Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

OBJECTIVE To investigate the relationship of long non-coding RNA （LncRNA） metastasis-associated lung adenocarcinoma transcript 1 （MALAT1） and doxorubicin （DOX） resistance in osteosarcoma （OS） cells. METHODS MG-63 and MG-63/DOX cells were treated with different concentrations of DOX （0， 0.01， 0.05， 0.1， 1 μmol/L）， and survival rates and half maximal inhibitory concentration were determined using CCK-8 assay. The expressions of LncRNA MALAT1 in MG-63 and MG-63/ DOX cells were detected by real-time quantitative fluorescence PCR. MG-63/DOX cells were divided into Control group， knocking down LncRNA MALAT1 negative control （sh-NC） group， sh-MALAT1 group， sh-MALAT1+anti-NC group， and sh-MALAT1+ anti-miR-154-5p group. The expressions of LncRNA MALAT1， miR-154-5p and cyclin D1 （CCND1） mRNA in MG-63/DOX cells of each group were detected. The effects of knocking down LncRNA MALAT1 on the proliferation， migration， invasion， and apoptosis of MG-63/DOX cells were detected by CCK-8 assay， scratch test， Transwell experiment and flow cytometry， respectively. The expression of proliferating cell nuclear protein （PCNA） and CCND1 protein in MG-63/DOX cells was detected by Western blot assay. Interactions between LncRNA MALAT1 and miR-154-5p， miR-154-5p and CCND1 were detected by dual luciferase reporter gene experiment. RESULTS Compared with 0 μmol/L DOX， 0.01， 0.05， 0.1 and 1 μmol/L DOX could reduce the survival rates of MG-63 and MG-63/DOX cells （except for 0.01 μmol/L DOX） （P＜0.05）， IC50 were 0.07 and 0.13 μmol/L， respectively. The survival rate， cell migration number and invasion number of MG-63/DOX cells， scratch closure rate， mRNA expressions of LncRNA MALAT1， mRNA and protein expressions of CCND1， and PCNA protein expression in sh-MALAT1 group were significantly lower than sh-NC group and Control group； the apoptosis rate and miR-154-5p expression were significantly higher than sh-NC group and Control group （P＜0.05）. sh-MALAT1+anti-miR-154-5p group was able to reverse the aforementioned biological effects in sh-MALAT1 group （P＜0.05）. In MG-63/DOX cells transfected with both MALAT1-wild type （WT） and CCND1-WT， the luciferase activity in the miR-154-5p mimic group was significantly lower than mimic negative control group （P＜ 0.05）. CONCLUSIONS Knocking down LncRNA MALAT1 can inhibit the DOX resistance of OS cells， and its mechanism may be targeting the miR-154-5p/CCND1 axis.

This article systematically analyzes the historical evolution of the name， origin， quality evaluation， harvesting， processing and other aspects of Picrorhizae Rhizoma by referring to the medical books， prescription books， and other documents of the past dynasties， combined with relevant modern research materials， in order to provide a basis for the development and utilization of famous classical formulas containing this medicinal herb. The research results indicate that Picrorhizae Rhizoma was first recorded in New Revised Materia Medica from the Tang dynasty. Throughout history， Huhuanglian has been used as its official name， and there are also aliases such as Gehu Luze， Jiahuanglian and Hulian. The main source of past dynasties is the the rhizomes of Picrorhiza kurrooa and P. scrophulariiflora. In ancient times， Picrorhizae Rhizoma was mainly imported by foreign traders via Guangzhou and other regions， and also produced in China， mainly in Xizang. In ancient times， it was harvested and dried in early August of the lunar calendar， while in modern times， it is mostly harvested from July to September， with the best quality being those with thick and crispy rhizomes without impurities， and bitter taste. Throughout history， Picrorhizae Rhizoma was collected， washed， sliced， and dried before being used as a raw material for medicine， it has a bitter and cold taste， mainly used to treat bone steaming， hot flashes， infantile chancre fever， and dysentery. There is no significant difference in taste and efficacy between ancient and modern times. Based on the research results， it is recommended that the rhizomes of P. scrophulariiflora in the 2020 edition of Chinese Pharmacopoeia， or the rhizomes of P. kurrooa， can be used in famous classical formulas containing this medicinal herb， which can be processed according to the processing requirements marked by the original formula. For those without clear processing requirements， the dried raw products are used as medicine.

Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy， reasoning， deduction， and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind， fire， phlegm， and blood stasis" in stroke， thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile， the article traced the construction process of xiang thinking， and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives， state， attribute， origin， and law. Furthermore， the relationship between the process of constructing xiang thinking and the origin of etiology， identification methods， pathogenesis evolution， and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored， so as to provide insights into research on the etiology and pathogenesis of stroke， as well as clinical diagnosis and treatment approaches.

Objective To investigate the impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

BACKGROUND:At present,the dental composite resin filling material composed of resin matrix monomer is the first choice material for the filling treatment of dental defects,but with the increase of its use time in the oral environment,the dental tissue will develop secondary caries and the filling material will wear and break.The main cause of these problems is the polymerization shrinkage of the filling material and its mismatch with the mechanical properties of the dental tissue. OBJECTIVE:To synthesize a new type of dental composite resin monomer by adding initiators with different components,to improve the traditional double bond conversion rate of the system and further improve the mechanical properties of the material. METHODS:A new composite resin matrix system was prepared by adding different initiators to the monomer of 3,3′,5,5′-tetramethoxybiphenyl-4,4′-diol epoxy acrylate resin.In group A,camphorquinone with a mass fraction of 1.1%was added.In group B,1-phenyl-1,2-propanedione with a mass fraction of 2.1%was added.In group C,a mixture of camphorquinone and 1-phenyl-1,2-propanedione(a mass ratio of the two was 1:1)with a mass fraction of 3.1%was added.The double bond conversion,polymerization shrinkage and mechanical properties of the samples were determined. RESULTS AND CONCLUSION:(1)The double bond conversion rate of groups B and C was higher than that of group A(P<0.05).The polymerization shrinkage of group B was higher than that of group A(P<0.05),while that of group C was lower than that of group A(P<0.05).(2)The flexural strength,elastic modulus and compressive strength of groups B and C were higher than those of group A(P<0.05,P<0.01).Vickers hardness of group B was higher than that of group A(P<0.05),and the Vickers hardness of group C was lower than that of group A(P<0.01).(3)These findings suggest that 1-phenyl-1,2-propanedione is an initiator with ideal performance.The combined application of 1-phenyl-1,2-propanedione and camphorquinone can effectively improve the double bond conversion rate of the resin matrix system and further improve the mechanical property of the resin.

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.