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Objective:To investigate the molecular mechanism for regulation of trophoblast invasion by piR-3127964, which is differentially expressed in placental tissues of preeclamptic and healthy pregnant women.Methods:Placenta samples of healthy (control group, n=12) and preeclamptic pregnant (PE group, n=10) women who delivered by caesarean section and chorionic villi specimens of patients undergoing artificial abortion were collected in the Department of Obstetrics of the First Affiliated Hospital of Chongqing Medical University during November 2020 to August 2021. Total RNA was extracted from placenta samples and sequenced and the expression of piR-3127964 in different tissues was determined by real-time quantitative-polymerase chain reaction (qRT-PCR). The expressions of PIWI proteins including PIWIL-1, PIWIL-2 and PIWIL-3 in different tissues were detected by Western blot. The expressions of two candidate targets, guanine nucleotide-binding protein-like 3-like (GNL3L) mRNA and sialophorin (SPN) mRNA were evaluated by qRT-PCR after exogenous treating HTR-8/SVneo cells with mimics, inhibitor or negative control of piR-3127964, respectively. qRT-PCR was also used to detect the relative expression of GNL3L and SPN at mRNA level in placentas of all women. The interactions between GNL3L/SPN and piR-3127964 were analyzed by double luciferase reporter gene detection. The localization of piR-3127964 and SPN in chorionic villi was detected by fluorescence in situ hybridization and immunofluorescence. Transwell assay was performed to analyze the influence of piR-3127964 on the invasion of HTR-8/SVneo cells and the possible mechanism. Independent sample t-test, analysis of variance, and LSD post test were used for analysis Results:(1) Enrichment pathways of candidate targets predicted by differentially expressed piR-3127964 were associated with cell motility. There were statistically significant differences in piR-3127964 expression in villi, healthy and preeclamptic placentas (2.950±0.853 vs 1.036±0.303 vs 0.254±0.155, F=27.35, P<0.05), and piR-3127964 was predominantly expressed in extravillous cytotrophoblasts (EVTs). (2) The expression of PIWIL-3 protein in placentas of preeclamptic patients was significantly lower than that in healthy placentas and villi (0.810±0.400 vs 3.175±0.429 and 6.843±1.379, F=49.36, P<0.05). (3) Compared with the control group, exogenous piR-3127964 mimics (piR-mimics) and inhibitors (piR-inhibitor) significantly affected the expression of SPN mRNA (0.971±0.045 vs 0.732±0.010, F=6.50; 1.076±0.073 vs 1.293±0.092, F=7.58; both P<0.05), while the expression of GNL3L mRNA had no significant correlation with piR-3127964 level. (4) The luciferase activity of wild-type SPN (SPN-WT) plasmids was significantly affected by piR-mimics (1.010±0.049 vs 0.645±0.047, t=9.34, P<0.05) and piR-inhibitor (1.035±0.058 vs 1.397±0.015, t=－10.60, P<0.05). (5) SPN mRNA was significantly upregulated in placentas of preeclamptic patients than in healthy placentas (2.097±0.239 vs 1.305±0.290, t=－4.22, P<0.05), but no significant difference in the expression of GNL3L mRNA was observed. Immunofluorescence experiment showed that SPN was expressed in EVTs. (6) The invasive potential of HTR8/SVneo cells treated with piR-inhibitor was significantly inhibited, but this effect could be reversed by SPN knockdown (160.714±53.860 vs 371.667±103.061 and 344.333±120.267, F=9.76, both P<0.05). Conclusions:piR-3127964 expression is abnormally downregulated in placentas of preeclamptic patients, resulting in inhibition of trophoblasts invasion through upregulation of SPN expression, which may be related to the pathogenesis of preeclampsia.
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Objective To investigate the gene mutations of Chinese patients with pancreatic cancer in the coastal regions of Eastern China, and to provide a basis for individualized treatment. Methods A total of 40 patients who were admitted and diagnosed with malignant pancreatic tumor after surgical treatment in The Affiliated Hospital of Qingdao University, Qingdao Municipal Hospital, Yantaishan Hospital, and Yantai Sino-France Friendship Hospital from January 2017 to June 2019 were enrolled. Next-generation sequencing (NGS) was used to detect gene mutations in tumor tissue and somatic cells, and the map of gene mutations was plotted to analyze genomic alterations. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results Among the 40 patients, 34 (85.0%) had pancreatic ductal adenocarcinoma, 3 (7.5%) had solid pseudopapillary neoplasm of the pancreas, 1 (2.5%) had pancreatic neuroendocrine tumor, and 2 (5.0%) had unclear typing. KRAS (80.0%, 32/40), TP53 (70.0%, 28/40), CDKN2A (32.5%, 13/40), SMAD4 (17.5%, 7/40), and AKT2 (17.5%, 7/40) were the most common mutations, and there was no significant difference in survival time between the patients with these five common gene mutations (all P > 0.05). Conclusion NGS technology can provide comprehensive and accurate information of genomic alterations and may provide novel potential biomarkers for the diagnosis and precise treatment of pancreatic cancer. The analysis of mutant genes also lays a foundation for the individualized treatment of pancreatic cancer.
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【Objective】 To investigate the factors influencing the production of platelet antibody and its effect on clinical platelet transfusion. 【Methods】 This is a single-center prospective observational study. The research subjects were patients with hematological diseases in West China Hospital of Sichuan University from October 1, 2018 to September 30, 2019, and their plasma were collected before platelet transfusion to detect platelet antibodies using solid-phase agglutination method. According to the results of platelet antibody screening, the patients were divided into platelet antibody positive group and negative group. The t test and nonparametric Mann-Whitney U test were used to compare the transfusion efficacy of two groups. Patients’ demographic and clinical information, including age, gender, diagnosis, the units of platelets and RBC transfused, were collected via HIS6.2.0 and whole process management system of blood in clinical (version 3.0) to analyze the influence of age, gender and the disease on the positive rate of platelet antibodies, as well as the profile of platelet antibodies in patients with different diseases, the correlation between the positive rate of platelet antibodies and the history of blood/platelets transfusion. In additional, the platelet transfusion process was observed on site. 【Results】 A total of 316 patients with hematologic diseases were included in this study, mainly with acute myeloid leukemia(188/316, 59.5%). All patients were transfused 1671 U platelet [1~17(5.3±3.1)U each person] and 1896 U RBC products [0~38(7.8±4.6)U each person] during the treatment. Out of the 316 patients, platelet antibodies were found in 85 (26.9%) of them. No significant differences in the positive rates of platelet antibody after transfusion were notice by genders or ages(P>0.05). The incidence of platelet antibody was related to diseases (P<0.05), with MDS as the highest (57.1%), followed by aplastic anemia (36.4%) and myeloid leukemia (27.7%). In additional, the positive rate of platelet antibody increased with the number of previous platelet transfusions(P<0.05). The 316 patients were divided into positive group and negative group according to the results of platelet antibody screening. The corrected count of increment (5.2×109/L vs 11.5×109/L, P<0.01) and absolute platelet increase(8×109/L vs 17×109/L, P<0.01)in positive group were lower than those in negative group. The positive group were transfused more units of platelets(1.7 U vs 1.2 U, P<0.01)and red blood cells(1.5 U vs 1.1 U, P<0.05)per week than negative group. The platelet transfusion interval was shorter in positive group than negative group (3.1 days vs 3.6 days, P<0.05), but there was no significant difference in red blood cell transfusion interval (3.1 days vs 3.8 days, P>0.05) between two groups. The minimum PLT count(5×109/L vs 9×109/L, P<0.01), average PLT count(27×109/L vs 40×109/L, P<0.01)and average Hb(71 g/L vs 77 g/L, P<0.05)in positive group were lower than those in negative group during hospitalization, but there was no significant difference in the minimum Hb(56 g/L vs 59 g/L, P>0.05)between two groups. According to transfusion events on site, the incidence of acute adverse reactions to transfusion was 13% (169/1 291). 【Conclusions】 The positive rates of platelet antibodies in patients with hematologic diseases were relatively high. In addition, the efficacy of platelet transfusion in positive group were worse than that in the negative group. It is recommended that platelet antibody testing should be routinely performed before transfusion in hematologic disease patients to select crossmatch-compatible platelets in order to improve the effectiveness of platelet transfusion.
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Gemcitabine (GEM) is a commonly used drug in the clinical treatment of non-small cell lung cancer. Due to the accumulation of cells mediating immune escape and T cell depletion after chemotherapy, tumor microenvironment (TME) tends to be immunosuppressive status, which ultimately leads to tumor metastasis. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. Therefore, we observed the immunomodulatory effects of micro-particulate Ganoderma lucidum spore β-glucan (PGSG) on macrophages in vitro experiments. Next, mice subcutaneous Lewis lung cancer models were established to observe the anti-tumor effects of PGSG through oral administration of PGSG combined with GEM. Flow cytometry analysis was used to analyze the ratio of anti-tumor T cells in tumors and spleen, as well as the proportion of myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) and regulatory cells (Tregs). The results showed that PGSG can up-regulate the expression of major histocompatibility antigens (MHC-II), CD40, CD86 and CD80 on the surface of macrophages, enhance the ability to phagocytosis of neutral red and further mediate the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-10 (IL-10). In vivo experiments, combined administration can significantly decrease the volume and weight of tumors, reduce the ratio of MDSC (CD11b+Gr-1+), M-MDSC (CD11b+Ly6G-Ly6Chigh) and Treg (CD4+Foxp3+). At the same time, PGSG promoted the conversion of M2 (F4/80+CD206+) to M1 (F4/80+MHC-II+) and enhanced the response of helper T cell-1 (Th1) (CD4+IFN-γ+) and cytotoxic T lymphocyte (CTL) (CD8+IFN-γ+), which is of great significance for killing tumors. These results suggest that PGSG can regulate innate and adaptive antitumor immune responses, reshape the immunosuppressive microenvironment and enhance the anti-lung cancer effect of GEM.
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OBJECTIVES@#This study aimed to evaluate the application value of a modified retroauricular hairline incision and a sternocleidomastoid flap with an inferior pedicle in the resection of benign parotid gland tumors.@*METHODS@#Forty-eight patients with benign parotid gland tumors were retrospectively analyzed: 19 cases were included in the experimental group with an improved retroauricular hairline incision and a sternocleidomastoid flap with an inferior pedicle, and 29 cases were assigned in the control group with a modified facelift incision. Operation time, postoperative drainage, postoperative esthetic degree, and incidence of facial nerve paralysis, salivary fistula, and Frey's syndrome were compared.@*RESULTS@#After the esthetic procedure, the average score of the experimental group was higher than that of the control group, and the esthetic effect of the former was better than that of the latter (@*CONCLUSIONS@#The modified retroauricular hairline incision and sternocleidomastoid flap with an inferior pedicle can be applied to resect benign parotid gland tumors safely. It shows a better cosmetic effect and does not cause obvious postoperative complications. Therefore, it should be promoted for tumor treatments.
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Humans , Esthetics, Dental , Parotid Gland/surgery , Parotid Neoplasms/surgery , Postoperative Complications , Retrospective Studies , Sweating, GustatoryABSTRACT
Objective:To study combined adjuvant transcatheter arterial chemoembolization (TACE) with anti-tumor drug treatment on early hepatocellular carcinoma (HCC) recurrence in patients with microvascular invasion (MVI) after partial hepatectomy with curative intent.Methods:The clinical and pathological data of 169 patients with HCC who underwent partial hepatectomy with curative intent from January 2015 to December 2018 at the Affiliated Hospital of Qingdao University were retrospectively analyzed. MVI was diagnosed by postoperative histopathology. There were 147 males and 22 females, with the median age 56 years(ranged 32-79 years). The patients were divided into surgery group ( n=62, patients who did not receive adjuvant therapy), TACE group ( n=42, patients who only received TACE) and combined group ( n=65, patients who received TACE with anti-tumor drug) according to the therapies after resection. Patients in each group were further divided into grade M1 (mild) and grade M2 (severe) subgroups according to the severity of MVI. All patients were followed-up for observing tumor recurrence. The relapse-free survival in the three groups were compared using the Kaplan-Meier method and the log-rank test was used to compare the tumor-free survival rates. Results:The tumor-free survival rates of 169 patients at 1 and 2 years after operation were 59.2% and 40.8%. The tumor-free survival rates at 1 and 2 years after operation were 45.2% and 25.8% in surgery group, 61.9% and 40.5% in TACE group, 70.8% and 52.3% in combined group respectively. The differences among the three groups were significant: TACE group was better than surgery group, and combined group was better than TACE group, combined group was better than surgery group (all P<0.05). In TACE group and combined group, tumor-free survival rates of M1patients better than M2 patients, and the difference was significant ( P<0.05). Among M1 patients and M2 patients, tumor-free survival rates of combined group patients were better than surgery group and TACE group, the difference was significant (all P<0.05). The cumulative tumor-free survival rate was not significantly affected by different antineoplastic agents. Conclusion:Adjuvant TACE reduced the early recurrence rate of HCC patients with MVI. Adjuvant TACE combined with anti-tumor drug further reduced early tumor recurrence.
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This study evaluated the effects of epimedium polysaccharide(EPS) on the solubility of icariin and baohuoside Ⅰ so as to preliminary explore its solubilization function and the underlying mechanism. The solubility of these two insoluble flavonoids in water and polysaccharide solutions was compared by high performance liquid chromatography, and the mechanism was investigated by diffe-rential scanning calorimetry(DSC) and critical micelle concentration determination. The results indicated that their solubilization in crude EPS solutions was concentration-dependent. The solubility of icariin and baohuoside Ⅰ in 20 mg·mL~(-1) EPS-1-1 was 9.05 times and 5.76 times that in water, respectively; while their solubility in 20 mg·mL~(-1) EPS-2-1 was 10.55 and 8.39 times that in water, respectively. The change of the DSC thermograms suggested the formation of new complexes from icariin and baohuoside Ⅰ with polysaccharides. The critical micelle concentrations proved the micellar properties of both EPS-1-1 and EPS-2-1. In short, EPS can significantly increase the solubility of icariin and baohuoside Ⅰ, the mechanism of which may be related to the formation of micellar complexes between EPS and insoluble flavonoids.
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Epimedium , Flavonoids , Polysaccharides , SolubilityABSTRACT
【Objective】 To demonstrate the real incidence and clinical features of acute transfusion reactions (ATRs) and analyze its association with transfusion effectiveness. 【Methods】 The blood transfusion process of patients in the Hematology Department in our hospital from March 16, 2018 to March 16, 2019 was observed and followed up. The vital signs and clinical features were recorded, the clinical data and relevant laboratory examination results were collected, and the correlation between ATRs, clinical features and transfusion effectiveness was statistically analyzed. 【Results】 A total of 2500 transfusions were observed in the Hematology Department, out of which 138 patients developed 242 ATRs. The overall incidence of ATRs was 9.68% (95% CI, 8.52%~10.94%) and the incidence of ATRs during platelets transfusion was the highest. The clinical features of most ATRs were mild and no fatal consequences occurred. No significant difference was found in the association between transfusion effectiveness with ATRs in platelets and red blood cells transfusion (P>0.05). 【Conclusion】 None of the ATRs observed in this study resulted in serious consequences or had effect on the transfusion effectiveness. The characteristics presented in these reactions may provide certain references for clinical practice.
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OBJECTIVE@#To evaluate the effects of membrane induced by antibiotic-loaded bone cement in skin grafting for tendon exposed wound healing.@*METHODS@#A total of 10 traumatic patients with tendon exposed wound were admitted to our department between February 2016 and December 2018, including 6 males and 4 females, with a mean age of 34.6 years old (ranged, 19 to 43 years old), and treatment duration ranged from 2 to 6 months. There were 7 cases of traffic accidents, 3 cases of mechanical belt injuries, including 8 cases of lower leg and foot wounds and 2 cases of hand back wounds. These tendons exposed wound were covered by antibiotic-loaded bone cement at the earlier stageto induce the formation of the biomembrane, and then skin grafting were performed on the induced membrane. The survival, appearance, texture, sensation of the skin grafting and healing condition of the wounds were studied.@*RESULTS@#Among the 10 patients, skin graft survived well in 8 patients. Partial skin graft necrosis occurred in 2 patients and cured by dressing.@*CONCLUSION@#Using antibiotic bone cement to seal the wound to form induction membrane followed by skin grafting can effectively repair the tendon exposed wound, which has the characteristics of simple operation and less trauma.
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Adult , Female , Humans , Male , Young Adult , Anti-Bacterial Agents , Bone Cements , Plastic Surgery Procedures , Skin Transplantation , Soft Tissue Injuries , Tendons , Treatment Outcome , Wound HealingABSTRACT
In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1∶20 solid - liquid ratio and 55 ℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4+ T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.
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Objective:To investigate the regulatory effect of Sinisan(SNS) on the polarization of RAW264.7 macrophages induced by lipopolysaccharide (LPS). Method:RAW264.7 cells stimulated by LPS were used as the in vitro model. The cells were intervened with the different concentrations of SNS in advance. The effects of different concentrations of SNS on the proliferation of RAW264.7 cells were detected by methyl thiazolyl tetrazolium (MTT) colorimetry. The degree of cell differentiation was detected by enzyme-linked immuno sorbent assay(ELISA) method. The contents of M1 polarization factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and M2 polarization factors interleukin-10 (IL-10) in cell culture supernatant were detected by ELISA method, mRNA levels of M1 polarization factors TNF-α, IL-6 and M2 polarization factors IL-10, arginase-1 (Arg-1) were detected by Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) method. Result:SNS had no effect on the cell viability of RAW264.7 cells, inhibited LPS-induced cell proliferation, decreased LPS-stimulated cell differentiation, down-regulated M1 polarizing factors TNF-α, IL-6, IL-1β release and TNF-α, IL-6 mRNA levels, and increased the release of IL-10 and mRNA levels of IL-10 and Arg-1. Conclusion:SNS inhibits the inflammation of RAW264.7 cells induced by LPS, and its mechanism may be related to the regulation of polarization balance of M1/M2 macrophages.
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Objective@#To study the effect of atorvastatin combined with Zhibitai in the treatment of coronary heart disease with hyperlipidemia and its influence on the level of high-sensitivity C-reactive protein(hsCRP).@*Methods@#A total of 136 patients with coronary heart disease and hyperlipidemia admitted to the Third People's Hospital of Jingdezhen from September 2016 to September 1818 were randomly divided into control group and combination group using stochastic comprehensive balance method, with 68 cases in each group.The control group was treated with atorvastatin and the combination group was treated with lipidine plus atorvastatin. The patient's treatment effect, including the blood lipid compliance rate and the occurrence of adverse reactions during the treatment were observed, as well as the patient's pre-and post-treatment triglyceride(TG), 12h serum total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol(LDL-C)and high-sensitivity C-reactive protein(hsCRP)and other indicators were measured.@*Results@#(1)The blood lipid compliance rate(89.86%) in the combined group was higher than that in the control group(59.70%), the difference was statistically significant(χ2=14.915, P=0.000). (2)The incidence of adverse reactions in the combined group(1.45%) was lower than that in the control group(17.91%), the difference was statistically significant(χ2=8.836, P=0.003). (3)The results showed that the TC, TG, LDL-C, hsCRP and other indicators of the combined group were lower than those of the control group and before treatment, while the HDL-C index of the combined groupwas higher than that of the control group and before treatment, the differences were statistically significant(t=20.800, 4.903, 11.657, 4.346, 6.262, P=0.000, 0.000, 0.000, 0.000, 0.000).@*Conclusion@#Zhibitai combined with atorvastatin in the treatment of coronary heart disease patients with hyperlipidemia has remarkable effect.It can accurately control TC, TG, LDL-C, HDL-C and hsCRP, improve blood lipid control rate.
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Objective@#To investigate the mechanism of wild-type p53-induced phosphatase (Wip1) in regulating p53-dependent apoptosis of trophoblasts for further understanding the etiology of preeclampsia (PE).@*Methods@#Placenta tissues were collected from normal (n=15) and PE (n=13) gravidas who underwent caesarean section in the First Affiliated Hospital of Chongqing Medical University from June 2017 to December 2018. Chorionic villus and decidua tissues were collected from another 10 women who aborted in early pregnancy. Two in vitro trophoblastic hypoxia cultures were established by subjecting human chorionic trophoblast cells (HTR8/SVneo) to either hypoxia intervention in incubator (HII) or simulated ischemic buffer (SIB). Wip1 expressions at the transcriptional and protein levels were determined by real-time quantitative polymerase chain reaction and Western blotting, respectively. The localization of Wip1 in placental tissues and HTR8/SVneo cells was determined by immunohistochemistry and immunofluorescence. Cell apoptosis was assessed by flow cytometry after viral infection and hypoxia. And the changes of pathway-related molecules including p53, phospho-p53 (p-p53), mouse double minute 2 homolog (Mdm2) and cleaved caspase3 (cl-cas3) were measured by Western blotting. The impact of Wip1 on Mdm2-p53 interaction was examined by co-immunoprecipitation. NVP-CGM097, an Mdm2-p53 specific inhibitor, was administered in PE cell models to verify the regulation of Wip1 on trophoblastic apoptosis through Mdm2-p53 pathway. Independent student's t-test, Welch's t-test and one-way analysis of variance were used as statistical methods.@*Results@#(1) Wip1 expression, which was mainly in trophoblast cells, was significantly elevated in human PE placentas (mRNA: 1.711±0.141 vs 0.860±0.126, t=4.496; protein: 0.449±0.027 vs 0.192±0.019, t=7.902) and in both in vitro trophoblastic PE models (protein in HII: 1.376±0.086 vs 0.977±0.114, t=2.792; SIB: 1.243±0.057 vs 0.381±0.045, t=11.910) compared with the corresponding control groups (all P<0.05). (2) Compared with corresponding control groups, overexpression of Wip1 suppressed the hypoxia-induced upregulation of p53 (HII: 0.185±0.024 vs 0.572±0.072; SIB: 0.400±0.067 vs 0.803±0.064), cl-cas3 (HII: 0.243±0.034 vs 0.529±0.072; SIB: 0.179±0.011 vs 0.368±0.025) and p-p53/p53 protein expression (HII: 1.326±0.129 vs 2.100±0.187; SIB: 0.473±0.028 vs 0.925±0.036) and also reduced the apoptosis rate [HII: (8.925±1.092)% vs (17.610±1.980)%; SIB: (13.910±1.886)% vs (24.650±1.622)%], which in turn promoted Mdm2-p53 binding (all P<0.05). However, knockdown of Wip1 gene expression in HTR8/SVneo cells brought about opposite effects (all P<0.05). (3) Neither overexpression nor knockdown of Wip1 influenced p53 or cl-cas3 expression when Mdm2-p53 interaction was blocked by NVP-CGM097.@*Conclusions@#Mdm2-p53 interaction promoted by Wip1 upregulation could compensate for the trophoblastic p53 accumulation in response to hypoxia, while exogenous upregulation of Wip1 in trophoblasts may reverse hypoxia-induced apoptosis. Therefore, this might provide a new therapeutic target for PE.
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Objective To investigate the mechanism of wild-type p53-induced phosphatase (Wip1) in regulating p53-dependent apoptosis of trophoblasts for further understanding the etiology of preeclampsia (PE). Methods Placenta tissues were collected from normal (n=15) and PE (n=13) gravidas who underwent caesarean section in the First Affiliated Hospital of Chongqing Medical University from June 2017 to December 2018. Chorionic villus and decidua tissues were collected from another 10 women who aborted in early pregnancy. Two in vitro trophoblastic hypoxia cultures were established by subjecting human chorionic trophoblast cells (HTR8/SVneo) to either hypoxia intervention in incubator (HII) or simulated ischemic buffer (SIB). Wip1 expressions at the transcriptional and protein levels were determined by real-time quantitative polymerase chain reaction and Western blotting, respectively. The localization of Wip1 in placental tissues and HTR8/SVneo cells was determined by immunohistochemistry and immunofluorescence. Cell apoptosis was assessed by flow cytometry after viral infection and hypoxia. And the changes of pathway-related molecules including p53, phospho-p53 (p-p53), mouse double minute 2 homolog (Mdm2) and cleaved caspase3 (cl-cas3) were measured by Western blotting. The impact of Wip1 on Mdm2-p53 interaction was examined by co-immunoprecipitation. NVP-CGM097, an Mdm2-p53 specific inhibitor, was administered in PE cell models to verify the regulation of Wip1 on trophoblastic apoptosis through Mdm2-p53 pathway. Independent student's t-test, Welch's t-test and one-way analysis of variance were used as statistical methods. Results (1) Wip1 expression, which was mainly in trophoblast cells, was significantly elevated in human PE placentas (mRNA: 1.711±0.141 vs 0.860±0.126, t=4.496; protein: 0.449±0.027 vs 0.192±0.019, t=7.902) and in both in vitro trophoblastic PE models (protein in HII: 1.376±0.086 vs 0.977±0.114, t=2.792; SIB: 1.243±0.057 vs 0.381±0.045, t=11.910) compared with the corresponding control groups (all P<0.05). (2) Compared with corresponding control groups, overexpression of Wip1 suppressed the hypoxia-induced upregulation of p53 (HII: 0.185±0.024 vs 0.572±0.072; SIB: 0.400±0.067 vs 0.803±0.064), cl-cas3 (HII: 0.243±0.034 vs 0.529±0.072; SIB:0.179±0.011 vs 0.368±0.025) and p-p53/p53 protein expression (HII: 1.326±0.129 vs 2.100±0.187; SIB:0.473±0.028 vs 0.925±0.036) and also reduced the apoptosis rate [HII: (8.925±1.092)% vs (17.610±1.980)%;SIB: (13.910±1.886)% vs (24.650±1.622)%], which in turn promoted Mdm2-p53 binding (all P<0.05). However, knockdown of Wip1 gene expression in HTR8/SVneo cells brought about opposite effects (all P<0.05). (3) Neither overexpression nor knockdown of Wip1 influenced p53 or cl-cas3 expression when Mdm2-p53 interaction was blocked by NVP-CGM097. Conclusions Mdm2-p53 interaction promoted by Wip1 upregulation could compensate for the trophoblastic p53 accumulation in response to hypoxia, while exogenous upregulation of Wip1 in trophoblasts may reverse hypoxia-induced apoptosis. Therefore, this might provide a new therapeutic target for PE.
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Objective To study the effect of atorvastatin combined with Zhibitai in the treatment of coronary heart disease with hyperlipidemia and its influence on the level of high-sensitivity C-reactive protein ( hsCRP). Methods A total of 136 patients with coronary heart disease and hyperlipidemia admitted to the Third People 's Hospital of Jingdezhen from September 2016 to September 1818 were randomly divided into control group and combi-nation group using stochastic comprehensive balance method , with 68 cases in each group.The control group was treated with atorvastatin and the combination group was treated with lipidine plus atorvastatin .The patient's treatment effect,including the blood lipid compliance rate and the occurrence of adverse reactions during the treatment were observed,as well as the patient's pre-and post-treatment triglyceride ( TG),12h serum total cholesterol ( TC), high-density lipoprotein-cholesterol ( HDL-C), low density lipoprotein-cholesterol ( LDL-C) and high-sensitivity C-reactive protein(hsCRP)and other indicators were measured.Results (1)The blood lipid compliance rate(89.86%) in the combined group was higher than that in the control group (59.70%),the difference was statis-tically significant(χ2 ＝14.915,P＝0.000).(2)The incidence of adverse reactions in the combined group (1.45%) was lower than that in the control group (17.91%), the difference was statistically significant ( χ2 ＝8.836, P ＝ 0.003).(3)The results showed that the TC,TG,LDL-C,hsCRP and other indicators of the combined group were lower than those of the control group and before treatment ,while the HDL-C index of the combined groupwas higher than that of the control group and before treatment ,the differences were statistically significant ( t＝20.800,4.903, 11.657,4.346,6.262,P＝0.000,0.000,0.000,0.000,0.000).Conclusion Zhibitai combined with atorvastatin in the treatment of coronary heart disease patients with hyperlipidemia has remarkable effect .It can accurately control TC,TG,LDL-C,HDL-C and hsCRP,improve blood lipid control rate.
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OBJECTIVE@#The purpose of this study was to assess the association between triglycerides (TG), total cholesterol (TC) at baseline, and type 2 diabetes mellitus (T2DM) incidence in a general Chinese population. Further, it aimed to evaluate the ability of TG and TC to predict T2DM incidence.@*METHODS@#Qingdao Diabetes Prevention Program participants recruited between 2006 and 2009 were followed up in 2012-2015. TG, TC, and T2DM status were measured. Cox proportional hazards models were used to estimate the association between TG, TC, and T2DM incidence. The receiver operating characteristic (ROC) curve was used to evaluate the ability of TG and TC to identify T2DM participants.@*RESULTS@#The incidence of T2DM significantly increased with TG in women and TC in both men and women (Ptrend 1.15 and > 1.23 mmol/L in men and women, respectively. For TC, they were > 5.17 and > 5.77 mmol/L in men and women, respectively. The area under the ROCs of TG and TC were 0.54 (0.51-0.57) and 0.55 (0.52-0.58), respectively, in men, and 0.60 (0.58-0.62) and 0.59 (0.56-0.61), respectively, in women.@*CONCLUSION@#Elevated TG and TC were risk factors for T2DM incidence. However, no predictive capacity was found for both factors to identify T2DM incidence in Chinese men and women. Hence, TG and TC levels in both Chinese men and women might be used for decreasing the incidence of T2DM but no clinical predictive capacity for T2DM.
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Conventional oxygen therapy (COT) is generally provided through a low flow rate device including a nasal cannula or facemask. Since the benefits of high-flow nasal cannula (HFNC) oxygen therapy in adults with acute respiratory failure (ARF) have firstly been demonstrated by Roca et al and because of its effectivity and comfort and good compliance, it has shown greater advantageous than COT and it has been increasingly used in adults with mild to moderate ARF and obtained very nice therapeutic effect. However, because of the specificity of emergency environment and the more complexity of HFNC system than COT, the use of HFNC in department of emergency is still controversial. Since HFNC system delivers oxygen by high-flow rate, the dilution of inspired oxygen concentration (FiO2) by room air can be maximally decreased, and the system can provide the highest flow rate up to 60 L/min, being greater than the patients' peak inspiration flow flow (PIF); the high flow rate can dilute the carbon dioxide (CO2) concentration in the anatomical dead space, and the above several factors can guarantee that HFNC may deliver 0.21-1.00 relatively constant FiO2. Therefore, HFNC as a new noninvasive supplemental oxygen therapy has been increasingly widely studied and used in the adult patients with ARF. In this article, we will review the HFNC physiological effects and its advances in application for adult patients in department of emergency.
ABSTRACT
AIM:To investigate the effects of kaempferol-3-O-rutinoside(KR)on the proliferation,migration of vascular smooth muscle cells(VSMC)and the activation of transforming growth factor βreceptor 1(TGFBR1)signaling pathway in the cells.METHODS: The viability of VSMC was detected by MTT assay.The proliferation of VSMC was measured by EdU staining.The migration ability of VSMC was examined by Transwell assay.The protein levels of the mi-gration-associated proteins matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9)were detected by Western blot.Molecular docking study was conducted to explore the interaction between KR and TGFBR 1.The protein le-vels of the phosphorylated TGFBR1,Smad2 and Smad3 were determined by Western blot.RESULTS: KR inhibited the viability of VSMC in a dose-and time-dependent manner.KR reduced the ratio of EdU-positive cells in a dose-dependent manner.KR dose-dependently suppressed the migration ability of VSMC and decreased the protein levels of MMP 2 and MMP9(P<0.05).KR docked into TGFBR1 with the binding energy of -9.804 kcal/mol by forming hydrogen bonds with SER-280,ARG-215,ASP-290 and LYS-335 of TGBFR1.KR dose-dependently suppressed the activation of TGFBR 1 and its downstream proteins Smad2 and Smad3(P<0.05).CONCLUSION: KR inhibits the proliferation and migration of VSMC,possibly via blocking the TGFBR1 signaling pathway.
ABSTRACT
Objective To provide an optimal working process for crossmatching by full-automatic blood typing instrument.Methods Two workflows were applied to crossmatch test by full-automatic blood typing instrument.One was diluting red blood cells of donor samples to concentrate of 1%,the other was detecting directly the donor′s packed red blood cells.Compared consistency and processing time of the two different workflows.Results Cross match results of two workflows were consistent well(U=0,P>0.05).The average processing times before testing and undergoing testing were not significantly different(t=0.692,t=0.562,P>0.05),whereas the average processing times after testing and throughout testing were significantly different(t=146.485,t=67.053,P<0.05).Conclusion The workflow of diluting donor′s sample before testing saved processing time and better suits hospital having a large quantity of specimens.
ABSTRACT
To enhance the efficiency of the extraction for Epimedium koreanum Nakai polysaccharides, we conducted the Box-Benhnken experiment and examined the response surface. C57 BL6 mice were used as Lewis-bearing mice model in the study of the polysaccharides in the regulation of tumor immunity. In the first place, different factors including extraction time, temperature, and ratio were evaluated in the yield of polysaccharides. The second order polynomial equation was formed to fit the experimental data. The optimal condition was temperature 87℃, extraction time 3.84 h, and ratio of solution and material 1:16.33 to get polysaccharides from Epimedium koreanum Nakai. Under this condition, model-predicted and experimentally measured values of polysaccharide yield were 1.045% and 1.023%, respectively, with a relative error between them at 2.15%. The extraction method is reliable, simple and applicable to the extraction of Epimedium poly-saccharides. In addition, this data suggests that Epimedium polysaccharides have obvious immune-regulatory activities in the tumor-bearing mice through increasing the immune-enhancing cytokines to override the immune-suppressing factors.