Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

Male ; Humans ; Liquid Chromatography-Mass Spectrometry ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Varicocele/diagnosis* ; Biomarkers

Pulmonary hypertension (PH) is a progressive and fatal disease. The dysfunction of pulmonary artery endothelial cells (PAECs) is one of its important pathogenic factors. PAECs are monolayer flat epithelial cells, which play an important role in maintaining pulmonary vascular homeostasis. Studies have found that PAECs show damage and apoptosis at the early stage of PH development, while PAECs show anti-apoptotic characteristics at the late stage of PH development. The transition of PAECs into mesenchymal cells induced by hypoxic and inflammatory factors is also involved in the pathogenesis of PH. Carcinoid metabolism and mitochondrial dysfunction, bone mor- phogenic type 2 receptor mutation, epigenetic changes and inflammation of PAECs are the main pathogenesis of pulmonary vascular endothelial dysfunction in PH patients. New therapeutic measures targeting PAECs dysfunction are expected to play an important role in the treatment of PH in the future.

Objective: To explore the prevalence of elevated blood pressure and overweight/obesity and their comorbidities among Tibetan middle school students in Lhasa, and to analyze their association with lifestyle and other factors, so as to provide a basis for the intervention measures targeting elevated blood pressure, overweight and obesity among middle school students in high altitude area. Methods: Using a stratified cluster random sampling method in September 2021, a total of 1 488 Tibetan junior and high students from Lhasa City were investigated with blood pressure measurement, physical examination and questionnaire survey. The influencing factors of elevated blood pressure, overweight and obesity and their comorbidities association were analyzed by multivariate Logistic regression. Results: The prevalence of elevated blood pressure, overweight/obesity and their comorbidities were 17.8%, 17.4% , 5.0% respectively. Multivariate Logistic regression analysis showed that age( OR =0.81), residence, body mass inex(BMI) and gender were the influencing factors of elevated blood pressure; and the risks of elevated blood pressure in female students were higher than male students ( OR =1.89), suburban students were higher than urban students ( OR =8.06), overweight and obesity groups were higher than normal groups ( OR =2.55, 2.87) ( P <0.05). Adjusting for confounding factors such as gender, residence and school, and BMI (only for elevated blood pressure), daily screen time ≥2 h was positively correlated with elevated blood pressure, overweight/obesity and its comorbidities ( OR =1.56, 1.59 , 2.51) ( P <0.05). Conclusions The prevalence of elevated blood pressure, overweight/obesity are relatively high in Lhasa. Longer screen time is a common factor affecting with elevated blood pressure, overweight/obesity and comorbidities among Tibetan students. Measures should be taken intervene in the lifestyle of Tibetan students, in order to reduce elevated blood pressure and overweight/obesity.

Objective To investigate the mechanism of iron death induced by TRPC6/NF-κB in glomerular podiocytes mediated by high homocysteine(Hcy).Methods Mouse glomerulopocytes were cultured in vitro and divided into Control group(0 μmol/L Hcy)and Hcy group(80 μmol/L Hcy).After 48h of intervention,Western blot was used to detect the expression levels of iron death related proteins GPX4 and SLC7A11 and TRPC6 and NF-κ B.Real-time quantitative fluorescence PCR(qRT-PCR)and immunofluorescence were used to detect the expression of TRPC6.The level of podocyte apoptosis was detected by flow cytometry.Malondialdehyde(MDA)assay kit was used to determine intracellular MDA levels.After transfection of TRPC6 interference fragment and TRPC6 negative control(NC),qRT-PCR was divided into Control,si-NC and si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3).Western Blot was divided into Control,Hcy,si-NC+Hcy,si-TRPC6+Hcy.The expression of TRPC6 mRNA was detected by qRT-PCR.The expression levels of GPX4,SLC7A11,NF-κB and TRPC6 were detected by Western Blot.The level of podocyte apoptosis after interference was detected by flow cytometry.Results(1)Compared with Control group,the expression levels of iron death related proteins GPX4 and SLC7A11 in Hcy group were decreased,and the apoptosis rate was increased(P<0.05).(2)Compared with Control group,TRPC6 protein,mRNA levels and immunofluorescence expression were increased in Hcy group.The level of MDA and the expression of NF-κB signaling pathway protein increased in Hcy group,and the comparison between the two groups had statistical significance(P<0.05).(3)Compared with the si-NC group,the mRNA expression level of TRPC6 in si-TRPC6(Si-TRPC6-1,Si-TRPC6-2,Si-TRPC6-3)group was decreased,and the interference effect of Si-TRPC6-3 was the best(P<0.05).After transfecting TRPC6 NC and TRPC6 interference fragment and administering Hcy,there was no difference in GPX4,SLC7A11,NF-κB and TRPC6 expression in si-NC+Hcy group compared with Hcy group.Compared with the si-NC+Hcy group,the si-TRPC6+Hcy group had higher expression of iron death related proteins,GPX4 and SLC7A11,lower expression of NF-κB and TRPC6,and decreased apoptosis rate(P<0.05).Conclusion This study confirmed that TRPC6/NF-κB can regulate iron death of renal podocytes under the induc-tion of Hcy,which is one of the mechanisms leading to kidney injury.

Background N-hexane has been a widely used solvent in industrial production, but it is volatile at room temperature and can be accumulated in the body, and its prolonged occupational exposure may lead to serious chronic diseases in workers. Objective To use four risk assessment models to evaluate the health risk levels of n-hexane-exposed workers, discuss the applicability of the four models in the health risk assessment of n-hexane exposure, and make an important supplement to the health risk assessment of n-hexane in China. Methods In 2022, a total of 167 jobs (1724 workers) exposed to n-hexane in 85 manufacturing enterprises in Jiangsu Province were selected, and a cross-sectional study was conducted and included questionnaire surveys and evaluation of on-site air n-hexane of each job. Subsequently, the China’s classification standards of occupational hazards at workplaces (China model), U.S. Environmental Protection Agency (EPA) model, Singapore semi-quantitative risk assessment model (Singapore model), and the International Council on Mining and Metals (ICMM) model were applied to the quantitative, semi-quantitative, and qualitative assessments of the occupational health risk level of n-hexane-exposed workers. Results All job’s 8-h time-weighted average concentrations (C_TWA) of n-hexane were within the national occupational exposure limits (OELs). The results of the China model graded all jobs as relatively harmless. The Singapore model graded all jobs as low risk, except that two monitoring sites of adhesive jobs were assessed as medium risk. The ICMM quantitative model evaluated all jobs as intolerable for n-hexane airborne exposure, while the matrix method evaluated all jobs as low risk. The U.S. EPA model identified five sites involving painting, printing, and adhesive jobs as high risk and the other jobs as low risk. Conclusion Inconsistent grading results are observed by using the four models for the occupational health risk assessment of n-hexane exposure, that is, harmless for all jobs by China model, while medium and high risks by Singapore model and U.S. EPA model. Therefore, we recommend to combine the Singapore model and the U.S. EPA model with the China model to assess the occupational risk of n-hexane-exposed workers by considering actual concentrations of exposure.

Ubiquitination, a diverse post-translational modification, is carried out by enzymes including E1-activating enzymes, E2-conjugating enzymes, E3 ligases, and deubiquitinating enzymes (DUBs). Ubiquitin itself possesses 7 lysine residues and N-terminal methionine, allowing for the formation of polyubiquitin chains with different lengths and linkages. These chains exhibit various topologies that can be recognized by proteins containing ubiquitin-binding domain, thereby transmitting distinct cellular signals. To unravel the physiological mechanisms associated with ubiquitin, numerous ubiquitin probes have been developed. This review provides an overview of recent advancements in the field of ubiquitin probes, focusing on activity-based and affinity-based probes. Activity-based probes are designed to covalently bind to DUBs, E1s, or E3s, enabling the identification and characterization of these enzymes. Affinity-based probes, on the other hand, selectively bind to ubiquitin-binding domains, facilitating the identification of proteins that interact with ubiquitin. Moreover, this review comprehensively discusses the synthetic methodologies employed for the acquisition of ubiquitin probes. These includes meticulous discussions on the synthesis of individual monomeric modules, the establishment of isopeptide linkages, as well as the incorporation of reactive functional groups. Additionally, the review explores the emerging area of cell-penetrating ubiquitin probes and highlights their latest applications in living cells. These probes incorporate cell-penetrating peptides to enable their internalization into cells, allowing for direct visualization and manipulation of ubiquitin-modified proteins within their native environment. Overall, this review offers insights into the design, synthesis, and applications of ubiquitin probes, highlighting their significance in elucidating ubiquitin-mediated cellular processes.

Objective To investigate the clinical features and risk factors of primary biliary cholangitis(PBC)comorbid with metabolic associated fatty liver disease(MAFLD)and the interaction between the two diseases.Methods A total of 187 patients who were diagnosed with PBC,MAFLD,or PBC with MAFLD in The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2022 were enrolled and divided into PBC group with 70 patients,PBC+MAFLD group with 38 patients,and MAFLD group with 79 patients.Related data were collected,including general information,clinical symptoms,serological parameters,transient elastography(FibroScan),and non-invasive fibrosis markers,which were compared between the three groups.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups,the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups,and the binary Logistic regression analysis was used for multivariate analysis.Results There were significant differences between the three groups in sex,age,height,weight,body mass index(BMI),and history of autoimmune diseases(P<0.05).In the PBC+MAFLD group,female patients accounted for 89.5%,with a mean age of 57.26±12.72 years and a BMI of 23.35±3.70 kg/m2,and in the PBC group,the detection rate of autoimmune diseases was 25.7%(18 patients).There were significant differences between the three groups in the incidence rates of weakness,poor appetite,pruritus,jaundice,varices,ascites,and splenomegaly(all P<0.05).The PBC+MAFLD group had the common symptoms of weakness in 18 patients(47.4%),poor appetite in 15 patients(39.5%),abdominal pain in 14 patients(36.8%),and abdominal distension in 16 patients(42.1%);the MAFLD group had the common symptoms of abdominal pain in 34 patients(43%)and abdominal distension in 32 patients(40.5%);the PBC group had the common symptoms of weakness in 37 patients(52.9%),poor appetite in 25 patients(35.7%),jaundice in 25 patients(35.7%),abdominal pain in 18 patients(25.7%),abdominal distension in 25 patients(35.7%),varices in 19 patients(27.9%),ascites in 23 patients(32.9%),and splenomegaly in 44 patients(62.9%).The PBC+MAFLD group had a controlled attenuation parameter(CAP),which was higher than that of the PBC group,and the PBC group had significantly higher levels of liver stiffness measurement,aspartate aminotransferase-to-platelet ratio index(APRI),and fibrosis-4(FIB-4)than the MAFLD group(all P<0.05).The factors without multicollinearity were included in the regression analysis,and with the PBC group as the reference group,FIB-4(odds ratio[OR]=0.218,95%confidence interval[CI]:0.069-0.633,P<0.05)and history of autoimmune diseases(OR=0.229,95%CI:0.067-0.810,P<0.05)were influencing factors for the onset of PBC with MAFLD;with the MAFLD group as the reference group,ALT(OR=0.157,95%CI:0.025-1.000,P<0.05)and TBil(OR=0.995,95%CI:0.990-0.999,P<0.05)were influencing factors for the onset of PBC with MAFLD.Conclusion PBC with MAFLD lacks specific clinical manifestations,and PBC patients tend to have more severe clinical manifestations and a higher incidence rate of liver function decompensation.PBC comorbid with MAFLD may not aggravate the disease progression of PBC.

Objective:To analysis the laws and regulations related to human genetic resources, this study analyzed the current management status and trends at home and abroad, explored the related issues of human genetic resources data management, and provided reference for further promoting and standardizing the management of human genetic resources data in my country.Methods:This article analyzed the current management status of human genetic resources data from three levels: relevant policies, management frameworks, data platforms and sample databases through literature review and expert consultation and policy research.Results:Countries paid more and more attention to human genetic resources, and the construction of my country′s human genetic resources management system is constantly advancing and improving. In the data era, the management of human genetic resources was facing new problems and challenges, requiring further strengthening the research and management of relevant data.Conclusions:At present, the management of human genetic resource data in my country needs to be strengthened. On the one hand, it is necessary to promote the implementation and coordinated management of specific systems on human genetic resources data. On the other hand, it is necessary to strengthen the effective protection and sharing of human genetic resource data.