Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.

ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days， the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting， all successful modeling rats were randomly executed within 3 days after vaginal opening， when aged 7 and 12 weeks. Then we measured the rats’ body weight and length， determined the concentrations of glucose， insulin， blood lipids， estradiol， leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat， uterus and ovary. ResultsFor body weight and length， rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening， but which did not affect their subsequent growth and development， and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening， insulin levels had significant difference between the two groups （P = 0.001）， the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times， no significant difference was noted in estradiol， leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However， the changes due to precocious puberty are temporary and reversible， and they may become normal in adulthood.

Objective To analyze and identify the volatile constituents in different parts(flowers,stems and leaves)of Huai chrysanthemumin,and to lay a theoretical foundation for the comprehensive utilization for it.Methods The volatile oil in different parts of Huai chrysanthemumin were extracted by hydrodistillation,respectively.Their constituents were analyzed by gas chromatography-mass spectrometry(GC-MS).The compounds were identified by library search and literature screening.The relative percentage of each compound was obtained by the area normalization method.The differences in their chemical compositions were analyzed by Venn diagram,principal component analysis(PCA)and cluster heat map analysis.Results A total of 62 volatile chemical components were identified from different parts of Huai chrysanthemumin,including monoterpenes,sesquiterpenes,and their derivatives,as well as a small amount of aliphatic compounds.32,42 and 40 volatile components were detected from the flowers,stems and flowers,respectively.Furthermore 17 volatile components were shared by three parts,whereas 5,6 and 16 volatile components were unique to the flowers,stems and leaves,respectively.The results of stoichiometric analysis showed that both PCA and cluster heat map analysis could separate the flowers,stems and leaves,and their volatile components were different.Conclusion The types and contents of the volatile oil in the stems,leaves and flowers of Huai chrysanthemumin have certain variability,which provide a scientific basis for the further medicinal or industrial exploitation of different parts of Huai chrysanthemumin.

Objective: To explore the association between dietary behaviors and sleep duration among middle school students in Shanghai, so as to provide reference for interventions targeting insufficient sleep. Methods: From May to June 2021, a stratified cluster random sampling method was employed to select a sample of 10-17yearold middle school students for monitoring their healthrisk behaviors. A total of 5 538 valid questionnaires were collected. The survey included items such as daily sleep duration, weekly consumption of sugary beverages, freshly squeezed fruit juice, fresh fruits, fresh vegetables, fried foods, milk and yogurt, breakfast habits, and frequency of eating outside. Statistical analysis was conducted using Chisquare test, Wilcoxon ranksum test, and multivariable Logistic regression model. Results: About 73.7% of middle school students reported insufficient sleep in Shanghai. There was a positive correlation between the average daily consumption of fresh fruits and breakfast consumption with sleep duration. In other words, a higher frequency of consuming fresh fruits (OR=1.29) and eating breakfast (OR=1.07) were associated with a higher likelihood of sufficient sleep. Conversely, there was a negative correlation between the frequency of consuming desserts (OR=0.78) and fried foods (OR=0.88) and sleep duration (P<0.05). Conclusions Increasing the consumption of fresh fruits and maintaining regular breakfast habits while reducing the intake of fried foods can contribute to achieving sufficient sleep among middle school students. When implementing interventions to improve sleep among middle school students, promoting healthy and balanced diets can be considered as one of the intervention strategies.

Objective: To understand the relationship between stress and Internet addiction among middle school students in Shanghai, so as to provide a scientific basis for promoting students mental health and preventing Internet addiction. Methods: From May to June 2021, a stratified random cluster sampling method was used to select 6 123 middle and high school students in Shanghai for health risk behavior monitoring. Daily Stressors Evaluation Scale for Urban Secondary School Students was used to evaluate students' stress, and the Internet Addiction Test compiled by Young was used to evaluate students Internet addiction. The correlation between student stress and Internet addiction was analyzed by Kruskal-Wallis H test , Chi square test and multiple Logistic regression. Results: Total stress score of middle school students in Shanghai was 24 (12, 39), academic stress score was 8 (5, 13), physical and psychological stress score was 6 (2, 10), interpersonal stress score was 5 (1, 9), and family stress score was 4 (1, 8). The detection rate of Internet addiction was 4.7%. Multivariate Logistic regression analysis showed that the risk of Internet addiction among middle school students with high levels of stress was 8.05 times(95% CI =4.59-14.12) that of students with low levels of stress( P <0.05). The risk of Internet addiction among middle school students with high levels of academic stress, physical and psychological stress, interpersonal stress and family stress was 5.98(95% CI =3.69-9.70), 6.92(95% CI =4.03-11.88), 4.85(95% CI =3.11-7.55), and 4.18(95% CI =2.73-6.40) times that of students with low levels of stress, respectively( P <0.05). Conclusion The academic stress, physical and psychological stress, interpersonal stress, and family stress among middle school students can all lead to an increased risk of Internet addiction.

Objective To establish and optimize a method for simultaneous determination for the contents of sodium,potassium,calci-um and magnesium ions in serum using microwave digestion combined with ion chromatography,and evaluate its performance.Methods Serum samples were pretreated by microwave digestion,and four cations were quantitatively determined using ion chromatography.The linearity,precision,recovery and accuracy of the established method were verified with reference to the EP6-A and EP15-A3 docu-ments issued by the Clinical and Laboratory Standards Institute(CLSI).Results The imprecisions of determinations for sodium,po-tassium,calcium and magnesium ions expressed as coefficient of variation(CV)were 0.10％to 0.36％,0.15％to 0.48％,0.22％to 0.87％and 0.21％to 0.73％,respectively.The recoveries with adding standard of the four cations were between 97.3％and 103.0％.Referred to RELA2020 and RELA2021,the deviations of the analysis results were-0.57％to-0.14％,-0.84％to-0.16％,-1.82％to-0.37％,and-0.60％to 0.34％for sodium,potassium,calcium,and magnesium,respectively,and all the comparisons were pas-sed.The limits of detection/quantification were 0.017 5/0.058 3 mmol/L,0.000 5/0.001 7 mmol/L,0.009 9/0.032 9 mmol/L and 0.001 1/0.003 5 mmol/L for the four cations,indicating that after pretreatment,no significantly interfere from other impurities for the results of determination was found.Conclusion A method for simultaneous determination of sodium,potassium,calcium and magnesi-um ions in serum was successfully established and optimized using microwave digestion combined with ion chromatography.The method showed good precision and accuracy,simple operation,short time consumption and low cost,thus it could be used for quality improve-ment of clinical electrolyte testing in serum.

Objective:To develop a candidate reference method for cortisol in human serum by isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS).Methods:An isotope-labeled internal standard was added to samples, followed by alkalizing with sodium carbonate solution and liquid-liquid extraction with n-hexane/ethyl acetate. Isoelution with a methanol aqueous solution was employed for liquid chromatographic separation, while ESI in the positive ion and multiple reaction monitoring mode were used for mass spectrometry. The volume of sample, standard, and internal standard solutions were all controlled by weighing, and the results were calculated by bracketing method. The accuracy, precision, specificity, linearity, LOD and LOQ of this method were evaluated referring to the CLSI C62-A and C50-A guidelines and the domestic expert consensus documents.Results:The method demonstrated excellent accuracy and precision with the bias of ERM-DA192, ERM-DA193 and RELA 2021-2023 all being less than 2%. The recovery of added cortisol ranged from 98.2% to 101.1%. Both intra- and inter-assay imprecisions was <2%. The method was free from interference by structural analogue and showed a good linearity in the range of 25-1 600 nmol/L. The LOD and LOQ were 0.5 nmol/L and 1.0 nmol/L, respectively. A cortisol assay kit (chemiluminescence immunoassay) traced to this candidate reference method was used to determine 46 clinical serum samples concurrently, and the two methods exhibited good correlation.Conclusions:A candidate reference method for the determination of cortisol in serum was established, demonstrating high sensitivity, good repeatability and accuracy. This method can serve as a reference for the measurement traceability and accuracy evaluation of routine methods.

Objective To explore potential genes associated with the pathogenesis of hypospadias using weighted Gene co-expression network analysis(WGCNA).Methods The WGCNA algorithm was used to process the hypospadias-related dataset GSE35034,and then a gene co-expression weight network was constructed to screen the modules with the highest correlation with hypospadias,and the genes in the modules were enriched and detected by gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG).Differential analysis was also performed to screen out differential genes.The differential genes were imported into the String database.Using Cytoscape software,the hub genes in the network were identified.The results screened by the above three methods were combined and analyzed,and the core genes in the intersection set were screened.Using the external dataset GSE121712,the core genes were verified by mRNA expression changes and subject work characterization receiver operating characteristic(ROC)curve diagnosis.Results Fifteen co-expression modules were obtained based on the WGCNA method.Ninety-three common differential genes meeting the conditions were obtained by differential analysis.Ten core genes were finally obtained by Cytoscape software analysis.Finally MEbrown module,differential genes and the 10 core genes yielded a total of 2 intersecting genes:FBXL16 and SYNDIG1.ROC curves verified that the intersecting genes were differentially expressed in patients with hypospadias versus normal subjects.Conclusion In this study,two key genes with significant correlation with hypospadias were obtained by WGCNA,which may be used for the early diagnosis and treatment of hypospadias after further study.

Objective:To explore the effect of oral nutritional supplements (ONS) during labor on delivery outcomes in low-risk pregnant women and the risk factors of cesarean section.Methods:A retrospective analysis was conducted in a total of 206 full-term pregnant women with singleton and cephalic presentation at the delivery center in our hospital from March 15th to May 15th, 2022. Standard diet education was given to all those women by midwives. Pregnant women who received the enteral nutrient solution prepared by the Department of Clinical Nutrition during labor were in the ONS group ( n = 110), while those who did not were in the control group ( n = 96). The baseline characteristics and delivery outcomes were compared between the two groups, and the risk factors of cesarean section were also analyzed. Results:There were no significant differences in terms of maternal age, height, baseline weight, baseline body mass index (BMI), weight gain during pregnancy, prenatal BMI, gestational week, intraspinal labor analgesia, oxytocin, gastrointestinal intolerance, neonatal length, and weight between the two groups ( P > 0.05). However, the total oral energy intake during labor in the ONS group was significantly higher than that in the control group ([1 349.99± 569.51] kJ vs [249.59 ± 455.19] kJ, P < 0.01). The rate of vaginal delivery in the ONS group was significantly higher than that in the control group (93.6% vs 81.3%, P = 0.01), and the duration of the first stage of labor ([487.06 ± 232.94] min vs [416.17 ± 191.13] min, P = 0.03) was also significantly longer in the ONS group. There were no significant differences between the two groups in terms of the duration of the second and third stages of labor, perineal laceration, cervical laceration, vaginal laceration, amount of bleeding, hospital stay, and Apgar score after birth ( P > 0.05). Multivariate logistic regression analysis showed that maternal age was a risk factor for changing to cesarean section in women with low-risk pregnancies ( OR 1.20, 95% CI 1.03 to 1.40, P = 0.02), while ONS during labor ( OR 0.31, 95% CI 0.11 to 0.85, P = 0.02) and intraspinal labor analgesia ( OR 0.10, 95% CI 0.04 to 0.26, P < 0.01) were protective factors. Conclusions:ONS during labor can significantly increase the vaginal delivery rate, without increasing the incidence of gastrointestinal intolerance in low-risk pregnant women. Maternal age is a risk factor for cesarean section while ONS during labor and intraspinal labor analgesia are protective factors in women with low-risk pregnancies.

Atherosclerosis is a vascular disease characterized by arterial occlusion formed by the pathological accumulation of pathological vascular cells and apoptotic cell debris. Atherosclerotic vulnerable plaque is an important pathological basis for inducing severe thrombotic cardiovascular events， and the study of its etiology and pathogenesis has always been a hot issue in the field of cardiovascular research. Efferocytosis is a new type of programmed death cell removal， which refers to the process of macrophages phagocytosing and degrading apoptotic cells to prevent secondary necrosis. It is a key homeostatic mechanism in the body's physiological process. In the pathological state， the dysfunction of efferocytosis causes the pathological accumulation of apoptotic cells and necrotic debris， leading to the occurrence of secondary cell necrosis and the continuous release of intracellular toxic content and inducing inflammatory regression disorders and cholesterol metabolism disorders， which are closely related to the occurrence and development of atherosclerotic vulnerable plaques. The theory of ''blood stasis and toxin'' is an important theory of traditional Chinese medicine （TCM） to explain the occurrence and development of atherosclerosis. Atherosclerosis starts from the pathological state of blood stagnation. Prolonged blood stagnation leads to blood stasis and toxic substances. Blood stasis and toxic pathogens interact with each other in blood vessels and eventually form plaques in blood vessels. The theory of ''blood stasis and toxin causing a catastrophe'' is an important understanding of the occurrence and development of acute cardiovascular events. From the perspective of TCM theory， the pathophysiological mechanism of efferocytosis is similar to the etiology and pathogenesis of the ''blood stasis and toxin'' in TCM. Therefore， this paper took the theory of ''blood stasis and toxin'' as the breakthrough point to explore the mechanism of efferocytosis in atherosclerotic vulnerable plaques， and proposed a detoxification and blood circulation method to regulate cell burial to prevent and treat atherosclerotic vulnerable plaques. The research strategy aims to provide new ideas and theoretical basis for the prevention and treatment of atherosclerosis by detoxification and blood circulation.