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Objective To investigate the relationship between the expression of long non-coding RNA HOXA-AS2(lncRNA HOXA-AS2),long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1),and long non-coding RNA CRNDE(lncRNA CRNDE)in endometrial carcinoma and the clinical pathological character-istics and prognosis of patients.Methods Collect samples of endometrial carcinoma cancer tissues and adja-cent tissues excised during surgery from 119 endometrial carcinoma patients admitted to a hospital from Octo-ber 2017 to February 2020.The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in tissues were retrospectively analyzed,as well as their relationship with clinicopathological features and 3-year survival rate of patients.Results The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were higher than those in adjacent tissues,with statistical signifi-cance(P＜0.05).The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were positively correlated(rHOXA-As2 vs.FOXD2-AS1=0.384,P=0.001;rHoXA-AS2 vs.CRNDE=0.576,P＜0.001;rFoXD2-AS1 vs.CRNDE=0.326,P=0.003).In the HOXA-AS2,FOXD2-AS1 and CRNDE high expression group,the proportion of patients with international federation of gynecology and ob-stetrics(FIGO)stage Ⅲ+Ⅳ,lymph node metastasis,deep infiltration and low differentiation was higher than that in the low expression group,with statistical significance(P＜0.05).The 3-year survival rate of low HOXA-AS2 expression group in endometrial cancer patients(52/60,86.67％)was higher than that of high HOXA-AS2 expression group(40/59,67.79％),the difference was statistically significant(x2=6.039,P＜0.05).The 3-year survival rate of patients with endometrial cancer with low FOXD2-AS1 expression group(53/59,89.83％)was higher than that of patients with endometrial cancer with high FOXD2-AS1 expression group(39/60,65.00％),and the difference was statistically significant(x2=10.456,P＜0.05).The 3-year sur-vival rate of low CRNDE expression group in endometrial cancer patients(51/60,85.00％)was higher than that of high CRNDE expression group(41/59,69.49％),and the difference was statistically significant(x2=4.079,P＜0.05).HOXA-AS2,FOXD2-AS1,and CRNDE were risk factors for death in endometrial carcinoma patients(P＜0.05).Conclusion The expression of HOXA-AS2,FOXD2-AS1,and CRNDE in endometrial carcinoma cancer tissue is closely related to the clinical pathological characteristics and prognosis of patients.
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Objective To investigate the impact of quercetin(Que)on postherpetic neuralgia(PHN)and chemokine ligand 3(CCL3,namely MIP-1α)/C-C chemokine receptor 1(CCR1)/C-C chemokine receptor 5(CCR5)signaling pathway in rats.Methods Sixty rats were divided into the control group(Con),the PHN group(model group),the L-Que(30 mg/kg)group,the M-Que(60 mg/kg)group,the H-Que(120 mg/kg)group and the H-Que+pathway activator MIP-1α(120 mg/kg Que+0.4 mg/kg recombinant MIP-1α)group.The mechanical paw withdrawal threshold(PWT)and thermal pain threshold(TWL)of rats were detected in each group.The kit was used to detect adenosine,Adenine ribonucleotide(AMP),adenosine diphosphate(ADP)and tumor necrosis factor in spinal dorsal horn samples-α(TNF-α),and interleukin-1 β(IL-1 β)levels in spinal dorsal horn samples.HE staining was applied to observe the pathological sections of spinal dorsal horn.Immunofluorescence staining was used to detect the activation of microglia in spinal dorsal horn.Western blot assay was applied to detect MIP-1α/CCR1/CCR5 signaling pathway protein expression.Results In the PHN group,the dorsal horn of the spinal cord was ruptured,the arrangement of nerve bundles was disordered,and inflammatory cell infiltration,edema,and slight atrophy of neurons appeared.Compared with the Con group,the PWT value,adenosine,AMP and ADP levels were obviously decreased in the PHN group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1-positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).After treatment with Que,the disordered arrangement of nerve bundles was improved,the infiltration of inflammatory cells was reduced,and the phenomenon of neuronal atrophy disappeared.Compared with the PHN group,the PWT value,adenosine,AMP and ADP levels were obviously increased in the L-Que group,the M-Que group and the H-Que group(P＜0.05).TWL value,TNF-αand IL-1β levels,the number of Iba1-positive microglia,and MIP-1α,CCR1 and CCR5 protein levels were obviously decreased(P＜0.05).The effect of Que was dose dependent.Compared with the H-Que group,PWT value,adenosine,AMP and ADP levels were obviously decreased in the H-Que+MIP-1α group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1 positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).Conclusion Que may reduce the inflammatory response in rats by inhibiting the MIP-1α/CCR1/CCR5 signaling pathway,thereby reducing PHN.
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Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.
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Objective:To explore expression of each member of miR17-92 cluster in peripheral blood mononuclear cells(PBMCs)of patients with gout,to predict their possible targets and pathways of action,and to evaluate their possible mechanism and clinical significance in gout.Methods:A total 67 gouty arthritis(GA)patients were selected,including 22 patients with acute gout arthritis(AG)and 45 patients with intermittent gout(IG),and 35 normal health control(HC)were selected in Affiliated Hospital of North Sichuan Medical College.RT-qPCR measured expressions of miR17-92 cluster,IFN-γ,IL-10 and some members of JAK-STAT pathway,and relevant laboratory indicators were collected to analyze correlation between each other.Results:Relative expressions of miR17,miR18a,miR19a,miR20a and miR19b were significantly changed in AG,IG and HC(H=8.753,P<0.05;H=6.338,P<0.05;H=6.523,P<0.05;H=9.061,P<0.05;H=9.729,P<0.01).JAK3 and STAT2 expressions were statistically different in AG,IG and HC groups(H=10.349,P<0.01;H=14.801,P<0.01).Expression of IFN-γ was statistically different among AG,IG and HC groups(H=8.734,P<0.05).In AG patients,miR18a expression was inversely correlated with IBIL,Crea,MO and HGB.miR19a ex-pression was negatively associated and TC,UA and HGB.miR20a expression was negatively associated with Crea.miR19b expression was negatively associated with UA and HGB.In IG patients,miR17 expression was negatively associated with IBIL,WBC,LY and MO.miR18a expression was positively associated with ALP,miR19a expression was negatively associated with TC and UA,and miR20a expression was negatively associated with ADA and UA.Conclusion:miR17-92 cluster may regulate development and partici-pate in clinical pathology of gout by targeting JAK-STAT pathway.
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@#Objective To investigate the clinical significance of CD7 expression in childhood acute myeloid leukemia(AML).Methods A retrospective analysis was performed on 60 children with AML admitted to Jiangxi Province Children's Hospital from October 2016 to December 2020.According to the results of immunophenotyping,the children were divided into CD7 positive(CD7+)group and CD7 negative(CD7-)group.The clinical characteristics,immunophenotype and treatment effect of the two groups were compared.Results Among 60 children with AML,18 cases were CD7+,and the positive rate was 30.00%,mainly M2 and M5,the expression rate of M2 was 55.56%,which was higher than that of other subtypes.The CD7+ group had significantly higher white blood cell count and bone marrow blast granulocyte count than the CD7-group(P<0.05).There were no significant differences in platelet count,hemoglobin,lactate dehydrogenase,creatinine and other laboratory indicators between the two groups(P>0.05).After 1 course of standard induction chemotherapy,the CD7+ group had a significantly lower complete remission rate than the CD7-group(P<0.05).There was no statistically significant difference(P>0.05)in the overall survival rate and disease free survival rate between the two groups of patients at 1 year and 2 years.Conclusion Compared with CD7-children,the peripheral white blood cell count and bone marrow blast cell count of CD7+ children were significantly higher,and the complete remission rate of induction chemotherapy was significantly lower.The expression of CD7 antigen has a significant predictive value for the poor prognosis of children with AML,which may provide new ideas for the treatment strategy of children with AML,and lay the foundation for further exploring the mechanism of CD7 in the development of AML.
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Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.
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The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.
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Mice , Animals , Depression/etiology , Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor , Serotoninالملخص
OBJECTIVE@#To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML).@*METHODS@#TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors.@*RESULTS@#The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049).@*CONCLUSION@#In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.
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Humans , Adult , Prognosis , Leukemia, Myeloid, Acute/metabolism , Survival Analysis , Proportional Hazards Models , Risk Factors , 1-Acylglycerophosphocholine O-Acyltransferaseالملخص
Objective This study conducted the ARIMA model to analyze the cost structure and trend of inpatients with diabetes in a grade-A tertiary hospital and provide scientific basis for effectively controlling diabetes hospitalization expenses and reduce patient's economic burden.Methods The data of 18 371 inpatients with diabetes from 2012 to 2022 in a grade-A tertiary hospital were collected.We collected inpatient data of diabetes from 2012 to 2021 to fit the average inpatient expenses and drug proportion,and used data 2022 to verify the effect of model prediction.We predicted the average inpatient expenses and drug proportion from 2023 to 2025.Results The difference between the predicted value and the actual value was small,and the mean absolute percentage error was within the acceptable range.ARIAM model could be used to predict the expenses of diabetes.Conclusion The average cost of hospitalization showed a decreasing trend,and"the five colors,one map,one index"manage-ment model has achieved results.The proportion of drugs decreased obviously,but the composition of hospitalization expenses should be further optimized.The research of expenses prediction based on diabetes needs to be depended.
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OBJECTIVE@#To characterize the paraspinal muscles of adolescent idiopathic scoliosis (AIS) patients, and to further explore its etiology.@*METHODS@#Clinical records and paraspinal muscle biopsies at the apex vertebra region during posterior scoliosis correction surgery of 18 AIS were collected from November 2018 to August 2019. Following standardized processing of fresh muscle tissue biopsy, serial sections with conventional hematoxylin-eosin (HE) and histochemical and immunohistochemical (IHC) with antibody Dystrophin-1 (R-domain), Dystrophin-2 (C-terminal), Dystrophin-3 (N-terminal), Dystrophin-total, Myosin (fast), major histocompatibility complex 1 (MHC-1), CD4, CD8, CD20, and CD68 staining were obtained. Biopsy samples were grouped according to the subjects' median Cobb angle (Cobb angle ≥ 55° as severe AIS group and Cobb angle < 55° as mild AIS group) and Nash-Moe's classification respectively, and the corresponding pathological changes were compared between the groups statistically.@*RESULTS@#Among the 18 AIS patients, 8 were in the severe AIS group (Cobb angle ≥55°) and 10 in the mild AIS group (Cobb angle < 55°). Both severe and mild AIS groups presented various of atrophy and degeneration of paraspinal muscles, varying degrees and staining patterns of immune-expression of Dystrophin-3 loss, especially Dystrophin-2 loss in severe AIS group with significant differences, as well as among the Nash-Moe classification subgroups. Besides, infiltration of CD4+ and CD8+ cells in the paraspinal muscles and tendons was observed in all the patients while CD20+ cells were null. The expression of MHC-1 on myolemma was present in some muscle fibers.@*CONCLUSION@#The histologic of paraspinal muscle biopsy in AIS had similar characteristic changes, the expression of Dystrophin protein was significantly reduced and correlated with the severity of scoliosis, suggesting that Dystrophin protein dysfunctions might contribute to the development of scoliosis. Meanwhile, the inflammatory changes of AIS were mainly manifested by T cell infiltration, and there seemed to be a certain correlation between inflammatory cell infiltration, MHC-1 expression and abnormal expression of Dystrophin. Further research along the lines of this result may open up new ideas for the diagnosis of scoliosis and the treatment of paraspinal myopathy.
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Humans , Adolescent , Scoliosis/surgery , Paraspinal Muscles/pathology , Dystrophin , Non-alcoholic Fatty Liver Disease/pathology , Kyphosis/pathology , Biopsyالملخص
The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.
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Male , Humans , Middle Aged , Autoantibodies , Myositis/diagnosis , Autoimmune Diseases , Muscle, Skeletal/pathology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Necrosis/pathology , Muscular Diseases/drug therapyالملخص
BACKGROUND@#Legg-Calvé-Perthes disease (LCPD) is still a refractory disease in children’s orthopedics. With the introduction of the concept of ‘‘osteoimmunology’’, the immune-inflammatory mechanisms between bone and immune system have become a research focus of LCPD. However, few studies have reported on the pathological role of inflammation-related receptors such as toll-like receptors (TLRs) as well as immune cells such as macrophages in LCPD. This study was for investigating the mechanism of TLR4 signaling pathway on the direction of macrophage polarization and the repair of avascular necrosis of femoral epiphysis in LCPD. @*METHODS@#With GSE57614 and GSE74089, differentially expressed genes were screened. Through enrichment analysis and protein–protein interaction network, the functions of TLR4 were explored. Furthermore, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), hematoxylin & eosin (H&E) staining, micro-CT, tartrate-resistant acid phosphatase (TRAP) dyeing and western blotting were performed for determining the influences of TAK-242 (a TLR4 inhibitor) on the repair of avascular necrosis of femoral epiphysis in rat models. @*RESULTS@#Totally 40 co-expression genes were screened as well as enriched in TLR4 signaling pathway. Immunohistochemistry and ELISA analyses certified that TLR4 facilitated macrophage polarization toward the M1 phenotype and prevented macrophage polarization toward the M2 phenotype. Besides, the results of H&E and TRAP staining, micro-CT, and western blotting showed that TAK-242 can inhibit osteoclastogenesis and promote osteogenesis. @*CONCLUSION@#Inhibition of TLR4 signaling pathway accelerated the repair of avascular necrosis of femoral epiphysis by regulating macrophage polarization in LCPD.
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BACKGROUND@#Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood.@*METHODS@#Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.@*RESULTS@#In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.@*CONCLUSIONS@#CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.
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Objective:To investigate basic public health service personnel allocation in five regions of Guizhou province, providing reference and strategies for the construction of grass-roots disease prevention and control system in Guizhou province and the training of grass-roots public health service talents in colleges and universities.Methods:According to the topographical features of Guizhou province, stratified random sampling was completed in five regions including Guiyang, Zunyi, Liupanshui, Qianxinan Buyei and Miao Autonomous Prefecture, Qiannan Buyei and Miao Autonomous Prefecture. Questionnaires and on-the-spot symposiums were conducted among basic public health service personnel from 20 township health centers and 20 community health service centers.Results:Women (82.7%), 25-35 years of age (41.7%), working years < 5 years (65.7%), and junior professional titles (59.7%) accounted for a higher proportion of the staff in the five regions. Basic public health service personnel in Guiyang had the highest percentage of undergraduate education (47.5%) and those in other regions had the highest percentage of a junior college education. 40.3% and 26.4% of basic public health service personnel were devoted to nursing and clinical specialties, and only 3.2% of basic public health service personnel were devoted to general practice and preventive medicine. The number of public health practitioners (assistants) per 10,000 residents was 0.05, and 43.5% of public health practitioners had multiple duties.Conclusion:The professional structure of public health personnel is not reasonable at the grass-roots level in Guizhou province. There is an extreme shortage of public health practitioners (assistants), the professional title is low, staffing is inadequate, and staff loss is serious.
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OBJECTIVE@#Compared with the method of optical microscopy, to evaluate the accuracy of fragmented red cells(FRC) detection by Sysmex XN-3000.@*METHODS@#A total of 111 samples were collected from patients diagnosed as thrombotic thrombocytopenic purpura, autoimmune disease, hematological disease, malignant tumor and health examination in our hospital from June 2019 to February 2021, including 74 cases in the case group and 37 cases in the healthy control group. All samples were detected by optical microscope and Sysmex XN-3000, respectively. ROC was used to evaluate the detection ability of Sysmex XN-3000 for schistocyte. Bland-Altman method was used to evaluate the consistency of the results of the two methods for detection of schistocyte, and Pearson correlation analysis was conducted for the difference of the results.@*RESULTS@#The area under the ROC curve was 0.890(95% CI: 0.828-0.952, P<0.01). Sysmex XN-3000 count did not quantitatively agree with schistocyte counts by microscopy in the case group(mean of difference:-1.53, 95% limits of agreement: -8.78~5.72). There was a weak positive correlation between platelet count and the difference of analyzer and microscopic results (r=0.32,P<0.05).@*CONCLUSION@#Sysmex XN-3000 can be used as a reference for qualitative determination of schistocyte. However, the sensitivity of Sysmex XN-3000 should be improved. It is still necessary to combine with manual microscopy. The quantitative results are not reliable now and cannot be used as a reference for monitoring the results of schistocyte in clinical patients after treatment.
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Humans , Neoplasms , Platelet Count , Purpura, Thrombotic Thrombocytopenic , ROC Curve , Reproducibility of Resultsالملخص
OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
الموضوعات
Humans , Chromosome Aberrations , In Situ Hybridization, Fluorescence , Multiple Myeloma/genetics , Mutationالملخص
To investigate the effect of Xinan Fang Yisheng-Qingluo-Huoxie prescription(YSF)on OPG/RANKL pathway in rats with rheumatoid arthritis induced by complete Freund's adjuvant(CFA)and its mechanism. Methods Thirty-two male SD rats were randomly divided into normal group, AIA group, QLY group and YSF group, with 8 rats in each group. AIA rats were induced except for the normal group. QLY and YSF were administered intragastrically on the first day after the model was successful for 30 days. The body weight and AI score of rats were observed. HE staining was used to observe the histomorphological changes of the ankle joint of rats. The expression of MMP3 and P-P65 was observed by immunohistochemistry. Serum levels of TNF-α, IL-1β, OPG and RANKL were detected by ELISA. The expression of OPG and RANKL proteins in synovium of rats was detected by Western blot and RT-PCR. Results Compared with AIA model, the body weight of the rats gradually returned to normal, and inflammation score decreased. HE staining showed that the bone was well preserved, no synovial infiltration was observed after YSF administration, and MMP3 and P-P65 showed low expression. The levels of TNF-α, IL-1β and RANKL in serum were significantly down-regulated, while the levels of OPG and OPG/RANKL were significantly up-regulated. In addition, Western blot and RT-PCR showed that OPG and OPG/RANKL were highly expressed in synovium of rats, while RANKL was on the contrary. Conclusions YSF may decrease inflammatory score and expression of TNF-α and IL-1β in serum by inhibiting inflammatory response. What's more, the increase of OPG/RANKL ratio can regulate the environment of joint bone destruction, thus alleviating RA.
الملخص
Objective:To explore the mechanism of Xiaojinwan in treating breast cancer bone metastases through cell experiments and bioinformatic analysis. Method:The inhibitory effect of Xiaojinwan on MCF-7 cell viability was detected by cell counting kit-8 （CCK-8） assay. The key components and targets responsible for Xiaojinwan in inhibiting breast cancer bone metastases were predicted by network pharmacology and molecular docking. The active components and targets of Xiaojinwan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCSMP） and SwissTarget Prediction， and the breast cancer bone metastases-related targets from GeneCards and DisGeNET. The results were imported into STRING for constructing a protein-protein interaction （PPI） network， followed by Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using DAVID. A network of the active components of Xiaojinwan-breast cancer bone metastases-related targets-pathways was constructed using Cytoscape 3.7.2. AutoDock 4 was employed for molecular docking. The protein expression levels of matrix metallopmteinase-9 （MMP-9）， hypoxia-inducible factor 1<italic>α </italic>（HIF1A）， and androgen receptor （AR） were assayed by Western blot. Result:Xiaojinwan inhibited the viability of MCF-7 cells and acted on breast cancer bone metastases through such processes as redox and protein autophosphorylation. KEGG enrichment analysis showed that HIF-1， vascular endothelial growth factor （VEGF） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathways were involved. As verified by molecular docking， the active components such as eucalyptin stably bound to AR and MMP-9. Western blot indicated that Xiaojinwan dose-dependently inhibited the expression of MMP-9 and HIF1A proteins in MCF-7 cells. Conclusion:Xiaojinwan acts on AR and MMP-9 through HIF， VEGF and other related signaling pathways， thereby improving hypoxia in tumor microenvironment， inhibiting angiogenesis， and reducing cell invasion and viability.
الملخص
OBJECTIVE@#To investigate the effect and mechanism of a novel emodin derivative YX-18 on Burkitt lymphoma (BL) cells.@*METHODS@#MTT assay was used to detect the effect of YX-18 on the proliferation of BL cell lines CA46 and Raji. Annexin V-PE/7-AAD double staining assay was used for detecting the effect of YX-18 on the apoptosis of CA46 and Raji cells. PI/RNase staining was used to test the effect of YX-18 on CA46 and Raji cell cycle. JC-1 method was used to measure the changes of mitochondrial membrane potential after YX-18 treatment, and DAPI staining was used to detect the morphology of apoptotic cells. Western blot was used to analyze the distribution changes of NF-κB pathway protein (P65, P-P65, IκB, P-IκB) in the cytoplasm and cell nucleus, and also the expression changes of cyclin-related protein P21, CDK2, P-CDK2, Cycling D1, Cycling E1, and the apoptosis-related protein Caspase-3, Caspase-8, Caspase-9 and the proliferation-related protein C-MYC, BCL-2 by YX-18. Real-time fluorescence-quantitative PCR was used to evaluate the effects of YX-18 on mRNA levels of C-MYC and Ki-67 genes in CA46 and Raji cells, and EBNA-1 and EBER genes of EBV in Raji (EBV@*RESULTS@#Novel Emodin derivative YX-18 could effectively inhibit the proliferation of BL cell lines CA46 and Raji, showing a time-dependent effect (24, 48 and 72 h: r@*CONCLUSION@#The novel emodin derivative YX-18 can significantly inhibit the proliferation of Burkitt lymphoma cells, and induce the cell apoptosis and cycle arrest. The inhibitory effect of YX-18 on the proliferation of Burkitt lymphoma cells may be related with the effect of Caspase apoptosis pathway, the proliferation and apoptosis-related molecules, such as C-MYC and Ki-67, and also to the inhibition of NF-κB pathway.
الموضوعات
Humans , Apoptosis , Burkitt Lymphoma , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Emodin/pharmacology , NF-kappa Bالملخص
OBJECTIVE@#Hemorrhoidal disease (HD) is the most common proctological disease, with an estimated prevalence rate of 4.4%, and a peak in individuals between 45 and 65 years of age. This study was done to evaluate whether Lian-Zhi-San (LZS), a clinically used anti-hemorrhoidal ointment could alleviate the inflammatory injury, with its associated changes of inflammatory cytokines and morphology of anorectal tissues, in an experimental model of HD in rats.@*METHODS@#HD was induced by croton oil preparation (COP) applied to the anorectal region. Rats were then treated with cotton swabs soaked in LZS ointment, water or white vaseline, twice a day for 7 d. At the end of the experiment, HD was evaluated by measuring hemorrhoidal and biochemical parameters along with histopathological observations.@*RESULTS@#In this study, COP induced a significant increase in the macroscopic severity score, anorectal coefficient and Evans blue extravasation, compared to normal rats. Additionally, it greatly enhanced the expression and secretion levels of some important inflammation-related cytokines along with marked histological damage, compared to normal rats. Rats treated with LZS ointment experienced significantly ameliorated Evans blue extravasation (P < 0.05), decreased macroscopic severity score (0.86 ± 0.14 vs. 1.65 ± 0.16) and the anorectal coefficient (P < 0.01); its use also attenuated tissue damage and inhibited the expression and secretion levels of inflammation-related cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α).@*CONCLUSION@#This study validates a preliminary understanding of the use of LZS ointment to treat inflammatory factors and tissue damage in an experimental model of HD in rats.