The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

Type 2 diabetes mellitus （T2DM） and hypertension are common and frequent chronic non-communicable diseases， which often coexist in clinical practice， resulting in a large number of cardiovascular events and deaths， and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards， guidelines， and animal model evaluation methods of T2DM with hypertension at home and abroad， this study summarized， evaluated， and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin （STZ） in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine （TCM） are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages， the ideal modeling method for T2DM with hypertension is the two-kidney， one clip （2K1C） method （a surgical induction method） combined with feeding a high-fat and high-sugar diet and STZ injection. However， the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome， which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem， it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome， which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way， ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM， which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time， breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

Type 2 diabetes mellitus （T2DM） and hypertension are common and frequent chronic non-communicable diseases， which often coexist in clinical practice， resulting in a large number of cardiovascular events and deaths， and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards， guidelines， and animal model evaluation methods of T2DM with hypertension at home and abroad， this study summarized， evaluated， and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin （STZ） in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine （TCM） are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages， the ideal modeling method for T2DM with hypertension is the two-kidney， one clip （2K1C） method （a surgical induction method） combined with feeding a high-fat and high-sugar diet and STZ injection. However， the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome， which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem， it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome， which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way， ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM， which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time， breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.

Objective: To analyze the status of outdoor activities on weekends among children and adolescents of different educational stages in Shanghai and their impact on myopia, so as to provide a basis for formulating more specific prevention and control protocol of myopia. Methods: From September to October 2022, a stratified cluster random sampling method was employed to select 84 schools (27 kindergartens, 21 primary schools, 15 junior high schools and 21 high schools) across Shanghai, enrolling a total of 28 654 children and adolescents aged 4 to 18 for the study. Ophthalmic examinations were conducted to ascertain the prevalence of myopia among children and adolescents. Additionally, a questionnaire survey was administered to collect data on outdoor activity duration and associated factors. Multivariate Logistic regression analysis was utilized to investigate the associated factors of outdoor activity levels on weekends. Results: The overall myopia detection rate among children and adolescents was 58.4%, with a higher rate observed in girls (59.2%) compared to boys (57.6%). The myopia detection rates for children and adolescents with an average daily outdoor activity duration of ≥2 h and <2 h on weekends were 54.6% and 68.8%, and the differences were statistically significant ( χ 2=8.12,460.89, P <0.01). Multivariable Logistic regression analysis revealed that girls ( OR =0.80), those with a myopic parent ( OR =0.68), schools from urban districts ( OR =0.72), higher education stages (primary school: OR =0.65, junior high school: OR =0.24, high school: OR =0.14) and spending≥2 h/d on homework during weekends ( OR =0.57) among children and adolescents were less likely to engage in outdoor activities for ≥2 h on weekends ( P <0.01). After incorporating gender, parental myopia status, educational stage, school location, average daily duration on weekends for spending on homework, electronic product usage and outdoor activities as dependent variables in a multivariate Logistic regression analysis, the results showed that children and adolescents with an average outdoor activity duration for ≥2 h on weekends had a lower risk of myopia ( OR =0.86, P < 0.01). Conclusions The level of outdoor activity among children and adolescents on weekends needs to be improved. Outdoor activities on weekends is an associated factor for myopia among children and adolescents. Particularly, girls, those with myopic parents, schools from urban districts, and spending long hours on homework during weekends among children and adolescents require increased attention.

Objective: To investigate the visual acuity and correction conditions of children and adolescents in Shanghai, so as to provide a scientific basis for developing intervention measures to prevent myopia and protect vision among children and adolescents. Methods: From October to December 2022, a stratified cluster random sampling survey was conducted, involving 47 034 students from 16 municipal districts in Shanghai, covering kindergartens (≥5 years), primary schools, middle schools, general high schools and vocational high schools. According to the Guidelines for Screening Refractive Errors in Primary and Secondary School Students, the Standard Logarithmic Visual acuity Chart was used to examine naked vision and corrected vision of students, and general information was collected. The distribution and severity of visual impairment in different age groups were analyzed, and χ 2 tests and multivariate Logistic regression were used to explore factors associated with visual impairment. Results: The detection rate of visual impairment among children and adolescents was 76.2%, with a higher rate among females (78.8%) than males ( 73.8 %), higher among Han ethic students ( 76.2 %) than minority students (71.2%), and higher among urban students (76.7%) than suburban students (75.8%), all with statistically significant differences ( χ 2=162.6, 10.4, 5.5, P <0.05). The rate of visual impairment initially decreased and then increased with age, reaching its lowest at age 7 (53.8%) and peaking at age 17 (89.6%) ( χ 2 trend = 3 467.0 , P <0.05). Severe visual impairment accounted for the majority, at 56.6%, and there was a positive correlation between the severity of visual impairment and age among children and adolescents ( r =0.45, P <0.05). Multivariate Logistic regression showed that age, BMI, gender, ethnicity and urban suburban status were associated with visual impairment ( OR =1.18, 1.01, 1.38 , 0.79, 0.88, P <0.05). Among those with moderate to severe visual impairment, the rate of spectacle lens usage was 62.8%, yet only 44.8 % of those who used spectacle lens had fully corrected visual acuity. Females (64.9%) had higher spectacle lens usage rates than males (60.6%), and general high school students had the highest spectacle lens usage (83.9%), and there were statistically significant differences in gender and academic stages ( χ 2=57.7, 4 592.8, P <0.05). Conclusions The rate of spectacle lens usage among students with moderate to severe visual impairment is relatively low, and even after using spectacle lens, some students still do not achieve adequate corrected visual acuity. Efforts should focus on enhancing public awareness of eye health and refractive correction and improving the accessibility of related health services.

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

Objective: To explore the association of latent profiles of mobile phone dependence and self control with physical exercise among junior high school students, so as to provide references for the prevention of mobile phone dependence and the improvement of self control among junior high school students. Methods: From April to May 2024, a stratified random cluster sampling method was used to select a total of 2 311 students from grade 7 to grade 9 in three public junior high schools in Xiangxi Autonomous Prefecture, Hunan Province. Latent profile analysis was conducted to identify the latent profiles of mobile phone dependence and self control among junior high school students. Pearson correlation analysis was used to examine the correlation between mobile phone dependence and self control, and Chi square test was used to analyze the distribution differences of latent profiles of adolescents across different demographic characteristics. Multiple Logistic regression analysis was applied to explore the association between mobile phone dependence, self control, and physical exercise. Results: Four latent profiles of mobile phone dependence and self control were identified: low dependence-moderate self control group ( n =885, 38.3%), moderate dependence-low self control group ( n =910, 39.4%), high dependence-no self control group ( n =232, 10.0%), and no dependence-high self control group ( n =284, 12.3%). Significant differences were observed in the distribution of latent profiles across gender, grade and only child status ( χ 2=10.85, 35.72, 13.85， P <0.05). Logistic regression analysis showed that, after controlling for demographic variables, compared with the low dependence-moderate self control group, physical exercise was negatively associated with the moderate dependence-low self control group ( OR =0.79) and the high dependence-no self control group ( OR =0.81), while positively associated with the no dependence-high self control group ( OR =1.58) ( P <0.01). Conclusions The influence of physical exercise on junior high school students different potential profile types of mobile phone dependence and self control is different. Schools and families should adopt targeted physical exercise interventions based on the characteristics of different profiles to promote the physical and mental health of junior high school students.

Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.