glucose of patients with cardiovascular diseases, improve cardiopulmonary function, and improve exercise endurance and quality of life. At the same time, this paper also summarized that the individualized exercise prescription should be formulated in compliance with the principle (individuality, effectiveness, safety, professionalization, comprehensiveness and permanence), exercise intensity evaluation method (from previous heart rate, fatigue grading methods into cardiopulmonary exercise test) and the contents of the individualized exercise prescription (with a focus on the exercise intensity formulation).
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Objective:To evaluate the effects of aerobic exercise, resistance exercise, and aerobic combined resistance exercise (combined exercise) on blood lipids for patients with type 2 diabetes with network meta-analysis, to develop exercise prescription. Methods:Randomized controlled trials (RCTs) about the above exercises for blood lipid in patients with type 2 diabetes were searched in databases of PubMed, Ovid, Web of Science, Cochrane Library, Springer Link, Science Direct, CNKI, Wanfang data and CBM, and were supplied by retrospective references. After evaluating the methodological quality of the RCTs, the data were analyzed with R-Studio, Stata 14.0 and Review Manager 5.3. Results:A total of 21 RCTs were recalled, with 1735 patients. Two poor quality literatures were excluded based on sensitivity analysis. Compared with the control group, all three kinds of exercise significantly reduced the level of fasting glucose, total cholesterol, triglyceride, low density lipoprotein, increased the level of high density lipoprotein, with good homogeneity. Rank probability graph showed that the combined exercise was the best for fasting glucose, total cholesterol triglyceride and high density lipoprotein, while aerobic exercise was the best for low density lipoprotein. Conclusion:It is the best to select the combined exercise to improve fasting glucose, total cholesterol, triglycerides and high density lipoprotein, and aerobic exercise for low density lipoprotein.
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Ultramicroelectrode was usually used in scanning electrochemical microscope(SECM) as a probe. The redox reaction on the probe is a diffusion process. But the fast moving of probe in SECM will affect the diffusion process, resulting in unclear obtained images. A new SECM image-processing technique was proposed in this paper involving combination of LoG algorithm and New edge-directed interpolation (NEDI) interpolation algorithm. LoG algorithm is helpful for the clarity of SECM images, but leading to some loss of edge information. Fortunately, NEDI algorithm based on edge directed interpolation can solve this problem well. Two substrates with gold interdigitated electrode and gold electrode array were prepared by ion sputtering method. The SECM images were obtained of the gold interdigitated electrode, gold electrode array and ITO substrate printed with fingerprints. The corresponding images treated by LoG filter and these for NEDI interpolation were compared and analyzed. The image-processing technique combining the LoG algorithm with the NEDI interpolation algorithm can significantly improve the clarity and resolution of SECM image.