ObjectiveBased on cyclic adenosine monophosphate （cAMP）/cAMP-regulated guanine nucleotide exchange factor 1 （Epac1）/Ras-homologous protein 1 （Rap1） signaling pathway to explore the myocardial protective mechanism of Yiqi Huoxue prescription on coronary heart disease （CHD） rats with Qi deficiency and blood stasis syndrome. MethodEighty-eight specific-pathogen-free （SPF） grade male Sprague-Dawley （SD） rats were divided into a sham operation group （n=12） and an experimental group （n=76） according to the random number table. The experimental group underwent a restricted diet and exhaustive swimming combined with left anterior descending （LAD） coronary artery ligation to construct a model of CHD with Qi deficiency and blood stasis syndrome， and electrocardiograms （ECGs） of rats before and after the LAD operation were collected. After the model was successfully established， the rats were randomly divided into model group， Yiqi Huoxue prescription low-dose group （4.28 g·kg^-1）， medium-dose group （8.55 g·kg^-1）， high-dose group （17.1 g·kg^-1）， and Western medicine group （isosorbide mononitrate tablets， 3.6 mg·kg^-1）. Rats were intragastrically administered assigned drugs for 4 weeks consecutively， while the sham operation group and the model group were administered with equal volumes of double distilled water. Twenty-four hours after the final administration， the rats were anesthetized with isoflurane to detect the left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， left ventricular fractional shortening （FS， %）， and ejection fraction （EF， %） by echocardiography. Blood samples were collected from the abdominal aorta for hemorheological measurements， and plasma cAMP levels were determined using enzyme-linked immunosorbent assay （ELISA）. Myocardial tissue was collected for hematoxylin-eosin （HE） staining and Masson staining to observe myocardial pathological damage， and a transmission electron microscope was used to observe ultrastructural changes of myocardial tissue， fluorescent quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the expressions of myocardial Epac1， Rap1 GTPase activating protein （Rap1GAP） and Rap1 mRNA， and Western blot was used to detect the expressions of myocardial Epac1， Rap1GAP and Rap1 protein. ResultCompared with those in the sham operation group， LVEDD and LVISD of rats in the model group significantly increased （P<0.01）， and the ratios of EF and FS significantly decreased （P<0.01）， indicating symptoms of heart function decline， referred to as "heart Qi deficiency". The viscosity of whole blood and plasma significantly increased （P<0.01）， and the content of cAMP significant increased （P<0.01）. In addition， there was a significant proliferation of collagen fibers in myocardial tissue （P<0.01）， and the ultrastructure of the myocardial tissue was severely damaged， indicating pathological changes consistent with "blood stasis". Real-time PCR results showed that Epac1 and Rap1 mRNA levels in the model group were significantly reduced （P<0.01）， while Rap1GAP mRNA levels were significantly increased （P<0.01）. Western blot analysis showed a significant decrease in Epac1 protein expression （P<0.01） and a significant increase in Rap1GAP protein expression （P<0.05）. Compared with the model group， Yiqi Huoxue prescription improved cardiac function， reduced blood viscosity， lowered plasma cAMP levels， decreased collagen fiber proliferation， and improved myocardial ultrastructure damage in CHD rats with Qi deficiency and blood stasis syndrome. The high-dose group showed the most significant effects. In the high-dose group， Epac1 mRNA and protein expression levels significantly increased （P<0.01）， Rap1 mRNA expression significantly increased （P<0.01）， and Rap1GAP mRNA and Rap1GAP/Rap1 protein expression levels significantly decreased （P<0.05， P<0.01）. ConclusionYiqi Huoxue prescription can improve cardiac function， reduce blood viscosity and plasma cAMP levels， improve myocardial damage， and reduce collagen fiber proliferation in CHD rats with Qi deficiency and blood stasis syndrome. The myocardial protection mechanism may be related to the regulation of the cAMP/Epac1/Rap1 signaling pathway.

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population. Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA). Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively). Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.

Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.

In recent years， the field of network pharmacology （NP） has developed rapidly， but the flawed and routine workflow has seriously affected the scientificity and reliability of NP analysis results. For complex diseases caused by environmental and genetic factors， symptomatic treatment or drugs targeting a single pathophysiological process cannot prevent or delay the progression of the disease， so the drug development fails or withdraws from the market. Therefore， there is an urgent need to develop new ideas for NP analysis that combines multiple pathophysiological processes. The key pathophysiological process is an important and complete set of pathological changes in the process of the occurrence， development， and outcome of the disease， which represents the current comprehensive and profound understanding of the nature of the disease. In order to improve the quality of NP research and promote the healthy development of the NP field， this paper proposes a new idea of NP analysis based on key pathophysiological processes. Based on the long-term clinical practice of traditional Chinese medicine and the key pathophysiological process of the disease， the method comprehensively analyzes the pharmacological mechanism and active ingredients of traditional Chinese medicine compound from the perspective of key pathophysiological process， which increases the scientifically， reliability， and repeatability of the analysis results. This paper takes Alzheimer's disease （AD） as an example to illustrate the necessity， feasibility， main workflow， advantages， and disadvantages of this method， and it is expected to screen disease-modifying drugs that prevent or reverse the course of the disease and promote the clinical transformation of research results.

The healthy development of science and technology (Sci. & Tech) innovation is inseparable from Sci. & Tech ethics. The innovation subject is the driving force of Sci. & Tech innovation. The improvement of Sci. & Tech ethical management ability is conducive to improving the China’s Sci. & Tech ethics governance system. Therefore, this paper deeply analyzed the current status of Sci. & Tech ethics management of the 76 innovation subjects from five aspects, and found that the construction of Sci. & Tech ethics management of Chinese innovation subjects has achieved initial results, but there was still room for further improvement. Based on the problems existing in the Sci. & Tech ethics management of innovation subjects, this paper proposed six strategic suggestions that strengthening the construction and research of artificial intelligence ethics management systems, establishing and improving ethics committees and management systems, actively implementing the registration of Sci. & Tech ethics management information, regularly organizing and participating in various forms of Sci. & Tech ethics training, attaching importance to the reserve and cultivation of composite Sci. & Tech ethics management talents, and cooperating to establish a Sci. & Tech ethics case library, with a view to enhancing the Sci. & Tech ethics management ability of Chinese innovation subjects to adapt to the needs of the healthy development of Sci. & Tech in China.

Objective:To construct an evaluation index system for comprehensive budget management at public hospitals and conduct empirical research for reference in evaluation of comprehensive budget management at public hospitals.Methods:From May to June 2022, based on the Implementation Measures for the Comprehensive Budget Management System of Public Hospitals and its interpretations, literature analysis, and expert interviews, a preliminary evaluation index system was developed for comprehensive budget management of public hospitals. Then the Delphi method was applied for two rounds of expert consultation, with experts invited to evaluate the importance of indexes, while the analytic hierarchy process was used to calculate the weight values of indexes. Based on such a comprehensive budget management evaluation index system, a questionnaire was developed, and tertiary public hospitals were selected based on the principle of convenient sampling. Then a questionnaire survey was conducted from June to October 2022. The questionnaire was filled out by hospital level leaders(chief accountants), finance/audit leaders, and directors of finance/audit/operation management departments from the sample hospitals with professional knowledge and rich operational management experience in budget management. The comprehensive budget management level of the sample hospital was thus evaluated based on the survey results. Results:The comprehensive budget management evaluation index system for public hospitals was composed of 2 first-level indexes, 4 second-level indexes, and 20 third-level ones. The weights for the 2 first-level indexes of target building and management orientation were both 0.500, while the weights for the 4 second-level indexes, namely strategic implementation, comprehensive coverage, performance evaluation, and adaptation matching were all 0.250. Among the third-level indexes, the weights of budget execution, system improvement, system establishment, organizational construction, and revenue and expenditure business ranked top five, with weights of 0.070, 0.069, 0.066, 0.066, and 0.064, respectively. A total of 95 hospitals were selected for questionnaire survey, and the evaluation found 46 of them with a comprehensive budget management level of " excellent" and " good" , 27 with a " moderate" level, and 22 with a " poor" and " very poor" level. Scores of the third-level indexes were between 39-94 points, while the score of 6 third-level indexes were below 60 points, namely interconnection, budget analysis, compatibility and adaptation, system improvement, participation level, and assessment application.Conclusions:The evaluation index system for comprehensive budget management at public hospitals in this study proves rational and practical, serving as a reference for the evaluation of comprehensive budget management at public hospitals and related researches.

Objective This study aims to investigate the sex difference in the hippocampus and parahippocampus in patients with bipolar disorder. Methods We acquired T1－weighted structural MRI from 133 bipolar type I patients (60 males) and 144 normal controls (81 males). The General Linear Model was used to examine the relationship between sex and brain volumes of the hippocampus and parahippocampus, with age and intracranial volume as covariates. Results Patients showed significantly smaller volumes of the bilateral hippocampus and parahippocampus (P＜0.01). There were sex－by－diagnosis interactions in the left parahippocampus gyrus (F=6.534, P=0.044). Male patients had significant smaller volumes of the left parahippocampus gyrus compared to the male normal controls (P＜0.001) whereas the volumes were not significantly different between female patients and female normal controls (P＞0.05). Conclusion The results suggest sex difference in the left parahippocampus gyrus volume in patients with bipolar type I disorder, which deserves further investigation in the future bipolar imaging researches.

AIM:To investigate the regulation mechanism for insufficient KChIP 2 expression induces Ito,f downregulation and arrhythmogene-sis in cardiac hypertrophy .METHODS:Bidirectional manipulations of MG 53 expression were performed by adenoviral overexpression of MG53 or knockdown of MG53 with RNA interference in neonatal rat ventricular myocytes with or without PE stimulation .Ito,f was re-corded with patch clamp in whole-cell mode 48 h after adenoviral transfection .Then the WT or MG53 knockout ( MG53 -/-) mouse model of left ventricular hypertrophy induced by transverse aortic constriction ( TAC) were used to detect the susceptibility to ventricu-lar arrhythmia.RESULTS: Here, we show muscle-specific MG53 regulates KChIP2 expression and Ito,f densities, where they are downregulated in hearts from MG53 knockout mice and MG53 knockdown rat cardiomyocytes , but upregulated in MG53 overexpressed cells.MG53 expression is decreased in phenylephrine ( PE)-induced cardiomyocyte hypertrophy and restoration of MG 53 rescues PE-induced downregulation of KChIP2 and Ito,f.Furthermore, MG53 is decreased in a mouse model of hypertrophy induced by transverse aortic constriction and ablation of MG 53 increases the susceptibility to ventricular arrhythmia by exaggerating Ito,f remodeling.CON-CLUSION:These findings establish MG53 as a novel regulator of Ito,f and its central role in arrhythmogenesis in hypertrophy .

Objective To explore the clinical effect of the radial artery perforator flap on repairing soft tissue defect after palm postoperative scar contracture. Methods Eighteen patients with palm scar contracture were selected. The palm soft tissue defect was repaired by radial artery perforator flap after the operation of scar removal and soft tissue release. The areas of soft tissue ranged from 5 cm × 3 cm to 8 cm × 5 cm. The area of donor flap exceeds 20%of the wounds area, and wounds were repaired by free skin grafting. Six months after operation, the hand function was compared with that before operation. Results All the patients were followed up for 6-15 months (mean 10.8 months), all flaps survived with good shape, and flap donor site wounds were healed by skin grafting. The patients were evaluated 6 months after operation according to the Chinese Medical Hand Surgery Society of upper part of functional assessment criteria: excellent in 11 cases, good in 5 cases and general in 2 cases, but preoperative functional evaluation was excellent 0 case, good in 3 cases, general in 7 cases and poor in 8 cases. Compared with that before operation, the postoperative function was significantly improved. Conclusions It is a commendable approach of repairing soft tissue defect after postoperative palm scar contracture by radial artery perforator flap, because it can provide reliable blood supply, and significantly improve hand function with exactly clinical effect.