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Objective@#To investigate the prevalence and associated factors of depressive symptoms among middle and high school students in Zhejiang Province, so as to provide scientific basis for the implementation of depressive intervention.@*Methods@#Based on the health status and associated factors of middle and high school students in the project "Monitoring of Common Diseases and Health Influencing Factors of Students" during 2018 to 2021, a total of 73 309 students including middle school, ordinary high school and vocational high school surveyed in 11 cities of Zhejiang Province were selected by multi stage stratified cluster random sampling method. From 2018 to 2021, there were 6 008, 21 917, 23 712 and 21 672 students, respectively. The Chi square test and Logistic regression model were used to analyze the influencing factors of depressive symptoms in middle and high school students.@*Results@#From 2018 to 2021, depressive symptoms detection rate of middle school students was 14.8%, with higher rate in girls (17.1%) than in boys (12.7%), higher rate in high school (17.1% in ordinary high school, 17.6% in vocational high school) than middle school (12.5%)( χ 2=278.77, 327.22, P <0.05). Univariate analysis showed that there were statistically significant differences in depressive symptoms detection rate among middle school students with different years (2018: 16.7%，2019: 17.9% , 2020: 13.1%, 2021: 13.0%), residence (yes: 16.3%, no:13.5%), body mass index classification (not overweight or obesity: 14.8%, overweight: 14.2%, Obesity: 15.7%), weekly exercise days (0-2 d: 17.1%, 3-5 d: 12.5%, 6-7 d: 13.1%) and bullying (yes: 35.5%, no: 10.7%) ( χ 2=293.40, 118.35, 7.83, 287.24, 4 978.84, P <0.05). Multivariate Logistic regression analysis showed that female students, ordinary high schools, vocational high schools, obesity, school bullying were positively correlated with depression ( OR =1.65, 1.70, 1.60, 1.12, 5.21), exercise 3 to 5 days per week, exercise 6 to 7 days per week were negatively correlated with depression ( OR=0.77, 0.81, P <0.01).@*Conclusions@#Depressive symptoms among middle and high school students in Zhejiang Province are prominent. Strengthening mental health education for students and providing attention and support from families, schools, and society are essential steps to reduce the occurrence of depressive symptoms among these students.
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Objective:To conduct the genetic analysis of a family with one patient suffering from juvenile Parkinson's disease(JP)and discuss the clinical manifestations,genetic mutation characteristics,and treatment plans prompted by PRKN gene compound heterozygous mutations,and to enhance the clinicians'awareness of this disease.Methods:The clinical data of one patient with JP caused by PRKN gene mutations was analyzed,the clinical manifestations and genetic mutation features of the patient were summarized,and the related literatures were reviewed.Results:The patient,a 16-year-old male,was admitted to the hospital due to unstable gait,trembling limbs with rigidity in both lower limbs for three years.The examination results revealed a panic gait,clear consciousness,fluent speech,normal muscle strength in limbs,increased"gear-like"muscle tone in both upper limbs,and"lead-pipe"rigidity in both lower limbs;the sensory functions and tendon reflexes were normal.The head,neck,and thoracic magnetic resonance imaging(MRI)results showed no abnormalities.18F-fluorodeoxyglucose(18F-FDG)positron emission tomography/computed tomography(PET/CT)results showed that the head size and shape were normal,the glucose metabolism in the left cerebellum and middle temporal gyrus was slightly decreased,and the glucose metabolism in bilateral thalami,right frontal lobe,parietotemporal lobe,and left medial frontal lobe was increased.The dopamine transporter(DAT)PET/CT results showed that there was no radioactive distribution in the brain cortex and the DAT distribution in the posterior part of both striata was decreased.The whole-exome sequencing results showed the patient had two PRKN gene mutations,such as codons c.8T>A and c.850G>C compound heterozygous mutations,and each mutation was from one parent;the patient's father carried the c.8T>A mutation,the patient's mother carried the c.850G>C mutation,and the patient's sister had the same genetic mutation site as the patient's father.Conclusion:PRKN gene compound heterozygous mutations may be the basis of the disease in this family.Identification of the mutation c.8T>A expands the mutation spectrum of the PRKN gene,and provides the valuable information for the research on the pathogenic genetic mutations of the JP patients.
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Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.
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Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.
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The Rainbow Model of Integrated Care(RMIC)is a new conceptual framework that integrates primary care principles,integrated care characteristics,and a triple aim framework based on the Rainbow Model,which helps researchers better understand the concept of integrated care from a primary care perspective and thus scientifically conduct integrated care practice programs.This paper reviews the emergence and development of RMIC,its conceptual framework,and its application in integrated care,with the aim of providing a guiding basis for improving the quality of integrated care and positively transforming the health care delivery model in China.
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Long-term burden of illness and associated medication usage make osteoporosis(OP) a common complication of respiratory diseases. The pathogenic risk factors and treatment strategies for respiratory diseases related OP are similar to primary OP. However, due to differences in the pathogenesis of each disease, there are distinctions in the characteristics of bone loss and treatment approaches. Therefore, targeted diagnostic and therapeutic plans need to be formulated. This article provides a comprehensive review of secondary OP caused by common respiratory diseases in terms of epidemiological characteristics, related risk factors or possible mechanisms, changes in bone metabolic indexes or characteristics of bone damage, and progress in diagnosis and treatment. The aim of this review is to offer insights into the prevention and treatment of secondary OP related to respiratory diseases and promote the development of a multidisciplinary collaborative approach.
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AIM To compare the components difference between Lonicera fragrantissima Lindl.et Paxt.(LFL)and Lonicerae japonicae Flos(LJF),and to evaluate the medicinal value of LFL,so as to provide reference for the development and utilization of LFL and LJF.METHODS With 70%methanol as extraction solvent,the components were analyzed by UPLC-TOF-MS,and the contents of 20 components were determined by HPLC-QQQ-MS.The components difference was determined by multivariate statistical analysis.RESULTS A total of 52 components were identified in the buds of LFL and LJF.There were 4 different components in LJF,and the contents of 20 quantitative components were significantly different.The contents of isochlorogenic acid C,ferulic acid,luteolin and rutin in the buds of LFL were more than 2 times that of LJF,and the contents of marchanic acid and marchanin were 11.96 times and 37.23 times that of LJF respectively.Maganin,isochlorogenic acid A,maganic acid,rutin and dicomachanic acid are the key differentiating components of LFL and LJF.CONCLUSION The buds of LFL and LJF have similar species,but the content difference is obvious.The buds of LFL have important medicinal value,which need further development and utilization.
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The brain’s neural circuits consist of a large number of highly unstable networks. Despite the existence of many internal and external factors that continuously disturb the balance, our brains employ an array of homeostatic mechanisms that allow neurons or neural circuits to sense how active they are, and when they deviate from a target value, whereby a force must be generated to move neuronal activity back toward this target. Sleep is one of the well-known physiological states in the regulation of homeostasis. Sleep pressure increases during wakefulness and decreases during sleep. When sleep is lost (e.g., sleep deprivation), this loss is compensated by extending or strengthening subsequent sleep. These phenomena are known as sleep homeostasis. The dysregulation of sleep homeostasis accompanies brain-related diseases such as schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder. More importantly, it can significantly undermine the basis of traditional sleep hygiene practices for these diseases. Therefore, clarifying the mechanisms of sleep homeostasis is important for therapy, but it remains an unsolved mystery. In addition to pharmacological treatment, non-invasive brain stimulation has become one of the most promising tools for clinical treatment in recent years due to its low cost, portability and low incidence of side effects. In order to promote relevant technologies, this review will focus on the electrophysiological mechanisms of sleep homeostasis. We first discuss the electrophysiological marker of sleep homeostasis, slow-wave activity, then move to the neuronal firing rates, finally discuss more aspects of sleep homeostasis, including differences in brain area, sleep stages, learning and individual differences.
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Based on the long bud stage phenotype of a new Lonicera japonica Flos variety "Huajin 6", using "Huajin 6" and "Da Mao Hua" as materials, probing the mechanism of its phenotype formation. Detection of endogenous Jasmonic acid hormones (JAs) content; the genes related to jasmonic acid (JA) synthesis were identified by transcriptome analysis of Lonicera japonica; flower buds and flowers of "Huajin 6" and "Da Mao Hua" were collected at different periods, and the qRT-PCR (quantitative real-time PCR) technique was used to analyze the trend of the expression of synthesis-related enzyme genes in Lonicera japonica Flos during the bud stage. The study found that the content of JAs in "Huajin 6" Lonicera japonica Flos was significantly lower than that in "Da Mao Hua"; applying exogenous methyl-jasmonate (MeJA) to "Huajin 6" can restore its flowering phenotype, making it close to wild type Lonicera japonica Flos; there are significant differences in the expression of two allene oxide synthase genes (AOS), three lipoxygenase genes (LOX), and two allene oxide cyclase genes (AOC) in the flowers and buds of "Huajin 6" and "Da Mao Hua" at different periods. It is hypothesized that the low expression of JA synthesis-related enzyme genes in " Huajin 6" leads to the blockage of JA synthesis, which causes the formation of the long bud phenotype. This study laid a certain foundation for the genetic breeding of Lonicera japonica, provided a new idea for the improvement of Lonicera japonica varieties, and provided a reference for the study of JAs in plant flower organs.
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Biochemical liver function tests are important methods to determine liver function in clinical practice， but abnormal liver biochemical parameters are not completely equivalent to liver damage. Some genetic and immune factors can also cause abnormal liver biochemical parameters， but with good prognosis in most cases. This article summarizes the causes of some benign abnormal liver biochemical parameters， so as to help clinicians to broaden their thinking of diagnosis and treatment， take into account genetic and immune factors， and avoid misdiagnosis and mistreatment.
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Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.
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Objective To investigate the clinical application value of the non-shared incentive diffusion weighted imaging(ZOOM-DWI)technique at cervical level in diagnosis of cervical spondylotic myelopathy(CSM).Methods A total of 49 CSM patients(patient group),and 50 healthy volunteers(control group)were recruited.All subjects underwent conventional MRI and ZOOM-DWI of the cervical spine and neurologic modified Japanese Orthopaedic Association(mJOA)scores in patients with CSM.The apparent diffusion coefficient(ADC)value in the spinal cord at the narrowest area(C5-C6)of the compression site of patients,the ADC value at the disc level in each upper and lower level,and the spinal ADC value at the cervical level C2-C3 were measured.The ADC values of control group C2-C3,C3-C4,C4-C5,C5-C6,C6-C7 were measured.Within-group comparisons of the spinal cord ADC values for each segment between patient and control groups were performed using analysis of variance and post hoc comparisons(SNK-q).The ADC values at the narrowest point of the patient group and control group were tested by independent sample t-test.The Pearson correlation analysis was performed between patients'C5-C6 ADC values and mJOA scores.Results The mean ADC values showed no significantly different levels in the control group.Among the ADC values at each measurement level in the patient group,except for C4-C5 and C6-C7 where the difference was not statistically significant,the remaining pair-wise comparisons all showed statisti-cally significant differences(F=24.368,P＜0.001),with the highest ADC value at C5-C6.The C5-C6 ADC value in the patient group was significantly higher compared to the control group(t=9.414,P＜0.001),with statistical significance.The ADC values at the patient stenosis showed a significant negative correlation with the mJOA score(r=-0.493,P＜0.001).Conclusion Cervical ZOOM-DWI technique can be applied to diagnose CSM,and spinal ADC values can be used as reliable imaging data for diagnosing CSM.
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BACKGROUND:Collagen is the most abundant extracellular matrix component,which is closely related to the structure and function of the extracellular matrix of skeletal muscle,but the effect and mechanism of recombinant human collagen(rhC)produced by bioengineering technology on the extracellular matrix of skeletal muscle are unclear. OBJECTIVE:To investigate the effect of rhC supplementation on the remodeling of skeletal muscle extracellular matrix after eccentric exercise,thereby revealing the possible mechanism by which rhC improves the injury of skeletal muscle extracellular matrix and promote the recovery after exercise. METHODS:A total of 104 healthy male C57 mice aged 8 weeks old were randomly divided into control group(normal saline),low-dose rhC group(0.2 g/kg),medium-dose rhC group(1.0 g/kg),and high-dose rhC group(2.0 g/kg).Two mice in each group were selected after continuous 7 days of intragastric intervention,and organs were dissected for hematoxylin-eosin staining to determine inflammatory infiltrates.On the 8th day,the remaining mice were subjected to eccentric exercise.The structural changes of the skeletal muscle extracellular matrix were observed under scanning electron microscopy immediately(0),24,48,and 96 hours after eccentric exercise.Meanwhile,grip strength,creatine kinase activity,and protein levels of matrix metalloproteinases 2,9,14 and tissue inhibitor of metalloproteinase-2 in skeletal muscle were detected by western blot assay. RESULTS AND CONCLUSION:Hematoxylin-eosin staining results indicated that short-term rhC supplementation showed no significant effects on the morphology of the heart,liver,spleen and kidney.After one-time eccentric exercise,the recovery rate of grip strength in the medium-and high-dose rhC groups was significantly increased(P＜0.01).The trend of creatine kinase changes was consistent in all groups and there was no significant difference between groups.The recovery process of the extracellular matrix in the low-dose rhC group was faster than that in the control group,and the muscle tract membrane in the medium-and high-dose rhC groups was more complete.The protein level of matrix metalloproteinase 9 in the high-dose rhC group was significantly decreased(P＜0.05).The protein levels of matrix metalloproteinase 14 in the medium-and high-dose rhC groups were significantly decreased(P＜0.05).The protein levels of matrix metalloproteinase 2 in the medium-and high-dose rhC groups were significantly decreased(P＜0.05).Tissue inhibitor of metalloproteinase-2 protein levels in the medium-and high-dose rhC groups were significantly increased(P＜0.05).The ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase-2 in each rhC group was significantly decreased(P＜0.05).To conclude,pre-supplementation of 1.0 and 2.0 g/kg rhC for 7 days can inhibit extracellular matrix degradation in skeletal muscle after exercise by modulating matrix metalloproteinases and matrix metalloproteinase inhibitors,thereby promoting recovery of skeletal muscle strength in mice.
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BACKGROUND:As a common clinical digestive disorder,irritable bowel syndrome becomes an advantageous disease of acupuncture treatment.However,the therapeutic mechanisms remain unclear.The methodological characteristics of omics coincide with the multi-target and multi-level characteristics of acupuncture,providing the possibility of revealing the principle of acupuncture in the treatment of the disease. OBJECTIVE:To investigate the pathogenesis of irritable bowel syndrome with diarrhea(IBS-D)and the effect of acupuncture at the combined points(selected based on etiologies and symptoms)on IBS-D based on proteomics. METHODS:Twelve 3-month-old male Sprague-Dawley rats were randomly divided into three groups:a control group,an IBS-D model group and an acupuncture group.The IBS-D rat models were prepared using the CAS method.After successful modeling,bilateral Zusanli points,bilateral Neiguan points and Guanyuan points were selected for acupuncture treatment in the acupuncture group,with a frequency of 120 times/minute,1 minute of acupuncture every 4 minutes,and 15 minutes of needle retention,at an interval of 1 day every 6 days,for 28 days in total.Rats in the normal control group and the model group were not given any intervention.The pressure threshold of rat abdominal retraction reflex was measured to evaluate the visceral hypersensitivity of rats.Proteomics analysis was performed using the liquid chromatography-tandem mass spectrometry-based platform.MaxQuant software,Perseus software and DAVID,KOBAS,VENNY,STRING online tools were used for the bioinformatics analysis of proteomic data.Visualization analysis was done using Cytoscape 3.7.1 software. RESULTS AND CONCLUSION:There were 47 differentially expressed proteins between the IBS-D model and control groups.Function analysis of differentially expressed proteins revealed that the pathogenic mechanism of IBS-D was associated with abnormal energy metabolism,the imbalance of colon motor function and increased visceral sensitivity.Important proteins related to IBS-D pathogenesis included Atp5a1,Atp5c1,Idh3b,Atp2a3,Pdhb,Ppp1ca and Mapk3.Sixty-one differentially expressed proteins were identified between the acupuncture group and IBS-D model group.Acupuncture at the combined points reversed the up-regulation of nine differentially expressed proteins and the down-regulation of nine differentially expressed proteins.Bioinformatics analysis revealed that acupuncture at the combined points for IBS-D could function via multi-targets and multi-pathways,reverse the damage of energy metabolism caused by IBS-D,and play a role against oxidative stress and inflammation,thereby relieving pain and regulating the imbalance of intestinal function.Important proteins related to acupuncture effects included Atp5a1,Atp5c1,Pdhb,Sars,Uqcrc2,Prdx2,Prdx4,Ppp1ca,Manf and Tmsb4x3.All these findings preliminarily illustrate the potential molecular mechanisms of IBS-D and the effect of acupuncture at the combined points in the treatment of IBS-D at the protein level,which provide a basis for the clinical application of acupuncture at the combined points.
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Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.
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BACKGROUND@#Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood.@*METHODS@#The yki -gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1 , Acly , and Fasn et al .@*RESULTS@#In this study, it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocytes. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila . Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients.@*CONCLUSION@#Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.
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Humans , Insulin-Like Growth Factor Binding Protein 3/metabolism , Culture Media, Conditioned/pharmacology , Cachexia/pathology , Gastrointestinal Neoplasms , Somatomedins/metabolism , Insulins/metabolism , LipidsABSTRACT
The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Subject(s)
Rats , Mice , Animals , Rats, Sprague-Dawley , Angiotensin II/pharmacology , Fibroblasts , Mice, Inbred C57BL , Fibrosis , Collagen/pharmacology , Collagen Type I/metabolism , RNA, Messenger/metabolism , Myocardium/pathologyABSTRACT
OBJECTIVE@#To study epidemiological characteristics and hospitalization costs of female inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing.@*METHODS@#A retrospective study was conducted to analyze electronic hospitalization summary reports of female inpatients with AECOPD in Beijing from 2013 to 2020. Clinical characteristics (age distribution and comorbidities), epidemiological characteristics (temporal and spatial distribution characteristics), hospi-talization times and costs of patients were described.@*RESULTS@#A total of 57 911 subjects in 166 hospitals were included in this study, with a mean age of (78.84±8.59) years and the highest number of patients aged 80-89 years (49.06%), followed by patients aged 70-79 years (31.08%), and the lowest number of patients under 50 years (0.41%). The proportions of patients with coronary heart disease, hypertension and heart failure were 30.60%, 30.52% and 26.54% respectively. The median number of daily hospitalizations during the study period was 18 (IQR: 16). The number of daily hospitalizations for AECOPD showed an overall growth trend over the eight years from 2013 to 2020, starting to increase significantly in 2015 and continuing to increase until 2019, then followed by a decline in 2020. The proportion of inpatient admissions was higher in winter and spring (54.09%) than that in summer and autumn (45.91%). The top three districts in terms of the proportion of total inpatient admissions were Xicheng district (14.18%), Chaoyang district (14.12%) and Fengtai district (13.47%). The density of inpatients was relatively high in the western regions, central urban areas and northeastern regions of the city, while the density of inpatients was relatively low in the near suburbs. The median number of hospital days for female patients with AECOPD was 12 days, and the median hospital costs was CNY 20 648.37. Patients from urban areas had longer hospitalization times and higher hospitalization costs than those from suburban areas (P < 0.001). Western medicine expenses accounted for the largest proportion of total hospital expenses (33.32%). During the study period, hospitalization costs exhibited an overall pattern of initial growth, followed by subsequent decline, eventually stabilizing. The differences in hospitalization costs among the patients with different comorbidities were significant.@*CONCLUSION@#Female hospitalized patients with AECOPD in Beijing were older than 70 years, often complicated by cardiovascular disease. AECOPD occurred mainly in winter and spring, with regional differences. The hospitalization costs were closely associated with the patients' age, comorbidities, and the geographicical region.
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Humans , Female , Aged , Aged, 80 and over , Inpatients , Beijing , Retrospective Studies , Pulmonary Disease, Chronic Obstructive/epidemiology , HospitalizationABSTRACT
The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.