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.

Hepatic osteodystrophy is a common complication in patients with chronic liver disease and is influenced by various risk factors， and it has become one of the important influencing factors for the prognosis of liver transplantation. By analyzing the influencing factors for bone health and bone metabolism during the perioperative period of liver transplantation， this article emphasizes the importance of a comprehensive assessment of bone health and necessary interventions at this stage， with an aim to reduce the risk of postoperative complications and improve the long-term prognosis of patients. A deeper exploration of the association between hepatic osteodystrophy and the prognosis of liver transplantation can help to reveal the key influencing factors for postoperative outcomes， thus providing a theoretical basis for optimizing postoperative management strategies. Furthermore， advances in this research field will offer new insights into the treatment of patients receiving liver transplantation， and it is expected to further improve quality of life and long-term survival rate.

Femoral intertrochanteric fracture is one of the common types of fractures in the elderly. With the general improvement of medical and living standards, the number of elderly people is increasing, and the problem of osteoporosis has also become relatively prominent. Therefore, low violence can usually cause fractures in this area of the elderly, which has a significant negative impact on the quality of life of elderly patients. With the further development of medical technology and internal fixation materials, the emergence of proximal femoral nail antirotation(PFNA) has greatly improved the treatment effect of femoral intertrochanteric fractures in elderly patients. However, with the increasing number of patients treated, internal fixation failures have gradually been reported. In recent years, proximal femoral biomimetic intramedullary nail(PFBN) has been reported to have good clinical efficacy. Therefore, this article mainly elaborates on the theoretical basis, design characteristics, biomechanics, and clinical efficacy research of PFBN, providing more reference for the clinical treatment of femoral intertrochanteric fractures in elderly patients in the future.

Crohn's disease(CD)is an autoimmune intestinal disease characterised by chronic and non-specific inflammation,and the exact etiology and pathogenesis are still unclear.Neutrophil gelatinase associated lipocalin(NGAL),a secreted glycoprotein and isolated from neutrophils,is widely involved in pathophysiological processes such as intestinal inflammation response,apoptosis and tumour progression.It has been found that NGAL has the potential to be a clinical biological marker in clinical diagnosis and monitoring of CD activity.Therefore,this paper reviews the application value of NGAL in different clinical samples of CD,in order to provide reference for clinical diagnosis and treatment of CD.

Background:Previous studies have proved that neutrophil gelatinase-associated lipocalin(NGAL)plays an important role in the progression of Crohn's disease(CD),and may serve as a potential biomarker for disease activity prediction,severity assessment,treatment response evaluation and prognosis monitoring.However,the diagnostic value of NGAL in perianal fistulizing Crohn's disease(pfCD)is still unclear.Aims:To investigate the serum level of NGAL and its diagnostic value in patients with active pfCD.Methods:A total of 66 patients diagnosed as pfCD from July 2021 to June 2023 at Longhua Hospital,Shanghai University of Traditional Chinese Medicine were enrolled,including 36 active pfCD patients and 30 inactive pfCD patients.The disease activity and perianal fistula activity were assessed by Crohn's disease activity index(CDAI)and perianal disease activity index(PDAI),respectively.Serum NGAL,fecal calprotectin(FC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),as well as CDAI score and PDAI score were compared between the active and inactive pfCD patients,and the correlations of NGAL with the other parameters in active pfCD patients were analyzed.ROC curve was drawn to evaluate the values of serum NGAL,FC,CRP and ESR for diagnosis of active pfCD.Results:The serum NGAL,FC,CRP,ESR,CDAI score and PDAI score in active pfCD patients were significantly higher than those in inactive pfCD patients(all P＜0.001).NGAL was positively correlated with FC(r=0.64,P＜0.001),CRP(r=0.55,P＜0.001),ESR(r=0.53,P＜0.001),CDAI score(r=0.59,P＜0.001)and PDAI score(r=0.54,P＜0.001)in active pfCD patients.The optimal cut-off values of NGAL,FC,CRP and ESR were 220.5 μg/L,146.0 μg/g,7.9 mg/L and 23.5 mm/h,respectively,for the diagnosis of active pfCD,and the area under the curve were 0.922(95％CI:0.850-0.995),0.888(95％CI:0.806-0.970),0.853(95％CI:0.763-0.944)and 0.830(95％CI:0.731-0.930),respectively.Conclusions:Serum NGAL level is associated with the disease activity of pfCD,and can be used as a non-invasive biomarker for the clinical diagnosis of active pfCD.

Objective:To evaluate the role of Z-DNA-binding protein 1 (ZBP1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in lipopolysaccharide (LPS)-adenosine triphosphate (ATP)-induced pyroptosis in macrophages of mice.Methods:The RAW264.7 macrophages from mice were routinely cultured and divided into 6 groups ( n=9 each) using a random number table method: control group (group C), LPS-ATP group, LPS-ATP+ transfection negative control scRNA group (group LPS-ATP+ scRNA), LPS-ATP+ ZBP1 small interference RNA group (group LPS-ATP+ siRNA), LPS-ATP+ dimethyl sulfoxide group (group LPS-ATP+ DSMO), and LPS-ATP+ RIPK1 inhibitor nec-1 group (group LPS-ATP+ nec-1). The siRNA technique was used to inhibit the expression of ZBP1 in group LPS-ATP+ siRNA. The RIPK1 inhibitor nec-1 was given to inhibit the expression of RIPK1 protein in group LPS-ATP+ nec-1. Group C was routinely cultured. Cells were incubated with 10 μg/ml LPS for 24 h, then 5 mmol/L ATP was added, and the cells were incubated for 30 min to develop the cell pyroptosis model in the remaining 5 groups. The cell survival was detected by the CCK-8 assay. The concentrations of interleukin-1beta (IL-1β), IL-6, IL-18 and tumor necrosis factor-alpha (TNF-α) in cell supernatant were determined by enzyme-linked immunosorbent assay. The pyroptosis was determined by propidium iodide fluorescence staining. Western blot was used to detect the expression of ZBP1, RIPK1, caspase-1 and GSDMD. Results:Compared with group C, the cell survival rate was significantly decreased, the cell pyroptosis rate and concentrations of IL-1β, IL-6, IL-18 and TNF-α in the supernatant were increased, and the expression of ZBP1, RIPK1, caspase-1 and GSDMD was up-regulated in group LPS-ATP ( P<0.05). Compared with group LPS-ATP, no significant change was found in the parameters mentioned above in group LPS-ATP+ scRNA and group LPS-ATP+ DSMO ( P>0.05). Compared with group LPS-ATP+ scRNA, the cell survival rate was significantly increased, the cell pyroptosis rate and concentrations of IL-1β, IL-6, IL-18 and TNF-α in the supernatant were decreased, and the expression of ZBP1, RIPK1, caspase-1 and GSDMD was down-regulated in group LPS-ATP+ siRNA ( P<0.05). Compared with group LPS-ATP+ DMSO, the cell survival rate was significantly increased, the cell pyroptosis rate and concentrations of IL-1β, IL-6, IL-18 and TNF-α in the supernatant were decreased, the expression of ZBP1, caspase-1 and GSDMD was down-regulated ( P<0.05), and no significant change was found in the expression of ZBP1 in group LPS-ATP+ nec-1 ( P>0.05). Conclusions:Activation of ZBP1/RIPK1 signaling pathway is involved in LPS-ATP-induced pyroptosis in macrophages of mice.

Objective:To evaluate the relationship between inositol-requiring enzyme 1α-X box-binding protein 1 (IRE1α-XBP1) signaling pathway in endoplasmic reticulum and neutrophil extracellular traps during endotoxin-induced acute lung injury (ALI) in mice.Methods:Forty-eight SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 25-30 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (C group), STF-083010 group (ST group), lipopolysaccharide (LPS)-induced ALI group (ALI group) and LPS-induced ALI + STF-083010 group (ALI+ ST group). The ALI model was established by inhaling aerosolized LPS in ALI group and ALI+ ST group. The equal volume of aerosolized normal saline was inhaled in C and ST groups. IRE1α inhibitor STF-083010 50 mg/kg was intraperitoneally injected at 1 h before developing the model in ST and ALI+ ST groups, and the equal volume of normal saline was intraperitoneally injected in the other two groups. The mice were sacrificed after anesthesia at 24 h after developing the model. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected for determination of the pathological changes (by light microscopy) which were scored, wet/dry lung weight (W/D) ratio, concentrations of interleukin-1beta (IL-1β), IL-18 and myeloperoxidase (MPO) in the BALF supernatant, and expression of phosphorylated IRE1α(p-IRE1α), XBP1s and citrullinated histone H3 (Cit H3) in lung tissues (using Western blot). Results:Compared to group C, the lung injury scores and W/D ratio were significantly increased at 24 h after developing the model, the concentrations of IL-1β, IL-18 and MPO in BALF were increased, and the expression of p-IRE1α, XBP1s and Cit H3 in lung tissues was up-regulated in ALI and ALI+ ST groups. Compared to group L, the lung injury scores and W/D ratio were significantly decreased at 24 h after developing the model, the concentrations of IL-1β, IL-18 and MPO in BALF were decreased, and the expression of p-IRE1α, XBP1s and Cit H3 in lung tissues was down-regulated in group ALT+ ST ( P<0.05). Conclusions:The IRE1α-XBP1 signaling pathway in endoplasmic reticulum is involved in endotoxin-induced ALI by up-regulating the expression of neutrophil extracellular traps in mice.

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

Objective:To evaluate the clinical efficacy and safety of neuro-endoscopic evacuation and microsurgery via keyhole approach in early spontaneous supertentorial intracerebral hemorrhage (ICH). Methods:A prospective multi-center randomized controlled trial was performed; 114 patients with spontaneous supertentorial ICH (time from onset to surgery<6 h) admitted to Departments of Neurosurgery, Shunde Hospital of Southern Medical University, Jiangmen Central Hospital, Affiliated Hospital of School of Medicine of Yanbian University from January 2019 to December 2021 and met the surgical indications were selected. They were divided into endoscopic group (evacuation of intracerebral hematoma under neuroendoscope, n=71) and microscopic group (microsurgery of intracerebral hematoma via keyhole approach, n=43) according to different surgical methods. After 1:1 propensity score matching of the general data, surgical time, hematoma clearance rate, early postoperative re-bleeding rate, Glasgow coma scale (GCS) scores 7 d after surgery, activity of daily living (ADL) scores 6 months after surgery, mortality, and surgery-related complications of 66 patients (33 from each group after matching) were compared. Results:The difference of surgical time between endoscopic group and microscopic group was statistically significant (125[102, 157] mins vs. 175[125, 260] mins, P<0.05). However, hematoma clearance rate (93.00%[80.88%, 96.52%] vs. 93.31%[88.15%, 96.03%]), early postoperative re-bleeding rate (15.2% vs. 9.1%), GCS scores 7 d after surgery (13[10, 15] vs. 12[8, 14]), ADL scores 6 months after surgery (65[45, 85] vs. 55[0, 85]), mortality rate (18.2% vs. 21.2%) and incidences of postoperative intracranial infection and acquired pulmonary infection were not statistically significant between the two groups ( P>0.05). Conclusion:Comparing with microsurgery via keyhole approach, neuro-endoscopy could shorten the surgical time, but not improve the prognosis or safety in early spontaneous supertentorial ICH patients.