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 differences in indwelling duration, clinical scenarios, and complications between the modified midline catheter (MMC) and the central venous catheter (CVC) in the treatment of patients in the medical intensive care unit (ICU) and the risk factors for complications based on real-world data. METHODS: A retrospective cohort study was conducted. The adult patients admitted to the medical ICU of the Third Xiangya Hospital of Central South University and had undergone placement of either a MMC or a CVC between January 1, 2023, and July 31, 2024, were consecutively enrolled by querying the hospital's electronic medical record system. Based on the type of catheter inserted, the patients were divided into the MMC group and the CVC group. The two groups were compared regarding the selection of catheters in the context of different underlying diseases, the actual clinical application after catheterization, catheter-related complications, the international normalized ratio (INR) and platelet count (PLT) during puncture and catheterization, the length of ICU stay, total length of hospital stay, catheter indwelling duration, and mortality during hospitalization. Multivariate Logistic regression analysis was employed to identify independent risk factors for catheter removal. RESULTS: Among the 274 patients, 52 received a MMC and 222 received a CVC. The utilization rate of MMC was significantly higher than that of CVC in patients with acute respiratory distress syndrome (ARDS), cardiovascular disease, and cancer [ARDS: 92.3% (48/52) vs. 70.3% (156/222), cardiovascular disease: 84.6% (44/52) vs. 54.5% (121/222), cancer: 30.8% (16/52) vs. 17.1% (38/222), all P < 0.05]. However, the use of MMC was significantly lower than CVC when vasoactive drug infusion was required [57.7% (30/52) vs. 79.7% (177/222), P < 0.05]. A significantly higher proportion of patients in the MMC group had a catheter indwelling time ≥ 12 days as compared with the CVC group [32.7% (17/52) vs. 13.5% (30/222), P < 0.05]. There were no statistically significant differences in other underlying diseases, venous access usage, INR and PLT during puncture and catheterization, length of ICU stay, total length of hospital stay, and in-hospital mortality of patients between the two groups. Regarding catheter-related complications, although the incidence of partial or complete catheter removal in the MMC group was significantly higher than that in the CVC group [36.5% (19/52) vs. 5.4% (12/222), P < 0.05], the incidence of puncture site fluid leakage, puncture site skin allergy, and deep vein thrombosis were significantly lower than those in the CVC group [puncture site fluid leakage: 1.9% (1/52) vs. 22.1% (49/222), puncture site skin allergy: 0% (0/52) vs. 20.7% (46/222), deep vein thrombosis: 3.8% (2/52) vs. 16.7% (37/222), all P < 0.05]. Furthermore, the proportion of patients experiencing three or more types of complications in the MMC group was significantly lower than that in the CVC group [5.8% (3/52) vs. 17.6% (39/222), P < 0.05]. Multivariate Logistic regression analysis of risk factors for catheter removal identified the use of a MMC [odds ratio (OR) = 8.518, 95% confidence interval (95%CI) was 3.710-19.560, P < 0.001] and a catheter indwelling time ≥ 12 days (OR = 3.133, 95%CI was 1.297-7.567, P = 0.011) as independent risk factors. CONCLUSIONS MMC was more frequently used in patients with ARDS, cardiovascular disease, and cancer, whereas CVC was primarily employed for vasoactive drug infusion. The use of MMC and a longer indwelling time were identified as independent risk factors for catheter removal. Despite a higher removal rate, the overall incidence of complications was significantly lower with MMC than with CVC. These findings suggest that MMC could serve as a routine alternative to CVC in most of clinical scenarios, provided that measures are implemented to prevent removal.
Humans ; Retrospective Studies ; Intensive Care Units ; Catheterization, Central Venous/methods* ; Central Venous Catheters ; Risk Factors ; Length of Stay ; Male ; Female ; Middle Aged ; Adult ; Catheters, Indwelling ; Aged

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Bitter taste receptors,also known as type 2 taste receptors(T2Rs),are found not only in the mouth's taste bud cells but also in various tissues and cells,including macrophages.Macrophages,known for their re-markable plasticity,play a crucial role in regulating innate immunity,managing inflammation,and orchestrating immune responses to antigens,pathogens,and environmental factors.Recently,the study of the expression and function of bitter taste receptors within macrophages has garnered significant interest.This review summarizes the expression levels and dis-tribution characteristics of bitter taste receptors in macrophages and examines their effects on macrophage polarization,phagocytosis,and chemotaxis,as well as their potential molecular mechanisms.The purpose of this review is to provide in-sight and perspectives for research on the regulatory role of T2Rs in macrophage functions.

Anaphylaxis to perioperative drugs has an insidious and rapid onset, can be life-threatening, and often results in the suspension of surgery. Neuromuscular blocking agents (NMBAs) are currently considered to be the most common cause of anaphylactic reactions among anesthetic drugs. With the increasing amount of anesthesia and surgery in the world, there are more and more NMBAs use, and the corresponding allergic risk is also increasing. With the use of NMBAs, their antagonists, such as neostigmine and sugammadex, are often used too, which have more and more allergy reports in clinical practice. Due to the complex mechanism of allergy caused by NMBAs and their antagonists, it is difficult to find out the culprit drug. The cross-reactivity between NMBAs is common, so it is often difficult to choose alternative drugs. This article summarized the epidemiology, pathological mechanisms, diagnostic methods and procedures, immediate treatment, and prevention strategies of anaphylaxis caused by these drugs.

Background::Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy. Methods::A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety. Results::There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred. Conclusion::The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.

Anaphylaxis to perioperative drugs has an insidious and rapid onset, can be life-threatening, and often results in the suspension of surgery. Neuromuscular blocking agents (NMBAs) are currently considered to be the most common cause of anaphylactic reactions among anesthetic drugs. With the increasing amount of anesthesia and surgery in the world, there are more and more NMBAs use, and the corresponding allergic risk is also increasing. With the use of NMBAs, their antagonists, such as neostigmine and sugammadex, are often used too, which have more and more allergy reports in clinical practice. Due to the complex mechanism of allergy caused by NMBAs and their antagonists, it is difficult to find out the culprit drug. The cross-reactivity between NMBAs is common, so it is often difficult to choose alternative drugs. This article summarized the epidemiology, pathological mechanisms, diagnostic methods and procedures, immediate treatment, and prevention strategies of anaphylaxis caused by these drugs.

Objective:To assess the shielding requirements of low energy X-ray intraoperative radiotherapy room under the domestic and foreign standards and guidelines, to measure the sured transmission factors for a range of shielding materials, the ambient dose equivalent rate around concerned positions and the shielding effect of protective devices, so as to provide references for shielding design of such radiotherapy units and applications of radiological protection devices.Methods:The required shielding thicknesses for a treatment room with INTRABEAM intraoperative radiotherapy system were calculated under the Chinese national standard GBZ 121, IPEM report No. 75 and NCRP report No. 151, respectively. The transmission factors for a range of shielding materials including solid water slab, shielding sheet and shielding apron were measured. Moreover, the ambient dose equivalent rates were measured under the simulated working conditions and the shielding effectiveness of a lead screen was evaluated.Results:The required lead thicknesses calculated under different standards and guidelines were less than 0.6 mm for all the concerned points, with the differences at sub-millimeter level. The low energy X-rays generated by this equipment attenuated rapidly in the shielding materials. The measured transmission factors of 0.05 mm lead equivalent shielding sheet and 0.25 mm lead equivalent shielding apron were 0.068 and 0.003 8, respectively. When the radiation was delivered using spherical applicator without any attenuation, the ambient dose equivalent rates at 1 m and 2 m from the X-ray source were 10.7 and 2.6 mSv/h, respectively. The corresponding measurement values decreased to 3.8 and 0.9 μSv/h, respectively, when the spherical applicator was inserted into a small water tank. Meanwhile, the ambient dose equivalent rate at 2 m was reduced to the background level when using protective screen.Conclusions:The shielding requirements for a low energy X-ray intraoperative radiotherapy facility are minimal, with low effective energy of X-rays generated by this equipment, but the dose rate close to the unshielded radiation source is high. The shielding scheme of treatment room should be optimized in design and the protective device should be used in a reasonable way.

Objective:The preseason prophylactic treatment of seasonal allergic rhinitis (AR) caused by pollens could alleviate AR symptoms during the pollen season. This study aimed to evaluate the effect of prophylaxis usage of suplatast tosilate on the life quality of AR patients in the pollen season, and investigate the potential mechanism of action through transcriptomic analysis.Methods:This is a randomized controlled study. AR patients allergic to weed pollens were recruited from Allergy Clinic of Peking Union Medical College Hospital from January 2020 to June 2020, and divided into prophylactic group who started to take suplatast tosilate as prophylaxis 2 weeks before the spread of weed pollens[n=10, 4 men and 6 women with age range of (34±6) years old] and control group who did not use any prophylactic treatment[n=24, 12 men and 12 women with age range of (33±9) years old]. The differences of age ( t=0.381, P=0.706) and gender ( χ2=0.595, P=0.715) distribution between the patients of two groups were not statistically significant. All the subjects filled in the rhinoconjunctivitis quality of life questionnaire (RQLQ) while onset of AR symptoms, and peripheral blood was drawn for transcriptomic analysis 1 month before and during the pollen season. Differences between groups were statistically analyzed through chi-square test and t test. Results:There was no significant difference in visual analogue scale of rhinitis symptom in the last pollen season between prophylactic group and control group[ 8.0 (6.4, 9.3) vs 7.3 (6.1, 8.0), Z=1.180, P=0.254]. The RQLQ score of prophylactic group was superior to that of control group in the weed pollen season (2.9±0.9 vs 3.7±0.9, t=-2.438, P=0.026). 210 differentially expressed genes of fold change ≥2 were identified, with 147 genes upregulated and 63 genes downregulated in the prophylactic group compared to the control group. Gene Ontology annotation showed that IL-12 and IL-23 related pathways were downregulated in prophylactic group ( P=0.006 48). Polymerase Chain Reaction (PCR) verification of differentially expressed genes indicated that the relative expression level of HLA-G in prophylactic group was significantly lower than that in control group (0.23±0.19 vs 1.00±0.49, t=4.016, P=0.006). Conclusion:The prophylactic treatment of suplatast tosilate showed some benefit to the life quality of seasonal AR patients during the pollen season, and the potential mechanism might be related with the downregulation of IL-12 and IL-23 pathways and decreased expression of HLA-G.

Objective:The preseason prophylactic treatment of seasonal allergic rhinitis (AR) caused by pollens could alleviate AR symptoms during the pollen season. This study aimed to evaluate the effect of prophylaxis usage of suplatast tosilate on the life quality of AR patients in the pollen season, and investigate the potential mechanism of action through transcriptomic analysis.Methods:This is a randomized controlled study. AR patients allergic to weed pollens were recruited from Allergy Clinic of Peking Union Medical College Hospital from January 2020 to June 2020, and divided into prophylactic group who started to take suplatast tosilate as prophylaxis 2 weeks before the spread of weed pollens[n=10, 4 men and 6 women with age range of (34±6) years old] and control group who did not use any prophylactic treatment[n=24, 12 men and 12 women with age range of (33±9) years old]. The differences of age ( t=0.381, P=0.706) and gender ( χ2=0.595, P=0.715) distribution between the patients of two groups were not statistically significant. All the subjects filled in the rhinoconjunctivitis quality of life questionnaire (RQLQ) while onset of AR symptoms, and peripheral blood was drawn for transcriptomic analysis 1 month before and during the pollen season. Differences between groups were statistically analyzed through chi-square test and t test. Results:There was no significant difference in visual analogue scale of rhinitis symptom in the last pollen season between prophylactic group and control group[ 8.0 (6.4, 9.3) vs 7.3 (6.1, 8.0), Z=1.180, P=0.254]. The RQLQ score of prophylactic group was superior to that of control group in the weed pollen season (2.9±0.9 vs 3.7±0.9, t=-2.438, P=0.026). 210 differentially expressed genes of fold change ≥2 were identified, with 147 genes upregulated and 63 genes downregulated in the prophylactic group compared to the control group. Gene Ontology annotation showed that IL-12 and IL-23 related pathways were downregulated in prophylactic group ( P=0.006 48). Polymerase Chain Reaction (PCR) verification of differentially expressed genes indicated that the relative expression level of HLA-G in prophylactic group was significantly lower than that in control group (0.23±0.19 vs 1.00±0.49, t=4.016, P=0.006). Conclusion:The prophylactic treatment of suplatast tosilate showed some benefit to the life quality of seasonal AR patients during the pollen season, and the potential mechanism might be related with the downregulation of IL-12 and IL-23 pathways and decreased expression of HLA-G.