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.

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.
Angiogenic Proteins/therapeutic use* ; Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Endothelial Cells ; Humans ; Nanoparticles ; Nucleic Acids/therapeutic use*

Objective:To investigate the effect of continuous intracranial pressure (ICP) and brain oxygen partial pressure (PbtO 2) monitoring and guiding treatment after the application of standard large bone flap decompression and microhematoma removal in patients with severe traumatic brain injury (TBI). Methods:A retrospective analysis was done of 41 patients with TBI in Department of Neurosurgery in the Inner Mongolia People's Hospital from January 2018 to May 2020. Patients with Glasgow coma scale (GCS)<8 points were treatesd with microscopical removal of hematoma and contusion brain tissue and standard large bone flap decompression. Intraoperative intracranial pressure and brain tissue oxygen partial pressure monitoring probes were placed. Postoperatively, continuous intracranial pressure monitoring and partial oxygen pressure monitoring of brain tissue were performed, and target-based treatment under ICP and PbtO 2 monitoring was performed. According to the Glasgow Outcome (GOS) score after six months, patients were divided into a good outcome group (4-5 scores) and a poor outcome group (1-3 scores). There were 26 cases in good prognosis group and 15 cases in poor prognosis group. Linear regression analysis was used to further evaluate the relationship between PbtO 2, ICP and GOS score. The measurement data of normal distribution were compared by independent sample t-test. The counting data were expressed in cases (%), and the comparison between groups was adopted χ 2 inspection. The general linear bivariate Pearson correlation test was used. Results:The mean value of PbtO 2 (17.42±5.34) mmHg in the poor prognosis group was lower than that in the good prognosis group (24.65±5.61) mmHg, with statistical significance ( t=4.04, P<0.001). The mean value of ICP (22.32±3.45) mmHg in the poor prognosis group was higher than that (17.32±3.23) mmHg in the good prognosis group, with statistical significance ( t=4.15, P<0.001). Using PbtO 2 and ICP as independent variables and GOS score after 6 months as dependent variable, a regression equation was established ( Y=4.040 X+7.497; Y=-2.549 X+28.63). The mean value of PbtO 2 was positively correlated with GOS scores after 6 months in patients with severe head injury ( r=0.75, P<0.001). The mean value of ICP was negatively correlated with the prognosis of patients with severe head injury ( r=-0.87, P<0.001). Conclusion:The treatment guided by ICP combined with PbtO 2 monitoring is valuable in improving the prognosis of patients with severe traumatic brain injury after standard decompressive craniectomy, and may improve the prognosis 6 months after the injury.

Objectives:To investigate the clinical impacts of chronic total occlusion (CTO) in acute non-ST segment elevation myocardial infarction (NSTEMI) patients underwent primary percutaneous coronary intervention (PCI).Methods:A total of 2 271 acute NSTEMI patients underwent primary PCI from China Acute Myocardial Infarction Registry were enrolled in this study and divided into the CTO group and the non-CTO group according to the angiography. The primary endpoint was in-hospital mortality and mortality during a 2-year follow-up. The secondary endpoint was major adverse cardiovascular events (MACE) including revascularization, death, re-myocardial infarction, heart failure readmission, stroke and major bleeding.Results:Thirteen-point four percent of the total acute NSTEMI patients had concurrent CTO. In-hospital mortality (3.6% vs. 1.4%, P<0.01) and 2-year mortality (9.0% vs. 5.1%, P<0.01) were significantly higher in the CTO group than those in the non-CTO group, respectively. Multiple regression analyses showed that chronic obstructive pulmonary disease ( HR 7.28, 95% CI 1.50-35.35, P=0.01) was an independent risk factor of in-hospital mortality, and advanced age ( HR 1.04, 95% CI 1.01-1.07, P<0.01), and low levels of ejection fraction ( HR 0.95, 95% CI 0.93-0.98, P<0.01) were independent risk factors of 2-year mortality. CTO ( HR1.67, 95% CI 1.10-2.54, P=0.02) was an independent risk factor of revascularization, but not a risk factor of mortality. Conclusions:Although acute NSTEMI patients concurrent with CTO had higher mortality, CTO was only an independent risk factor of revascularization, but not of mortality. Advanced age and low levels of ejection fraction were independent risk factors of long-term death among acute NSTEMI patients.

Objective:To investigate the effect of transcranial direct current stimulation (tDCS) on the behavior and the mismatch negativity (MMN) component of the auditory evoked potential of autistic children.Methods:Thirty-four autistic children were randomly divided into an anode stimulation group ( n=19) and a pseudo-stimulation group ( n=16). Both groups were given one hour of routine rehabilitation five times a week for 4 weeks, while the anode stimulation group was additionally provided with 20 minutes of tDCS 3 times a week. Before and after the treatment, both groups′ behavior was evaluated by using autism behavior checklist (ABC) as well as any changes in MMN of the auditory evoked EEG signals. Results:There were no significant differences between the two groups in any of the measurements before the treatment. Afterwards behavior had improved significantly in both groups, with significantly greater improvement in the stimulated group. In the stimulated group the average MMN amplitude had increased significantly and the average latency had decreased significantly. However, no such significant changes were observed in the pseudo-stimulation group. There was a significant linear correlation between the changes in the incubation period of MMN components and the improvements in ABC, vestibular functioning, tactile defense and proprioception.Conclusion:Anodal tDCS combined with conventional rehabilitation therapy can effectively increase the MMN amplitude and shorten the latency in autistic children, improving their brain function.

Objective:To investigate the effects of continuous monitoring intracranial pressure (ICP) and brain oxygen partial pressure (PbtO 2) on the prognosis of patients with severe craniocerebral injury. Methods:A prospective randomized controlled trial was conducted. Seventy patients with severe craniocerebral injury with a Glasgow coma score (GCS) 4-8 admitted to the neurosurgical intensive care unit (NICU) of the People's Hospital of Inner Mongolia Autonomous Region from January 2017 to May 2020 were enrolled, and they were divided into ICP monitoring group and ICP+PbtO 2 monitoring group by random number table. Patients in ICP monitoring group received ICP monitoring and were given traditional treatment of controlling ICP and cerebral perfusion pressure (CPP), the therapeutic target was ICP < 20 mmHg (1 mmHg = 0.133 kPa) and CPP > 60 mmHg. Patients in ICP+PbtO 2 monitoring group were given ICP and PbtO 2 monitoring at the same time, and oxygen flow was adjusted on the basis of controlling ICP and CPP to maintain the PbtO 2 > 20 mmHg, and the therapeutic target of ICP and CPP was the same as the ICP monitoring group. ICP and PbtO 2 values were recorded during monitoring in the two groups, the results of CPP, GCS and arterial blood gas analysis were recorded, and the prognosis at 3 months and 6 months after injury was compared by Glasgow outcome scale (GOS) score between the two groups. GOS score > 3 was considered as good prognosis. Kaplan-Meier survival curve was drawn, and the 3-month and 6-month cumulative survival rates of the two groups were analyzed. Linear regression analysis was used to further evaluate the relationship between PbtO 2 and GOS score. Results:Finally, a total of 70 patients with severe craniocerebral injury were enrolled in the analysis, 34 patients received ICP combined with PbtO 2 monitoring and guided therapy, and 36 patients received ICP monitoring alone. The average ICP of ICP+PbtO 2 monitoring group was significantly lower than that of ICP monitoring group (mmHg: 13.4±3.2 vs. 18.2±8.3, P < 0.01). Although the CPP in both groups was great than 60 mmHg, the average CPP of ICP+PbtO 2 monitoring group was significantly higher than that of ICP monitoring group (mmHg: 82.1±10.5 vs. 74.5±11.6, P < 0.01). No significant difference was found in average GCS score or arterial partial pressure of carbon dioxide (PaCO 2) between the ICP+PbtO 2 monitoring group and ICP monitoring group [GCS score: 5.3±2.3 vs. 5.2±2.2, PaCO 2 (mmHg): 33.5±4.8 vs. 32.6±5.2, both P > 0.05]. The average arterial partial pressure of oxygen (PaO 2) of ICP+PbtO 2 monitoring group was obviously higher than that of ICP monitoring group (mmHg: 228.4±93.6 vs. 167.3±81.2, P < 0.01). Compared with the ICP monitoring group, the good outcome rates of 3 months and 6 months after injury in the ICP+PbtO 2 monitoring group were significantly higher (3 months: 67.6% vs. 38.9%, 6 months: 70.6% vs. 41.7%, both P < 0.05). Kaplan-Meier survival curve showed that the 3-month and 6-month cumulative survival rates of ICP+PbtO 2 monitoring group were significantly higher than those of ICP monitoring group (3 months: 85.3% vs. 61.1%, Log-Rank test: χ2 = 5.171, P = 0.023; 6 months: 79.4% vs. 55.6%, Log-Rank test: χ2 = 4.511, P = 0.034). Linear regression analysis showed that PbtO 2 was significantly correlated with GOS score at 3 months and 6 months after injury in patients with severe craniocerebral injury ( r values were 0.951 and 0.933, both P < 0.01). Conclusions:PbtO 2 compared with ICP monitoring guiding therapy is valuable in improving the prognosis of patients with severe craniocerebral injury. It can improve the prognosis at 3-6 months after injury.

Endo-β-N-acetylglucosaminidase is used widely in the glycobiology studies and industries. In this study, a new endo-β-N-acetylglucosaminidase, designated as Endo SA, was cloned from Streptomyces alfalfae ACCC 40021 and expressed in Escherichia coli BL21 (DE3). The purified recombinant Endo SA exhibited the maximum activity at 35 ºC and pH 6.0, good thermo/pH stability and high specific activity (1.0×10⁶ U/mg). It displayed deglycosylation activity towards different protein substrates. These good properties make EndoSA a potential tool enzyme and industrial biocatalyst.
Cloning, Molecular ; Enzyme Stability ; Escherichia coli ; genetics ; Gene Expression ; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase ; genetics ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Streptomyces ; enzymology ; genetics

Objective: To evaluate the prognostic value of the thrombolysis in myocardial infarction (TIMI) and global registry of acute coronary events (GRACE) risk scores for in-hospital mortality in Chinese non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods: Data of present study derived from the prospective, multi-center registry trial of Chinese AMI (CAMI). Among 31 provinces, municipalities or autonomous districts in China, at least one tertiary and secondary hospital was selected. From January 2013 to September 2014, 5 896 consecutive non-ST-segment elevation myocardial infarction patients who were admitted to 107 hospitals within 7 days of symptom onset were enrolled. For each patient, TIMI and GRACE risk scores were calculated using specific variables collected at admission. Their prognostic value was evaluated by the endpoint of in-hospital mortality. Results: Among 5 896 NSTEMI patients (age was (65.4±12.1) years old), 68.2% (n=4 020) were males. The in-hospital mortality was 6.0% (n=353) and the median length of hospital stay was 10.0 (7.0, 13.0) days. The incidence of pre-hospital cardiac arrest was 3.6% (n=213) among 5 896 NSTEMI patients. Six hundreds and forty five patients (10.9%) received primary percutaneous coronary intervention, and 6 patients underwent emergent coronary artery bypass grafting surgery (0.1%), and the median time of reperfusion was 529.5 (256.0, 1 065.0) minutes. The prescription percentage of statins, β-blocker, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers, and aldosterone antagonists were 94.8% (n=5 587), 71.7% (n=4 228), 65.5% (n=3 864) and 26.0% (n=1 533) respectively. The area under the curve of GRACE risk score for in-hospital mortality (0.7930 (95%CI 0.767-0.818)) was better than that of TIMI risk score (0.5588 (95%CI 0.532-0.586), P<0.001). Conclusion GRACE risk score demonstrates better predictive accuracy than TIMI risk score for in-hospital mortality in NSTEMI patients in this patient cohort.

Objective To explore the diagnosis and treatment of atypical severe combined immunodeficiency disease (SCID). Methods The clinical data of atypical SCID in 7 children with IL2RG,JAK3,and RAG1 mutations were reviewed and analyzed from September 2012 to June 2017. Results In 7 cases (6 males and 1 female), there were 5 infants, 1 toddler and 1 school-age child. Cases 2, 4, and 6 were classic SCID clinical phenotypes. Cases 1, 3, 5, 7 were atypical SCID clinical phenotypes. Case 6 were diagnosed with Omenn syndrome. Cases 2, 5 were classic SCID immune phenotypes, cases 1, 3, 4, 6, 7 were atypical SCID immune phenotypes, and case 1 had maternal chimera. The next generation sequencing indicated that case 1 had a compound heterozygous JAK3 mutation with c.3097-1G>A/c.946-950GCGGA>ACinsGGT.Cases 2,3,and 4 had IL2RG mutations,with c.865C>T/p.R289X,c.664C>T/R222C,52delG,respectively.Case 5 had JAK3 mutations with c.2150A>G/p.E717G and c.1915-2A>G.Sanger sequencing indicated that case 6 had a RAG1 mutation of complex heterozygosity with c.994C>T/p.R332X and c.1439G>A/p.S480N. Case 7 had homozygous RAG1 mutation with c.2095C>T/p.R699W.Conclusion Under certain conditions,gene mutation can lead to atypical clinical and/or immune phenotypic SCID.