Objective To investigate the protective effect of herba artemisiae scopariae extract on multidrug resistance protein 3(MDR3)gene mutation-induced neonatal parenteral nutrition-associated cholestasis(PNAC)and its possible mechanism.Methods ①Human primary hepatocytes were treated with cell culture in vitro,CRISPR/Cas9 lentivirus infection and MDR3 mutant gene lead-in.The levels of hepatic and biliary biochemical indexes[alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil),total bile acid(TBA)]in the supernatant of hepatocytes before and after 16,32,48 hours were compared to determine the time required for fatty acid induction of PNAC hepatocyte model with MDR3 gene mutation.② Human primary hepatocytes were divided into blank control group,MDR3 gene wild type group,MDR3 gene mutation group,and herba artemisiae scopariae extract intervention group according to random number table method.The blank control group was treated with culture medium only,the MDR3 gene wild type group was infected with lentivirus and mixed with wild type MDR3 gene and culture medium,the MDR3 gene mutation group was infected with lentivirus and cultured in culture medium with the mutant genes lead-in of LV-MDR3KI(c.485T>A,c.2793insA,c.1031G>A,c.3347G>A)mutation,while the MDR3 mutant gene was lead-in by lentivirus infection and cultured in culture medium,and then pretreated with 100 g/L herba artemisiae scopariae extract in the herba artemisiae scopariae extract intervention group,then the four groups of hepatocytes were induced with 1%fat emulsion,and the treatment time was the time needed to construct the PNAC hepatocytes model with MDR3 gene mutation.The levels of ALT,AST,TBil,DBil,IBil and TBA in the supernatant of hepatocytes were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression abundance of adenosine triphosphate binding cassette proteins(ABCB4,ABCB11,ABCC2,ABCC3,ABCC4)encoding MDR3,bile salt export pump(BSEP),multidrug resistance associated protein(MRP)2-4,and tumor necrosis factor-α(TNF-α)genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared to the blank control group and MDR3 gene wild type group,there was no significant difference in the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 gene mutant group before and 16 hours after induction with 1%fat emulsion,however after treated with 1%fat emulsion for 32 hours and 48 hours,the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 mutant hepatocytes were significantly increased(P<0.05),consequently the time required for fatty acid induction of PNAC hepatocyte model was 32 hours.At 32 hours after treatment with fat emulsion,the levels of ALT,AST,TBil,DBil,TBA in the supernatant of hepatocytes in the herba artemisiae scopariae extract intervention group were significantly decreased[ALT(ng/L):148.3±2.3 vs.164.9±7.0,AST(ng/L):2767.4±78.8 vs.3239.4±107.1,TBil(μmol/L):7.6±0.2 vs.13.6±0.3,DBil(μmol/L):1.8±0.1 vs.5.7±0.2,TBA(μmol/L):3.4±0.2 vs.6.7±0.1,all P<0.05].The ABCB4,ABCC2,ABCC3,ABCC4 mRNA expression of MDR3,MRP2,MRP3,MRP4 in the blank control group,MDR3 wild type group,MDR3 gene mutation group and the herba artemisiae scopariae extract intervention group had no significant difference.The expression of TNF gene mRNA was highly expressed in MDR3 gene mutation group(2-??Ct:1.258±0.200 vs.1.001±0.052),and was low expressed in the herba artemisiae scopariae extract intervention group(2-??Ct:0.387±0.247 vs.1.258±0.200),and there was a significant difference between the two groups(both P<0.05).Compared to the MDR3 gene mutation group,the ABCB11 gene encoding BSEP mRNA expression in the herba artemisiae scopariae extract intervention group was significantly increased(2-??Ct:2.955±0.479 vs.1.333±0.529,P<0.05).Conclusion The herba artemisiae scopariae extract has a protective effect on PNAC induced by MDR3 gene mutation,which may be related to antagonizing inflammatory reaction,decreasing the expression of TNF mRNA and improving the expression of ABCB11 gene encoding BSEP.

Background and objective Metabolic change is one of the important characteristics of radiation pneu-monitis.Radiotherapy,as a conventional method for the treatment of thoracic tumors,can not only effectively kill tumor cells,but also cause adverse reactions such as local inflammation and fibrosis,which leads to limited therapeutic effect and profound impact on the quality of life of patients.Therefore,it is of great significance to explore the metabolic changes caused by radio-therapy.The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line(murine lung epithelial-12,MLE12).Methods MLE12 cells were cultured in vitro and randomly divided into radiation group(IR)and control group(NC).Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator.Cell supernatant samples were collected at 48 h after irradiation.Metabolomic analysis of the samples was performed by liq-uid chromatograph mass spectrometer(LC/MS).Results LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation.A total of 38 secretory metabolites were altered in the IR group compared with the NC group.According to the annotation of Kyoto Encyclopedia of Genes and Genomes(KEGG)database,the differential metabo-lites are mainly involved in nucleotide metabolism,amino acid metabolism and lipid metabolism,among which the difference in nucleotide metabolism is the most significant.Conclusion The metabolism ofMLE12 cells was significantly affected by X-ray irradiation,mainly affecting the nucleotide metabolic pathways,including purine and pyrimidine metabolites and related meta-bolic pathways.

Objective To investigate the impact of variations in RNA-binding motif protein 20(RBM20)and muscle-restricted coiled-coil(MURC)digenic heterozygosity variation on the structural and biological characteristics of human cardiomyocyte AC 16(an adult left ventricular myocardial cell line).Methods Cardiomyocyte AC 16 cell lines were constructed with control,negative scramble,wild-type,MURC single-gene mutant,RBM20 single-gene mutant,and RBM20 and MURC digenic mutant groups.The localization of RBM20 and MURC in cardiomyocytes,cell area,cytoskeletal arrangement,cytoskeleton-related proteins,cell polarity,and intracellular calcium concentration were observed using Western blotting,immunofluorescence staining,and reverse transcription polymerase chain reaction.Myocardial apoptosis was detected using flow cytometry.Ki-67 staining and wound healing assays were performed to detect cardiomyo-cyte proliferation and migration,respectively.Results Digenic mutations had a more pronounced impact than single-gene mutations in RBM20 or MURC on the structural and biological characteristics of cardiomyocytes,manifested by increased cell area,upregulated mRNA expression of hypertrophy-related genes,such as myosin heavy chain 7 and alpha-actin,increased cytoskeleton disturbance,decreased flu-orescence intensity of cytoskeletal proteins β-tubulin and Vinculin(all P＜0.01);increased fluorescence intensity of the polarity protein Part 6(P＜0.05);and significantly elevated cardiomyocyte apoptosis rate,decreased proliferative activity,and elevated migration rate and intracellular calcium ion concentration(all P＜0.01).Conclusion The digenic heterozygous variation in RBM20 and MURC may induce changes in the morphological structure and biological characteristics of myocardial cells,including increased cell area,cytoskeleton dis-turbance,cell polarity,increased apoptosis rate and mobility,decreased cell proliferation activity,and calcium processing ability.

Objective:To analyze independent factors for treatment-requiring retinopathy of prematurity (TR-ROP) and establish a predictive nomogram model for TR-ROP.Method:A retrospective cohort study. A total of 6 998 preterm infants who were born at Guangdong Women's and Children's Hospital between January 1, 2012 and March 31, 2022 and were screened for retinopathy of prematurity (ROP) were included in the study. TR-ROP was defined as type 1 ROP and aggressive ROP; 22 independent factors including general information, maternal perinatal conditions, interventions and neonatal diseases related to ROP were collected. The infants were divided at the level at an 8:2 ratio according to clinical experience, with 5 598 in the training cohort and 1 400 in the validation cohort. t test was used for comparison of quantitative data and χ 2 test was used for comparison of counting data between groups. Multivariate logistic regression analysis was carried out for the indicators with differences in the univariate analysis. The visualized regression analysis results of R software were used to obtain the histogram. The accuracy of the nomogram was verified by C-index and receiver operating characteristic curve (ROC curve). Results:Among the 6 998 children tested, 4 069 were males and 2 920 were females. Gestational age was (33.69±3.19) weeks; birth weight was (2 090±660) g. There were 376 cases of TR-ROP (5.4%, 376/6 998). The results of multivariate logistic regression analysis showed that gestational age [odds ratio ( OR) =0.63, 95% confidence interval ( CI) 0.47-0.85, P=0.002], intrauterine distress ( OR=0.30, 95% CI 0.10-0.99, P=0.048), bronchopulmonary dysplasia ( OR=0.23, 95% CI 0.09-0.60, P=0.003), hypoxic-ischemic encephalopathy ( OR=5.40, 95% CI 1.45-20.10, P=0.012), blood transfusion history ( OR=4.05, 95% CI 1.50-10.95, P=0.006) were the independent influencing factors of TR-ROP. Based on this and combined with birth weight, a nomogram prediction model was established. The C-index of the training set and validation set were 0.940 and 0.885, respectively, and the area under ROC curve were 0.945 (95% CI 0.930-0.961) and 0.931 (95% CI 0.876-0.986), respectively. The sensitivity and specificity were 86.2%, 94.0% and 83.2%, 93.3%, respectively. Conclusions:Gestational age, intrauterine distress, bronchopulmonary dysplasia, hypoxic-ischemic encephalopathy and blood transfusion history are the independent factors influencing the occurrence of TR-ROP. The TR-ROP nomogram prediction model based on independent influencing factors has high sensitivity and specificity.

Objective To investigate the surgical outcomes and strategies selection of endoscopic endonasal approach and craniotomy in the treatment of cranial base chordomas.Methods Thirty-one patients diagnosed pathologically with cranial base chordoma in Tianjin huanhu hospital from Jan.2010 to Sep.2020 were analyzed retrospectively.The patients were divided into the endoscopic endonasal group and the craniotomy microscope group according to the different surgical approaches.The surgical results and follow-up between the two groups were compared.Results In the endoscopic endonasal group,there were 7 cases of gross total resection,9 cases of subtotal resection and 2 cases of partial resection.The main complications included death in 2 cases,cerebrospinal fluid leakage in 8 cases,cranial nerve injury in 2 cases and hypopituitarism in 1 case.In the craniotomy microscope group,there were 2 cases of gross total resection,10 cases of subtotal resection,and 1 case of partial resection.The main complications included cerebrospinal fluid leakage in 1 case,cranial nerve injury in 3 cases,epilepsy in 1 case and epidural hematoma in 1 case.There was no statistical significance in the resection rate between the two groups(P＞0.05).The rate of cerebrospinal fluid leakage in the endoscopic group was significantly higher than that in the craniotomy microscope group,and the comparison was statistically significant(P＜0.05).There was no statistically significant between the two groups for tumor recurrence or progression.Conclusions The endoscopic endonasal approaches for resection of cranial base chordomas have improved the gross total resection rate,but craniotomy is still an important surgical method for tumor resection.It is necessary to select an appropriate surgical approach according to the lesion location and pattern of tumor growth.

Objective:To explore the application value of three dimensional T 1 weighted sampling perfection with application-optimized contrasts by using different flip angle evolutions (3D T 1-SPACE) combined with three dimensional time of flight MR angiography (3D-TOF MRA) in the follow-up of stent-assisted coil embolization for intracranial aneurysm. Methods:From December 2017 to October 2018, 25 patients with intracranial aneurysm who underwent stent-assisted coil embolization in Henan Provincial People′s Hospital were enrolled. All of them had wide neck intracranial aneurysms and were followed up for 6 to 10 months after endovascular treatment using 3D-TOF MRA, 3D T 1-SPACE sequence and DSA. The DSA and 3D-TOF MRA were performed to evaluate aneurysm remnants using Raymond grade scale. Meanwhile, 3D-TOF MRA and 3D T 1-SPACE sequence were performed to evaluate in-stent lumen visibility using the 4-point scale. The paired sample Wilcoxon test was used to evaluate the aneurysm remnants and the parent artery patency. DSA was used as the gold standard to calculate the specificity and accuracy of the aneurysm remnants evaluated by 3D-TOF MRA. Results:Six to ten months′ follow up after the procedure, for aneurysm occlusion, the Raymond grade scale of the 25 patients evaluated by DSA indicated grade 1 in 23 patients, 2 in 1 and 3 in 1. For patients evaluated by 3D-TOF MRA, the results demonstrated grade 1 in 21 patients, 2 in 3 and 3 in 1. There was no difference between the 2 methods ( Z=-0.557, P=0.577). The in-stent lumens of parent vessel evaluated by 3D-TOF MRA showed that there were 14 patients with grade 3, 8 patients with grade 2 and 3 patients with grade 1. However, 3D T 1-SPACE demonstrated that all 25 patients were grade 4. The 3D T 1-SPACE was superior to evaluate the in-stent lumens than 3D-TOF MRA ( Z=-4.484, P<0.001). Taking DSA as standard, the specificity and accuracy of the aneurysm remnants evaluated by 3D-TOF MRA were 86.9% (20/23) and 84.0% (21/25), respectively. Conclusion:3.0 T 3D T 1-SPACE MR sequence can be used to assess parent artery patency, with in-stent lumen being clearly visible. 3D-TOF MRA can evaluate intracranial aneurysm remnants. The combination of these two MRI imaging techniques can be used as an optional follow-up evaluation after the endovascular treatment of intracranial aneurysms.

Objective:To evaluate the safety and efficacy of endovascular interventional treatment of the intracranial vertebrobasilar trunk large aneurysms (VBTLAs) compared with conservative treatment.Methods:This is a prospective multi-center cohort study. From October 2012 to October 2018, a total of 69 patients with intracranial vertebrobasilar trunk large aneurysm (diameter>10 mm) from Henan Province People's Hospital and People's Liberation Army Rocket Medical Center were included in this study. Patients themselves chose either endovascular interventional therapy (interventional group) or conservative treatment (conservative group) after discussion with their doctors. The χ 2 test was used to compare the incidence of deaths, stroke, and all other serious adverse events including other site bleeding, myocardial infarction and others between the two groups. Results:A total of 69 patients were enrolled, of whom 51 patients were enrolled in interventional group, 18 patients underwent endovascular reconstructive therapy, 11 patients underwent deconstructive therapy, and 4 patients underwent conjunction interventional treatments. Eighteen patients were enrolled in conservative group, of whom 11 cases received simple risk factor control, 7 cases received antiplatelet and risk factors control. The proportions of hypertensive patients 94.4% (17/18) and giant aneurysms 50.0% (9/18) in the conservative group were higher than those in the surgery group 64.7% (33/51, χ 2=4.500, P=0.034), 19.6% (10/51, χ 2=4.730, P= 0.030).The incidence of all serious adverse events associated with protocol was 15.7% (8/51) in the interventional group and 44.4% (8/18) in the conservative group [risk ratio (RR) =0.353, 95% confidence intervals (CI): 0.156-0.801], and the difference was significant (χ 2=4.668, P=0.031). The incidence of fatal events associated with protocol was 2.0% (1/51) in the interventional group and 38.9% (7/18) in the conservative group (RR=0.050, 95%CI: 0.007-0.382), and the difference was significant (χ 2=14.281, P<0.001). The incidence of hemorrhage events associated with protocol was 2.0% (1/51) in the interventional group and 22.2% (4/18) in the conservative group (RR=0.088, 95%CI: 0.011-0.738), and the difference was significant (χ 2 =5.391, P=0.020). Follow-up imaging showed that the occlusion rate of aneurysms in 44 patients in the interventional group was 56.8% (25/44) after a median follow-up of 6 months. Imaging follow-up was obtained in 9 patients, whose occlusion rate of aneurysms was 0 and the median follow-up time was 12 months, in the conservative group. The difference was significant(χ 2 =7.534, P=0.006). Conclusion:Compared with conservative treatment, endovascular intervention of the intracranial VBTLAs has lower incidences of serious adverse events and death events.

Objective:To compare procedural parameters and perioperative complications between the first-generation Pipeline embolization device (PED Classic) and the second-generation Pipeline embolization device (PED Flex).Methods:A total of 53 patients who underwent intracranial aneurysm treatment with the PED Classic from February 2015 to August 2016 and 118 patients who underwent treatment with the PED Flex from January 2018 to July 2019 at Zhengzhou University People's Hospital were enrolled in this retrospective study. Procedure time, contrast dosage, fluoroscopy time and perioperative complications in the two groups were recorded. Independent sample t-test was performed to analyze the difference of procedure time, contrast dosage and fluoroscopy time between the two groups, and Chi-square test was performed to analyze the perioperative complications. Results:There were 53 cases with 73 aneurysms in the PED Classic group and 118 cases with 146 aneurysms in the PED Flex group. The procedure time was (159.0±42.0) min in the PED Classic group, and (121.9±46.0) min in the PED Flex group. The difference was statistically significant ( t=5.012, P<0.001). The contrast dosage was (156.4±39.4) ml in the PED Classic group and (110.1±38.5) ml in the PED Flex group. The difference was statistically significant ( t=7.229, P<0.001). The difference of fluoroscopy time between PED Classic group and PED Flex group was also statistically significant ( t=10.196, P<0.001), with the average of (34.7±5.7) min and (22.8±7.6) min, respectively. The perioperative complications rate in the PED Classic group (9.4%, 5/53) was higher than that of the PED Flex group (2.5%, 3/118), but there was no statistical significance between the two groups (χ 2=2.503, P=0.114). Conclusion:The use of PED Flex seems safe in treating intracranial aneurysms, and the device deployment is easier compared with the use of PED Classic. However, serious complications remain to be noted.

Objective To investigate the association between concentrations of environmental air pollutants and the daily number of outpatient visits for urticaria in Beijing. Methods Time series analysis in combination with distributed lag non?linear model(DLNM)and Spearman′s rank correlation test was used to analyze the association between PM2.5 concentrations and the daily number of outpatient visits for urticaria. All effect estimates were expressed as a risk ratio(RR)for the daily number of outpatient visits with an interquartile range(IQR)increase of 82.8 μg/m3 in PM2.5. Results From January 1st 2013 to June 30th 2014, the daily average PM2.5 concentration, temperature, relative humidity and number of visits for urticaria were 89.3 μg/m3, 12.7 ℃, 51.9% and 27.3 respectively. Spearman′s rank correlation test showed that the daily average PM2.5 concentration and number of visits for urticaria were correlated with daily mean temperature(rs =-0.21, 0.36, respectively, P < 0.05)and relative humidity(rs = 0.49, 0.31, respectively, P < 0.05), but no correlation was observed between daily average PM2.5 concentrations and daily number of visits for urticaria(rs=0.01, P>0.05). There was no significant correlation between daily number of outpatient visits for urticaria and daily PM2.5 concentration lagged by 0-14 days(RR=1, 95%CI:0.89, 1.13). After potential confounding factors were adjusted, an 82.8μg/m3 increase in daily PM2.5 concentration at lag 0-20 days was significantly associated with a 22%(95%CI:3%, 46%)increase in daily number of outpatient visits for urticaria, suggesting that the lagged effect of PM2.5 was obviously increased. Conclusion The association between PM2.5 concentrations and the number of visits for urticaria is easily affected by meteorological factors and biological confounding factors, and relative humidity and mean temperature are both positively correlated with the number of visits for urticaria.

Objective:To explore changes of central retinal vascular caliber and fractal dimension (Df) and their cor‐relation with blood pressure in hypertensive population .Methods :A total of 2169 subjects>30 years old were en‐rolled in this cross‐sectional study .They were divided into hypertension group (n=819) and non‐hypertension group (n=1350) .Fundus photos were collected in all subjects ,and semi‐automatic software was used to quantitatively ana‐lyze central retinal vascular caliber and Df ,and they were compared between two groups .Results:Compared with non- hypertension group ,there were significant reductions in central retinal arteriolar equivalent [CRAE ,(135.2 ± 10.72) μm vs .(132.25 ± 11.56) μm] ,central retinal venular equivalent [CRVE ,(184.95 ± 16.29) μm vs . (182.52 ± 17.07)μm] and Df [ (1.38 ± 0.05) vs .(1.34 ± 0.05)] in hypertension group , P<0.01 all .After adjus‐ting for age and gender ,analysis of covariance indicated that CRAE and Df of hypertension group were still signifi‐cantly lower than those of non - hypertension group (P<0.01 both) .Linear correlation analysis indicated that sys‐tolic blood pressure (SBP) ,diastolic blood pressure (DBP) and pulse pressure (PP) were inversely correlated with CRAE and Df ( r= -0.340~ -0.174 , P<0.01 all) .After adjusting for cardiovascular risk factors ,multi‐factor linear regression analysis indicated that CRAE and Df were still inversely correlated with SBP ,DBP and PP (stand‐ardizedβ= -0.190~ -0.134 ,P<0.01 all) .Df of hypertension course >5 years group was significantly lower than that of ≤5 years group [ (1.33 ± 0.05) vs .(1.35 ± 0.05)] , P<0.01. Conclusion:CARE ,Df are significantly in‐versely correlated to SBP ,DBP and PP in hypertensive population ,while correlation of Df is most .