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Objective To observe the clinical efficacy of acupuncture combined with Guanxinning Tablets in the treatment of heart vessel obstruction type of chest obstruction syndrome.Methods Eighty patients with heart vessel obstruction type of chest obstruction syndrome were randomly divided into the observation group and the control group,with 40 cases in each group,the control group was given conventional western medicine treatment,the observation group was given acupuncture combined with Guanxinning Tablets on the basis of the treatment in the control group,and the patients in the two groups were treated continuously for 30 days.The clinical efficacy of the two groups was evaluated after 1 month of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes in the traditional Chinese medicine(TCM)scores,including chest tightness,palpitations,stabbing pains in the chest,and dark complexion,as well as the frequency and duration of angina pectoris were observed before and after the treatment in the two groups.The changes of serum monocyte chemotactic factor 1(MPC-1),hs-CRP,tumor necrosis factor α(TNF-α),mitogen-activated protein kinase(MAPK),and Toll-like receptor 4(TLR4)were observed before and after treatment in the two groups.Results(1)The total effective rate was 95.00%(38/40)in the observation group and 75.00%(30/40)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the TCM syndrome scores of patients in the two groups,including chest tightness and palpitations,chest tingling,and dark complexion,were significantly improved,and the observation group was significantly superior to the control group in improving the TCM syndrome scores of chest tightness and palpitations,chest tingling,and dark complexion,and the difference was statistically significant(P<0.05).(3)After treatment,the frequency and duration of angina attacks in the two groups were significantly improved,and the observation group was significantly superior to the control group in improving the frequency and duration of angina attacks,and the difference was statistically significant(P<0.05).(4)After treatment,the serum hs-CRP,MPC-1,and TNF-α levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the serum hs-CRP,MPC-1 and TNF-α levels,and the difference was statistically significant(P<0.05).(5)After treatment,the serum MAPK and TLR4 levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving serum MAPK and TLR4 levels,and the difference was statistically significant(P<0.05).Conclusion Acupuncture combined with Guanxinning Tablets for the treatment of heart vessel obstruction type of chest obstruction syndrome can significantly improve the clinical symptoms of the patients,effectively alleviate the body's inflammatory response,reduce the level of serum MAPK and TLR4,and the clinical efficacy is remarkable.
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People frequently struggle to juggle their work, family, and social life in today’s fast-paced environment, which can leave them exhausted and worn out. The development of technologies for detecting fatigue while driving is an important field of research since driving when fatigued poses concerns to road safety. In order to throw light on the most recent advancements in this field of research, this paper provides an extensive review of fatigue driving detection approaches based on electroencephalography (EEG) data. The process of fatigue driving detection based on EEG signals encompasses signal acquisition, preprocessing, feature extraction, and classification. Each step plays a crucial role in accurately identifying driver fatigue. In this review, we delve into the signal acquisition techniques, including the use of portable EEG devices worn on the scalp that capture brain signals in real-time. Preprocessing techniques, such as artifact removal, filtering, and segmentation, are explored to ensure that the extracted EEG signals are of high quality and suitable for subsequent analysis. A crucial stage in the fatigue driving detection process is feature extraction, which entails taking pertinent data out of the EEG signals and using it to distinguish between tired and non-fatigued states. We give a thorough rundown of several feature extraction techniques, such as topology features, frequency-domain analysis, and time-domain analysis. Techniques for frequency-domain analysis, such wavelet transform and power spectral density, allow the identification of particular frequency bands linked to weariness. Temporal patterns in the EEG signals are captured by time-domain features such autoregressive modeling and statistical moments. Furthermore, topological characteristics like brain area connection and synchronization provide light on how the brain’s functional network alters with weariness. Furthermore, the review includes an analysis of different classifiers used in fatigue driving detection, such as support vector machine (SVM), artificial neural network (ANN), and Bayesian classifier. We discuss the advantages and limitations of each classifier, along with their applications in EEG-based fatigue driving detection. Evaluation metrics and performance assessment are crucial aspects of any detection system. We discuss the commonly used evaluation criteria, including accuracy, sensitivity, specificity, and receiver operating characteristic (ROC) curves. Comparative analyses of existing models are conducted, highlighting their strengths and weaknesses. Additionally, we emphasize the need for a standardized data marking protocol and an increased number of test subjects to enhance the robustness and generalizability of fatigue driving detection models. The review also discusses the challenges and potential solutions in EEG-based fatigue driving detection. These challenges include variability in EEG signals across individuals, environmental factors, and the influence of different driving scenarios. To address these challenges, we propose solutions such as personalized models, multi-modal data fusion, and real-time implementation strategies. In conclusion, this comprehensive review provides an extensive overview of the current state of fatigue driving detection based on EEG signals. It covers various aspects, including signal acquisition, preprocessing, feature extraction, classification, performance evaluation, and challenges. The review aims to serve as a valuable resource for researchers, engineers, and practitioners in the field of driving safety, facilitating further advancements in fatigue detection technologies and ultimately enhancing road safety.
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Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.
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Mitochondrial quality control plays an important role in maintaining homeostasis of mitochondrial network and normal function of mitochondria. ATPase family AAA domain-containing protein 3A (ATAD3A) is one of the mitochondrial membrane proteins involved in the regulation of mitochondrial structure and function, mitochondrial dynamics, mitophagy and other important biological processes. Recent studies show that ATAD3A not only interacts with Mic60/Mitofilin and mitochondrial transcription factor A (TFAM) to maintain mitochondrial cristae morphology and oxidative phosphorylation, but also interacts with dynamin-related protein 1 (Drp1) to positively/negatively regulate mitochondrial fission. In addition, ATAD3A serves as a bridging factor between the translocase of the outer mitochondrial membrane (TOM) complex and translocase of the inner mitochondrial membrane (TIM) complex to facilitate the import of PTEN-induced putative kinase protein 1 (PINK1) into mitochondria and its processing displays a pro-autophagic or anti-autophagic activity. This article reviews the role and mechanism of ATAD3A in regulating mitochondrial quality control. Firstly, as an inner mitochondrial membrane protein, ATAD3A is involved in maintaining the stability of mitochondrial crista structure, and its gene deletion or mutation will cause the loss and breakage of crista. Secondly, ATAD3A is also involved in maintaining mitochondrial respiratory function and mitochondrial nucleoid homeostasis, and its gene deletion or mutation can reduce the activity of mitochondrial respiratory chain complex and enhance the size and movement of nucleoid. Thirdly, ATAD3A participates in the negative regulation of mitochondrial fusion, but its role in mitochondrial fission may dependent on specific cell types, as it can promote and/or inhibit the mitochondrial fission by increasing and/or decreasing phosphorylation or oligomerization of Drp1. Finally, ATAD3A can interact with mitophagy-related proteins (e.g. PINK1, autophagy/beclin-1 regulator 1 (AMBRA1), acylglycerol kinase (AGK)) to enhance/reduce PINK1-Parkin-dependent mitophagy.
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Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.
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Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.
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Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.
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OBJECTIVE@#To investigate the effect of adipocytes in the bone marrow microenvironment of patients with multiple myeloma (MM) on the pathogenesis of MM.@*METHODS@#Bone marrow adipocytes (BMA) in bone marrow smears of health donors (HD) and newly diagnosed MM (ND-MM) patients were evaluated with oil red O staining. The mesenchymal stem cells (MSC) from HD and ND-MM patients were isolated, and in vitro co-culture assay was used to explore the effects of MM cells on the adipogenic differentiation of MSC and the role of BMA in the survival and drug resistance of MM cells. The expression of adipogenic/osteogenic differentiation-related genes PPAR-γ, DLK1, DGAT1, FABP4, FASN and ALP both in MSC and MSC-derived adipocytes was determined with real-time quantitative PCR. The Western blot was employed to detect the expression levels of IL-6, IL-10, SDF-1α, TNF-α and IGF-1 in the supernatant with or without PPAR-γ inhibitor.@*RESULTS@#The results of oil red O staining of bone marrow smears showed that BMA increased significantly in patients of ND-MM compared with the normal control group, and the BMA content was related to the disease status. The content of BMA decreased in the patients with effective chemotherapy. MM cells up-regulated the expression of MSC adipogenic differentiation-related genes PPAR-γ, DLK1, DGAT1, FABP4 and FASN, but the expression of osteogenic differentiation-related gene ALP was significantly down-regulated. This means that the direct consequence of the interaction between MM cells and MSC in the bone marrow microenvironment is to promote the differentiation of MSC into adipocytes at the expense of osteoblasts, and the cytokines detected in supernatant changed. PPAR-γ inhibitor G3335 could partially reverse the release of cytokines by BMA. Those results confirmed that BMA regulated the release of cytokines via PPAR-γ signal, and PPAR-γ inhibitor G3335 could distort PPAR-γ mediated BMA maturation and cytokines release. The increased BMA and related cytokines effectively promoted the proliferation, migration and drug resistance of MM cells.@*CONCLUSION@#The BMA and its associated cytokines are the promoting factors in the survival, proliferation and migration of MM cells. BMA can protect MM cells from drug-induced apoptosis and plays an important role in MM treatment failure and disease progression.
Subject(s)
Humans , Osteogenesis/genetics , Bone Marrow/metabolism , Multiple Myeloma/metabolism , Drug Resistance, Neoplasm , Peroxisome Proliferator-Activated Receptors/pharmacology , Cell Differentiation , Adipogenesis , Cytokines/metabolism , Adipocytes/metabolism , Bone Marrow Cells/metabolism , Cells, Cultured , PPAR gamma/pharmacology , Tumor MicroenvironmentABSTRACT
The metabolism study of radiolabeled drugs plays an important role in the development of new drugs. It provides information on drug absorption, metabolism, tissue distribution and excretion, and plays an irreplaceable role in the metabolite safety evaluation and mass balance of new drugs. The new guidance draft on clinical trials of radiolabeled drugs recently released by the US FDA puts forward higher standards and has been widely concerned by the industry. In recent years, in the research and development of new drugs in China, 14C labeled drugs have been used to carry out clinical metabolism studies, which has overcome key technical bottlenecks and accumulated experience. This paper summarizes the above research progress, analyzes the existing problems, and preliminarily looks forward to the future technological development and application.
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Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.
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Objective To master the changes of foodborne disease pathogen spectrum in Yichang during 2014-2020, and to understand the impact of the toilet revolution on the pathogen spectrum of foodborne diseases in Yichang. Methods The basic information on the cases of foodborne diseases in Yichang from 2014 to 2020 was collected. The fecal specimens were collected to detect pathogens, including Salmonella , Vibrio parahaemolyticus, Shigella, and diarrheogenic Escherichia coli and Norovirus. The distribution of foodborne pathogenic bacteria in food was obtained from the surveillance project report of food microorganisms and their pathogenic factors in Yichang. From 2017 to 2020, water samples from the Yangtze River were collected from May to October with frequent intestinal diseases to detect pathogenic bacteria of foodborne diseases. Results The monitoring results of foodborne diseases showed that the detection rate of norovirus increased to 6.12% year by year from 2015 to 2017, and plummeted to 0.43% in 2018, with a statistically significant difference (χ2=60.962,P2=106.47,P2=44.036 , P<0.05). Conclusion The toilet revolution can reduce the detection rate of pathogens of foodborne diseases in Yichang and reduce the detection rate of Salmonella in Yangtze River water, but it has little impact on the composition of foodborne disease pathogen spectrum.
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Pancreatic cancer remains one of the deadliest cancer types with few effective treatment options. While the overexpression of ubiquitin-specific protease 14 (USP14) has been observed in many tumor cells, including pancreatic cancer cells, its precise role in pancreatic cancer is not well defined. Here, we investigated the biological function of USP14 in pancreatic cancer and its molecular mechanisms. Our analysis of the Cancer Genome Atlas database revealed that USP14 was highly expressed in pancreatic cancer tissues,and further investigation revealed that its expression level was negatively correlated with the prognosis of patients. In SW1990 and MIAPaCa2 pancreatic cancer cells,we established stable USP14-knockdown cell lines using the shRNA-USP14 lentivirus and found that USP14 knockdown inhibited the proliferation and migration ability of pancreatic cancer cells by CCK8, colony formation assay, wound-healing and Transwell assays. Western blotting analysis showed that downregulation of USP14 expression resulted in a decrease in CyclinD3 protein levels, while overexpression of USP14 increased the protein levels in SW1990 and MIAPaCa2 pancreatic cancer cells. Furthermore, co-immunoprecipitation demonstrated that USP14 interacts with CyclinD3 and ubiquitination assays show that overexpression of USP14 reduces the ubiquitination level of CyclinD3. Moreover, CRISPR / Cas9-mediated USP14 knockout in SW1990 pancreatic cancer cells resulted in decreased CyclinD3 protein levels. These findings suggest that USP14 promotes the proliferation and migration ability of pancreatic cancer cells by interacting with CyclinD3, highlighting USP14 as a potential therapeutic target for pancreatic cancer.
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PURPOSE@#SAM junctional tourniquet (SJT) has been applied to control junctional hemorrhage. However, there is limited information about its safety and efficacy when applied in the axilla. This study aims to investigate the effect of SJT on respiration when used in the axilla in a swine model.@*METHODS@#Eighteen male Yorkshire swines, aged 6-month-old and weighing 55 - 72 kg, were randomized into 3 groups, with 6 in each. An axillary hemorrhage model was established by cutting a 2 mm transverse incision in the axillary artery. Hemorrhagic shock was induced by exsanguinating through the left carotid artery to achieve a controlled volume reduction of 30% of total blood volume. Vascular blocking bands were used to temporarily control axillary hemorrhage before SJT was applied. In Group I, the swine spontaneously breathed, while SJT was applied for 2 h with a pressure of 210 mmHg. In Group II, the swine were mechanically ventilated, and SJT was applied for the same duration and pressure as Group I. In Group III, the swine spontaneously breathed, but the axillary hemorrhage was controlled using vascular blocking bands without SJT compression. The amount of free blood loss was calculated in the axillary wound during the 2 h of hemostasis by SJT application or vascular blocking bands. After then, a temporary vascular shunt was performed in the 3 groups to achieve resuscitation. Pathophysiologic state of each swine was monitored for 1 h with an infusion of 400 mL of autologous whole blood and 500 mL of lactated ringer solution. Tb and T0 represent the time points before and immediate after the 30% volume-controlled hemorrhagic shock, respectively. T30, T60, T90 and T120, denote 30, 60, 90, and 120 min after T0 (hemostasis period), while T150, and T180 denote 150 and 180 min after T0 (resuscitation period). The mean arterial pressure and heart rate were monitored through the right carotid artery catheter. Blood samples were collected at each time point for the analysis of blood gas, complete cell count, serum chemistry, standard coagulation tests, etc., and thromboelastography was conducted subsequently. Movement of the left hemidiaphragm was measured by ultrasonography at Tb and T0 to assess respiration. Data were presented as mean ± standard deviation and analyzed using repeated measures of two-way analysis of variance with pairwise comparisons adjusted using the Bonferroni method. All statistical analyses were processed using GraphPad Prism software.@*RESULTS@#Compared to Tb, a statistically significant increase in the left hemidiaphragm movement at T0 was observed in Groups I and II (both p < 0.001). In Group III, the left hemidiaphragm movement remained unchanged (p = 0.660). Compared to Group I, mechanical ventilation in Group II significantly alleviated the effect of SJT application on the left hemidiaphragm movement (p < 0.001). Blood pressure and heart rate rapidly increased at T0 in all three groups. Respiratory arrest suddenly occurred in Group I after T120, which required immediate manual respiratory assistance. PaO2 in Group I decreased significantly at T120, accompanied by an increase in PaCO2 (both p < 0.001 vs. Groups II and III). Other biochemical metabolic changes were similar among groups. However, in all 3 groups, lactate and potassium increased immediately after 1 min of resuscitation concurrent with a drop in pH. The swine in Group I exhibited the most severe hyperkalemia and metabolic acidosis. The coagulation function test did not show statistically significant differences among three groups at any time point. However, D-dimer levels showed a more than 16-fold increase from T120 to T180 in all groups.@*CONCLUSION@#In the swine model, SJT is effective in controlling axillary hemorrhage during both spontaneous breathing and mechanical ventilation. Mechanical ventilation is found to alleviate the restrictive effect of SJT on thoracic movement without affecting hemostatic efficiency. Therefore, mechanical ventilation could be necessary before SJT removal.
Subject(s)
Male , Animals , Swine , Shock, Hemorrhagic/therapy , Tourniquets , Axilla , Hemorrhage/therapy , Vascular Diseases , RespirationABSTRACT
OBJECTIVE@#The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.@*METHODS@#Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.@*RESULTS@#On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.@*CONCLUSION@#Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
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Humans , Animals , Mice , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Heterografts , Bone Marrow , Disease Models, Animal , T-Lymphocytes , Mice, SCIDABSTRACT
OBJECTIVE@#To explore clinical features, treatment methods and clinical effects of cervical spondylosis with proximal muscular atrophy.@*METHODS@#Eleven patients with proximal-type cervical spondylotic amyotrophy were retrospectively studied from September 2016 to November 2020, including 7 males and 4 females, aged 38 to 68 years old. Clinical symptoms, MRI and neuroelectrophysiological manifestations were analyzed, and patients were treated with conservative treatment or anterior cervical decompression fusion surgery, respectively. The efficacy was evaluated by manual muscle test (MMT) before and after treatment, and patients' satisfaction was followed up at the same time.@*RESULTS@#All patients were followed up for 6 to 19 months. All 11 patients were unilateral, mainly manifested by atrophy of deltoid muscle, supraspinatus muscle and infraspinatus muscle, and may be accompanied by ipsilateral neck and shoulder pain at early stage. MRI showed lesions at C4,5, C5,6 segments were more common. Electrophysiological examination showed the affected muscle was denervated, and amplitude of compound muscle action potential (CMAP) of innervated nerve on the affected side was lower than that on the healthy side. All patients were obtained bone fusion. One patient who were underwent anterior cervical corpectomy and fusion (ACCF) occurred developed contralateral C5 nerve root paralysis after operation, which recovered completely after 10 weeks of symptomatic treatment. At 12 months after operation, the efficacy was evaluated according to MMT, 3 patients were treated conservatively, 2 patients excellent and 1 good;in 8 patients treated by operation, 3 patients were excellent, 4 good, and 1 moderate.@*CONCLUSION@#The incidence of cervical spondylosis with proximal muscular atrophy is low, which is manifested as unilateral proximal muscle atrophy and may be accompanied by ipsilateral neck and shoulder pain in the early stage. Combined with MRI and neuroelectrophysiological examination, misdiagnosis could be reduced. In the early stage of disease, especially in the case of nucleus pulposus protrusion leading to nerve compression, conservative treatment could be taken. When the conservative treatment is ineffective or the pain cannot be tolerated, anterior decompression surgery is recommended, and the overall effect is satisfactory.
Subject(s)
Male , Female , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Shoulder Pain , Cervical Vertebrae/pathology , Muscular Atrophy/surgery , Decompression, Surgical/methods , Spondylosis/surgery , Treatment Outcome , Spinal Fusion/adverse effectsABSTRACT
Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.
Subject(s)
Humans , Salmonella enterica/genetics , Serogroup , Anti-Bacterial Agents/pharmacology , Multilocus Sequence Typing , Cities , London , Clonidine , Phylogeny , Genomics , Drug Resistance , Electrophoresis, Gel, Pulsed-Field , Microbial Sensitivity TestsABSTRACT
Enterotoxigenic Escherichia coli(ETEC)infection can induce watery diarrhea,leading to dehydration,electrolyte disturbance,and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera(rBS/WC)vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC,as well as the effectiveness,safety,and health economics of rBS/WC vaccine,National Clinical Research Center for Child Health(The Children’s Hospital,Zhejiang University School of Medicine)and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.
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@#Objective - - To prepare the GDH 5 air sampling tube for simultaneous collection of eight kinds of chloro nitrobenzene ( ) , compounds CNBs in the air of workplace and establish a matching determination method using gas chromatography. Methods - - , Eight kinds of CNBs in vapor and aerosol state were collected by self developed GDH 5 air sampling tube desorbed , , , by toluene separated by polysiloxane gas chromatography column detected by microcell electron capture detector and Results - ( - quantified by external standard method. It was determined that the air sampling tube was assembled by XAD 2 ion ) - , exchange resin and glass fiber filter membrane. The linear range of CNBs was 0.80 240.00 mg/L and the linear correlation - - coefficients were greater than 0.999 9. The detection limit was 7.87 13.03 μg/L. The minimum detectable concentration was 0.60 3, - 3( ) 1.33 μg/m and the minimum quantitative concentration was 2.00 4.22 μg/m sample 45.00 L . The average desorption - - (RSD) - , - RSD efficiency was 101.2% 110.0%. The within run relative standard deviation was 0.8% 4.1% and the between run - Conclusion - was 0.3% 5.8%. The samples could be stored for more than 30 days at room temperature. GDH 5 air sampling tube and its associated determination method can be used for the collection and determination of eight kinds of CNBs in workplace air.
ABSTRACT
Hallmarks of the pathophysiology of glaucoma are oxidative stress and apoptotic death of retinal ganglion cells (RGCs). Ginkgo biloba extract (EGb) with multi-target, multi-pathway functions has been reported to exert positive pharmacological effects on oxidative stress and damaged RGCs. However, the ingredients and anti-apoptotic targets of EGb in the treatment of open-angle glaucoma (OAG) have not been fully elucidated. Therefore, in-depth analysis is necessary for further research. Ginkgo biloba-related and anti-apoptotic targets were identified and then combined to obtain the intersection, representing the potential anti-apoptotic targets of Ginkgo biloba. In addition, compound-anti-apoptotic target and OAG-target protein-protein interaction network were merged to obtain five core genes and compound-OAG-anti-apoptotic target protein-protein interaction network. Consequently, the active compounds and anti-apoptotic targets of Ginkgo biloba in the treatment of OAG were identified, namely luteolin, β-sitosterol, kaempferol, stigmasterol, quercetin, and p53, Bax, Bcl-2, Caspase-3 and Caspase-9, respectively. For the anti-apoptotic targets of Ginkgo biloba in the treatment of OAG, Gene Ontology (GO) and pathway analysis were executed to confirm the gene functions of Ginkgo biloba in antagonizing apoptosis of RGCs. The pathway enrichment was mainly involved in transcriptional activation of p53 responsive genes, activation of caspases and apoptotic processes. Finally, we confirmed the results of the network analysis by H2O2 treated RGC-5 cells in vitro. The results demonstrated that EGb protection can effectively diminish H2O2-induced apoptosis by inhibiting p53 acetylation, reducing the ratio of Bax/Bcl-2 and suppressing the expression of specific cleavage of Caspase-9 and Caspase-3.