Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective:To systematically evaluate the clinical efficacy of Ruiyun procedure for hemorrhoids(RPH)combined with milligan-morgan hemorrhoidectomy(MMH)in the treatment of mixed hemorrhoids compared with MMH alone.Methods:Relevant literature was retrieved from China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their establishment to Jan 2023 using computers.Clinical randomized controlled trials(RCTs)of RPH combined with MMH and MMH alone in the treatment of mixed hemorrhoids were selected and analyzed,and meta-analysis was conducted using RevMan5.3 software.Results:A total of 30 RCTs were included,involving 4 609 patients.Results of Meta-analysis showed that there were statistically significant differences in surgical efficacy(RR=1.05,95% CI:1.02-1.08,P= 0.003),postoperative margin edema(RR=0.36,95% CI:0.27-0.49,P＜0.01),postoperative anal pain(RR=0.35,95% CI:0.23-0.53,P＜0.01),postoperative rectal bleeding(RR=0.35,95% CI:0.17-0.72,P=0.004),postoperative anal stenosis(RR=0.26,95% CI:0.11-0.59,P=0.001)and postoperative urinary retention(RR=0.77,95% CI:0.63-0.93,P=0.007)between RPH combined with MMH group and MMH group.Conclusion:Compared with MMH alone,RPH combined with MMH in the treatment of mixed hemorrhoids can reduce the incidence of postoperative side effects,such as postoperative margin edema,anal pain,rectal bleeding,anal stenosis,and urinary retention,with a relatively higher efficiency.

Objective To investigate the authentic experience in social participation among the patients with enterostomy,and explore the primary obstacles in social participation,so as to provide a basis for targeted guidance and measures for psychological intervention.Methods A method of descriptive phenomenological research was used in this qualitative research.Ten patients discharged from our hospital after enterostomy surgery were enrolled in this study.The participants were interviewed with a semi-structured questionnaire through the method of purpose sampling.The data acquired from the interviews were analysed and summarised by using the Colaizzi seven-step analysis.Themes were classified and extracted by reading,analysing,reflecting,classifying of the acquired data.Results Three themes were extracted with eight dimensions covering(a)psychosocial disorders with the dimensions of stigma,ostomy-related anxiety and concern,(b)low social participation with the dimensions of low social initiative,estrangement of interpersonal relationships,increased economic burden of social interaction,and(c)poor social adaptability with the dimensions of negative coping style,poor operative skills in ostomy care and poor utilisation of information about ostomy.Conclusions Patients with enterostomy usually encounter various difficulties in social participation and are lack of corresponding support.Medical staff should pay attention to the positive psychological guidance over the period of hospitalisation as well as training in operation skills for stoma.Moreover,healthcare workers should provide the patients with high-quality and continuous care after the patients have returned home and increase psychological and social supports,as well as consultations to improve the quality of life of the patients with enterostomy.

Continuous renal replacement therapy (CRRT) has become an effective multiple organ support therapy instead of single renal replacement as initially expected, and it is widely used in intensive care unit (ICU). After the outbreak of coronavirus disease 2019 (COVID-19), a series of expert recommendation or consensus have been developed to diagnose and treat the disease, including CRRT in acute kidney injury (AKI) and hyper inflammatory response. However, CRRT in COVID-19 is extraordinarily different from regular one due to different pathophysiology and infectious clinical scenarios. Accordingly, the paper aims to elaborate the similarities and differences between CRRT in COVID-19 and routine treatment in terms of safety and accessibility, indications and timing, clinical operation, anticoagulation, fluid management, prevention and control of infectious diseases, etc.

BACKGROUND: Animal experiments demonstrated that adding ultraviolet blood irradiation and oxygenation (UBIO) in cardioplegic solutions has myocardial protection during cardiopulmonary bypass (CPB).OBJECTIVE: To investigate the myocardial protective effect of UBIO as cardiac arresting solution in the process of CPB in old patients undergoing valve replacement.DESIGN, TIME AND SETTING: The randomized controlled trial of biochemistry level was performed at Department of Cardiac Surgery, Guizhou Provincial People's Hospital, from October 2006 to April 2008.PARTICIPANTS: A total of 46 old patients scheduled for heart valve replacement were randomly divided into test group and control group, with 23 patients in each group.METHODS: The test group was infuoed with the UBIO blood as a cardiac arresting solution via the ascending aorta. The UBIO blood accumulated from the subclavian vein (10 mL/kg) was heparinized and dealt with the ultraviolet irradiation (wave length 240-300 nm) and oxygenation. And then it was infused for the first antegrade coronary perfusion when the ascending aorta was cross-clamped, when the UBIO blood was produced, the equivalent quantitative saline was infused from another vein. The 4:1 cold oxygenated blood hyperhalemia cardioplegia was perfused and then maintained for 30 minutes. The control group was the same as the test group except that the cardiac arresting solution presented without the 4:1 cold oxygenated blood.MAIN OUTCOME MEASURES: Blood samples were withdrawn from coronary venous sinus before cross-clamping and at minutes 5 and 10 after aorta declamping, to measure the levels of superoxide dismutase (SOD) and the content of malondialdehyde (MDA). Before the beginning of CPB, and at hours 4, 24, and 48 after the end of CPB, venous blood was drawn to test the serum cardiac troponin I(cTnI) and creatine kinase isozyme (CK-MB).RESULTS: MDA levels of plasma were less in the test group than that of the control group after aorta declamping (P < 0.05),while the SOD activity was obvious greater than the control group (P < 0.05). At hours 4-48 after CPB, CK-MB and cTnl levels were lower in the test group than the control group (P< 0.05).CONCLUSION: Antegrade coronary first perfusion with UBIO during CPB has evident cardiac protective in old patients undergoing valve replacement by elevating SOD activity, decreasing MDA level, relieving myocardial reperfusion injury, as well as decreasing myocardial damage markers levels.