Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

OBJECTIVES: This study aimed to analyze the application value of a modified tragus edge incision and transmasseteric anteroparotid approach to condyle reconstruction. METHODS: Condyle reconstruction was performed in 16 patients (9 females and 7 males) with modified tragus edge incision and transmasseteric anteroparotid approach. After regular follow-up, the function of condyle reconstruction was evaluated by clinical indicators, such as parotid salivary fistula, facial nerve function, mouth opening, occlusal relationship, and facial scar. The morphology of rib graft rib cartilage was evaluated by imaging indicators, such as panoramic radiography, CT, and three-dimensional CT image reconstruction. RESULTS: At 6-36 months postoperative follow-up, all patients had good recovery of facial appearance, concealed incisional scar, no parotid salivary fistula, good mouth opening, and occlusion. One case had temporary facial paralysis and recovered after treatment. Radiographic evaluation further showed that costochondral graft survived in normal anatomic locations. CONCLUSIONS The modified tragus edge incision and transmasseteric anteroparotid approach can effectively reduce parotid salivary fistula and facial nerve injury in condylar reconstruction. The surgical field was clearly exposed, and the incision scar was concealed without increasing the incidence of other complications. Thus, this approach is worthy of clinical promotion.
Male ; Female ; Humans ; Mandibular Condyle/surgery* ; Cicatrix/surgery* ; Fracture Fixation, Internal/methods* ; Mandibular Fractures/surgery* ; Oral Surgical Procedures/methods* ; Treatment Outcome

【Objective】 To establish and evaluate a fluorescent antibody to membrane antigen (FAMA) method for detecting antibodies against varicella-zoster virus (VZV) based on Vero E6 cells. 【Methods】 Based on the adapted VZV-Oka-E6 strain that VZV-Oka live attenuated varicella vaccine strain grew in Vero E6 cells, Vero E6 cells were infected with VZV-Oka-E6 of three different doses (10^4.65, 10^4.95 and 10^5.25 TCID50), and the cytopathic effect was observed under a microscope to determine the optimal infection dose of VZV-Oka-E6 strain. Then the detectable sensitivity of the infected cell antigen slides prepared after fixing the infected cells with different fixatives was compared to determine the optimal fixative. As a result, the FAMA method based on Vero E6 cells for the determination of neutralizing anti-VZV has been developed. The established FAMA assay was used to detect the international standard for varicella zoster immunoglobulin with different titers to determine the sensitivity of the assay. The specificity of the assay was evaluated by detecting specific antibodies against human herpes simplex virus (HSV) type 1 and type 2. The neutralizing anti-VZV antibodies of the international standard for varicella zoster immunoglobulin were detected using VZV-infected cell antigen slides prepared in the same batch and four different batches, respectively, to determine the intra-assay repeatability and inter-assay repeatability. The international standard for varicella zoster immunoglobulin with three known titers was detected to evaluate the relative accuracy of this assay. The anti-VZV titers in 20 apheresis plasma samples were determined with the newly established FAMA test and ELISA test, respectively, and the detection results of the two methods were compared using Spearman’s correlation test. 【Results】 The optimal infection dose of the VZV-Oka-E6 strain in FAMA assay was determined to be 10^5.25 TCID50, and acetone precooled at -20℃ was used as the fixative. The FAMA test has a high sensitivity with a detecting limit of 31.25 mIU/mL for neutralizing anti-VZV titers. The negative result was observed when detecting herpes simplex virus (HSV) type 1 and 2 specific antibodies. The international standard for varicella zoster immunoglobulin was detected by VZV infected cell antigen slides prepared in the same batch and 4 different batches, with the coefficient of variation being 29.95% and 26.71%, respectively. The detection value of the international standard for varicella zoster immunoglobulin with three different titer levels was consistent with their theoretical value. The correlation coefficient of the detection results of 20 apheresis plasma samples by the FAMA test and ELISA test was 0.268. 【Conclusion】 The VZV FAMA assay has good sensitivity, specificity, repeatability, and relative accuracy in detecting neutralizing anti-VZV titers. It can be applied for detecting neutralizing anti-VZV titers in apheresis plasma samples as well as the varicella-zoster immunoglobulin (VZIG) preparations.

Objective:To investigate the relationship between low vitamin D levels and the risk of Graves' disease.Methods:Computer was used to search PubMed, EMbase, China National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang Data) and China Biomedical Database (CBM). Relevant Chinese and English literatures were collected, including literatures of vitamin D, Graves' disease and autoimmune thyroid disease from the earliest publication time of the literature in the database to September 2019. Statistical software Stata 12.0 was used for Meta-analysis of the data. Heterogeneity test was conducted on the literature that met the inclusion criteria. According to the results, a random-effect model fixed-effect model was selected for comprehensive quantitative analysis. Standardized mean difference ( SMD) and 95% confidence interval ( CI) were calculated, and Egger's test was used to evaluate publication bias and sensitivity analysis. Results:A total of 29 literatures were included in the study, covering 2 281 patients with Graves' disease and 4 200 control population. Meta-analysis results showed: after the data were combined using a random-effects model, vitamin D levels in patients with Graves' disease were significantly lower than that in the control population ( SMD = - 0.90, 95% CI: - 1.14, - 0.66, P < 0.01﹚; heterogeneity analysis and Meta-regression analysis showed that the four factors of national development degree, geographical location, indicator measurement method and whether Graves' disease was primary were not the main source of heterogeneity. However, in developing countries or Asian, the vitamin D levels of patients with Graves' disease were significantly lower than that of the control population ( P < 0.01). In developed countries or Europe, the difference was not statistically significant ( P > 0.05). Sensitivity analysis and publication bias analysis showed that the results of this study had certain stability and reliability. Conclusion:Low vitamin D levels may increase the risk of Graves' disease.

Objective To investigate the mechanism by which hydrogen(H2) helps prevent acute lung injury induced by hyperoxia (HALI) in rats.Methods Thirty male Sprague-Dawley rats were randomly divided into three groups: control group, HALI group and H2 group, with 10 rats in each group.The control group was exposed to air at atmospheric pressure.Rats in HALI and H2 groups were exposed continuously to pure oxygen (100%O2) for 60 hours and during this period, 10 ml/kg of normal saline or H2-saturated normal saline was given every 12 hours by intraperitoneal injection to the HALI and H2 groups, respectively.After treatment, the arterial partial pressure of oxygen was examined and histopathological examination was conducted in each group.Then,RT-qPCR and Western blotting were performed to measure the transcriptional level and protein expression of heme oxygenase 1 (human heme oxygenase 1, HO-1) in rat lung tissue.Results Compared with the HALI group, H2 group showed significantly decreased severity of lung injury and a marked increase in the arterial oxygen saturation.Besides, H2 treatment induced up-regulation of HO-1 mRNA and protein levels.Conclusion The findings suggest that HO-1 may play an important role in the protection against HALI by H2.

Objective To develop an effective process for isolating and purifying haptoglobin ( Hp) from Cohn fractionⅣby a new ion exchange chromatography and to preliminarily identify and analyze the product of each purification step . Methods The fraction was first diluted and impurities were adsorbed with Rivanol .Then, the supernatant was treated with 50%ammonium sulfate.Finally, the precipitate was redissolved , and Hp was purified further with Q Sepharose Fast Flow chromatography .Native-PAGE was used to measure the activity of the haptoglobin-bound hemoglobin , while SDS-PAGE analysis and immunoblot were used for identification of the target protein .Results After pretreatment , some of the impuri-ties were removed from the Cohn fraction Ⅳ, and the target protein was enriched .In our case, the target protein was Hp and Hp2-2 was the main phenotype in the human plasma fraction Ⅳ.Target protein band and high purity were identified by SDS-PAGE.Immunoblot analysis further proved that this method could successfully isolate the target protein Hp , and the activity of 2.8 U/ml was measured by Native-PAGE method.Conclusion Haptoglobin is successfully isolated from human Cohn fractionⅣwith this method.The purification process is simple and suitable for scale-up production with a good prospect.

Objective To investigate impact of admission renal dysfunction on in-hospital and longterm outcome of patients with ST-elevation myocardial infarction (STEMI).Methods This was a multicentre,observational,prospective-cohort study.Totally 718 consecutive patients were admitted to 19 hospitals in Beijing within 24 hours of onset of STEMI.Estimation of glomerular filtration rate (eGFR) was calculated according to the abbreviated MDRD equation.The patients were categorized into two groups as renal preservation group(eGFR ≥60 ml · min-1 · 1.73 m-2) and renal dysfunction group(eGFR ＜ 60 ml ·min-1 · 1.73 m-2).The association between admission renal dysfunction and in-hospital and six-year outcome was evaluated.Results A total of 718 patients with STEMI were evaluated.There were 551 men and 167 women with age of (61.0 ± 13.0) years.One hundred and thirty-three patients(18.5％) had renal dysfunction.Patients with renal dysfunction were more often female and older,more patients had hypertension,diabetes and heart failure,and more patients had ≥ Killip Ⅱ classes on admission.These patients were less likely to present with chest pain.The in-hospital mortality(16.5％ vs 2.6％,P＜0.001),major adverse cardiac events(MACE) (60.9％ vs 24.4％,P ＜0.001),six-year all-cause mortality(35.3％vs 11.4％,P ＜ 0.001),six-year cardiac mortality (15.9％ vs 5.7％,P =0.001) and six-year MACE (52.4％ vs 28.0％,P ＜ 0.001)were markedly increased in renal dysfunction group than in renal preservation group.After adjusting for other confounding factors,renal dysfunction was an independent predictor of in-hospital MACE (OR 2.120,95％ CI 1.563-2.878,P =0.003),six-year all-cause mortality (RR 2.122,95％ CI 1.127-3.996,P =0.020) and six-year MACE(RR 1.586,95％ CI 1.003-2.530,P =0.047).Conclusions The mortality and MACE in STEMI patients with renal dysfunction were higher than in those with preserved renal function.Renal dysfunction evaluated by eGFR on admission is an important independent predictor of short-term and long-term outcome in patients with acute STEMI.

BACKGROUNDNumerous previous studies have shown that renal insufficiency (RI) in patients with acute coronary syndrome is associated with poor cardiovascular outcomes. These studies do not well address the impact of RI on the long-term outcome of patients with acute ST-elevation myocardial infarction (STEMI) in China. The aim of this study was to investigate the association of admission RI and inhospital and long-term mortality of patients with acute STEMI.

METHODSThis was a multicenter, observational, prospective-cohort study. 718 consecutive patients were admitted to 19 hospitals in Beijing within 24 hours of onset of STEMI, between January 1,2006 and December 31,2006. Estimation of glomerular filtration rate (eGFR) was calculated using the modified abbreviated modification of diet in renal disease equation-based on the Chinese chronic kidney disease patients. The patients were categorized according to eGFR, as normal renal dysfunction (eGFR ≥ 90 ml·min -1·1.73 m -2 ), mild RI (60 ml·min -1·1.73 m -2 ≤ eGFR < 90 ml·min -1·1.73 m -2 ) and moderate or severe RI (eGFR < 60 ml·min -1·1.73 m -2 ). The association between RI and inhospital and 6-year mortality of was evaluated.

RESULTSSeven hundred and eighteen patients with STEMI were evaluated. There were 551 men and 167 women with a mean age of 61.0 ± 13.0 years. Two hundred and eighty patients (39.0%) had RI, in which 61 patients (8.5%) reached the level of moderate or severe RI. Patients with RI were more often female, elderly, hypertensive, and more patients had heart failure and stroke with higher killip class. Patients with RI were less likely to present with chest pain. The inhospital mortality (1.4% vs. 5.9% vs. 22.9%, P < 0.001), 6-year all-cause mortality (9.5% vs. 19.8 vs. 45.2%, P < 0.001) and 6-year cardiac mortality (2.9% vs. 12.2% vs. 23.8%, P < 0.001) were markedly increased in patients with RI. After adjusting for other confounding factors, classification of admission renal function was an independent predictor of inhospital mortality (Odd ratio, 1.966; 95% confidence interval [CI], 1.002-3.070, P = 0.019), 6-year all-cause mortality (relative risk [RR] = 1.501, 95% CI: 1.018-4.373, P = 0.039) and 6-year cardiac mortality (RR = 1.663, 95% CI: 1.122-4.617, P = 0.042).

CONCLUSIONSRI is very common in STEMI patients. RI evaluated by eGFR is an important independent predictor of short-term and long-term outcome in patients with acute STEMI.

Aged ; Female ; Glomerular Filtration Rate ; physiology ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; mortality ; physiopathology ; Renal Insufficiency ; mortality ; physiopathology

Objective To evaluate the gender difference in the prognostic value of admission renal dysfunction (RD) for patients with acute ST-segment elevation (STEMI).Methods This was a multicenter,prospective cohort study.Four hundred and fifty STEMI patients within 24 h of onset and discharged successfully from 19 hospitals in Beijing were included in the study.All the patients were followed up six years later.According to gender,patients were categorized into two groups.Clinical characteristics,reperfusion therapy conditions and outcomes were analyzed.Multivariate Cox regression analysis was used to evaluate the possible gender difference in the prognostic value of RD.Results Among all the subjects,342 were men and 108 were women with age of (61.3 ± 12.5) years.Compared to man patients,women were older (P ＜ 0.001),and more subjects were with hypertension (67.6％ vs 49.7 ％,P =0.005),stroke (15.7％ vs 8.8％,P =0.039) and RD (17.9％ vs 6.7％,P =0.001).After adjustment of age,past medical history,and acute reperfusion therapy.Cox regression analysis showed that RD was associated with the risk of all-cause mortality (HR 3.771,95％ CI 1.382-10.294,P =0.010) and major adverse cardiovascular events (MACE,HR 2.292,95％ CI:1.091-4.817,P =0.029) in male patients.However,the associations between RD and all-cause mortality(HR 0.889,95％ CI 0.241-3.281,P =0.859),and MACE(HR 1.508,95％ CI 0.616-3.693,P =0.368)were disappeared in women.The interaction test showed that there existed significant interactions between gender and RD in all-cause mortality(HR 2.709,95％CI 1.150-6.384,P =0.023)and MACE(HR 1.977,95％ CI 1.009-3.876,P =0.023).Conclusions There is a considerable gender difference in the prognostic value of RD for the outcomes in patients with STEMI.RD seemed to be an important prognostic maker in male patients.

Plasma products are considered to be special medicinesderived from healthy human plasma .During 1980′s, events of transmission of human immunodeficiency virus through plasma products were frequently reported .Since then, ensuring the viral safety of plasma products has raised great concerns all over the world .So far, with decades of effort , most countries in the world have established rigorous systems with preventive measures to ensure the viral safety of plasma prod -ucts.These measures include control of source plasma , validated inactivation/removal of infectious agents , the adherence to current good manufacturing practices .Nevertheless , new infectious agents which may be threats to viral safety require continuous studies on appropriate countermeasures .