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PURPOSE: To characterize the phenotype and genotype of a Chinese family with autosomal-dominant retinitis pigmentosa (RP) accompanied by iris coloboma. METHODS: The proband, a 34-year-old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full-field electroretinography (ffERG). Genetic analyses were conducted through whole-exome sequencing (WES) to screen for variations. RESULTS: Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR-204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members. CONCLUSIONS: In this third independent and the first Asian family, the existence of a miR-204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR-204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal-dominant pattern, including in Chinese patients, miR-204 aberrations should be considered.
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Coloboma , MicroARNs , Linaje , Retinitis Pigmentosa , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Coloboma/genética , Coloboma/patología , Pueblos del Este de Asia , Iris/anomalías , Iris/patología , MicroARNs/genética , Fenotipo , Retinitis Pigmentosa/genéticaRESUMEN
Background Coal workers' pneumoconiosis (CWP) is a serious occupational lung disease and one of the prescript occupational diseases in China. Epithelial-mesenchymal transition (EMT) is involved in the diffuse fibrosis of lung tissue of pneumoconiosis patients, and its mechanism may be related to the polarization of macrophages regulated by let-7c. Objective To investigate the effect of let-7c on the regulation of macrophage polarization in EMT in rats induced by coal dust exposure with different content of free SiO2. Methods SD rats were randomly divided into a control group, a 5% SiO2 group, a 30% SiO2 group, and a 99.9% SiO2 group, with 16 rats in each group. The rats in each group were tracheally titrated with 100 μL of 20 mg·mL−1 suspension (5% SiO2, 30% SiO2, and 99.9% SiO2) or normal saline, respectively. Alveolar lavage fluid was collected at the ends of the 1st month and the 3rd month. The relative expression levels of M1 or M2 markers, CD86 or CD206, in alveolar macrophages (AMs) were detected by immunofluorescence. The inflammation and fibrosis of lung tissue were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), E-cadherin, and vimentin were detected by Western blotting. The expression levels of let-7c and c/EBP-δ genes were detected by real-time fluorescence quantitative PCR. Results The HE and Masson staining results showed that compared with the control group, the degree of pulmonary fibrosis in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased with the increase of dust exposure time. Compared with the control group, the expressions of CD86 and CD206 in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased at the end of the 1st month (F=330.904, 146.801, P<0.05), and the expression of CD86 in each group decreased gradually at the end of the 3rd month (F=331.781, P<0.05), but the expression of CD206 increased (F=1164.190, P<0.05). At the end of the 1st month, the expressions of TGF-β1 (F=8.847, P<0.05) and vimentin (F=13.275, P<0.05) gradually increased, and the expression of E-cadherin (F=6.253, P<0.05) gradually reduced in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group. At the end of the 3rd month, the expressions of TGF-β1 (F=16.833, P<0.05) and vimentin (F=55.021, P<0.05) increased, and the expression of E-cadherin (F=12.790, P<0.05) gradually decreased in all groups. The PCR results showed that compared with the control group, the expression of let-7c mRNA in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group increased at the ends of the 1st month and the 3rd month (F=11.251, 28.136, P<0.05). The expression of c/EBP-δ mRNA decreased in all groups at the ends of the 1st month and the 3rd month (F=49.204, 177.090, P<0.05). Conclusion In response to dust stimulation, let-7c promotes EMT by modulating macrophage polarization, which is involved in the formation of pulmonary fibrosis and thus influences the progression of CWP .
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Objective To investigate the feasibility of constructing a preeclampsia(PE)risk model based on multiple exosomal micrornas(miRNA)expression levels and to verify its efficacy in predicting PE.Methods A total of 1037 pregnant women who were archived in our hospital from June 2019 to December 2021 and whose gestational weeks were less than or equal to 20 weeks were selected as the research subjects.The expression of exosomal miRNA(including miR-155-5p,miR-215-5p,miR-203a-3p,miR-199a-5p and miR-125a-3p)in all samples was detected by qRT-PCR.Then,all patients were followed up to the end of pregnancy.The occurrence of PE during the follow-up period was counted,and all samples were divided into the PE group and the control group according to results.Cox regression was used to analyze the influencing factors of PE.The multi-miRNA risk model was constructed with ggrisk package,and the predictive effect of the model on PE was evaluated by receiver operating characteristic(ROC)curve.Results By the end of follow-up on October 31,2022,974 cases were finally followed up,and the follow-up completion rate was 93.92%.Among all the 974 patients who completed the follow-up,65 patients developed PE,so they were finally divided into the PE group,and 909 cases were used as the control group.The age,pre-pregnancy BMI and waist circumference at 12 weeks of gestation were higher in the PE group than those in the control group(P<0.05).The proportions of smoking history and drinking history were higher in the PE group than those of the control group(P<0.05).The contents of triglyceride(TG),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),alanyl aminotransferase(ALT),aspartate aminotransferase(AST),platelet distribution width(PDW),mean platelet volume(MPV),miR-155-5p,miR-199a-5p and miR-215-5p were higher in the PE group than those in the control group,while contents of thyroid stimulating hormone(TSH),miR-125a-3p and miR-203a-3p were lower in the PE group than those in the control group(P<0.05).The expression levels of miR-125a-3p,miR-155-5p,miR-199a-5p and miR-215-5p were independent predictors of PE(P<0.05).The predictive risk model constructed from the above miRNAs had good predictive value in the occurrence of PE(AUC=0.998),with a sensitivity of 98.46%(63/65)and a specificity of 93.94%(854/909).Conclusion miR-125a-3p,miR-155-5p,miR-199a-5p,miR-203a-3p and miR-215-5p are significantly related to the occurrence of PE,and the PE prediction model constructed with the above five miRNAs has better effect.
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Objective:To observe any effect of repetitive transcranial magnetic stimulation (rTMS) on sleep disorders among children with cerebral palsy (CP).Methods:A total of 102 children with CP and disordered sleep were randomly divided into an experimental group and a control group, each of 51. All were given routine rehabilitation and sleep health education, but the experimental group additionally received rTMS for two weeks. The polysomnography (PSG) results of the two groups were recorded and analyzed.Results:The PSG parameters had improved greatly in both groups after the treatment. The percentage of N2 sleep (depth of sleep during light sleep) in the severe cerebral palsy group and of N3 sleep (depth of sleep during deep sleep) in the moderate cerebral palsy group had increased significantly more than in the mild cerebral palsy group, on average. After the intervention the percentages of N2 and N3 in those with mixed cerebral palsy and of N3 in those with involuntary motor cerebral palsy had increased significantly more than in those with spastic cerebral palsy, on average.Conclusion:rTMS treatment can improve the sleep disorders of children with cerebral palsy, especially N2 sleep among children with moderate to severe cerebral palsy, N3 sleep in cases of mixed or dyskinetic CP.
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Infusion misdirection syndrome(IMS)is a rare and troublesome intraoperative complication during phacoemulsification cataract surgery, which usually occurs in hydrodissection, phacoemulsification or irrigation/aspiration(I/A). Under the factors of lax zonular fibers, lens dislocation, posterior capsular rupture, the anterior segment crowding, high perfusion pressure, the infusion fluid accumulates in the vitreous cavity or behind the vitreous, leading to intraocular hypertension, shallowness or even disappearance of the anterior chamber and eventually causing the suspension of surgery. It needs to be differentiated from suprachoroidal hemorrhage(SCH), capsular block syndrome(CBS), etc. After intraoperative emergency treatments, such as rest combined with intravenous drip of mannitol, pars plana needle aspiration or vitrectomy, a favorable prognosis can be obtained. This review discusses the pathogenesis, diagnosis, emergency management, prevention and prognosis of IMS during phacoemulsification cataract surgery, with the aim of providing clinical guidance for ophthalmologists.
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ObjectiveTo explore the antidepressant effect of Sophora flavescens seed extract and its molecular mechanism. MethodA mouse depression model was established by intraperitoneal injection of lipopolysaccharide(LPS), and normal group, model group, fluoxetine group(2.5 mg·kg-1), and S. flavescens seed low, medium and high dose groups(200, 400, 800 mg·kg-1) were set up for 7 d of consecutive gavage. Then the antidepressant effect of S. flavescens seed extract was evaluated by using open field test, elevated plus maze test and forced swimming test. Pathological morphological changes in the hippocampal tissue was observed by hematoxylin-eosin(HE) staining. Protein expression levels of G1/S-specific cyclin D1(Cyclin D1), Wnt1, β-catenin and phosphorylated glycogen synthase kinase-3β(p-GSK-3β) in mouse brain tissues were detected by Western blot. Hippocampal cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL). ResultThe results of mouse behavioral experiments showed that compared with the normal group, the speed of movement in the open field and the distance of movement in the central area of the open field, and the time spent on the open arms of the elevated plus maze were significantly reduced in the model group(P<0.01), while immobility time in the forced swimming test was significantly increased(P<0.05). Compared with the model group, the S. flavescens seed medium and high dose groups had increased speed of movement in the open field test and time spent on the open arms of the elevated plus maze test(P<0.05, P<0.01), and decreased immobility time in the forced swimming test(P<0.05), the distance of movement in the central area of the open field test increased in the high dose group(P<0.05). HE staining results showed that compared with the normal group, the hippocampal neuron structure of mice in the model group was damaged. Compared with the model group, after treatment of S. flavescens seed extract, the pathological state of the mouse hippocampal neuron structure was alleviated, and the neurons increased, were neatly arranged, and the cytoplasm was clear. Western blot results showed that the protein expression levels of Wnt1 and β-catenin in mouse brain tissue were significantly decreased(P<0.01), while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly increased(P<0.01) after LPS injection. Compared with the model group, protein expression levels of Wnt1 and β-catenin in brain tissue of S. flavescens seed medium and high dose groups were significantly increased(P<0.01), while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly decreased(P<0.01). TUNEL staining results showed that the hippocampal cell apoptosis rate in the model group was significantly increased compared with that of the normal group(P<0.01), while the hippocampal cell apoptosis rate in the S. flavescens seed medium and high dose groups was significantly decreased compared with that of the model group(P<0.01). ConclusionS. flavescens seed extract can effectively improve the severity of depression in LPS-induced depressed mice, and its molecular mechanism is related to the regulation of neuroinflammation and hippocampal neuronal apoptosis mediated by Wnt/β-catenin signaling pathway.
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Statins are a class of hydroxymethylglutaryl-CoA reductase inhibitors (HMG-CoA reductase inhibitors), which are widely used to reduce blood lipid in clinic, and are especially important for the prevention and treatment of cardiovascular diseases. In recent years, many studies at home and abroad believe that statins have a unique role in tumor prevention and treatment, and have been widely concerned. In terms of epigenetic regulation mechanism, statins mainly affect the progress of tumor through DNA methylation, histone modification and miRNA regulation. In addition, statins can also achieve their anti-tumor effects by promoting tumor cell autophagy, regulating tumor cell cycle, and promoting tumor cell apoptosis and other signaling pathways. Therefore, the research on statins provides ideas for the discovery of new anti-tumor treatments. In this paper, the role of statins in the prevention and treatment of common tumors is reviewed, including its mechanism of inhibiting the occurrence and development of tumors through epigenetic regulation and other related mechanisms, as well as its clinical research status.
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Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 107 CFU/ml and 108 CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 104 CFU/ml. Detection sensitivity of Yersinia pestis ≥103 CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥103 CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 104 CFU/m3, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.
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Humanos , Sensibilidad y Especificidad , TecnologíaRESUMEN
Objective: This study aimed to investigate the epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in (Hebei, Zhejiang, Shaanxi, Hunan) 4 provinces of China and the influence of demographic and economic characteristics on them. Methods: A total of 1 747 children and adolescents aged 7-17 from a Community-based Cohort Study on Nervous System Disease in 2018 were selected. High waist circumference, central obesity, elevated TG, elevated TC, elevated LDL-C, decreased HDL-C, elevated blood pressure, elevated blood glucose, and clustering of risk factors was analyzed. χ2 test was used for univariate analysis, multivariate logistic regression was used to analyze the correlation between demographic and economic factors and risk factors, and the Cochran-Armitage trend test was used for trend analysis. Results: The detection rates of high waist circumference, decreased HDL-C, elevated blood pressure, elevated TG, elevated blood glucose, central obesity, elevated TC, and elevated LDL-C were 29.08%, 15.28%, 13.17%, 13.05%, 11.79%, 7.33%, 6.53%, and 5.15%, respectively. The rate of clustering of risk factors was 18.37%. Multivariate logistic regression analysis showed that the risk of high waist circumference in girls was higher than that in boys (OR=1.67, 95%CI: 1.26-2.22), and the risk of elevated blood glucose and clustering of risk factors was lower than that in boys (OR=0.69, 95%CI: 0.49-0.99; OR=0.72, 95%CI: 0.53-0.99). The risk of high waist circumference, decreased HDL-C, and clustering of risk factors in 13-17 years old group was higher than that in the 7-year-olds group (OR=2.24, 95%CI: 1.65-3.04; OR=1.59, 95%CI: 1.20-2.11; OR=1.75, 95%CI: 1.26-2.44), but the risk of central obesity was lower (OR=0.54, 95%CI: 0.37-0.78). The risk of elevated TC, elevated TG, and decreased HDL-C in children and adolescents in southern was higher than that in northern parts of China (OR=1.88, 95%CI: 1.25-2.83; OR=1.61, 95%CI: 1.17-2.22; OR=1.55, 95%CI: 1.19-2.04), but the risk of high waist circumference and central obesity was lower than that in northern China (OR=0.57, 95%CI: 0.43-0.75; OR=0.62, 95%CI: 0.42-0.90). The risk of decreased HDL-C in rural children and adolescents was higher than in urban children and adolescents (OR=1.36, 95%CI: 1.02-1.83). The risk of multiple risk factors increased with the increase in average monthly household income per capita and BMI level. Conclusions: High waist circumference, decreased HDL-C and elevated blood pressure were prominent cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China in 2018. The region, average monthly household income per capita, and BMI were the main influencing factors of cardio-metabolic risk factors.
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Masculino , Femenino , Humanos , Niño , Adolescente , Obesidad Abdominal/epidemiología , LDL-Colesterol , Glucemia , Estudios de Cohortes , Índice de Masa Corporal , Factores de Riesgo , Obesidad , Hipertensión , China/epidemiología , Circunferencia de la CinturaRESUMEN
Objective To investigate the association between the interleukin 10 (IL-10) gene promoter region-592A/C (rs1800872) polymorphism and hypertensive disorders of pregnancy (HDP) in Han women of Qinghai province and to determine the expression of this gene in two groups (HDP group and healthy control group) preliminarily. Methods A total of 140 HDP patients (HDP group) and 140 normal pregnant women (control group) in Qinghai Province were selected. Using blood DNA as template, the IL-10-592A/C polymorphism typing of HDP group and control group was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified by sequencing. The expression of IL-10 mRNA in the placental tissues of the two groups was detected by Real-time PCR. Plasma IL-10 levels of the two groups were detected by ELISA. Results The frequencies of AA, AC and CC genotypes of IL-10 gene in HDP group and control group were 24. 29%, 44. 29%, 31. 42% and 13. 57%, 41. 43%, 45. 00% respectively, the difference in genotype distribution between the two groups was statistically significant (P<0. 05);AA genotype frequency in HDP group(24. 29%)was higher than that of control group(13. 57%)(P<0. 05), CC genotype frequency in HDP group (31. 42%) was lower than that in control group (45. 00%) (P < 0. 05), while there was no significant difference in genotype frequency of AC between the two groups (P<0. 05); The distribution of A and C allele frequencies of IL-10592A/C polymorphism was different between the two groups, and the A allele frequency of HDP group was higher than that of control group (
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This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-β1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-β1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-β1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.
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Ratones , Masculino , Animales , Fibrosis Pulmonar/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Epimedium/metabolismo , Fibronectinas/metabolismo , Metaloproteinasa 7 de la Matriz/uso terapéutico , Metaloproteinasa 8 de la Matriz/uso terapéutico , Vimentina/metabolismo , Interleucina-6/metabolismo , Ratones Endogámicos C57BL , Pulmón , Colágeno/metabolismo , Bleomicina/toxicidad , ARN Mensajero/metabolismo , Cadherinas/metabolismoRESUMEN
Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.
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Humanos , Autofagia , Diabetes Mellitus , Neuropatías Diabéticas/complicaciones , Medicina Tradicional China , Estrés Oxidativo , Células de Schwann/patologíaRESUMEN
Multiple myeloma (MM) is a common plasma cell malignancy, accounting for the second largest hematological malignancy. Proteasome inhibitors represented by bortezomib (BTZ) have been the main treatment for patients with newly diagnosed and relapsed or refractory myeloma in nearly two decades. Although BTZ has improved the prognosis of MM patients, MM remains incurable in most patients, mainly because MM cells become resistant to BTZ. This review is to better understand the mechanism of MM resistance to BTZ and explore possible new therapeutic strategies.
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Humanos , Bortezomib/uso terapéutico , Mieloma Múltiple/patología , Inhibidores de Proteasoma/farmacología , Pronóstico , Células Plasmáticas/patología , Resistencia a Antineoplásicos , Antineoplásicos/farmacología , Línea Celular TumoralRESUMEN
OBJECTIVE@#To study the expression level of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM), its relationship with clinical indicators, prognosis and potential role.@*METHODS@#Immunohistochemical staining was used to detect the expression of NAMPT in bone marrow biopsies of patients with newly diagnosed multiple myeloma (NDMM) and patients with iron deficiency anemia (IDA) hospitalized during the same period. According to the median expression level of NAMPT, NDMM patients were divided into high expression group and low expression group. The correlation between NAMPT expression level and clinical baseline data was analyzed, and survival analysis was performed to evaluate the relationship between NAMPT expression level and prognosis. The GSE24080 and GSE19784 datasets were used to analyze the effect of NAMPT on the prognosis. Gene set enrichment analysis (GSEA) explored the possible mechanism of NAMPT involved in MM cell function.@*RESULTS@#The mean staining intensity of NAMPT in bone marrow tissue of 31 NDMM patients was 0.007±0.002, and that of 10 IDA patients was 0.002±0.002 (P < 0.05). The median expression level of NAMPT was 0.0041 in NDMM patients, and the mean staining intensity of high expression group and low expression group was 0.007±0.005 and 0.002±0.001, respectively (P < 0.001). There were certain differences in lactate dehydrogenase (LDH), C-reactive protein (CRP) and ISS staging between high expression group and low expression group (P < 0.001), while no significant differences in other indicators. The overall response rate (ORR) of high expression group was significantly lower than that of low expression group (P < 0.001). The median survival time of patients in high expression group was significantly shorter than that in low expression group (P =0.024). The results of bioinformatics analysis showed that the event-free survival (EFS) rate and overall survival (OS) rate of low NAMPT group were both higher than high NAMPT group (P =0.037, P =0.009), and NAMPT was an independent prognostic factor for EFS and OS (P =0.006, P =0.020). GSEA suggested that NAMPT might affect MM cell function through mTORC1 signaling pathway.@*CONCLUSIONS@#The expression level of NAMPT in bone marrow of NDMM patients is significantly higher than that of IDA patients, and the high expression of NAMPT may be correlated with late ISS stage, and high level of LDH and CRP. Patients with high expression of NAMPT have worse response to bortezomib and survival time may be shorter. NAMPT may be involved in the occurrence and development of MM through mTORC1 signaling pathway.
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Humanos , Mieloma Múltiple/genética , Médula Ósea/patología , Nicotinamida Fosforribosiltransferasa , Relevancia Clínica , Pronóstico , Diana Mecanicista del Complejo 1 de la RapamicinaRESUMEN
The shortage of Paridis Rhizoma promotes comprehensive utilization and development research of waste aerial parts of the original plant. The chemical compositions of the aerial parts of Paris polyphylla var. chinensis were clarified based on the ultrahigh performance liquid chromatography tandem quadrupoles time of flight mass spectrometry(UPLC-QTOF-MS/MS) in the previous investigation, and a series of flavonoids and steroidal saponins were isolated. The present study continued the isolation and structure identification of the new potential compounds discovered based on UPLC-QTOF-MS/MS. By using silica gel, ODS, flash rapid preparation, and other column chromatography techniques, combined with prepared high performance liquid chromatography, five compounds were isolated from the 75% ethanol extract of the aerial parts of P. polyphylla var. chinensis, and their structures were identified by spectral data combined with chemical transformations, respectively, as(23S,25R)-23,27-dihydroxy-diosgenin-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-glucopyranoside(1),(25R)-26-O-β-D-glucopyranosyl-furost-5-en-3β,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside(2),(25R)-27-O-β-D-glucopyranosyl-5-en-3β,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranoside(3),(25R)-27-O-β-D-glucopyranosyl-5-en-3β,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-glucopyranoside(4), and aculeatiside A(5). Among them, compounds 1-4 were new ones, and compound 5 was isolated from P. polyphylla var. chinensis for the first time.
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Espectrometría de Masas en Tándem , Saponinas/análisis , Liliaceae/química , Cromatografía Líquida de Alta Presión , Rizoma/química , Melanthiaceae , Estructura MolecularRESUMEN
Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-β-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-β-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.
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Glicósidos/química , Medicina Tradicional China , Espectrometría de Masas en Tándem/métodos , Coptis chinensis , Medicamentos Herbarios Chinos/química , Alcaloides/análisis , Extractos Vegetales/química , Antineoplásicos , Plantas Medicinales/química , Agua , Cromatografía Líquida de Alta Presión/métodos , Coptis/químicaRESUMEN
Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.
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Humanos , Animales , Ratones , Medicina Tradicional China , Obesidad/tratamiento farmacológico , Tejido Adiposo/patología , Inflamación/tratamiento farmacológico , Macrófagos , Ratones Endogámicos C57BLRESUMEN
Objective:To evaluate the efficacy of low-dose radiotherapy in patients with advanced hypopharyngeal cancer without high-risk factors.Methods:Clinical data of 235 patients diagnosed with advanced hypopharyngeal cancer treated in Department of Head and Neck Surgery of Shandong Provincial ENT Hospital from December 2013 to August 2018 were retrospectively analyzed. All patients were divided into two groups: low-dose radiotherapy group (50 Gy, n=158) and high-dose radiotherapy group (>60 Gy, n=77). Clinical baseline characteristics, treatment, follow-up and survival of patients were collected. Survival curve was delineated using the Kaplan-Meier method, and the differences in survival between two groups were calculated using the log-rank test. Clinical baseline characteristics between two groups were compared by χ2 test. Univariate and multivariate analyses of prognostic factors were conducted by logistic regression model. Results:The median follow-up time was 45 months (5-94 months). The 3-year overall survival (OS) rate of the whole group was 68.5%, and 70.3% and 64.9% in the low-dose and high-dose groups, respectively ( P=0.356). The 3-year progression-free survival (PFS) rate of the whole group was 64.3%, and 65.8% and 61.0% in the low-dose and high-dose groups, respectively ( P=0.361). Univariate analysis showed that T stage, N stage, lesion location and degree of pathological differentiation significantly affected clinical prognosis (all P<0.05), whereas there was no significant relationship between age, sex, radiotherapy dose, interval between surgery and radiotherapy and survival. Multivariate analysis showed that T stage, N stage and the degree of pathological differentiation were the independent prognostic factors (all P<0.05) of the 3-year OS and PFS. Sex, radiotherapy dose and interval between surgery and radiotherapy were not correlated with OS and PFS. Conclusion:This study showed that for hypopharyngeal cancer patients without positive surgical margins and extracapsular extension, postoperative radiotherapy at a dose of 50 Gy given to tumor bed and selective lymph node drainage area does not compromise local disease control and OS.
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Objective:To explore the interventional effect of β-sitosterol on ovalbumin(OVA)-induced allergic asthma rats and its potential mechanism.Methods:SD male rats were randomly divided into normal group(CON),model group(M),positive drug dexamethasone group(DEX,0.075 mg/kg)and β-sitosterol group(Sit,50 mg/kg).A rat model of allergic asthma was estab-lished by intraperitoneal injection of OVA with aluminum hydrogen solution,and nebulized inhalation of OVA to stimulate.Rats were given intragastric administration 30 min before aerosol challenge,and after continuous administration for 7 days,the indicators of cough and asthma and tracheal phenol red excretion were detected.HE staining was used to observe pathological changes of lung tis-sue.Flow cytometry was used to detect reactive oxygen species(ROS)generation,apoptosis level and ratios of Th17 and Treg cells in peripheral blood.Biochemical method was used to detect contents of MDA,and activities of T-SOD and GSH-Px in rat lung tissues.ELISA was used to detect levels of Th17 and Treg-related cytokines(TNF-α,IL-4,IL-6,IL-17A,and IL-35).Results:Compared with model group,β-sitosterol significantly prolonged the incubation period of cough and gasp in rats with allergic asthma,reduced the frequency of cough and gasping,and promoted the excretion of phenol red in trachea;significantly reduced inflammatory infiltration in lung tissue of asthmatic rats;observably reduced MDA content in lung tissue,ROS of primary lung cell and apoptosis levels of asthmatic rats,increased the activities of T-SOD and GSH-Px;markedly reduced proportion of Th17 cells and levels of pro-inflammatory cyto-kines TNF-α,IL-4,IL-6 and IL-17A,increased proportion of Treg cells and levels of anti-inflammatory cytokine IL-35.Conclusion:β-sitosterol can ameliorate airway inflammation and oxidative damage in OVA-induced allergic asthmatic rats,and its mecha-nism may be related to the regulation of β-sitosterol on Th17/Treg immune imbalance and oxidative stress response.
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This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.