The theory of " heart governing the exterior" derives from Prohibition of Pricking in Suwen, which has an important position in the clinical practice of traditional Chinese medicine. This article sorts out the interpretation of " heart governing the exterior" of physicians in the past dynasties, and summarizes the clinical application of " heart governing the exterior" in chest painful impediment, warm disease, dermatosis, allergic rhinitis, tic disorder, and diabetic neuropathy. It is found that the theory of " heart governing the exterior" is widely used in clinical practice and has good effects. This paper further expands and enhances its theoretical connotation, that is, the physiological and pathological connection and clinical application of the three dimensions of heart yang, heart blood, and heart spirit with the life and mental activities dominated by it, as well as the overall external performance. In addition, by exploring the relationship between " heart governing the exterior" and " brain-heart axis" , " brain-skin axis" in Western medicine, it indirectly confirms the rationality of " heart governing the exterior" in Western medicine, and lays the foundation for the further development and application of the theory of " heart governing the exterior" .

Tumor microenvironment(TME)is the cellular environment for tumor development,growth,and metastasis.Adenosine(ADO)is an immunosuppressive metabolic product that is continuously upregulated in TME,with various types and wide distribution of receptors.The complex and dynamic interactions between ADO and tumor cells constantly influence tumor progression.ADO can di-rectly or indirectly promote tumor development and progression by promoting tumor generation and metastasis,mediating the immune escape of tumor,and modulating tumor-infiltrating immune cells.Based on the characteristics of ADOs in TME,this article reviews the latest advances in the dynamic alterations of ADO in TME,in order to provide insights into tumor treatment targeting the ADO pathway.

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective To explore the impact of Shexiang Baoxin Pill(SXBXP,a traditional Chinese patent medicine,broadly applied for the treatment of cardiovascular diseases)on coronary microvascular disease(CMD)and investigate the role and underlying mechanisms of muscone,a key bioactive component of the pills,in the treatment.Methods A total of 16 ob/ob mice(8 weeks old)were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group,receiving 10 mg/kg·d SXBXP or PBS via oral gavage,and another 8 wild-type mice with the same genetic background(WT group)were subjected as a negative control group.Cell model of CMD was established based on mouse coronary microvascular endothelial cells(MCMEC)under ischemia and hypoxic(HI)condition,and the cells were further treated with 20 μg/mL SXBXP(HI+SX)and 30 μmol/L muscone(HI+Muscone),respectively.Echocardiography was carried out for coronary flow reserve(CFR)and left ventricular function,and laser speckle imaging was applied to evaluate myocardial blood flow(MBF).Microvascular density in the heart was evaluated with CD31 immunofluorescence staining.The expression levels of vascular endothelial growth factor(VEGF)in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis.The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.Results In the ob/ob-Control group of mice,the levels of CFR,MBF,and cardiac microvascular density were significantly lower than those in the WT group(P<0.05),and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group(P<0.05),which indicates that SXBXP improves the CMD phenotype.The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice(P<0.05),while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group(P<0.05),illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis.In vitro experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition(P<0.05).Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC(P<0.05).These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.Conclusion SXBXP can improve CMD.Muscone,as a key component of SXBXP,promotes microvascular angiogenesis by inducing the expression of VEGF,then enhances myocardial perfusion,and consequently alleviates CMD.

Knee adduction moment(KAM)is a key biomechanical index in knee joint biomechanics research,which is closely related to the occurrence and development of knee osteoarthritis(KOA).Therefore,understanding the factors influencing KAM is important for the diagnosis and treatment of KOA diseases.This review summarizes the factors that may affect KAM based on relevant research.

Knee adduction moment(KAM)is a key biomechanical index in knee joint biomechanics research,which is closely related to the occurrence and development of knee osteoarthritis(KOA).Therefore,understanding the factors influencing KAM is important for the diagnosis and treatment of KOA diseases.This review summarizes the factors that may affect KAM based on relevant research.

Objective　To analyze the timeliness and influencing factors of antiretroviral treatment (ART) among HIV/AIDS patients in Hubei Province from 2017 to 2023. Methods Data were selected from the National AIDS Comprehensive Prevention and Treatment Information System for HIV-infected individuals and AIDS patients residing in Hubei Province from January 1, 2017, to December 31, 2023. Timely treatment was defined as the interval between diagnosis and the initiation of ART being ≤30 days, and non-timely treatment as >30 days. The annual timely treatment rates were calculated, and a time trend regression analysis of these rates was conducted using the Joinpoint regression program 4.9.0.0. The annual percentage change (APC) and average annual change percentage (AAPC) were computed to evaluate the global average change trend across intervals. Cox univariate and multivariate analyses were used to assess the impact of the patient's basic characteristics such as gender, age at diagnosis, ethnicity, education level, infection route, etc. Results Among the 21 332 HIV/AIDS patients, 81.52% were male, and the median age at diagnosis was 43 (28, 56 years). The proportion of patients initiating antiretroviral therapy within 30 days of diagnosis increased from 45.12% in 2017 to 67.61% in 2023, showing an upward trend in the timely treatment rate from 2017 to 2023 (AAPC=6.90). Cox multivariate analysis indicated that females were more likely to initiate treatment in a timely manner after diagnosis (HR=1.15, 95%CI: 1.10-1.21). Compared to cases aged 50 or above, younger age groups had lower treatment timeliness, with HRs (95%CI) of 0.79 (0.76-0.83) for those aged 25 -< 50, 0.67 (0.63-0.72) for those aged 15 -<25, and 0.55 (0.33-0.91) for those aged 0 -<15. Non-Han ethnicities showed lower timeliness in treatment initiation (HR=0.91, 95%CI: 0.83-0.99). Individuals with high school or technical secondary school education, and those with college or higher education, had lower treatment timeliness, with HR (95%CI) of 0.92 (0.88-0.97) and 0.97 (0.92-1.02), respectively. Married or partnered, and divorced or widowed individuals had lower treatment timeliness, with HR (95%CI) of 0.89 (0.86-0.94) and 0.8 (0.76-0.85), respectively. Cases in detention facilities had lower treatment timeliness (HR=0.37, 95%CI: 0.29-0.47). Cases from counseling and testing, and other sources had higher treatment timeliness, with HR (95%CI) of 1.09 (1.04-1.15) and 1.07 (1.00-1.15), respectively. Lower initial CD4+T lymphocyte counts were associated with higher treatment timeliness. Conclusions The timely treatment among HIV-infected individuals and AIDS patients in Hubei Province has improved year by year from 2017 to 2023. Gender, age at diagnosis, education level, marital status, infection route, sample source, and first CD4+T lymphocyte status are all factors that determine the timely treatment of HIV/AIDS.

Objective To understand the timeliness of antiretroviral therapy (ART) in newly reported HIV/AIDS cases in Yichang from 2016 to 2022 and its influencing factors, and to provide a scientific basis for improving the timeliness of ART in Yichang City. Methods HIV/AIDS cases data from January 1, 2016 to December 31, 2022 were collected, and chi-square tests and logistic regression were used to analyze the factors influencing the timeliness of ART. Results A total of 1 126 HIV/AIDS cases were collected, with local reported cases accounting for 83.13%. The male to female ratio was 5.15:1. The median age was 42 years old (28-53 years old). 41.03% of the cases were unmarried. 38.99% of cases had a first-time CD4+T lymphocytes (CD4 cells) count < 200 cells/µL. Cases with timely first CD4 cell test accounted for 67.85%. The overall timely rate of ART from 2016 to 2022 was 57.19%, with a median time from diagnosis to initiation of ART of 20 days. There was no statistically significant difference in the trend of ART timely rate from 2016 to 2022 (P=0.251). Cases with timely first CD4 cell test were more likely to initiate ART in time (OR=3.831, 95% CI:2.454-5.981), while cases reported from other areas (OR=0.497, 95% CI:0.345-0.716) and cases with higher first CD4 cell count levels (OR_≥500=0.473, 95% CI:0.312-0.718) were less likely to initiate ART in time. Conclusion The timely rate of antiviral treatment in Yichang City needs to be further improved. High attention should be paid to cases reported from other places, cases with delayed CD4 cell testing, and cases with high CD4 cell count levels. Treatment mobilization and referral should be done well, and early detection services should be provided in time.

Objective:To explore the pathogenicity and genotype-phenotype correlation of a c. 158G>A variant of phenylalanine hydroxylase ( PAH) gene among patients with PAH deficiency. Methods:Thirty seven children diagnosed with PAH deficiency at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University between July 2016 and June 2021 were selected as the study subjects. Clinical data and results of genetic testing were retrospectively analyzed.Results:Among the 37 patients, mild hyperphenylalaninemia (HPA) was observed in 34 cases, two PAH variants (including c. 158G>A), which formed a compound heterozygous mutation genotype, were detected in 33 patients, and the remainder one was found to harbor three PAH variants, including homozygous c. 158G>A variants and a heterozygous c. 842+ 2T>A variant. Classical phenylketonuria (PKU) was observed in 3 patients, and three PAH variants were detected in each of them, including two with c. [158G>A, 842+ 2T>A]/c.728G>A and c. [158G>A, 842+ 2T>A]/c.611A>G, respectively, and one with c. [158G>A, c. 722G>A]/c.728G>A. The c. 158G>A variant has a minimal influence on the PAH activity and is associated with a mild HPA phenotype. The variant should thereby be classified as likely benign. Conclusion:When the c. 158G>A variant and other pathogenic variants are arranged in cis position, the ultimate phenotype will be determined by the pathogenicity of other variants.