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.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective: To understand trends and related factors influencing overweight and obesity among primary and secondary school students in Tianjin, so as to provide a basis for formulating overweight and obesity prevention and control strategies. Methods: In September of each year from 2019 to 2023, a survey was conducted among 197 707 primary and secondary school students in 16 districts of Tianjin through a stratified random cluster sampling method. Physical examination was carried out in accordance with the Technical Standard for Physical examination for Student, and overweight and obesity survey was carried out. Basic information, smoking, drinking, diet, physical exercise, and sleep status were collected through questionnaire surveys. Results: The detection rates of overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023 were 39.07%, 43.33%, 41.54%, 43.92%, and 40.24%, respectively，showing an increasing trend(χ2trend=7.96,P<0.01). The detection rates of overweight increased in both vocational high schools and suburban counties (χ2trends=9.08, 47.18, P<0.01). The detection rates of obesity increased among both male and female students, in primary and vocational high schools and suburban counties (χ2trends=108.34, 15.99, 7.32, 10.95, 14.75, P<0.01). Multivariate Logistic regression analysis showed that smoking, drinking, unhealthful diet, and lack of proper physical exercise had a higher risk of obesity among primary and secondary school students (OR=1.26, 1.13, 1.08, 1.21, P<0.05). Stratified analysis showed that the risk of obesity was higher among boys with unhealthful and moderate lifestyle habits, as well as primary school students with unhealthful lifestyle habits (OR=1.15, 1.11, 1.27, P<0.05). Boys, girls and primary school students with unhealthful lifestyle habits, girls and ordinary high school students with moderate lifestyle habits had higher risk of being overweight (OR=1.14, 1.32, 1.21, 1.18, 1.40, P<0.05). Conclusions The detection rates of overweight and obesity among primary and secondary school students in Tianjin shows an increasing trend. Comprehensive lifestyle should be implemented to better prevent and control the risk of overweight and obesity.

Objective To explore the improve mechanism of ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix on kidney injury in diabetic kidney disease(DKD)rats.Methods The diabetes model was prepared by intraperitoneal injection of streptozotocin,and then fed with high sugar and high fat diet.The rats with successful DKD were randomly divided into model group,positive control group and experimental-L,-M,-H groups with 8 cases per group.Additionally,selected 8 Wistar rats as the blank group.The experimental-L,-M,-H groups were given 1.5,3.0 and 6.0 g·kg-1 ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix by gavage,respectively.The positive control group was given 1.75 × 10-3 g·kg-1irbesartan suspension by gavage.The blank and model groups were given equal volume of pure water by gavage.Six groups were administrated once a day for 12 consecutive weeks.The 24 h-urinary total protein were detected by coomassie brilliant blue method.The protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and andacyl-CoA synthetase long chain family member 4(ACSL4)in kidney tissue were detected by Western blot.Results The 24 h-UTP in the experimental-M,-H groups,positive control group,model group and blank group were(47.70±3.85),(43.57±6.38),(36.80±6.52),(64.34±13.38)and(7.58±3.71)mg;the relative expression levels of Nrf2 protein were 0.86±0.08,0.75±0.06,0.64±0.08,1.09±0.06 and 0.60±0.07;the relative expression levels of HO-1 protein were 0.77±0.04,0.63±0.07,0.47±0.05,1.04±0.06 and 0.34±0.07;the relative expression levels of ACSL4 protein were 0.62±0.07,0.55±0.07,0.46±0.06,1.08±0.07 and 0.30±0.01,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups and positive control group were significantly different(P＜0.05,P＜0.01).Conclusion Ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix can improve the damage of kidney tissue in DKD rats,and the mechanism may be related to ferroptosis caused by excessive activation of Nrf2/HO-1 signaling pathway.

The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the in vitro metabolism and products of 2-MDCK. The results indicate that 2-MDCK undergoes various metabolic reactions, including dehydrogenation, deamination, hydroxylation, and demethylation, leading to the formation of eight metabolites. By conducting actual testing on hair samples from 2-MDCK abusers, the existence of six metabolites was confirmed. Comparing the metabolic products in the liver microsomal in vitro model, M3.1 and M4.1 were identified as biomarkers for 2-MDCK consumption. Five samples of abusers of 2-methyl-dechloroketamine were provided by the Anti-Drug Brigade of the Hangzhou Public Security Bureau. Negative hair samples were provided by laboratory volunteers, and all samples were obtained with the informed consent of the volunteers. These findings provide a scientific basis for the detection and identification of 2-MDCK and its metabolites, as well as crucial support for the study of the metabolic mechanisms of similar novel psychoactive substances in the phenylcyclohexylpyridine class. This research holds significant importance in addressing the issue of abuse of new psychoactive substances.

Aim To establish a quantitative immunofluorescent bioactivity assay(ICW)for insulin glargine based on CHO-IN-SRB 1284 transgenic cells,and to study its equivalence with in-sulin bioassay of Ch.P.Methods The cells were diluted 25 times with 1.5 × 108 L-1 cell density plates and 1 500 μmol·L-1 insulin glargine,and then diluted with a 3-fold gradient se-ries.The cells were stimulated in microporous plates for 20 min.After fixation,permeation and antibody incubation.Quantitative immunofluorescence biological activity was detected by odyssey two-color infrared fluorescence imaging system.Results There was a good dose-effect relationship between the concentration of insulin glargine in ICW and its relative potency.The method had good specificity,and the relative accuracy,intermediate preci-sion and linearity met the requirements.The relative deviation of biological activity results of 7 batches of insulin glargine samples measured by the two methods was less than 10％.The results were analyzed by SPSS and SAS software,which showed that the methods were correlated and equivalent.Conclusions The quantitative immunofluorescence assay for the biological activity of insulin glargine can be established.The method has good spe-cificity,high accuracy and precision,and has correlation and e-quivalent with biotiter assay,which can be applied to in vitro ef-ficacy evaluation and quality control of insulin glargine.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective Based on the acupuncture literature data set,a named entity recognition method of acupuncture literature based on dictionary and deep learning model is proposed to improve the effect of acupuncture literature entity recognition.Methods In this paper,the entity recognition methods of acupuncture literature were explored,and the vector representation effects based on word2vec and ALBERTmodels and ALBERT+domain dictionary were compared.On this basis,a named entity extraction method combining domain dictionary and ALBERT-BiLSTM-CRF deep learning model was proposed.Results According to the extraction effect of three model entities,the P value of word2vec-BiLSTM-CRF is 81.82%,the R value is 70.76%,and the F1 value is 75.48%;ALBERT-BiLSTM-CRF has an P value of 83.10%,a R value of 81.14%and a F1 value of 81.98%."ALBERT-BiLSTM-CRF+dictionary"is 92.57%,91.42%and 91.85%.In terms of entity categories,the top three entities with the highest accuracy rate are acupuncture,needling and needling site,which are 98%,ninety-seven percent and ninety-seven percent respectively,while the three entities with the lowest accuracy rate are acupoint matching corresponding symptoms,disease names and sample size,which are 50.00%,50.68%and 52.43%respectively.Conclusion Compared with the original ALBERT-BiLSTM-CRF model,the precision rate,recall rate and F1 value increased after adding the dictionary,and the convergence speed of the model after adding the dictionary was twice that without adding the dictionary.It is effective to use"ALBERT-BiLSTM-CRF+dictionary"model to identify named entities in acupuncture literature.

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism* ; DNA-Binding Proteins/metabolism* ; Prolyl Hydroxylases/metabolism* ; Hypoxia ; Prostatic Neoplasms/pathology* ; Glycolysis ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Line, Tumor ; DNA Helicases/metabolism*

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.