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Objective To explore the impact of macrophage-to-myofibroblast transition(MMT)on pulmonary fibro-sis induced by acute lung injury by LPS.Methods Totally 21 male mice were randomly classified into 7 groups:control group,model group(LPS-PF)at different time points and intervention group of clodronate-liposomes(CL-LIP)treatement at different time points(n=3).Pulmonary fibrosis was identified by HE and Masson staining microscopy.The immuno-fluorescence technology was used for the evaluation of numbers of macrophage-to-myofi-broblast transition cells(MMT cell which co-expressed CD68 and α-SMA).Bone marrow-derived macrophages(BMDMs)were randomly classified into two group:control(Ctrl)group and TGF-β1-treated group induced by transforming growthfactor-β1.α-SMA,FN and Col1 were detected by RT-qPCR.The expression of α-SMA,Smad3 and p-Smad3 protein was evaluated by Western blot.Results At day 7,the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group(P<0.01);While the score signifi-cantly declined when the model was pretreated with CL-LIP(P<0.05).As detected by immuno-fluorescence stai-ning,in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P<0.01).When the BMDMs were stimulated by TGF-β1 at 24 h,48 h and 96 h respectively,a higher expression of α-SMA,FN,Col1,were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point(P<0.01).The expression of Smad3,p-Smad3 significantly higher in LPS-PF group(at both day 7 and day 10)and TGF-β1-treated group(at both 48 h and 96 h)as compared to cor-responding control group(P<0.01).Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS.Smad3 is proved to be involved in the MMT process.
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ObjectiveTo investigate the protective mechanism of Qianyang Yuyin granules (QYYY) on aldosterone-induced podocyte injury. MethodA total of 30 C57BL/6J mice were randomly divided into five groups: control group, model group, QYYY low dose (QYYY-L) group, QYYY high dose (QYYY-H) group, and spironolactone (SPL) group, with six mice in each group. Except for the control group, mice were implanted with osmotic minipumps and injected continuously with aldosterone (300 μg·kg-1·d-1) to induce renal injury. The drug administration group was given low and high doses (2.6, 5.2 g·kg-1·d-1) of QYYY and SPL (18 mg·kg-1·d-1) for 28 days. The renal pathological changes of mice were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of Nephrin, Desmin, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved Caspase-3, nuclear receptor subfamily 3 group C member 2 (NR3C2), extracellular regulated protein kinases (ERK), and phospho-ERK (p-ERK) in kidney tissue were detected by Western blot. The apoptosis levels of kidney tissue were detected by TdT-mediated dUTP nick and labeling (TUNEL) staining, and the superoxide dismutase (SOD) levels were detected. In vitro, the mice were divided into five groups: Control group, model group (aldosterone concentration of 200 nmol·L-1), QYYY-L group, QYYY medium dose (QYYY-M) group, and QYYY-H group (25, 50, and 100 mg·L-1). The effect of different concentrations of QYYY on the relative viability of aldosterone-induced podocytes was detected by cell proliferation and viability assay (CCK-8). The expressions of Nephrin, Desmin, Bax, Bcl-2, cleaved Caspase-3, NR3C2, and p-ERK/ERK were detected by Western blot. AnnexinV-FITC/PI flow cytometry was used to detect the apoptosis levels of podocytes. Reactive oxygen species (ROS) in podocytes were observed by DCFH-DA. ResultCompared with the control group, the model group showed structural pathological changes and fibrotic conditions in the kidney, increased apoptosis levels (P<0.01), and decreased SOD levels (P<0.01). Aldosterone concentration at 200 nmol·L-1 showed a significant decrease in podocyte activity (P<0.05). Podocytes in the model group showed structural pathological changes, disordered arrangement of intercellular microfilaments, increased apoptosis levels (P<0.01), and increased intracellular ROS levels (P<0.01). The protein expressions of Nephrin, Bcl-2, and p-ERK/ERK in kidney tissue and podocytes were decreased (P<0.05, P<0.01). The protein expressions of Desmin, Bax, cleaved Caspase-3, and NR3C2 were increased (P<0.05, P<0.01). Compared with the model group, QYYY alleviated the structural damage and fibrosis of the kidney, decreased the apoptosis levels (P<0.05, P<0.01), and enhanced the SOD content of the kidney (P<0.05, P<0.01). QYYY improved the activity of podocytes (P<0.05, P<0.01), restored the foot process structure of podocytes, and decreased apoptosis levels (P<0.01) and ROS levels of podocytes (P<0.01). The protein expressions of Nephrin, Bcl-2, and p-ERK/ERK in kidney tissue and podocytes were increased (P<0.05, P<0.01), and the protein expressions of Desmin, Bax, cleaved Caspase-3, and NR3C2 were down-regulated (P<0.05, P<0.01). ConclusionQYYY improves aldosterone-induced podocyte injury by regulating the NR3C2/ROS/ERK pathway.
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Recent studies have shown that ozone therapy, a widely used immunotherapy in various diseases, can play a therapeutic role in the novel coronavirus infection by enhancing lung function, reducing inflammatory reactions, and bolstering immune system performance. This article reviews the pathophysiological basis of novel coronavirus infection and the mechanisms involved in ozone therapy for its treatment, also summarizes the clinical evidence and safety assessment of ozone therapy in combating novel coronavirus infections.
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Objective:To analyze the correlation between peripheral blood lymphocyte subsets and unex-plained repeated implantation failure(URIF),and to investigate its predictive value for the diagnosis of URIF.Methods:A total of 156 patients with URIF who underwent treatment in the Department of Reproductive Medi-cine,The Second Affiliated Hospital of Kunming Medical University from October 1,2019 to December 1,2021 was selected as the URIF group.Meanwhile,age-matched 41 women with a history of healthy delivery in the past one year were selected as the control group.The percentages of peripheral blood lymphocyte subsets in the two groups were measured by flow cytometry,and the results were statistically analyzed.Receiver operating charac-teristic(ROC)curve was used to evaluate the predictive effect of lymphocyte subsets on URIF.Results:Com-pared with the control group,the percentage of CD3 + CD4 +[(34.03±7.26)%vs.(36.79±6.35)%,P = 0.017]、CD3 +HLA-DR +[(2.60±2.28)%vs.(3.60±2.39)%,P =0.017]、CD3 + CD16 + CD56 +[(1.24±1.04)%vs.(2.62±2.57)%,P<0.000]and CD4 +/CD8 +(1.37±0.48 vs.1.57±0.51,P =0.023)were sig-nificantly increased in URIF group,and were related to the increase of previous failure times to a certain extent.ROC analysis showed that CD3 + CD4 +>35.35%(AUC 0.624),CD3 + HLA-DR +>2.35%(AUC 0.669),CD3 +CD16 +CD56 +>1.86%(AUC 0.660)and CD4 +/CD8 +>1.26(AUC 0.628)could be used as an inde-pendent predictor for the diagnosis of URIF.Among the pair-wise combined indexes,CD3 + HLA-DR + combined with CD3 + CD16 + CD56 + had the highest prediction accuracy(AUC 0.739,Sensitivity 73.3%,Specificity 68.3%).The combination of the four indicators had the highest accuracy(AUC0.767,Sensitivity 68.6%,Specifici-ty 73.2%).Conclusions:There is immune dysfunction in patients with URIF,and the imbalance of peripheral blood lymphocyte subsets may be an important factor leading to embryo implantation failure.CD3 +CD4 +、CD4 +/CD8 +、CD3 +HLA-DR +and CD3 +CD16 +CD56 +could be used as independent indicators for the diagnosis of abnormal peripheral blood lymphocyte subsets in patients with URIF.The combination of them improves the accuracy of prediction,and it has a positive reference significance for dynamic monitoring and early intervention of URIF pa-tients in the process of assisted reproduction technology.
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At present, heart transplantation is the most effective treatment for end-stage heart failure. Nevertheless, the shortage of donors is becoming an increasingly severe challenge. In recent years, rapid development of mechanical circulatory support technologies has provided multiple therapeutic options for patients with end-stage heart failure. As an important mechanical circulatory support device, ventricular assist device (VAD) are divided into durable VAD (dVAD) and temporary VAD (tVAD) according to the duration of assistance. dVAD shows application potential in bridging heart transplantation, destination therapy and bridge to decision. With technological progress and experience accumulation in clinical application, VAD is evolving towards the direction of more biocompatible, lighter, more bionic and intelligent. In this article, the development of VAD, application status at home and abroad and the overall application of VAD in our hospital were reviewed, aiming to provide reference for promoting the clinical application of VAD in China.
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ObjectiveTo investigate the clinical efficacy and possible mechanism of Erzhi Tiangui prescription on repeated implantation failure (RIF) of kidney deficiency syndrome. MethodSeventy patients with RIF of kidney deficiency syndrome who underwent natural cycle frozen-thawed embryo transfer (FET) in the Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were enrolled and randomly divided into a treatment group (35 cases) and a control group (35 cases). Patients in the treatment group took oral Erzhi Tiangui prescription from the third day of each menstrual cycle two months before the FET cycle and continued to take it until the day of transplantation from the third day of the menstrual cycle in the month of transplantation. Those in the control group did not accept traditional Chinese medicine (TCM). In addition,10 patients who successfully achieved clinical pregnancy after the first natural cycle FET were screened from the reproductive medical record bank of this hospital and assigned to the normal group. Peripheral blood samples of patients in the three groups on the day of embryo transfer were collected from the specimen bank of the Reproductive and Genetic Center. Serum soluble programmed death molecule-1 (sPD-1),soluble programmed death molecule-ligand 1 (sPD-L1),transforming growth factor-β (TGF-β),interleukin-17 (IL-17), and interleukin-10 (IL-10) levels were measured by enzyme-linked immunosorbent assay (ELISA). The changes in kidney deficiency syndrome scores, the final biochemical pregnancy rates, clinical pregnancy rates, and embryo implantation rates of the treatment group and the control group before and after treatment were observed. ResultCompared with the normal group,the model group showed increased serum levels of sPD-1 and IL-17(r=0.347,P<0.05),decreased levels of IL-10 and TGF-β (P<0.01),and non-significant change in sPD-L1 level. Serum sPD-1 was positively correlated with IL-17 (P<0.05) and negatively correlated with IL-10(r=-0.521,P<0.01) and TGF-β(r=-0.457,P<0.01) in RIF patients with kidney deficiency syndrome. After TCM treatment,compared with the control group, the treatment group showed improved TCM syndrome score (P<0.05) and increased clinical pregnancy rate and embryo transfer rate(P<0.05),but there was no statistically significant difference in the biochemical pregnancy rate between the two groups. ConclusionAbnormal expression of sPD-1 in patients with RIF of kidney deficiency syndrome breaks the balance of T helper 17 (Th17)/regulatory T cell (Treg),which is not conducive to embryo implantation and pregnancy maintenance. Erzhi Tiangui prescription,a TCM for tonifying the kidney,can significantly improve the symptoms of kidney deficiency in patients with RIF of kidney deficiency syndrome,reduce the concentrations of sPD-1 and IL-17 in the peripheral serum,increase the levels of TGF-β and IL-10,regulate the peripheral Th17/Treg immune balance,and increase the implantation rate and clinical pregnancy rate,which has a high clinical value.
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Objective:To explore the predictive value of prognostic nutritional index(PNI)for recipients of heart transplantation.Methods:From January 2015 to December 2020, the relevant clinical data were reviewed retrospectively for 438 post-heart transplantation recipients at Union Hospital of Tongji Medical College of Huazhong University of Science and Technology.The optimal cut-off value of PNI was determined by receiver operating characteristic(ROC)curve.The inter-group differences of clinicopathologic characteristics were compared.Overall survival(OS)was calculated by Kaplan-Meier survival curve and compared by Log-rank test between two groups.The risk factors affecting OS were examined by univariate and multivariate Cox regression.Results:The optimal cut-off value of PNI was 49.3.They were assigned into two groups of low PNI(PNI≤49.3, 284 cases)and high PNI(PNI>49.3, 154 cases). As compared with high PNI group, low PNI group was significantly correlated with lower BMI, hemoglobin, neutrophil count, albumin, low-density lipoprotein, triglyceride, recipient/donor BMI ratio and recipient age and total bilirubin(all P<0.05). Cox regression multivariate analyses indicated that recipient age, waiting time, preoperative use of intra-aortic ballon pump(IABP)and lower PNI score were risk factors(all P<0.05). Kaplan-Meier survival curve revealed that OS was better in high PNI group than that in low PNI group( χ2=15.122, P<0.01). The area under the ROC curve of PNI for predicting OS was 0.603. Conclusions:PNI score upon admission is correlated positively with postoperative survival of heart transplantation patients.PNI has some predictive value for OS.When PNI score upon admission≤49.3, postoperative survival rate is relatively worse with a shorter postoperative survival.
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Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
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Gravidez , Feminino , Animais , Camundongos , Tetraploidia , Blastocisto , Embrião de Mamíferos , Diferenciação Celular , Desenvolvimento EmbrionárioRESUMO
Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
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Humanos , Células-Tronco Pluripotentes/metabolismo , Embrião de Mamíferos/metabolismo , Diferenciação Celular , Blastocisto , Linhagem da Célula , Desenvolvimento EmbrionárioRESUMO
Objective:To explore if protective effects of dapagliflozin (Dapa) administration on attenuating DOX-induced myocardial injury in rats.Methods:A total of 30 specific pathogens free grade 8 week old male Sprague Dawley rats. Rats were randomly divided into three groups. Control group (Con group, n = 5), rats received intraperitoneal saline (1.25 ml/kg) injection once per week plus saline (8 mg/kg) daily via gavage for 6 weeks. Dox group ( n = 15) rats received intraperitoneal Dox (2.5 mg/kg) injection once per week plus saline (8 mg/kg) daily via gavage for 6 weeks. Dox + Dapa group ( n = 10), rats received intraperitoneal Dox (2.5 mg/kg) injection once per week plus Dapagliflozin (4 mg/kg) daily via gavage for 6 weeks, observed to week 10. Survival status, echocardiography, pathology, and expression of Bcl-2, Bax gene and protein were observed. Results:The survival rate of ats in Con, Dox, and Dapa+Dox groups was 100.0%, 66.7% and 90.0% respectively. The echocardiography were performed in Con, Dox, and Dapa+Dox groups left ventricular ejection fraction was (95.40 ± 2.51)%, (83.09 ± 4.92)% and (91.71 ± 3.45)%, respectively; left ventricular fraction shortening was (66.80 ± 7.43)%, (47.27 ± 5.10)% and (59.43 ± 6.92)%, respectively; Both indexes in Dapa+Dox group was higher than that in Dox group, but lower than that in Con group, all P<0.05; Left ventricular end-diastolic diameter was (4.80 ± 0.83) mm, (5.90 ± 0.83) mm and (4.85 ± 0.69) mm respectively; left ventricular end-systolic diameterwas (1.80 ± 0.44) mm, (2.90 ± 0.53) mm and (2.00 ± 0.57) mm in Con, Dox, and Dapa + Dox groups, respectively; Both indexes in Dapa + Dox group was decreased than that in Dox group, but Dapa + Dox group was increased than that in Con group, all P<0.05. Pathologic changes have been shown that myocardial fibers arranged neatly in the Con group under HE staining, while those broken myocardial fibers disordered arranged in the Dox group, and those changes in the Dapa + Dox group were slightly relieved than that in Dox group. The collagen volume fraction of rats in Con, Dox and Dapa+Dox groups were (2.64 ± 1.04)%, (16.85 ± 1.70)% and (6.75 ± 1.89)% under sirius red staining, Dapa+Dox group was lower than that in Dox group but higher than that in Con group, all P<0.05. Pathologic changes under transmission electron microscope have been shown that a few of normal structure mitochondria in the Con group. A large number of swollen mitochondria with disappeared mitochondrial crest in the Dox group; but neatly arranged with mitochondrial crest blurred in the Dapa+Dox group. The quantitative real-time PCR was used to detected Bcl-2 and Bax, there were 0.93 ± 0.09, 0.35 ± 0.30 and 0.89 ± 0.25 in Bcl-2, 0.99 ± 0.10, 3.10 ± 0.10 and 0.86 ± 0.04) in Bax, while Bcl-2/Bax 0.94 ± 0.17, 0.11 ± 0.06 and 1.03 ± 0.27, respectively. The westernblot was used to detected Bcl-2 and Bax, there were 1.00 ± 0.18, 0.32 ± 0.20 and 1.30 ± 0.41 in Bcl-2, 0.66 ± 0.11, 2.44 ± 0.66 and 0.90 ± 0.61 in Bax, while Bcl-2/Bax: 1.50 ± 0.18, 0.12 ± 0.05 and 1.80 ± 0.82, respectively; the above results shown that both myocardial Bax mRNA and protein expression in Dox group were higher than that in Dapa + Dox group and Con group, both P<0.05, and there was no difference in the two later groups, P>0.05; both the myocardial Bcl-2 mRNA and protein expression in Dox group were lower than that in Dapa+Dox group and Con group, both P<0.05, and there was no difference between two later groups, P>0.05; Bcl-2/Bax in Dox group was significantly lower thanthat in Dapa+Dox groupand Con group, both P<0.05, and there was no difference between Dapa+Dox group and Con group, P>0.05. Conclusions:Simultaneous dapagliflozin treatment significantly attenuated DOX-induced cardiotoxicity, which might be related to prevent myocardial apoptosis.
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Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs,
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ObjectiveTo investigate the effect of entecavir (ETV) alone or combined with interferon (IFN) on the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for 409 patients with CHB who were admitted to Beijing Ditan Hospital from January 2008 to December 2014, and according to their antiviral therapy, they were divided into ETV+IFN group with 169 patients (IFN treatment for ≥6 months) and ETV group with 240 patients (ETV treatment for ≥12 months). The patients were followed up to June 2019, and the development of HCC was the outcome event. The Mann-Whitney U test was used for comparison of continuous variables between two groups, and the chi-square test was used for comparison of categorical variables between two groups. The propensity score matching (PSM) method was used to eliminate baseline differences between groups, the Kaplan-Meier method and the log-rank test were used to compare the incidence rate of HCC between groups, and the Cox proportional-hazards regression model analysis was used to investigate the risk factors for the development of HCC. ResultsThe median follow-up time in this study was 5.4 years (IQR: 4.9-7.9). There was no significant difference in the cumulative incidence rate of HCC between the two groups before and after PSM (before PSM: 1.2% vs 2.8%, χ2=1.423, P=0.233; after PSM: 1.7% vs 4.1%, χ2=1.676, P=0.195), and the subgroup analysis also showed no significant difference in the cumulative incidence rate of HCC between the two groups in the non-high risk population (1.3% vs 1.5%, χ2=0.335, P=0.563). The Cox proportional-hazards regression model showed that age was an independent risk factor for HCC (hazard ratio=1.107, 95% confidence interval: 1.005-1.219, P=0.038). ConclusionFor CHB patients without a high risk of cancer, compared with ETV monotherapy, ETV combined with IFN for at least 6 months does not significantly reduce the risk of HCC.
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Background@#Mature oocytes at the metaphase II status (MII-stage oocytes) played an important role in assisted reproductive technology in non-human primates. @*Objectives@#In order to improve the proportion of MII-stage oocytes retrieval, three different superovulation protocols were performed on 24 female cynomolgus monkeys. @*Methods@#All the monkeys received once-daily injection of follicle-stimulating hormone (25 international unit [IU]) on day 3 of the menstruation, 3-day intervals, twice daily for 8–12 days until the time of human chorionic gonadotropin (1,500 IU) injection, on the 14–17th day of menstruation collecting oocytes. The difference between protocol I and protocol II was that 0.1 mg the gonadotropin-releasing hormone agonist was injected on day 1 of the menstruation, while the difference between personalized superovulation protocol and protocol II was that oocytes could be collected on the 14–17th day of menstrual cycle according to the length of each monkey. @*Results@#The total number of oocytes harvested using the personalized superovulation protocol was much higher than that using protocol I (p < 0.05), and the proportion of MII-stage oocytes was significantly greater than that from either superovulation protocol I or II(p < 0.001 and p < 0.01 respectively), while the proportion of immature oocytes at the germinal vesicle was less than that from superovulation protocol I (p < 0.05). @*Conclusions@#The personalized superovulation protocol could increase the rate of MII-stage oocytes acquired, and successfully develop into embryos after intracytoplasmic sperm injection, and eventually generated fetus.
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OBJECTIVE: To explore the role of N~6-methyladenosine(m~6A) catalytic enzymes(methyltransferases and demethylases) in cadmium-induced oxidative damage in human renal epithelial cells(HK-2 cells), and to analyze the correlation between nuclear factor-erythroid 2-related factor 2(NRF2) and m~6A catalytic enzymes. METHODS: i) HK-2 cells in logarithmic growth phase were randomly divided into control group and 6 cadmium sulfate treatment groups, then treated with 0, 2, 4, 8, 16, 32 and 64 μmol/L cadmium sulfate solution for 24 hours. The cell survival rates were detected by CCK-8 assay, and the appropriate doses of cadmium sulfate were selected for subsequent experiments. ii) HK-2 cells in logarithmic growth phase were randomly divided into control group and low-, medium-, and high-dose groups, and treated with 0, 4, 8, and 16 μmol/L cadmium sulfate solution respectively for 24 hours. Subsequently, the levels of reactive oxygen species(ROS) were detected by fluorescence probe. The mRNA expression of NRF2, the m~6A methyltransferases such as methyltransferase like proteins(METTL) 3, METTL14, METTL16 and the m~6A demethylases such as fat mass and obesity associated protein(FTO), AlkB family of nonheme Fe(Ⅱ)/α-ketoglutarate(α-KG)-dependent dioxygenases 5(ALKBH5) were determined by real-time polymerase chain reaction. RESULTS: i) The survival rate of HK-2 cells was more than 60.00% and lower than that of the control group(P<0.05) after the cells were stimulated with 16 μmol/L of cadmium sulfate. Therefore, 4, 8 and 16 μmol/L of cadmium sulfate were selected as the stimulation concentrations in the follow-up experiments. ii) The relative expression of NRF2, METTL3, METTL14 and METTL16 in HK-2 cells in low-dose group increased(all P<0.05), while the levels of ROS and the relative mRNA expression of NRF2, METTL3, METTL14, METTL16 and FTO in HK-2 cells in medium and high-dose groups increased(all P<0.05) when compared with the control group. There was no significant difference in the expression of ALKBH5 mRNA among these 4 groups(P>0.05). In the correlation analysis, NRF2 mRNA expression was positively correlated with the mRNA expression of METTL3 and METTL16 [Pearson correlation coefficient(r) = 0.61 and 0.66, respectively, all P<0.05]. There was no correlation between NRF2 mRNA expression and METTL14, FTO and ALKBH5(r=0.53, 0.48, and 0.01 respectively, all P>0.05). CONCLUSION: Cadmium sulfate may increase intracellular ROS level, up-regulate NRF2 expression and activate NRF2 signaling pathway as well as enhance the expression of METTL3 and METTL16 in HK-2 cells, thus increasing intracellular oxidative damage and decreasing the cell survival rate.
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Objective@#To investigate IMRT planning process using the combined application of failure modes and effects analysis (FMEA) and fault tree analysis (FTA) by reference to the report of Task Group 100 of the AAPM, and stablish and optimize the quality.@*Methods@#A multidisciplinary team detailed the process mapping of IMRT planning using Eclipse TPS. The team evaluated the potential failure modes (FMs) of every process step. The evaluation was divided into two groups according to whether quality management (QM) was considered. For every FM, occurrence (O), severity (S) and detectability (D) by consensus were evaluated, and the product of O, S and D yielded the risk priority number (RPN), which permitted the ranking of the FMs. Finally, FTA was used to determine the root factors contributing to the riskiest failure modes.@*Results@#The IMRT plan process consisted of 10 major sub-processes and 33 steps, which amounted to 47 failure modes. For the group without quality management, the RPN of FMs was between 13.2-271.8, 27 of which had RPN≥80, and 18 FMs had S≥8. For the group with quality management, the RPN of FMs was between 11.2-158.4, 11 of which had RPN≥80. The difference of RPN between the two groups was statistically significant (RPN of the group without QM=101.17±66.34, RPN of the group with QM=59.54±35.64, t=8.501, P<0.05). Finally, FTA was used to determine the root factors contributing to the FMs, i. e., prescription dose definition and importing images.@*Conclusions@#The FMEA and FTA methods are operable and practical, which can systematically and comprehensively analyze the potential failures and risks existing in the process of IMRT plan. And the FMEA and FTA can contribute to establish and optimize the quality management program in radiotherapy.
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Clinically, hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of morbidity and mortality. Hepatitis B virus infection is the main cause of hepatocellular carcinoma in China and it is a serious threat to people's health. Antiviral drugs such as nucleos(t)ide analogues and interferon can inhibit viral replication and liver fibrosis progression and reduce the occurrence of hepatitis B-related HCC. This article reviews the effects of different antiviral therapy on the occurrence of hepatitis B-related hepatocellular carcinoma in recent years.
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Objective To investigate IMRT planning process using the combined application of failure modes and effects analysis ( FMEA) and fault tree analysis ( FTA) by reference to the report of Task Group 100 of the AAPM, and stablish and optimize the quality. Methods A multidisciplinary team detailed the process mapping of IMRT planning using Eclipse TPS. The team evaluated the potential failure modes ( FMs ) of every process step. The evaluation was divided into two groups according to whether quality management ( QM) was considered. For every FM, occurrence ( O) , severity ( S) and detectability ( D) by consensus were evaluated, and the product of O, S and D yielded the risk priority number ( RPN) , which permitted the ranking of the FMs. Finally, FTA was used to determine the root factors contributing to the riskiest failure modes. Results The IMRT plan process consisted of 10 major sub-processes and 33 steps, which amounted to 47 failure modes. For the group without quality management, the RPN of FMs was between 13. 2-271. 8, 27 of which had RPN≥80, and 18 FMs had S≥8. For the group with quality management, the RPN of FMs was between 11. 2-158. 4, 11 of which had RPN≥80. The difference of RPN between the two groups was statistically significant ( RPN of the group without QM=101. 17±66. 34, RPN of the group with QM=59. 54±35. 64, t=8. 501, P<0. 05). Finally, FTA was used to determine the root factors contributing to the FMs, i. e., prescription dose definition and importing images. Conclusions The FMEA and FTA methods are operable and practical, which can systematically and comprehensively analyze the potential failures and risks existing in the process of IMRT plan. And the FMEA and FTA can contribute to establish and optimize the quality management program in radiotherapy.
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Objective To summarize the surgical strategies of orthotopic cardiac transplantation for congenital dextrocardia .Methods Three patients with congenital dextrocardia suffered from endstage heart failure and underwent orthotopic cardiac transplantation from March 2014 to September 2017 .They were aged 10 ,29 ,13 years respectively .Donor hearts were from brain death donors and procured with extra length on inferior vena cava , aorta and pulmonary artery tissues . After cardiectomy , left atrial-atrial anastomosis was performed initially between donor ' s left-upper pulmonary vein orifices and recipient's left-lower pulmonary vein orifices .Apex was orientated at a 90 degrees' clockwise to right . Then aorta ,inferior and superior vena cava and last pulmonary artery were anastomosed continuously . The prosthetic conduits were also used owing to a lack of tissue . Results All operations were successful . The cold ischemic time was (130-375 ) (251 .00 ± 122 .53) min ,cardiopulmonary bypass time (127-212 )(179 .67 ± 55 .72 ) min and aortic clamp time (38-105 ) (65 .33 ± 35 .166) min . Two patients had stable hemodynamics and recovered well after HTx .During a follow-up period of 1 .5-3 .5 years , echocardiography showed excellent cardiac functions without blood flow obstruction . Chest radiology showed well-placed donor heart in right mediastinum .One left-sided patient with total cavopulmonary connection before HTx died at 59 days after HTx because of pneumonia and multiple organ failure .Conclusions Heart transplantation is curative for patients with congenital dextrocardia and surgical strategies are the key factor of successful treatment .
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To explore the role of P53, pairing box gene 8 antibody (PAX8), and calcium omentum protein (Calretinin) in the origin of epithelial ovarian cancer. Methods: A total of 63 tissue samples of ovarian tumor and fallopian tubes were collected. Immunohistochemistry methods were used to analyze the expression of P53, PAX8, and Calretinin. The relationship between these protein levels and the classification of ovarian tumors was evaluated. Results: In epithelial ovarian cancer, the P53 or PAX8 was correlated with the occurrence of high-grade carcinoma, while the calretinin was correlated with the occurrence of low-grade carcinoma (P<0.05). The combination of PAX8 with Calretinin was correlated with the grade of ovarian tumor (P<0.05). The combination of P53 with Calretinin was correlated with the grade of tumor (P<0.05). The combination of P53 with PAX8 was correlated with the grade of tumor (P<0.05). The expression of P53 in fallopian tubes was correlated with the malignant degree of epithelial ovarian cancer (P<0.05). The degree of fallopian tube lesions in patients with ovarian cancer was correlated with epithelial ovarian cancer. The malignant lesions of tubal epithelium was correlated with high-grade carcinoma, while the normal or atypical hyperplasia of tubal epithelium was correlated with low-grade carcinoma (P<0.05). Conclusion: P53 and Calretinin combined with PAX8 show a synergistic effect on the differentiation of epithelial ovarian cancer grade. The morphology of HE and the expression of TP53 in the fallopian tube epithelium play an auxiliary role in the diagnosis of epithelial ovarian cancer.
Assuntos
Feminino , Humanos , Carcinoma Epitelial do Ovário , Epitélio , Tubas Uterinas , Neoplasias Ovarianas , Fator de Transcrição PAX8RESUMO
Objective To investigate the value of two-dimensional and three-dimensional ultrasonography in differential diagnosing cesarean scar pregnancy (CSP) and lower uterine cavity non-scar pregnancy.Methods Totally 67 patients with CSP (CSP group)and 29 patients with lower uterine cavity non-scar pregnancy (lower uterine cavity non-scar pregnancy group) were enrolled.Two-dimensional and three-dimensional ultrasonography were performed to observe the gestational sac implantation site,the relationship between gestational sac and cesarean section scar and the main source of blood flow,and the residual muscle thickness of cesarean section scar was measured as well.Logistic regression model was established,and the diagnostic efficacy was evaluated with ROC curve.Results Statistical differences of relationship between gestational sac and scar,the main source of blood flow and residual muscle thickness were found between CSP group and lower uterine cavity non-scar pregnancy group (all P<0.001).The area under the ROC curve of the Logistic regression model was 0.878 (P<0.001).Taking prediction accuracy of 0.680 as a cut-off value,the accuracy of this model in predicting was 86.46%,the sensitivity was 89.55% and the specificity was 79.31%.Taking gestational sac implanted scars and nourish the blood flow from the lower anterior wall of the uterus as the diagnostic criteria for CSP,the Kappa value of two-dimensional and three-dimensional ultrasonograpby in diagnosis CSP and non-scar pregnancy was 0.699 and 0.711,respectively.Conclusion Comprehensive analysis of the relationship between gestational sac and scars,the main source of blood flow and residual muscle thickness with Logistic regression model can improve differential diagnostic efficacy of CSP with lower uterine cavity non-scar pregnancy.