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OBJECTIVE To compare anti-ischemic stroke （IS） effect of different extraction parts from Gastrodia elata， and to provide reference for screening the anti-IS effective parts of G. elata. METHODS G. elata was extracted and separated by ethanol reflux extraction and ethyl acetate extraction. The rat model of diffuse cerebral thrombosis was induced by internal carotid artery injection of arachidonic acid （AA）； the anti-IS effect of G. elata powder， ethanol extract of G. elata， residue of ethanol extract of G. elata， ethyl acetate extract of G. elata， residue of ethyl acetate extract of G. elata， gastrodin and aspirin （positive control drug） were investigated with the content of Evans blue （EB） in the ischemic brain tissue as index. RESULTS Compared with model group， aspirin， ethanol extract of G. elata and ethyl acetate extract of G. elata could significantly decrease the content of EB in the ischemic brain tissue of model rats （P＜0.05）. G. elata powder had the tendency to reduce the content of EB in the ischemic brain tissue of model rats， without statistical significance （P＞0.05）. The residue of ethanol extract of G. elata， residue of ethyl acetate extract of G. elata and gastrodin had little effect on the content of EB in the ischemic brain tissue of model rats. CONCLUSIONS Both ethanol extract of G. elata and ethyl acetate extract of G. elata have anti-IS effects， which are stronger than that of G. elata powder.
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Objective@#To investigate the epidemiological characteristics of overseas imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021, so as to provide insights into the prevention and control of overseas imported arthropod-borne infectious diseases.@*Methods@#The data pertaining to imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System, and the temporal distribution, regional distribution, population distribution, sources, diagnosis and treatment of imported dengue fever and malaria cases were descriptively analyzed.@*Results@#Totally 4 332 overseas imported dengue fever cases and 2 011 overseas imported malaria cases were reported in Yunnan Province form 2015 to 2021, which accounted for 30.09% of all reported dengue fever cases and 98.53% of all reported malaria cases. The number of overseas imported dengue fever and malaria cases peaked from August to November (83.13% of all imported dengue fever cases) and from April to July (59.08% of all imported malaria cases), and the cases were predominantly reported in Dehong Prefecture (50.99% and 58.88%), with farmers as the predominant occupation (40.21% and 67.93%). The dengue fever and malaria cases were mainly imported from Southeast Asia (99.04% and 88.21%), and the proportions of definitive diagnosis of dengue fever and malaria were 88.33% and 97.80% at township hospitals, respectively.@*Conclusions@#The number of overseas imported dengue fever and malaria cases peaked from August to November and from April to July in Yunnan Province from 2015 to 2021, and the cases were predominantly reported in Dehong Prefecture and imported from Southeast Asia, with farmers as the predominant occupation.
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ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.
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AIM: To compare the visual function of low-vision patients with primary retinal pigmentosa(RP)before and after wearing amber filter.METHODS: Self-control before and after study. A total of 30 patients(60 eyes)with low vision who were diagnosed with primary RP in the ophthalmology clinic of Xi'an No.1 Hospital from August 2021 to March 2022 were collected. The uncorrected distance visual acuity(UCDVA), best-corrected distance visual acuity(BCDVA), uncorrected near visual acuity(UCNVA), best-corrected near visual acuity(BCNVA), visual field and Farnsworth-Munsell(FM)-100 color visions were recorded before and after wearing amber filter. The contrast sensitivity(CS)in three visual environments including bright room, darkroom and darkroom with glare was measured and recorded respectively, and the changes of those parameters were analyzed before and after wearing filter.RESULTS: UCDVA and BCDVA after wearing the filter were better than those before wearing(t=-2.32, P&#x003C;0.001; t=-6.77, P&#x003C;0.001), while there was no statistically significant difference in UCNVA and BCNVA before and after wearing filter. The visual field index(VFI)after wearing filter was lower than that before wearing(t=8.62, P&#x003C;0.001), and the mean defect(MD)of visual field was greater than that before wearing(t=7.73, P&#x003C;0.001). FM100 color chess test showed that both total error score(TES)and partial error score(PES)in multiple regions were higher than those before wearing filter(P&#x003C;0.001). After wearing, the CS of each frequency band in the environment of bright room and darkroom with glare was higher than that before wearing(P&#x003C;0.001), and there was no statistically significant difference in each frequency band before and after wearing amber filter under the environment of darkroom without glare.CONCLUSION: Patients with low vision of primary RP showed improved UCDVA and BCDVA, but unchanged UCNVA and BCNVA after wearing amber filter, while the visual field and color discrimination were worse than those before wearing filter. The CS of the bright room and darkroom with glare environment was improved than before wearing filter, while there were no significant changes in CS under darkroom without glare.
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Objective:To construct and validate a nomogram predictive model for readmission risk within 1 year of children with type 1 diabetes.Methods:A total of 395 children with type 1 diabetes who were hospitalized in four hospitals in Xi′an City from February 2019 to February 2021 were selected as the research subjects. The children were divided into training set ( n = 219) and verification set ( n = 175) in 5∶4 ratios. A nomogram prediction model for readmission risk within 1 year of children with type 1 diabetes was constructed based on the training set data, and internal validation was carried out. The external validation was carried out based on validation set data. Results:A total of 85 (21.5%) children were readmitted within 1 year. Mean glycohemoglobin A1c ≥ 7.5%, co-infection, complications of diabetes, and family history of diabetes were risk factors for readmission within 1 year of children with type 1 diabetes ( OR values were 4.010 - 5.510, P<0.05), and age of onset >7 years old was a protective factor ( OR = 0.070, P<0.05). The internal verification of nomogram model showed that the area under ROC curve was 0.778 (95% CI 0.703- 0.853), and the observed curve in calibration curve was basically consistent with the predicted curve. The external verification showed that the area under ROC curve was 0.748 (95% CI 0.642- 0.854), and the observed curve in calibration curve was basically consistent with the predicted curve. Conclusions:The nomogram predictive model for readmission risk within 1 year of children with type 1 diabetes is scientific and practical, and has certain clinical value in guiding targeted prevention and intervention of readmission of children with type 1 diabetes within one year.
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The paper takes the shared terms of tongue manifestations in the book World Health Organization International Standard Terminologies on Traditional Medicine in the Western Pacific Region.2007 and ISO 23961-1:2021 Traditional Chinese medicine-Vocabulary for diagnostics-Part 1:Tongue,as the basic contrastive analysis corpus, and. makes Diagnostics of Traditional Chinese Medicine edited by Zhu Wenfeng and the eighth edition of Oxford Advanced English-Chinese Dictionary as reference books . Based on the translation theory of "Adaptation" and "Selection", the main characteristics of the terminology standards of tongue manifestation in the two versions are analyzed and summarized from the dimension of language, culture and communication. And then, problems such as selection of terms, difference of term property and structure, single choices of term-selection standard for compound tongue manifestations, different contexts for the same term and a lack of certain terminologies are found. Thus, this paper finds that to achieve different communicative effects in the context, the differences of the applicable objects of terms should be considered. These findings suggest that terms of WHO serve as the tool of education and training, targeting practitioner as main user, while terms of ISO serve as information objectivization, aiming to specify data exchange for diagnostic instrument.
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Objective:To explore the value of video-electroencephalography (VEEG) combined with amplitude-integrated electroencephalography (aEEG) in evaluating the condition and prognosis of neonatal hyperbilirubinemia brain injuries.Methods:A total of 120 children with hyperbilirubinemia treatedin the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from July 2019 to July 2020 were enrolled. According to MRI with or without T 1 weighted imging (T 1WI) hyperintensity changes in the globus pallidus, they were divided into the brain injury group (52 cases) and the normal group(68 cases). According to the severity of brain injury, the brain injury group was divided into bilirubin encephalopathy group (23 cases) and subclinical bilirubin brain injury group (29 cases). According to the scores of Gesell Development Scale, the brain injury group was divided into good prognosis group (37 cases)and poor prognosis group (15 cases). The diagnostic value in brain injury with hyperbilirubinemia, the evaluation of the severity of brain injury and the predictive value of VEEG and aEEG were analyzed. Results:The abnormal rates of VEEG and aEEG in the brain injury group were higher than those in the normal group: 76.92% (40/52) vs. 8.82% (6/68), 80.77% (42/52) vs. 11.76% (8/68), the differences were statistically significant ( χ2 = 57.81 and 57.73, P<0.01). The abnormal rates of VEEG and aEEG in bilirubin encephalopathy group were higher than those in subclinical bilirubin brain injury group: 91.30% (21/23) vs. 65.52% (19/29), 95.65% (22/23) vs. 68.97% (20/29), the differences were statistically significant ( χ2 = 4.80 and 5.88, P<0.05). There was no significant difference in abnormal rates of VEEG and aEEG between the good prognosis group and poor prognosis group ( P>0.05). The results of operating characteristic curve analysis showed that the areas under the curve of VEEG combined with aEEG in the diagnosis of brain injury with hyperbilirubinemia, evaluation of the severity of brain injury, predicting the prognosis of children were higher than those of each examination method used alone ( P<0.05). Conclusions:VEEG combined with aEEG has diagnostic value for neonatal brain injury with hyperbilirubinemia, and has evaluation value for severity and prognosis of the disease.
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Objective:To investigate the mechanism of levosimendan on acute kidney injury after cardiopulmonary resuscitation (CPR) in rats.Methods:Twenty-five healthy adult male SD rats were randomly divided into three groups: control group ( n=5), levosimendan group ( n=10) and experimental group ( n=10). A cardiac arrest-cardiopulmonary resuscitation model was established using smothering method in the experimental group and levosimendan group. The levosimendan group was treated with levosimandan during and after resuscitation, while the experimental group was given equivalent volume of saline solution during and after resuscitation, and the control group was only given equivalent volume of saline without performance of CPR. The rats in the three groups were sacrificed at 6 h after resuscitation. The serum and kidney tissue samples were collected. Serum biochemical indicators [serum creatinine (Scr), blood urea nitrogen (Bun), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] were measured. HE staining and Paller score were used to identify the degree of kidney damage. Apoptosis was estimated by TUNEL staining. Western blot was used to detect the expression levels of phosphorylation of extracellular regulated protein kinases (p-ERK). One-way analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between groups were performed using the least significant difference t-test. Results:Scr (85.02±1.31) μmol/L, Bun (7.36±0.13) mmol/L, Paller score (7.3±0.2), IL-1β (302.20±17.35) pg/mL, IL-6 (564.60±23.24) pg/mL and TNF-α (1346±83.73) pg/mL in the experimental group were significantly higher than those of the control group [(15.94±0.96) μmol/L, (2.95±0.18) mmol/L, (0.7±0.2), (7.27±0.44) pg/mL, (51.30±2.87) pg/mL, and (10.39±0.52) pg/mL] (all P<0.01). Compared with the experimental group, Scr (63.88±2.01) μmol/L, Bun (5.45±0.47) mmol/L, paller score (4.8±0.2), IL-1β (78.61±3.66) pg/mL, IL-6 (297.90±13.64) pg/mL and TNF-α (276.2±20.18) pg/mL were significantly decreased in the levosimendan group (all P<0.01). TUNEL staining showed that levosimendan could improve the apoptosis of renal cells ( P<0.01). The expression of p-ERK protein in the levosimendan group was significantly higher than that in the experimental group ( P<0.01). Conclusions:Lovosimendan could attenuate acute kidney injury following cardiac arrest and cardiopulmonary resuscitation via suppression apoptosis. The mechanism of levosimendan protective effect might be associated with activation of ERK signaling pathway.
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@#Stimulator of interferon genes (STING) is an important factor in the auto-immune response of our bodies.Considering the mechanism of activating CD8+ T cells after the activation of STING protein, the combination of STING agonists and immune checkpoint inhibitors for the treatment of tumor immunotherapy has good clinical application prospect.In this paper, the research progress of molecular types, mechanism of action and structural modifications of STING agonists were reviewed.The developing tendency were outlined to provide some references for further investigation.
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Compared with cold lateral condensation and continuous wave of condensation which are classically used in clinical, newly emerging single-cone obturation technique is easy-to-operate as well as time-saving. Especially when combined with bioceramic root canal sealers of improved physicochemical and biological properties, single-cone obturation technique showed satisfactory short-term outcomes in clinical observations. However, difficulties still exist in avoiding the root canal overfilling and in operating the retreatment. Besides, the long-term effects of single-cone obturation with bioceramic sealers still remain unclear. This article makes an overview on the history and development of single-cone obturation ,and provides analysis of its pros and corns. Furthermore, we would also like to summarize its clinical application and look into its future improvements.
Subject(s)
Epoxy Resins/chemistry , Gutta-Percha/chemistry , Retreatment , Root Canal Filling Materials/therapeutic use , Root Canal Obturation/methods , Root Canal TherapyABSTRACT
A retrospective analysis of a case of death from sudden convulsions caused by oral high-dose diquat was conducted, and the mechanism and treatment of central damage caused by diquat were investigated to lay the foundation for increasing the success rate of treatment of high-dose diquat poisoning. At the same time, at the same time, our clinical treatment experience has also been accumulated.
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Humans , Diquat , Poisoning , Retrospective Studies , SeizuresABSTRACT
Objective:To systematically evaluate the efficacy and safety of tissue adhesive combined with lauromacrogol (modified Sandwich method) for gastric varices.Methods:Literature in the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang were searched by two independent researchers from the establishment of the databases to June 30, 2020, and qualified data from the eligible literature were extracted. Revman 5.3 was used to analyze outcomes including hemostatic efficiency, incidence of postoperative fever, chest and abdominal pain, ulcer, ectopic embolism and complications, and postoperative re-bleeding rate (Mantel-Haenszel method).Results:A total of 8 randomized controlled trials including 898 patients were included in this meta-analysis. The results showed that compared with the classic Sandwich method, the modified version had a better hemostatic effect ( P=0.01, OR=2.07, 95% CI: 1.17-3.68) and a lower incidence of postoperative ectopic embolism ( P=0.001, OR=0.06, 95% CI: 0.01-0.34). There were no significant differences in the incidences of postoperative fever ( P=0.58, OR=0.86, 95% CI: 0.52-1.44), chest and abdominal pain ( P=0.83, OR=0.95, 95% CI: 0.58-1.56), local ulcer ( P=0.31, OR=0.66, 95% CI: 0.30-1.47) , re-bleeding ( P=0.14, OR=0.76, 95% CI: 0.53-1.09) or overall incidence of adverse reactions ( P=0.24, OR=0.66, 95% CI: 0.33-1.32). Conclusion:The modified Sandwich method of tissue adhesive combined with lauromacrogol is an effective and safe method in the treatment of gastric varices.
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@#Mixed lineage leukemia 1(MLL1) is a member of the "SET" histone methyltransferases family.MLL1 methyltransferase complex, consisting of MLL1, WDR5, RbBP5, Ash2L and DPY-30, regulates methylation level of histone H3 lysine 4 and is essential for the development of human hematopoietic system and self-renewal of blood cells.As an oncogenic protein produced by the translocation of MLL1 gene, the MLL1 fusion protein has been found in some patients with leukemia.Complete MLL1 enzyme complex is required to perform histone demethylation effect, therefore, targeting the protein-protein interaction of MLL1-WDR5 has become a potential strategy for the treatment of leukemia induced by MLL1 fusion protein.This review systematically summarizes the biological mechanism, structural information and inhibitors of MLL1-WDR5 protein-protein interaction, with a perspective based on previously reported data, aiming to provide some reference for further investigation.
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OBJECTIVE@#To investigate the effect of Chaihu Guizhi Decoction (CHGZD) combined with capecitabine on growth and apoptosis of subcutaneous triple-negative breast cancer xenografts in nude mice and explore the possible mechanism.@*METHODS@#Nude mouse models bearing subcutaneous triple-negative breast cancer xenografts were randomized into 6 groups (n=10) for treatment with distilled water (model group), low (10.62 g/kg), medium (21.23 g/kg) and high (42.46 g/kg) doses of CHGZD, capecitabine (0.2 mg/kg), or the combination of CHGZD (42.46 g/kg) and capecitabine (0.2 mg/k) once daily for 21 consecutive days. The general condition of mice was observed, and after 21-day treatments, the tumors were dissected for measurement of tumor volume and weight and histopathological examination with HE staining. Serum IL-6 levels of the mice were determined with enzyme-linked immunosorbent assay (ELISA), and the expression levels of IL-6, STAT3, p-STAT3, Bax, Bcl-2 and cyclin D1 in the tumor tissues were detected using real-time PCR and Western blotting.@*RESULTS@#Compared with those in the model group, the tumor-bearing mice receiving treatments with CHGZD showed significantly increased food intake with good general condition, sensitive responses, increased body weight, and lower tumor mass (P < 0.01). Compared with capecitabine treatment alone, treatment with CHGZD alone at the medium and high doses and the combined treatment all resulted in significantly higher tumor inhibition rates (P < 0.01), induced obvious tumor tissue degeneration and reduced the tumor cell density. Treatments with CHGZD, both alone and in combination with capecitabine, significantly decreased serum IL-6 level, lowered the mRNA expression levels of IL-6 and STAT3, the protein expressions of IL-6, STAT3 and P-STAT3 (P < 0.05), and the mRNA and protein expressions of Bcl-2 and cyclin D1 (P < 0.05), and increased the mRNA and protein expressions of Bax in the tumor tissues (P < 0.05).@*CONCLUSION@#CHGZD combined with capecitabine can significantly inhibit tumor growth in nude mice bearing triple-negative breast cancer xenografts, the mechanism of which may involve the inhibition of IL-6/STAT3 signaling pathway and regulation of Bax, Bcl-2 and cyclin D1 expressions to suppress tumor cell proliferation and differentiation and induce cell apoptosis.
Subject(s)
Animals , Humans , Mice , Capecitabine/pharmacology , Cyclin D1/metabolism , Drugs, Chinese Herbal , Heterografts , Interleukin-6/metabolism , Mice, Nude , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , Triple Negative Breast Neoplasms/drug therapy , bcl-2-Associated X Protein/metabolismABSTRACT
ObjectiveTo explore the mechanism of Xianglian Huazhuo prescription in the treatment of chronic atrophic gastritis （CAG） based on network pharmacology and animal experiments，so as to provide scientific basis for clinical application. MethodThe possible targets and pathways of Xianglian Huazhuo prescription in the treatment of CAG were obtained based on the prediction of network pharmacology. The CAG rat model was induced by sodium salicylate，N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） and hunger and satiety disorder. Then the CAG rats were treated with Xianglian Huazhuo prescription and morodan for 60 days. After administration，the rats were sacrificed，and the content of interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β） and vascular endothelial growth factor （VEGF） in serum was determined by enzyme linked immunosorbent assay（ELISA）. In addition， the protein expression of Bad and Bcl-2 in gastric mucosa was detected by immunohistochemistry （IHC）. ResultA total of 241 active components of Xianglian Huazhuo prescription and 53 core targets were obtained. Xianglian Huazhuo prescription affected multiple biological processes，such as cell proliferation and apoptosis，inflammatory reaction，regulation of DNA metabolism，and cell response to redox，as well as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt），TNF，mitogen-activated protein kinase （MAPK），cancer and cancer-related signaling pathways. The animal model verification showed that Xianglian Huazhuo prescription lowered the levels of IL-6，TNF-α，IL-1β and VEGF in serum of CAG rats，and reduced the protein expression of Bad and Bcl-2 in gastric tissue. ConclusionXianglian Huazhuo prescription could regulate PI3K/Akt signal pathway and improve gastric mucosal injury in CAG by participating in biological processes such as cell proliferation，apoptosis and inflammation.
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ObjectiveTo explore the mechanism of Xianglian Huazhuo prescription in the treatment of chronic atrophic gastritis （CAG） based on network pharmacology and animal experiments，so as to provide scientific basis for clinical application. MethodThe possible targets and pathways of Xianglian Huazhuo prescription in the treatment of CAG were obtained based on the prediction of network pharmacology. The CAG rat model was induced by sodium salicylate，N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） and hunger and satiety disorder. Then the CAG rats were treated with Xianglian Huazhuo prescription and morodan for 60 days. After administration，the rats were sacrificed，and the content of interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β） and vascular endothelial growth factor （VEGF） in serum was determined by enzyme linked immunosorbent assay（ELISA）. In addition， the protein expression of Bad and Bcl-2 in gastric mucosa was detected by immunohistochemistry （IHC）. ResultA total of 241 active components of Xianglian Huazhuo prescription and 53 core targets were obtained. Xianglian Huazhuo prescription affected multiple biological processes，such as cell proliferation and apoptosis，inflammatory reaction，regulation of DNA metabolism，and cell response to redox，as well as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt），TNF，mitogen-activated protein kinase （MAPK），cancer and cancer-related signaling pathways. The animal model verification showed that Xianglian Huazhuo prescription lowered the levels of IL-6，TNF-α，IL-1β and VEGF in serum of CAG rats，and reduced the protein expression of Bad and Bcl-2 in gastric tissue. ConclusionXianglian Huazhuo prescription could regulate PI3K/Akt signal pathway and improve gastric mucosal injury in CAG by participating in biological processes such as cell proliferation，apoptosis and inflammation.
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Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.
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Background Environmental pollutants can affect N6-methyladenosine (m6A) level in the body, but the change of m6A level in kidney after being exposed to cadmium (Cd) and the molecular mechanism of renal injury need to be further studied. Objective To analyze the associations of m6A modification and methyltransferases/demethylases with microRNA-21 (miR-21) and transforming growth factor- β1 (TGF - β1) in kidney of rats exposed to Cd. Methods Twenty-four SPF male SD rats were divided into 4 groups, with 6 rats in each group, and were exposed to Cd by subcutaneous injection of 2.0, 1.0, and 0.5 mg·kg−1 cadmium chloride (CdCl2) and equal volume of normal saline for 2 weeks, 7 d a week, respectively. The levels of N-acetyl-β-D-glucosidase (UNAG) and albumin (UALB) in urine, and the levels of m6A methylation and TGF-β1 in kidney were detected by enzyme-linked immunosorbent assay (ELISA). The level of blood urea nitrogen (BUN) was measured by urease method. The levels of renal oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected by total bile acid method, water-soluble tetrazolium asssay, and colorimetric method respectively. The relative levels of TGF-β1, methyltransferases, and demethylases in kidney were measured by reverse transcription-polymerase chain reaction. The expression of miR-21 in kidney was detected by fluorescent quantitative polymerase chain reaction. Results After 2 weeks of exposure to Cd, the body weights of rats in the 2.0 and 1.0 mg·kg−1 cadmium chloride groups decreased, and the ratio of kidney/body weight and the levels of BUN, UNAG, and TGF-β1 mRNA and protein increased in the 2.0 mg·kg−1 cadmium chloride group (P<0.05). The expression levels of m6A modification, methyltransferases METTL3, METTL14, Wilms’ tumor 1-associated protein (WTAP), and miR-21 were increased both in the 2.0 and 1.0 mg·kg−1 cadmium chloride groups, with significant differences compared with the control group (P<0.05). The results of correlation analysis showed that the m6A modification level was negatively correlated with SOD (r=−0.4489, P<0.05) and GSH-Px (r=−0.4874, P<0.05), METTL3 was negatively correlated with MDA (r=−0.5158, P<0.05), while there was a positive correlation between FTO and GSH-Px (r=0.4802, P<0.05). In addition, miR-21 was positively correlated with METTL3 (r=0.7491), METTL14 (r=0.6157), and WTAP (r=0.6660) (P<0.05), TGF-β1 was positively correlated with METTL3 (r=0.5025, P<0.05) but negatively correlated with FTO (r=−0.5634, P<0.05) . Conclusion Cd can induce m6A methylation and up-regulation of METTL3, METTL14, WTAP, and miR-21 expression levels in rat kidney tissues, indicating that m6A and miR-21 may be associated with Cd-induced renal fibrosis.
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Background Individual lead or cadmium exposure can cause abnormal blood glucose level and changes in telomere length, and the role of telomere length in the relationship between heavy metal joint exposure and blood glucose level is still unclear. Objective To explore the role of telomere length in the relationship between lead and cadmium coexposure and blood glucose. Methods A cross-sectional study was conducted. By convenient sampling method, 600 residents living in two communities in a city in North China were selected as participants from April to June 2016. Face-to-face interviews were performed to collect general demographics and lifestyles of the participants. The peripheral blood samples of the participants were collected for blood glucose and telomere length detection, the urine samples were collected for urinary cadmium, urinary lead, and urinary creatinine measurement, and both urinary cadmium and urinary lead were corrected by urinary creatinine. The included participants were divided into a control group, a high-cadmium and low-lead group, a high-lead and low-cadmium group, and a high-lead and high-cadmium group, according to the median levels of urinary cadmium and urinary lead. A restricted cubic spline model was constructed to analyze the relationship between urinary lead/cadmium levels and blood glucose concentrations in the four groups and the relationship between cadmium exposure and telomere length in the high-lead and high-cadmium group. Intermediary model test was conducted to analyze the effect of telomere length on the relationship between exposures to lead and cadmium and blood glucose. Results The included participants were divided into the control group (n=99), the high-cadmium and low-lead group (n=91), the high-lead and low-cadmium group (n=145), and the high-lead and high-cadmium group (n=265). The differences in age, education level, per capita monthly household income, smoking, blood glucose, and telomere length were statistically significant among the four groups (P＜0.05). The high-lead and high-cadmium group had the highest blood glucose concentration, (5.63±1.68) mmol·L−1, and the shortest telomere length, (2.63±1.05) Kb. The restricted cubic spline results showed that urinary cadmium level was correlated with blood glucose concentration in the high-lead and high-cadmium group (F=3.45, P=0.037), and there was a non-linear association (F=6.91, P=0.002); the association between urinary cadmium level and telomere length was also non-linear (F=5.93, P=0.043). The intermediary model test results showed that telomere length was a mediating variable between urinary cadmium level and blood glucose concentration, and the mediating effect size was 0.0192 (95%CI: 0.0007-0.0563), with a mediation ratio of 15.57%. Conclusion Correlations between urinary cadmium and blood glucose and between urinary cadmium and telomere length were observed in the high-lead and high-cadmium coexposure group, and telomere length may play a mediating role in the relationship between them.
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Objective:To investigate macular microvascular abnormalities in eyes with subfoveal fibrotic nodules secondary to Coats' disease.Methods:A cross-sectional study. From January 1, 2018 to July 30, 2021, 45 eyes of 45 patients diagnosed with Coats' disease with or without subfoveal fibrotic nodules in Eye and ENT Hospital, Shanghai Medical College of Fudan University were included in this study. There were 40 eyes in 40 males and 5 eyes in 5 females. All were under 21 years old. According to the presence or absence of subfoveal fiber nodules, the patients were divided into fibrotic group (26 cases, 26 eyes) and non-fibrotic group (19 cases, 19 eyes). Optical coherence tomography angiography was used to scan 3 mm×3 mm or 6 mm×6 mm macular area of both eyes. The software of the device automatically processed the images. The presence of FAZ edge anastomotic vascular arch ring breakage and abnormal microvascular branch (AMB) in the foveal avascular zone (FAZ) were observed.Results:In 26 eyes of fibrosis group, AMB originating from the parafoveal retinal capillary network was observed, which grew into and destroyed the integrity of the vascular arch ring at the edge of FAZ. AMB was crisscrossing and winding, and its curvature expands. B-scan images showed the blood flow signal in the subfoveal fiber nodule, and the blood flow signal traversed between the inner retina and the fiber nodule in 23 eyes (88.46%, 23/26). In the non-fibrosis group, all the vascular abnormalities were characterized by capillary dilation and defect, and no breakage of FAZ anastomotic vascular arch ring or AMB was observed.Conclusions:In Coats' disease with subfoveal fiber nodules, staggered and dilated AMBs emerge from the parafoveal vascular network, grow into and destroy the integrity of the vascular arch ring at the edge of FAZ, and grow down longitudinally into the fiber nodules.