Based on the traditional Chinese medicine theory that "all pain， itching， and sores are related to the heart"， this paper proposes treating recurrent aphthous ulcers from the perspective of the heart. It suggests that excessive heart fire and tissue erosion due to flaming fire in the heart meridian constitute the core pathogenesis of this condition. Hyperactive heart fire is identified as the key pathogenic factor， while heart yin deficiency， obstruction of the heart collaterals， and malnourishment of the heart spirit are considered significant contributing factors. Clinically， the treatment follows the principle of clearing heart fire as the main strategy， supplemented by nourishing yin， activating collaterals， and calming the spirit. The self-formulated Qingxin Yuchuang Formulation （清心愈疮方） serves as the base prescription， with flexible modifications incorporating the Yuyin Formulation （育阴方）， Huoxue Formulation （活血方）， and Yu'an Formulation （郁安方） to address specific syndromes involving heart yin deficiency， collateral blockage， and emotional disturbance.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R²Y=0.930, Q²=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.

The standardized use of interdisciplinary code classification system in the field of higher education management is critical to standardize talent cultivation and improve management efficiency. However, the phenomenon of "multiple codes for the same discipline" within interdisciplinary fields has complicated the standardized management of graduate students at colleges and universities. This paper focused on the cross-discipline of biomedical engineering, compared the status quo of the management of interdisciplinary codes in China and the United States of America, and analyzed the rules of cross-discipline management from the perspective of the development of the application of discipline codes. This study examined the causes of the multiple codes in the discipline of biomedical engineering and analyzed the complex situations of these codes in student recruitment, cultivation, and degree conferment. Additionally, the setting and management of biomedical engineering codes were preliminarily discussed. Measures for the improvement of the classification of interdisciplinary codes and new ideas for standardizing talent cultivation were proposed, with the purpose to enhance the capacity construction for medical education management.

This study aims to introduce the hotspots of frontier academic achievements into the teaching of undergraduate courses in biomedical engineering. To tackle the existing teaching problems and with the goal of solving engineering problems, we propose the idea of emphasizing innovation, strengthening practice, and highlighting the central position of learners, forming a hybrid teaching model that combines online and offline teaching methods and promotes in-class and out-of-class activities. The reform has shown effectiveness for mobilizing students' enthusiasm for independent learning and enhancing students' comprehensive practical ability and innovative thinking, which provides a reference for cultivating biomedical engineering professionals who meet the new needs of national strategic development.

Background::Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated.Methods::We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention’s Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models.Results::In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/10 5) and rural areas (123.0/10 5) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/10 5), the western region had a slightly lower mortality (123.5/10 5), and the eastern region had the lowest mortality (97.3/10 5). The age-specific mortality showed an accelerated upward trend from aged 55-59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02-3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion::The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

Aim To achieve efficient loading of doxo-rubicin(doxorubicin,dox)by synthesizing fluorinated nanomaterials,and to study the mechanism of nano-medicine against multidrug resistance in tumors.Methods The physicochemical properties of nano dox(nano-doxorubicin)at different degrees of fluorination(PF4 and PF8)were evaluated through various physi-cochemical parameters,and nano dox formulations were screened out with superior fluorination.The mechanism of nano dox in overcoming multidrug resist-ance in tumors was investigated and in vitro anti-tumor activity was studied through research on cytotoxicity,cellular uptake,apoptosis,and resistance against the P-glycoprotein(P-glycoprotein,P-gp)efflux pump.Results By examining various physicochemical indi-cators,PF8 exhibited superior nano performance in loading doxorubicin compared to PF4.Cytotoxicity ex-periments demonstrated that the IC50 value of nano dox was only 1/40 of free dox,indicating excellent in vitro activity of nano dox in overcoming resistance and inhib-iting cell proliferation.Cell uptake and apoptosis stud-ies indicated that nano dox could effectively enhance the uptake of doxorubicin in MCF-7/ADR cells and successfully enter the cell nucleus,ultimately leading to apoptosis-induced anticancer activity.Studies on drug efflux mediated by P-glycoprotein indicated that nano dox could rapidly enter MCF-7/ADR cells through an efficient cellular uptake pathway,effective-ly bypassing the P-glycoprotein efflux pump.This dual action resulted in increased drug uptake within resistant cells and a reduction in efflux,demonstrating the po-tential of nano doxorubicin to overcome drug resist-ance.Conclusions The design of fluorinated nano dox effectively circumvents the efflux of drug molecules by P-glycoprotein,enhancing drug uptake within re-sistant tumor cells and reducing efflux.This results in an effective strategy in combating multidrug resistance in tumors.

OBJECTIVE To explore the role and mechanism of dental pulp stem cells(DPSCs)in repairing hypoxic injury to rats pulmonary microvascular endothelial cells(PMVECs).METHODS ①PMVECs were treated with cobalt chloride at 0,10,25,50 and 100 μmol·L-1 for 72 h.CCK-8 was used to detect the cell viability,and the protein levels of hypoxia-inducible factor 1α(HIF-1α),zona occludens small-band protein 1(ZO-1),and occludin(OCLN)were detected by Western blotting.②There was a cell control group,model group,and model+DPSCs group,and the levels of reactive oxygen species(ROS)was detected by immunofluorescence staining after at 24 and 48 h of action.The levels of ZO-1 and OCLN proteins were detected by Western blotting.③ A cell control group,model group,model+DPSC group and model+DPSC cell knockdown superoxide dismutase 1(SOD1)group were set up.The mRNA level of SOD1 was detected by real-time fluorescence quantitative PCR 24 and 48 h later,while the protein levels of ZO-1 and OCLN were detected by Western blotting.RESULTS ① Com-pared with the cell control group,72 h of cobalt chloride 100 μmol·L-1 treatment of PMVECs resulted in a cell survival rate above 80%,a significant increase in the level of HIF-1α protein(P<0.05),a signifi-cant decrease in the levels of ZO-1 and OCLN proteins(P<0.01),and establishment of a model of hypoxic injury in PMVECs.② Compared with the cell control group,the ROS level was significantly higher in the model group(P<0.01).Compared with the model group,the ROS level was significantly lower in the model+DPSCs group(P<0.01),while the levels of ZO-1 and OCLN proteins were signifi-cantly higher in the model+DPSCs group(P<0.05).③ Compared with the DPSC group,ZO-1 and OCLN expressions were significantly decreased after knockdown of SOD1 in DPSCs(P<0.05,P<0.01).CONCLUSIONS DPSCs can repair hypoxic injury to PMVECs,and the anti-oxidative stress capacity of DPSCs plays an important role in hypoxic injury repair of PMVECs.

African swine fever virus(ASFV)I177L gene deletion vaccine is one of the key directions of African swine fever(ASF)live attenuated vaccine research and development.In order to effec-tively distinguish between the wild-type ASFV strain and the I177L gene-deleted strain,specific primers and probes were designed based on ASFV B646L and I177L genes,respectively.After screening and optimization,a duplex real-time PCR method was developed that can simultaneously detect these two genes.The results showed that ASFV B646L and I177L genes were detected spe-cifically and simultaneously by the method developed without cross-reactions with porcine circovir-us type 2,Seneca virus A,classical swine fever virus,foot-and-mouth disease virus,porcine respira-tory and reproductive syndrome virus.The detection limits of the duplex real-time PCR for recom-binant plasmids pUC57-B646L and pUC57-I177L were 1×103 copies/mL.The intra-and inter-as-say coefficients of variation were less than 4％,respectively.Detection of 122 pork and pork prod-ucts using the duplex real-time PCR developed and the real-time PCR recommended by WOAH showed that the coincidence rates of the two methods for B646L gene detection was 100％with two amplification curves appeared in the positive results of the established methods.The method established in this study can be used for the detection of ASFV I177L gene deletion strains,which provides technical support for ASF surveillance and epidemiological investigation.

Objective:To investigate the correlation of the clinical characteristics,fever characteristics,serum biomarkers with cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (R/R MM) treated with chimeric antigen receptor T cell (CAR-T) immunotherapy. Methods:104 R/R MM patients who received CAR-T cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to November 2021 were included,and the correlations of their clinical characteristics,fever characteristics,serum biomarkers with the severity of CRS were analyzed. Results:Among 104 R/R MM patients receiving CAR-T treatment,no CRS was observed in 8 cases (7.7％),and 96 cases (92.3％) developed CRS. Patients with high-risk cytogenetics had a higher risk of developing CRS (P=0.040),while patients who had previously received autologous hematopoietic stem cell transplantation (ASCT) had a lower risk of developing CRS (P=0.004). There was a significant difference in the duration of fever between patients with grade 1-2 and grade 3-5 CRS (P=0.006). The highest body temperature varied among patients with different treatment regimens (P=0.001). The decrease in total protein in patients with CRS was more significant than in patients without CRS (P=0.002). Within one month after CAR-T cell infusion,the degree of albumin recovery in patients with grade 3-5 CRS was lower than that in patients with grade 0-2 CRS (P=0.037). Compared to patients with grade 1-2 CRS,patients with grade 3-5 CRS showed a significant increase in heart rate after CAR-T cell infusion (P=0.013),while IL-6,C-reactive protein (CRP),and serum ferritin (SF) also showed significant increases (P=0.007,P<0.001,P=0.003). Conclusion:High-risk cytogenetics is a risk factor for severe CRS. Long duration of fever is a clinical characteristic of severe CRS. CRP can better reflect the severity of CRS.