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Metabolic associated fatty liver disease (MAFLD) is a liver disease with hepatocyte steatosis caused by metabolic disorders, which is closely related to obesity, diabetes, metabolic dysfunction, and other factors. Its pathological process changes from simple steatosis, liver inflammation to non-alcoholic steatohepatitis (NASH), and then leads to liver fibrosis, cirrhosis, and liver cancer. At present, no specific therapeutics are available for treatment of MAFLD targeting its etiology. Celastrol is the main active component of the traditional Chinese medicine Celastrus orbiculatus Thunb. In recent years, it has been found that celastrol shows important medicinal value in regulating lipid metabolism, reducing fat and weight, and protecting liver, and then ameliorates MAFLD. This article reviews the related research progress of celastrol in the prevention and treatment of MAFLD, so as to provide a reference for the comprehensive development and utilization of celastrol.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/patologia , Triterpenos Pentacíclicos/metabolismo , ObesidadeRESUMO
Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF-7, MDA-MB-453, MDA-MB-231, and SKBR3 cells compared to normal mammary epithelial cells MCF-10A while miR-448 was decreased. We found that downregulation of NEAT1 was able to inhibit the growth of breast cancer cells and miR-448 mimic exerted the similar function. Bioinformatics analysis and dual luciferase reporter assays confirmed the negative correlation between NEAT1 and miR-448 in vitro. In addition, ZEB1 was predicted as a novel mRNA target of miR-448. Overexpression of NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting miR-448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1 levels while miR-448 mimic can repress ZEB1. It was speculated in our study that NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by sponging miR-448 in breast cancer. To conclude, we uncovered that NEAT1 participated in breast cancer progression by regulating miR-448 and ZEB1. NEAT1 can be provided as a vital biomarker in breast cancer diagnosis and treatment therapy.
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Neoplasias da Mama/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Invasividade NeoplásicaRESUMO
For a long time, hydrogen (H2) has been considered as a physiological inert gas. However, recent studies have demonstrated that molecular H2 exerts significant therapeutic effects on various disease models due to its antioxidative, anti-inflammatory and anti-apoptotic capabilities, which have also been well confirmed in many clinical trials. Cardiovascular and cerebrovascular diseases (CCVDs) are the leading cause of death in the world, constituting a serious threat to human life and public health. In this paper, we reviewed the latest research progress of the biomedical effects of H2 in CCVDs and its possible molecular mechanisms, in the hope of providing new clues for the treatment of some CCVDs.
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Doenças Cardiovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Hidrogênio/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/prevenção & controle , HumanosRESUMO
To evaluate the protective effects of α-lipoic acid on the kidneys of Goto-Kakisaki (GK) diabetic rats, ten GK diabetic rats were randomly divided into a diabetic control group and a lipoic acid-treated diabetic group with α-lipoic acid 35 mg·Kg-1 intraperitoneal injections. Four healthy Wistar rats served as normal controls. Malonaldehyde (MDA), ascorbic acid (vitamin C), vitamin E, glutathione (GSH) and superoxide dismutase (SOD) levels in renal homogenate, and urine protein excretion were measured. The expression of mRNA for NF-κB, NADPH oxidase subunits p22phox and p47phox in renal tissue was examined by realtime PCR. Pathological changes in renal tissue were evaluated by light and electron microscopy. There were significant increases in urine protein excretion, MDA levels and the expression of mRNA of NF-κB, p22phox and p47phox, and significant decreases in GSH, SOD, vitamin C and vitamin E levels in the diabetic control group compared with the normal control group. Pathological changes of renal tissue were more progressive in the diabetic control group than in the normal control group. All the parameters above were improved in the α-lipoic acid-treated diabetic group. Oxidative stress is increased in the kidney of type 2 diabetic GK rats. It is associated with the progression of diabetic nephropathy. α-lipoic acid can protect renal function in diabetic rats via its antioxidant activity.
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Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ácido Tióctico/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Glutationa/metabolismo , Rim/fisiopatologia , Masculino , Malondialdeído/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Proteinúria/complicações , Ratos Wistar , Superóxido Dismutase/metabolismo , Ácido Tióctico/uso terapêuticoRESUMO
Objective: To analyze the efficacy of mycophenolate mofetil (MMF) and glucocorticoid administration in patients with thyroid-associated ophthalmopathy (TAO). Methods: Sixty patients with moderate to severe TAO treated in Jingzhou Central Hospital from January 2022 to June 2022 were selected and enrtolled in this study. The subjects were divided into experimental group (n=30) and control group (n=30) based on the random number table method. Glucocorticoid pulse therapy was provided in the control group, while MMF was given in the experimental group on the basis of Control group. Clinical activity score (CAS), quality of life (QOL), visual acuity, eyelid fissure width, intraocular pressure, and degree of exophthalmos were observed at the time of admission and at the 12th week and 24th post-treatment weeks. We compared the immune function (TRAb, IL-6, and CD4+/CD8+) of the two groups pre-treatment and 24 weeks post-treatment, and evaluated the clinical therapeutic effect. Results: The clinical effective rates at 12 and 24 weeks in the experimental group were higher (73.3% and 83.3%) than those in the control group (46.7% and 60.0%) (P <0.05). After 12 weeks of treatment, patients' CAS scores, and bilateral lid fissure width decreased and right eye visual acuity increased in the control group compared with those before treatment (P < 0.05); further, after 24 weeks of treatment, patients' QOL scores and bilateral visual acuity increased and CAS scores, bilateral lid fissure width and proptosis decreased compared with those before treatment, and patients' QOL scores, CAS scores and bilateral proptosis improved more than those at 12 weeks of treatment (P <0.05). Additionally, greater improvements were observed in the patients' QOL and CAS scores, and proptosis after 24-week treatment than after 12-week treatment (P<0.05). In the experimental group, the QOL score and binocular visual acuity increased, whereas the CAS score, intraocular pressure, lid width, and proptosis decreased after 12 weeks of treatment as compared to the values of these parameters in the pre-treatment period (P < 0.05); after 24 weeks of treatment, greater improvements were established in the ocular-related indexes improved compared to the pre-treatment period and after 12 weeks of treatment (P < 0.05). After 12 weeks of treatment, the patients in the experimental group had more considerable improvements in the right visual acuity, right intraocular pressure, and left lid fissure width than the control group (P < 0.05); at 24 weeks of treatment, patients in the experimental group had greater improvements in the QOL score, bilateral visual acuity, intraocular pressure, bilateral lid fissure width, and bilateral proptosis than the control group (P < 0.05). No significant differences were found in the values of TRAb, IL-6, and CD4+/CD8+ between the two groups before treatment (P>0.05); the values of TRAb, IL-6, and CD4+/CD8+ in the experimental group was significantly lower than those before treatment and in the control group after 24weeks of treatment. (P>0.05). No statistically significant difference was observed in the incidence of liver damage and menstrual disorders between the two groups during the 24 weeks of treatment (P>0.05). Conclusion: The combination of oral MMF and glucocorticoid shock therapy is an effective drug for the treatment of patients with moderately active TAO.
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Exoftalmia , Oftalmopatia de Graves , Humanos , Glucocorticoides/efeitos adversos , Oftalmopatia de Graves/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Qualidade de Vida , Interleucina-6 , Exoftalmia/tratamento farmacológico , Resultado do TratamentoRESUMO
Acute kidney injury (AKI) is the major complication of rhabdomyolysis (RM) clinically, which is usually mimicked by glycerol injection in basic research. Oxidative stress, inflammatory response and apoptosis are recognized to play important roles in development of this disease. Recently, numerous studies have reported the therapeutic effects of molecular hydrogen (H2) on oxidative stress and inflammation-related diseases. Here, the effects of H2 against glycerol-induced AKI and the underlying mechanisms were explored in rats. Low (4%) and high (67%) concentrations of H2 were prepared using a self-made device to investigate the dose-response. After 72 hours of glycerol injection (8 mL/kg), we found that glycerol triggered oxidative stress, inflammatory reactions, and apoptotic events. These caused subsequent renal damage, evidenced by a significant reduction of antioxidases and up-regulation of the relevant damaged biomarkers. H2 inhalation reversed the above alterations and exerted renoprotective effects. Interestingly, for RM/AKI-related factors, no consistent dose-response benefits of H2 were observed. However, higher concentration of H2 inhalation improved histological and morphological changes better. This study suggests that H2 is a potential alternative therapy to prevent or minimize RM induced AKI possibly via its antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic properties.
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Injúria Renal Aguda , Rabdomiólise , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose , Biomarcadores , Glicerol/toxicidade , Hidrogênio/efeitos adversos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Necroptose , Estresse Oxidativo , Ratos , Rabdomiólise/induzido quimicamente , Rabdomiólise/complicações , Rabdomiólise/tratamento farmacológicoRESUMO
Cancer neuroscience has emerged as a burgeoning field for the investigation of cancer-nervous system interactions. Perineural invasion (PNI) is defined as the presence of cancer cells that surround and/or invade the nerves infiltrating the tumor microenvironment. PNI is closely associated with increased tumor recurrence and diminished survival in many cancer types. Based on diverse in vitro, ex vivo, and in vivo models, mounting evidence suggests that the reciprocal crosstalk between nerves and cancer cells drives PNI, which is mediated by several factors including secreted neurotrophins, chemokines, exosomes, and inflammatory cells. Typical in vitro models using dorsal root ganglia (DRG) cells cocultured with cancer cells or other cell types allow the study of isolated factors. Ex vivo PNI models created by cocultivating cancer cells with explanted vagus and sciatic nerves enable the study of neuroaffinity in a time-saving and cost-efficient manner. In vivo models such as genetically engineered mouse models (GEMMs) and the chicken embryo chorioallantoic membrane (CAM)-DRG model, provide the nerve microenvironment needed to recapitulate the complex pathophysiological processes of PNI. Here, we summarize the current methods commonly used for modeling PNI and discuss the inherent pros and cons of these approaches for understanding PNI biology.
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Neoplasias Pancreáticas , Animais , Movimento Celular , Embrião de Galinha , Humanos , Camundongos , Modelos Teóricos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/patologia , Microambiente TumoralRESUMO
Medical effects of hydrogen have been reported in many studies. Due to difficulties in measuring hydrogen concentration in vivo after intake and high explosive risks of hydrogen, studies about dose-response relationships and tissue concentrations of hydrogen are few. Here, for the first time, we monitored real-time hydrogen concentrations in different tissues in rats including brain, liver, spleen, kidney, thigh muscle, inguinal white adipose tissue, and gonadal white adipose tissue after inhaling different concentrations of hydrogen (4%, 42%, and 67%) using an electrochemical sensor. Hydrogen concentrations in the same tissue showed a dose-dependent response. The equilibrium concentration values were highest in the brain and lowest in the thigh muscle. The saturation and desaturation curves changed more slowly in the thigh muscle and white adipose tissues than in other tissues. These results provide fundamental information for the selection of hydrogen dose applications in basic research and clinical trials. The experiments were approved by the Laboratory Animal Ethics Committee of Shandong First Medical University & Shandong Academy of Medical Sciences (No. 2020-1028) on March 18, 2020.
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Encéfalo , Hidrogênio , Abdome , Animais , Humanos , Microeletrodos , RatosRESUMO
BACKGROUND: This study was aimed to compare the sensitivity of transrectal ultrasound (TRUS) guided systematic biopsy (TRUS-SB), superb microvascular imaging guided targeted biopsy (SMI-TB), and elastography ultrasound guided targeted biopsy (EU-TB) in detecting prostate cancer (PCa). METHODS: One hundred and eighty-four patients with suspicious PCa were randomly divided into two groups, SMI-TB group (n=92) and EU-TB group (n=92). All the patients received a 2-core SMI-TB or a 2-core EU-TB before receiving a 12-core TRU-SB depending on the group. The 2-core SMI-TB was conducted at the most increased vascularity areas rated by a radiologist on a semi-quantitative criterion. The 2-core EU-TB was performed at the dark blue areas that identified as suspicious areas. The PCa detection rate was compared among TRUS-SB, SMI-TB, and EU-TB in the total population and in two groups. RESULTS: PCa was detected in 65 out of 184 patients. The SMI-TB group patients received 1,272 cores in total with a positive rate of 23.81% (40/168) for SMI-TB cores and 4.17% (46/1,104) for TRUS-SB cores. The EU-TB group patients received a total of 1,262 cores with a positive rate of 31.01% (49/158) for EU-TB cores and 5.34% (59/1,104) for TRUS-SB cores. Targeted cores (27.30%, 89/326) achieved significantly higher sensitivity in PCa detection than systematic cores (4.76%, 105/2,208) (SMI-TB vs. TRUS-SB: OR 7.188, P<0.001; EU-TB vs. TRUS-SB: OR 7.962, P<0.001). CONCLUSIONS: Superb microvascular imaging and elastography ultrasound guided targeted biopsy may result in higher prostate cancer detection rate as adjunct to gray-scale ultrasound guided systematic biopsy. However, targeted biopsy alone is not sufficient to detect PCa, compared with systematic biopsy.
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AIM To identify the chemical components of Longmu Qingxin Mixture by UPLC-Q-TOF-MS and study its material basis for the treatment of attention deficit hyperactivity disorder.METHODS The sample was detected by mass spectrometry in positive and negative ion mode on a Waters CORTECS? UPLC? T3 chromatographic column.The data were analyzed with Peakview 1.2 software and matched with the Natural Products HR-MS/MS Spectral Library 1.0 database,and the components were identified in combination with literature reports.The material basis of Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder was analysed according to the identified components.RESULTS Forty chemical components were identified,including 11 flavonoids,6 monoterpene glycosides,4 triterpene saponins,3 phenolic acids,6 alkaloids etc.,which mainly derived from Radix Astragali,Radix Paeoniae Alba,Radix Scutellariae,licorice root,Ramulus Uncariae cum,etc.,baicalein,formononetin,astragaloside Ⅳ and rhynchophylline may be the material basis for the therapeutic effect of Longmu Qingxin Mixture.CONCLUSION UPLC-Q-TOF-MS can quickly identify the chemical components of Longmu Qingxin Mixture.Flavonoids,triterpene saponins and alkaloids may be the material basis for Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder,which can provide the basis for its material basis research,quality standard establishment and pharmacological study of the dismantled formula.
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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 treatment strategy for complex Schatzker Ⅳ tibial plateau fracture.@*METHODS@#Forty-one patients with complex Schatzker type Ⅳ tibial plateau fractures were treated from January 2016 to January 2021, including 28 males and 13 females, aged from 19 to 65 years old with an average of (35.3±19.8) years old. Individualized treatment plan was developed according to preoperative imaging characteristics, medial surgical approach was mainly combined with other auxiliary incisions. Posteromedial inverted L approach was used in 18 patients, posteromedial approach and anterolateral extended approach in 19 patients, and posteromedial approach with anterolateral and lateral condylar osteotomy in 4 patients. Articular surface and facture healing were observed, range of knee joint motion was measured at 12 months after opertaion, and function of knee joint was evaluated by Lysholm scoring system.@*RESULTS@#Forty-one patients were followed up for 12 to 26 months with an average of (13.3±6.8) months. Twenty-nine patients and 10 patients were obtained complete fracture healing at 6 and 12 months after operation respectively, and fracture healing time was 4 to 13 months with an average of (5.0±3.7) months. Two patients occurred posterior medial internal fixation failure and varus deformity of knee joint, and the fracture healed and varus deformity was corrected after the second operation. Range of knee joint motion was (118±29) °, and Lysholm score was(83.0±16.0) points.@*CONCLUSION@#Individualized treatment should be reasonably selected for complex Schatzker Ⅳ tibial plateau fractures, the characteristics of lateral plateau fractures are an important reference for selecting surgical approaches, the effective fixation of posteromedial bone blocks should be pay full attention, and the overall treatment results are satisfied.
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Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Adolescente , Fraturas do Planalto Tibial , Placas Ósseas , Fraturas da Tíbia/cirurgia , Resultado do Tratamento , Articulação do Joelho/cirurgia , Fixação Interna de Fraturas/métodos , Estudos RetrospectivosRESUMO
ObjectiveTo investigate the influencing factors of intestinal metaplasia or atypical hyperplasia in chronic atrophic gastritis (CAG) patients and establish a prediction model. MethodThe clinical records and laboratory examination data of 335 CAG patients treated in the department of gastroenterology of the Second Affiliated Hospital of the Anhui University of Chinese Medicine from June 2016 to June 2021 were collected. Single and multiple Logistic regression analyses were used to explore the influencing factors of intestinal metaplasia or atypical hyperplasia in CAG patients by SPSS 26.0. A prediction model was constructed based on the data of the related influencing factors. In addition, 115 CAG patients diagnosed in the First Affiliated Hospital of Anhui Medical University from June 2019 to June 2021 were selected as external validation samples to verify and evaluate the prediction efficiency of the constructed prediction model. ResultMultiple Logistic regression analysis showed that pepsinogen Ⅰ[odds ratio(OR) 0.994,95% confidence interval(CI) (0.990,0.999),P<0.05],the number of focus[OR 6.765,95% CI(3.831,11.945),P<0.01], and Helicobacter pylori (Hp) infection[OR 0.546,95% CI(0.335,0.888),P<0.05] were independent risk factors for intestinal metaplasia or atypical hyperplasia in CAG patients(P<0.05). The formula of the prediction model is as follows:P=-1.558+0.606×Hp infection-0.006×pepsinogen Ⅰ+1.912×the number of focus. The receiver operating characteristic (ROC) curve showed the specific parameters as below: the area under the ROC curve of 0.76,the Youden index of 0.443,the best cut-off value of 0.52,sensitivity of 0.533,and specificity of 0.910. The prediction model was applied to the data of patients in the validation group for validation,and the predictive efficiency of the model was tested by decision curve analysis (DCA). The results showed that the model had a good fit and high predictive value. ConclusionPepsinogen Ⅰ,the number of focus, and Hp infection are independent risk factors for intestinal metaplasia or atypical hyperplasia in CAG patients. The prediction model constructed based on these factors has a good fit and high predictive value,which can provide references for the classification of CAG patients and the formulation of individual treatment protocols.
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Guanosine triphosphate cyclohydrolase (GTP cyclohydrolase,Gch) is a protease with a GTP- cyclohydro domain, which is widely found in vertebrates and invertebrates.Mammals and birds only have Gch 1.In teleost and amphibian, other two paralogs (Gch2 and Gch3) also exists besides Gchl, which also displayed functional differences.Gch is a rate-limiting enzyme that ultimately synthesized the tetrahydrobiopterin (BH4) using guanosine triphosphate as a substrate.BH4 is an essential coenzyme of aromatic amino acid hydroxylase and contributes to the synthesis of various hormones and neurotransmitters.The Gch is an initial step in the catalysis of various pterin biosynthesis and plays important roles in a series of physiological and pathological processes, such as skin pigmentation, ocular pigmentation, methotrexate, folic acid, and tetrahydrobiopterin.The physiological function of Gch is inextricably linked to the biosynthesis of BH4.As the only rate-limiting enzyme in BH4 biosynthesis, the activity of Gch is a useful indicator for the development of neurons and pigment cells.Besides, it is also an important marker of pigment synthesis and neurotransmitter biosynthesis.Nowadays, the functions of Geh in pathogenesis of tumor and cardiovascular diseases have been widely concerned, while the researches on the pigmentation and color formation are mainly concentrated in insects, and rarely in teleost.Therefore, this article summarized the characteristics of Gch genes, protein and the functions of Gch in fish coloration, which has important guiding significance for further illustration the mechanism of Gch in teleost pigmentation and fish color genetic improvements.
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OBJECTIVE@#To analyze the changes and characteristics of pediatric outpatient visits in a general hospital before and after the coronavirus disease (COVID-19) epidemic.@*METHODS@#Based on the registration data of pediatric outpatient visits in the information system (HIS)of Beijing Tsinghua Changgung Hospital, from January 1 2018 to December 31 2020, aged 0 to 16 years, we analyzed the changes of outpatient visits before and after the epidemic, focusing on respiratory infection including influenza. The relationship between the outpatient visits and age and quarterly distribution were also studied.@*RESULTS@#(1) Respiratory infection accounted for the majority of outpatient visits in 2018 and 2019 (60.6% and 60.5%, respectively). Non-respiratory infection accounted for the main proportion of outpatient visits in 2020, while respiratory infection accounted for only 47.4%. Annual respiratory infection visits, respiratory infectious diseases visits especially influenza visits all decreased significantly in 2020 compared with that in 2018 and 2019 (P < 0.05). (2)Respiratory infection visits were highest in the infant group, lowest in the school age group (P < 0.05) and highest in the fourth quarter each year. It decreased significantly in the second quarter of 2020 with statistical significance when compared with the other quarters of 2020(P < 0.05). (3)Influenza accounted for the highest proportion of respiratory infectious diseases visits in each year. It was highest in first quarter, which was significantly different from the other quarters of the year (P < 0.05). There were different distributions of influenza visits throughout 2018 and 2019, while it was only distributed in the first quarter and 99% in January in 2020.@*CONCLUSION@#The respiratory infection and influenza visits have decreased significantly in our pediatric outpatient department after the COVID-19 epidemic, which is considered closely related to the lifestyle and personal protection after the epidemic. It is recommended that health education on respiratory infection and influenza prevention should be strengthened, especially in winter and spring, to promote the development of good respiratory and hand hygiene habits.
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Criança , Humanos , Lactente , COVID-19 , Hospitais Gerais , Influenza Humana/epidemiologia , Pacientes Ambulatoriais , Pandemias , SARS-CoV-2RESUMO
Cardiovascular diseases (CVDs) and malignant tumors are the main causes of death worldwide. The etiology study of CVDs and malignant tumors has found a series of widely recognized risk factors. Medical practice and medical theory usually focus on one of the diseases, but more and more evidence reveals that malignant tumors usually involve the cardiovascular system, thus leading to thromboembolism, heart failure, etc. Anti-cancer treatment proves to induce CVDs, while CVDs seem to increase the risk of malignant tumors. This situation requires researchers to conduct further combined crossover study on both CVDs and malignant tumors. In this review, we discuss the potential common risk factors of cardiovascular diseases and malignant tumors, the pathological and physical mechanism of the two kinds of diseases, the cardiac toxicity induced by tumor therapy and the impact of cardiovascular drugs on cancer from the perspective of cardio-oncology, and in the endput forward the prospect of prevention and treatment.
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OBJECTIVE Diabetes-induced endothelial cell (EC) dysfunction and neovasculariza-tion impairment constitute vascular complications with limited treatment regimens.Transcription factor FOXO1 is a key angiogenic regulator and plays a pathologic role in progression of diabetes.The pres-ent study was designed to determine the involvement of FOXO1 in impaired EC function and post-isch-emic neovascularization in diabetes and investigate underlying mechanisms.RESULTS We found that FOXO1-selective inhibitor AS1842856 improved blood flow recovery and capillary density in ischemic hindlimb,and rescued the delay of wound closure with a concomitant augmentation of mean perfusion rate in diabetic mice. In vitro,treatment with AS1842856 or FOXO1 siRNA abrogated high glucose-in-duced apoptosis and ameliorated capillary tube formation in human umbilical vein endothelial cells(HU-VECs). FOXO1 inhibition relieved alterations in mitochondrial networks and significantly suppressed the over production of mitochondrial reactive oxygen species(mtROS)induced by high glucose in ECs. Expression of dynamin-relatedprotein-1 (Drp1) and phosphorylation at Ser616, a protein required for mitochondrial fission, were enhanced by hyperglycemia, which could be neutralized by FOXO1 inhibition. Moreover, the transcription of Rho-associated coiled-coil containing protein kinase 1 (ROCK1), which phosphorylates Drp1 at Ser616, was shown by luciferase assay to be directly regulated by FOXO1. CONCLUSION These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and func-tion in ECs,and FOXO1 may serve as a therapeutic target for microvascular complications of diabetes.
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Aquaporin 1 (AQP1), the first water channel protein discovered among the aquaporin family, is a hydrophobic transmembrane protein involved in transcellular water movement. Recent evidence shows that AQP1 plays a role in tumor cell proliferation and migration, angiogenesis and tumor development and progression, representing a potential therapeutic target. In this review, we discuss the structures, functions and inhibitors of AQP1, as well as the involvement of AQP1 in tumor development and progression.
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In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.