Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

OBJECTIVE: To investigate the frequency and related factors of ineffective triggering (IT) and double triggering (DT) in patients with acute brain injury undergoing invasive mechanical ventilation. METHODS: A retrospective cohort study was conducted using data from a single-center observational trial. Patients with acute brain injury [traumatic brain injury, stroke, and post-craniotomy for brain tumors] undergoing mechanical ventilation in the intensive care unit (ICU) of Beijing Tiantan Hospital, Capital Medical University between June 2017 and July 2019 were retrospectively analyzed. Demographic and clinical data were collected. Respiratory parameters and waveforms during the first 3 days of mechanical ventilation were recorded, with 15-minute waveform segments collected 4 times daily. Airway occlusion pressure (P_0.1) was measured via end-expiratory hold at the end of each recording. IT and DT were identified based on airway pressure, flow, and esophageal pressure waveforms, and the ineffective triggering index (ITI) and DT incidence were calculated. Multivariate Logistic regression was used to identify factors associated with IT and DT. RESULTS: A total of 94 patients with acute brain injury were ultimately enrolled, including 19 cases of traumatic brain injury (20.2%), 39 cases of stroke (41.5%), and 36 cases of post-craniotomy for brain tumor (38.3%). Supratentorial injury was observed in 49 patients (52.1%), while infratentorial injury was identified in 45 patients (47.9%). A total of 94 patients with 1 018 datasets were analyzed; 684 (67.2%) datasets were on pressure support ventilation (PSV), and 334 (32.8%) were on mandatory ventilation. IT was detected in 810 (79.6%) datasets, with a median incidence of 2.1% (0.3%, 12.0%). Datasets demonstrating IT were characterized by lower P_0.1, higher tidal volume (VT), reduced respiratory rate (RR), and decreased minute ventilation (MV) compared to those without IT. The proportion of datasets exhibiting IT was higher during PSV than in mandatory ventilation [83.8% (573/684) vs. 71.0% (237/334), P < 0.05], while, the prevalence of ITI ≥ 10% was lower [23.8% (163/684) vs. 33.5% (112/334), P < 0.05]. DT was detected in 305 datasets (30%), with a median incidence of 0.6% (0.4%, 1.3%). Datasets exhibiting DT were characterized by higher VT, reduced RR, and lower pressure support levels. The incidence of DT was lower in PSV compared to mandatory ventilation modes [0% (0%, 0.3%) vs. 0% (0%, 0.5%), P < 0.05]. The post-craniotomy for brain tumors group exhibited higher ITI, lower RR, reduced MV, and a greater proportion of infratentorial lesions, compared to the TBI group. The infratentorial lesion group demonstrated higher ITI and incidence of DT compared to the supratentorial lesion group [ITI: 3.1% (0.7%, 17.8%) vs. 1.5% (0%, 8.3%), incidence of DT: 0% (0%, 0.5%) vs. 0% (0%, 0%), both P < 0.05]. After adjusting for confounding factors through multivariate logistic regression analysis, infratentorial lesion [odds ratio (OR) = 2.029, 95% confidence interval (95%CI) was 1.465-2.811, P < 0.001], lower P_0.1 (OR = 0.714, 95%CI was 0.616-0.827, P < 0.001), and mandatory ventilation (OR = 1.613, 95%CI was 1.164-2.236, P = 0.004) were independently associated with IT. Additionally, infratentorial lesion (OR = 1.618, 95%CI was 1.213-2.157, P = 0.001), large tidal volume (OR = 1.222, 95%CI was 1.137-1.314, P < 0.001), lower pressure support levels (OR = 0.876, 95%CI was 0.829-0.925, P < 0.001), and mandatory ventilation (OR = 2.750, 95%CI was 1.983-3.814, P < 0.001) were independently associated with DT. CONCLUSION IT and DT were common in patients with acute brain injury. Infratentorial lesions and mandatory ventilation were independently associated with both IT and DT.
Humans ; Respiration, Artificial/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Brain Injuries, Traumatic/therapy* ; Logistic Models ; Aged ; Adult

Purpose To observe the clinical and pathological characteristics of indolent NK-cell lymphoprolifera-tive disorder(iNKLPD)of the gastrointestinal tract.Methods A retrospective analysis was conducted on the clinical pathological features,endoscopic findings,and immunophenotypes of 7 cases of iNKLPD.The study included in situ hybridization detection and literature review.Results The cohort comprised two males and five females,aged 28 to 54 years,with a median age of 40 years.The clinical manifestations varied,including acid reflux(two cases),nausea(three cases),stomach flatulence(five cases),and abdominal pain(one case).Lesions were observed at single sites in five cases and multiple sites in two cases.Involvement of the stomach,small intestine,and colon showed mucosal infiltration of small lymphocytes with abundant and clear cytoplasm,fine nuclear chromatin,and rare mitoses.Scat-tered eosinophils were observed in the background.Cases involving the gallbladder and bladder exhibited structural damage.The gallbladder lesion demonstrated cell with clear cytoplasm,condensed chromatin and prominent nucleoli.All cases were positive for CD3,CD56,CD7,TIA1 and Granzyme B,but negative for CD20,CD8 and CD5.Ki67 proliferation index from 10％to 50％.EBER in situ hybridization was negative in all cases.Follow-up periods ranged from 25 to 57 months(mean:38 months).All patients survived:four were asymptomatic,one had multiple-site in-volvement,and two experienced recurrence.Conclusion iNKLPD has an indolent clinical course and can involve multiple sites in the gastrointestinal tract and other organs.Differentiating it from invasive gastrointestinal lymphomas is critical to avoid misdiagnosis.

Purpose To compare the expression and pattern of EBNA2 in infectious mononucleosis(IM),EBV-positive diffuse large B-cell lymphoma(EBV+DLBCL),and EBV+DLBCL arising in immune deficiency/dysregulation(IDD-related EBV+DLBCL),and to investigate the potential diagnostic value of EBNA2 in IM and EBV-associated diffuse large B-cell lymphoma.Methods A retrospective study was conducted on 46 cases of IM,31 cases of EBV+DLBCL,and 16 cases of IDD(post-transplantation)-related EBV+DLBCL.Clinical information,immunohistochemis-try and EBER were reviewed to further confirm the diagnoses.All samples were stained for EBNA2.The expression ra-tio and intensity of EBER and EBNA2 in the same area were assessed.Results EBER was positive in all IM,EBV+DLBCL,and IDD(post-transplantation)-related EBV+DLBCL,while the positivity rate of EBNA2 was 95.65％,6.45％,and 100％,respectively.The positive intensity of EBNA2 was weak(71.73％),strong(87.5％)and nega-tive(93.54％)in IM,IDD(post-transplantation)-related EBV+DLBCL and EBV+DLBCL respectively.The average values of EBNA2/EBER were 31％,3％,and 78％among the three groups.The positivity rate and average value of EBNA2/EBER in IM were significantly higher than those in EBV+DLBCL(P＜0.001);however,the average value of EBNA2/EBER was significantly lower than that in IDD(post-transplantation)-related EBV+DLBCL(P＜0.001).The weak positive expression of EBNA2 in IM was significantly higher than that in EBV+DLBCL(P＜0.001),where-as strong positive expression of EBNA2 in IDD(post-transplantation)-related EBV+DLBCL was higher than that in IM(P＜0.001).Conclusion EBNA2 is often positive in IM and predominantly weakly positive,which is distinct from the pattern in EBV+DLBCL and IDD(post-transplantation)-related EBV+DLBCL.EBNA2 can serve as an effective marker for distinguishing them.

Objective To analyze the epidemiology and trends of measles,tuberculosis,pertussis,scarlet fever,influenza,mumps and rubella in Beijing between 2014 and 2023 in order to provide data for prevention and control of related diseases.Methods Data on the incidences of seven respiratory infectious diseases in Beijing between 2014 and 2023 was collected.Descriptive epidemiological methods were employed to analyze their demographic,temporal and spatial distribution.Joinpoint regression analysis was used to assess temporal trends in incidence.Results A total of 1 406 777 cases of seven respiratory infectious diseases were reported in Beijing between 2014 and 2023,which corresponded to an average crude rate of 649.76/100 000 reported annually.The crude rate of incidencewas higher among females than among males,with the most vulnerable age groups being 0-4 years and 5-19 years,and was higher in the six districts than on the outskirts.Most of the respiratory infectious diseases peaked in winter and spring.The annual increase in the incidence of respiratory infectious diseases in Beijing in this period averaged 27.27％,with no statistically significant differences in trends.The incidence rates of measles,tuberculosis,scarlet fever,mumps and rubella decreased significantly while those of pertussis and influenza increased,but with no statistically significant difference.Conclusion The overall incidence of major respiratory infectious diseases in Beijing is increasing.It is recommended that more people get vaccinated,surveillance of such diseases as pertussis and influenza be enhanced,and regional health resources be allocated more effectively,all of which will be critical to subsequent prevention and control of respiratory infectious diseases in Beijing.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of primary bladder lymphoma.Methods:A retrospective study was conducted on 23 cases of primary bladder lymphoma diagnosed at Beijing Friendship Hospital of Capital Medical University between February 2010 and April 2024. The clinicopathological data were collected and analyzed, and literature was reviewed.Results:Among the 23 cases, 7 were male and 16 were female, with a male-to-female ratio of 1.0∶2.5. The median age was 65 (58, 71) years, ranged 38-84 years. The main clinical manifestation was painless visible hematuria, followed by frequent urination, urgency, and lower abdominal discomfort. Only one case presented with fever, and all cases primarily presented as bladder masses or lesions. The histological types included 17 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), 4 cases of diffuse large B-cell lymphoma (DLBCL), 1 case of ALK-negative anaplastic large cell lymphoma (ALCL), and 1 case of indolent NK-cell lymphoproliferative disease (INKLPD). EMZL exhibited relatively uniform morphology. Among them, 2 cases showed marked plasmacytic differentiation, 1 case had an increased number of large cells, 6 cases had residual germinal centers, and 2 cases presented with lymphoepithelial lesions. All cases demonstrated irregular FDC networks. DLBCL cells were larger in size; 3 cases showed diffuse infiltration, while 1 case had scattered, clustered distribution in a background of small lymphocytes,and with aberrant expression of GATA3. ALCL negative ALCL showed classic anaplastic morphology with "kidney-shaped" nuclei. INKLPD cells were of medium size and irregular in shape, with some cells containing eosinophilic granules in the cytoplasm. EBER in situ hybridization was negative.Conclusions:The primary histological types of bladder lymphoma are EMZL and DLBCL, with occasional cases of T-cell lymphoma and INKLPD. Clinical manifestations lack specificity and may overlap with inflammatory conditions or epithelial tumors. Both clinicians and pathologists should be aware of these rare diseases to facilitate accurate diagnosis and treatment.

Objective To observe the synergistic effect of Shengxian Huaxian Prescription and its disassembled prescription on pulmonary fibrosis;To explore whether its mechanism is related to regulating the STAT6/PPAR-y pathway to promote polarization of M2 type macrophages towards M1 type.Methods Ten SD rats were randomly selected from 70 rats as blank group,and the remaining rats were re-established pulmonary fibrosis model by intratracheal infusion of bleomycin.After modeling,the rats were divided into model group,positive group,Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group,with 10 rats in each group.Shengxian Huaxian Prescription group,Shengxian group,Tongluo group and Bushen group were given 12.60,7.65,3.60 and 2.25 g/kg of corresponding TCM solution,respectively;the positive group was given 0.12 g/kg of pirfenidone suspension;the blank group and the model group were given equal volume of normal saline,once a day,for consecutive 28 days.The lung function of rats was detected,the contents of IL-6 and TGF-β1 in serum were detected by ELISA,the pathological changes in lung tissue were observed by Masson staining,the expression of CD68,iNOS and CD206,Arg-1 in lung tissue were detected by immunofluorescence,the expression of SOCS1,SOCS3,STAT6,p-STAT6 and PPAR-γ in lung tissue were detected by Western blot.Results Compared with the blank group,the PEF,PIF and EF50 in model group rats significantly decreased,and the contents of serum IL-6 and TGF-β1 significantly increased,Masson staining showed a large amount of collagen fiber deposition,Ashcroft score significantly increased,CD206,Arg-1,STAT6,p-STAT6,PPAR-y protein expression significantly increased(P＜0.01),the expressions of SOCS1 and SOCS3 protein significantly decreased(P＜0.01),while the expression of CD68 and iNOS were not significantly changed(P＞0.05).Compared with the model group,the PEF,PIF and EF50 in all administration groups significantly increased,and the contents of serum IL-6 and TGF-β1 significantly decreased,collagen fiber deposition in lung tissue were decreased to varying degree,Ashcroft score significantly decreased,the expression of CD206,Arg-1,STAT6,p-STAT6 and PPAR-γ protein significantly decreased(P＜0.01),the expressions of CD68,iNOS,SOCS1 and SOCS3 protein significantly increased(P＜0.05).The above indicators showed the most significant changes in Shengxian Huaxian Prescription group,followed by Shengxian group(P＜0.01,P＜0.05).Conclusion Both Shengxian Huaxian Prescription and its disassembled prescription have anti pulmonary fibrosis effects,and their mechanism may related to regulating the STAT6/PPAR-y pathway and promoting polarization of M2 type macrophages towards M1 type.Shengxian Huaxian Prescription group has the best effect,while Shengxian group play an important role in the prescription,and the compatibility between each group has a synergistic effect.

Objective Based on the intervention map to develop a comprehensive nutrition education program for pancreaticoduodenectomy patients and to explore the effect of its clinical application,aiming at providing references for clinical nursing practice.Methods A convenience sampling method was used to select 76 patients who were to undergo pancreaticoduodenectomy in the department of hepatobiliary and pancreatic surgery of a tertiary hospital in Anhui Province as the study subjects.The 38 patients admitted from October 2021 to September 2022 were in a control group,and the 38 patients admitted from October 2022 to July 2023 were in an experimental group.The experimental group received the comprehensive nutritional education programme constructed in this study,and the control group used conventional nutrition health education measures,and the length of intervention for both groups was from pre-hospitalization to discharge for 6 months.Nutrition-related indicators,postoperative complications,hospitalisation time,hospitalisation costs and satisfaction were compared between the 2 groups.Results A total of 64 patients completed this study,with 33 in the experimental group and 31 in the control group.Repeated measurement analysis of variance showed that the interaction effects of BMI,total serum protein and serum preprotein were statistically significant(P＜0.05).The incidence of complications,hospitalization days and hospitalization costs of the experimental group were lower than those of the control group(P＜0.05).The scores of nutrition education-related satisfaction in the experimental group were higher than those in the control group(P＜0.001).Conclusion A comprehensive nutritional education program based on intervention map can improve the nutritional status of pancreaticoduodenectomy patients to a certain extent,reduce the occurrence of complications,and promote patients'recovery.

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.