ObjectiveTo investigate the impact of anticentromere antibody （ACA） on the clinical features and prognosis of patients with primary biliary cholangitis （PBC） by comparing clinical classification， ursodeoxycholic acid （UDCA） response， GLOBE score， and UK-PBC score between ACA-positive PBC patients and ACA-negative PBC patients. MethodsA total of 749 patients who were admitted to Beijing Ditan Hospital， Capital Medical University， from August 2013 to December 2022 and were diagnosed with PBC were enrolled and divided into ACA-positive group with 147 patients and ACA-negative group with 602 patients. According to their conditions on admission， the two groups were compared in terms of the distribution of clinical types， i.e.， chronic progression-type PBC， portal hypertension-type PBC， and standard jaundice/liver failure-type PBC. There were 261 patients with complete data after 1-year follow-up， among whom there were 53 patients with positive ACA and 208 with negative ACA. A statistical analysis was performed， and propensity score matching was performed based on sex and age at a ratio of 1∶2. The two groups were compared in terms of 1-year UDCA response rate， GLOBE score， and UK-PBC score before and after matching. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the ACA-negative group， the ACA-positive group had a significantly higher age （61.28±10.35 years vs 56.74±12.17 years， t=4.164， P<0.001）， a significantly higher proportion of female patients （93.9% vs 77.6%， χ²=20.221， P<0.001）， a significantly higher proportion of patients with portal hypertension （48.3% vs 27.6%， χ²=23.289， P<0.001）， and a significantly lower proportion of patients with jaundice/liver failure （24.5% vs 38.5%， χ²=10.205， P<0.001）. After 1-year follow-up， for the 261 PBC patients with complete data， there was no significant difference in UDCA response rate before propensity score matching between the ACA-positive group and the ACA-negative group （41.5% vs 41.8%， P>0.05）， and there was a significant difference in the proportion of patients with a GLOBE score of >0.3 between the ACA-positive group and the ACA-negative group （92.5% vs 80.3%， χ²=3.935， P=0.047）. There were 53 patients in the ACA-positive group and 106 patients in the ACA-negative group after propensity score matching， and there were no significant differences between the two groups in UDCA response rate， GLOBE score， and UK-PBC score （all P>0.05）. ConclusionACA-positive patients tend to have an older age， with a higher proportion of female patients or patients with portal hypertension， while there is a relatively low proportion of patients with jaundice/liver failure. Positive ACA has no significant impact on UDCA response rate， GLOBE score， and UK-PBC score.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Objective To investigate the differences in clinical features between the primary biliary cholangitis(PBC)patients with negative or positive anti-mitochondrial antibody(AMA)by analyzing related immune and biochemical parameters.Methods This study was conducted among the patients who attended Beijing Ditan Hospital,Capital Medical University,from January 2013 to December 2022 and were diagnosed with PBC,and they were divided into AMA negative group with 139 patients(24.5%)and AMA positive group with 428 patients(75.5%).Propensity score matching at a ratio of 1∶1 was performed with age and sex as matching factors and a matching tolerance of 0.06.Liver function,coagulation,and immune parameters on admission were analyzed,as well as the changes in liver function and other indicators after 6 months of treatment and the response to ursodeoxycholic acid(UDCA)at 6 and 12 months of treatment.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.Results There were 139 AMA-negative PBC patients and 139 AMA-positive PBC patients after propensity score matching.Compared with the AMA positive group on admission,the AMA negative group had significantly lower levels of direct bilirubin and globulin(Glo)and significantly higher levels of albumin,albumin/globulin ratio,prealbumin,and fibrinogen(all P<0.05).After 6 months of UDCA treatment,there were significant differences in Glo and prealbumin between the AMA negative group and the AMA positive group(P<0.05).Both the AMA negative group and the AMA positive group had an increase in prealbumin after 6 months of treatment,and the AMA negative group had a significantly greater increase than the AMA positive group(U=41.00,P=0.015).After UDCA treatment for 6 and 12 months,there was no significant difference in treatment response to UDCA between the AMA negative group and the AMA positive group(all P>0.05).Conclusion After matching for age and sex,compared with the AMA-positive PBC patients,the AMA-negative PBC patients tend to have a milder degree of liver inflammation and damage,significantly greater improvements in inflammation and liver synthesis ability after UDCA treatment,and better response to UDCA.

Purpose/Significance To solve the problems of understanding the connotation of courses for ideological and political edu-cation and how to integrate the ideological and political elements into the courses effectively.Method/Process The study starts from the analysis of the ideological and political education and the characteristics of the digital image processing course in medical universities and colleges,determines curriculum ideological and political education objectives,formulates curriculum ideological and political implementa-tion strategies.Result/Conclusion The study realizes the teaching content design of digital image processing course integrated the ideo-logical and political elements.Through the online and offline combination,the study explores the implementation of ideological and politi-cal thinking in medical universities and colleges courses.

Objective:To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa.Methods:A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared.Results:(1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95% CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 ( P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 ( P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion ( P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions:In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

In this study, we aimed to construct a non-replication mRNA platform and explore the side effects of electroporation-mediated delivery of mRNA on the mice as well as the expression features of the mRNA. With luciferase gene as a marker, in vitro transcription with T7 RNA polymerase was carried out for the synthesis of luciferase-expressed mRNA, followed by enzymatic capping and tailing. The mRNA was delivered in vivo by electroporation via an in vivo gene delivery system, and the expression intensity and duration of luciferase in mice were observed via an in vivo imaging system. The results demonstrated that the mRNA transcripts were successfully expressed both in vitro and in vivo. The electroporation-mediated delivery of mRNA had no obvious side effects on the mice. Luciferase was expressed successfully in all the mRNA-transduced mice, while the expression intensity and duration varied among individuals. Overall, the expression level peaked on the first day after electroporation and rapidly declined on the fourth day. This study is of great importance for the construction of non-replication mRNAs and their application in vaccine or antitumor drug development.
Animals ; Electroporation/methods* ; Gene Transfer Techniques ; Luciferases/metabolism* ; Mice ; RNA, Messenger/genetics*

Objective To investigate the clinical features of patients with Polygonum multiflorum preparation-related liver injury with or without positive autoantibody based on propensity score matching, as well as the influence of positive autoantibody on the prognosis of such patients. Methods A total of 364 patients with Polygonum multiflorum preparation-related liver injury who were hospitalized in Beijing Ditan Hospital, Capital Medical University, from August 2008 to June 2021 were enrolled, and according to whether autoantibodies were detected, they were divided into negative autoantibody group (H0 group) with 157 patients and positive autoantibody group (H1 group) with 207 patients. After adjustment for confounding factors by propensity score matching, the two groups were compared in terms of biochemical parameters, severity of liver injury, classification of liver injury, and disease outcome when liver injury reached the peak. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Mann-Whitney U rank sum test was used for comparison of categorical data or ranked data between two groups. The Cox regression model was used to analyze the influencing factors for liver function recovery. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups. Results A total of 98 pairs of cases were successfully matched after propensity score matching. Comparison of biochemical parameters between the two groups at the peak of liver injury showed that compared with the H0 group, the H1 group had significantly higher levels of alkaline phosphatase (ALP), globulin, and total bile acid and a significantly lower level of albumin (all P < 0.05). There was no significant difference in the classification of liver injury between the two groups ( P > 0.05), and there was a significant difference in the severity of liver injury between the two groups ( Z =1.710, P =0.045). Antinuclear antibody (ANA) was the main positive autoantibody and accounted for 49%, and there was a significant difference in the severity of liver injury between the patients with different ANA antibody titers ( Z =20.252, P =0.001). Comparison of disease outcome in terms of whether liver function returned to normal within 6 months showed that the normalization rate of liver function within 6 months was 90.8% in the H0 group and 75.5% in the H1 group, and the H1 group had a lower normalization rate of liver function ( χ 2 =8.199, P =0.004). The Cox regression analysis showed that autoantibody (hazard ratio [ HR ]=5.248, 95% confidence interval [ CI ]: 1.554-17.718, P =0.008) and ALP ( HR =1.013, 95% CI : 1.002-1.025, P =0.026) were independent risk factors for liver function recovery. The Kaplan-Meier survival curve analysis showed that compared with the negative autoantibody group, the positive autoantibody group had a significantly higher risk of failure in liver function recovery after 6 months ( χ 2 =8.802, P =0.003). Conclusion Autoantibody has no significant influence on the classification of Polygonum multiflorum preparation-related liver injury, and compared with the patients with negative autoantibody, the patients with positive autoantibody tend to have more severe liver injury and a more obvious tendency of chronicity.

Objective:To investigate the clinical value of digital three-dimensional reconstruction model of pituitary adenoma in transsphenoidal endoscopic pituitary adenoma resection.Methods:Fifty-eight patients with endoscopic pituitary, admitted to our hospital from July 2020 to March 2022, were chosen. All patients accepted transsphenoidal surgery under microscope and were randomly assigned to a control group (without digital 3D reconstruction technology before surgery) and a model group (with digital 3D reconstruction technology before surgery). The tumor size, preoperative and postoperative hormone levels, surgical duration, intraoperative blood loss, extent of surgical resection, and complications 3 months after follow up were compared.Results:There was no significant difference in age, gender, tumor types, tumor sizes and Knosp grading between the two groups ( P>0.05), indicating comparability. The resection degree of pituitary tumor in model group was better than that that in control group; the proportion of patients with total and subtotal resection in the model group was significantly higher than that in the control group (24/29 vs. 16/29, P=0.045). Intraoperative blood loss, surgical duration and average hospital stay in the model group were significantly decreased as compared those in the control group ( P<0.05); the duration of tumor resection in the model group ([46.93±10.77] min) was significantly shorter than that in the control group ([56.00±12.47] min, P<0.05). The levels of prolactin and human growth hormone in the model group 1 and 7 d after surgery were decreased as compared with those in the control group, without significant differences ( P>0.05). Three months after follow-up, the incidences of diabetes insipidus, hyponatremia and hypopituitarism in model group were significantly lower than those in control group ( P<0.05). The satisfaction rate in the model group was significantly higher than that in the control group ( P<0.05). Conclusion:The construction of digital three-dimensional reconstruction model of pituitary adenoma is helpful in understanding the adjacent relationship between tumors, nerves, and blood vessels before surgery, develop personalized surgical plan and improve surgical efficiency.

Objective:To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester.Methods:A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared.Results:Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta ( P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95% CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness ( OR=0.033, 95% CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions:(1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.

【Objective】 To investigate the relationship between hepatitis B virus X （HBx） protein and EGFR promoter， and the role of HBx protein in activating EGFR/PI3K/p-Akt signaling pathway and inhibiting apoptosis. 【Methods】 EGFR promoter plasmids were constructed and the relationship between HBx and EGFR promoters was characterized using a luciferase reporter assay. EGFR-overexpressing trophoblast cells were constructed， and EGFR expression in the overexpressing cells was knocked down using EGFR shRNA. The expression and localization of EGFR/PI3K/p-Akt were detected by Western blotting and confocal laser microscopy. Cell apoptosis was analyzed using flow cytometry. HBV plasmids carrying either full-length HBx or HBx with a deletion mutation （ΔHBx） and HBx plasmids were transfected into two types of trophoblast cells； HBx and PI3K/p-Akt protein expressions were detected by Western blotting. Cell apoptosis was analyzed using flow cytometry. 【Results】 Co-transfection of HBx and EGFR promoter plasmids in JEG-3 and HTR-8/Svneo cells significantly elevated the expression of EGFR promoter driven luciferase compared with the control group （P<0.01）. In EGFR-overexpressing cells， the expression of PI3K/p-Akt was significantly increased （P<0.01）， whereas the apoptosis rate was significantly decreased for JEG-3 cells and HTR-8/Svneo cells （both P<0.01）. These results were reversed in the EGFR-knock down group. When the intracellular HBx protein was expressed in JEG-3 and HTR-8 cells， PI3K/p-Akt protein expression was significantly increased （both P<0.05）， and the proportion of apoptosis was significantly decreased （both P<0.05）. 【Conclusion】 In placental trophoblast cells， HBx protein activates the expression of EGFR by acting on the EGFR promoter， and inhibits the apoptosis of trophoblast cells via the downstream EGFR/PI3K/p-Akt signaling pathway.