Traditional Chinese Medicine(TCM)emphasizes syndrome differentiation and treatment,characterized by"maintaining the prescription if effective"and"changing the prescription if ineffective".Traditional randomized controlled trials(RCTs)are inadequate for evaluating the efficacy of dynamic treatment adjustments.The Sequential Multiple Assignment Randomized Trial(SMART)is an emerging adaptive research design that incorporates randomization at multiple stages,allowing for adjustments in subsequent interventions based on treatment responses.This approach is suitable for evaluating dynamic treatment regimens while retaining the low bias risk of traditional RCTs,making it highly promising for clinical research in TCM.This paper summarizes recent methodological advancements in SMART design,including different sample size estimation and statistical analysis methods for primary effect objectives,embedded adaptive intervention objectives,and optimization objectives,along with providing corresponding operational software.Additionally,it offers considerations for applying SMART design in TCM research,such as the selection of disease types,interventions,decision points,tailoring variables,sample size calculation,statistical methods,the importance of pilot trials,ethical considerations,and limitations.The aim is to promote the exploration and practice of this method in the field of TCM,thereby contributing to the generation of high-quality evidence-based evidence for TCM.

Green prescription is a written prescription aimed at improving health by promoting physical activity and improving diet， with advantages such as high cost-effectiveness， strong feasibility， and minimal harm to patients. The theory of traditional Chinese medicine （TCM） green prescription integrates the health philosophy of "following rule of yin and yang， and adjusting ways to cultivating health"， the exercise philosophy of balancing yin-yang and the five elements， and the dietary philosophy of moderation and balance， which embody core TCM concepts such as treating disease before its onset and harmony between humans and nature. It has also developed traditional exercise practices like Tai Chi， Baduanjin， Wuqinxi， Yi-Gin-Ching， and Qigong， as well as dietary adjustments like medicated diet and herbal wines. However， it is believed that the TCM green prescription currently suffers from insufficient evidence-based research， low patient awareness and acceptance， and weak basic research. Based on this， it is proposed that large-sample clinical trials should be conducted in the future to improve the quality of evidence-based medicine， basic research can be carried out with the help of artificial intelligence and other methods in research design， the hospital information system （HIS） can be used for control at the implementation level， and publicity and patient education can be strengthened through the new media， so as to promote the development and application of the TCM green prescriptions in the field of global health treatment.

Traditional Chinese Medicine(TCM)emphasizes syndrome differentiation and treatment,characterized by"maintaining the prescription if effective"and"changing the prescription if ineffective".Traditional randomized controlled trials(RCTs)are inadequate for evaluating the efficacy of dynamic treatment adjustments.The Sequential Multiple Assignment Randomized Trial(SMART)is an emerging adaptive research design that incorporates randomization at multiple stages,allowing for adjustments in subsequent interventions based on treatment responses.This approach is suitable for evaluating dynamic treatment regimens while retaining the low bias risk of traditional RCTs,making it highly promising for clinical research in TCM.This paper summarizes recent methodological advancements in SMART design,including different sample size estimation and statistical analysis methods for primary effect objectives,embedded adaptive intervention objectives,and optimization objectives,along with providing corresponding operational software.Additionally,it offers considerations for applying SMART design in TCM research,such as the selection of disease types,interventions,decision points,tailoring variables,sample size calculation,statistical methods,the importance of pilot trials,ethical considerations,and limitations.The aim is to promote the exploration and practice of this method in the field of TCM,thereby contributing to the generation of high-quality evidence-based evidence for TCM.

There are different views on the theory of “spleen governs time”， which is still a hot spot in the study of Zangxiang （藏象） theory. Based on Zangxiang time-space view， it is found that the thinking mode of the spleen governing time theory follows space-time logic. It is believed that the different time views of the spleen governing time are all formed based on the space view that the spleen belongs to earth and resides in the center， and the zang time theory is developed with the unified time and space logic. Guided by Zangxiang time-space view， the origin of the spleen belonging to earth and residing in the center is traced， and the theoretical connotation and its clinical application of spleen governing time under different time-space logic are explored with reference to the four season and five zang theory， five season and five zang theory， six season and six zang theory， and eight season and eight zang theory.

This paper systematically analyzed the understanding of qi from the perspectives of matter， energy， information and relationship reality， introduced the original holistic principle of systematic traditional Chinese medicine （TCM）， and considered the latest research results of qi （three-layer material theory）， trying to optimize the structure framework of the qi theoretical system and exhibit the occurrence and development rules of original qi. It emphasizes the hierarchical order of qi transformation following the original holistic principle， and takes this to guide the clinical understanding of “qi diseases”， helping doctors grasp the basic pathogenesis of the disease， that is abnormal qi movement， and helping them establish the awareness of providing systematic TCM treatment to patients by taking qi regulation as the key. At the same time， it discusses people within the structure of time and space， and points out that the treatment of diseases must comply with the principle of “the harmony of heaven， earth， and human beings”.

OBJECTIVE: To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis. METHODS: Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched. RESULTS: A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways. CONCLUSIONS Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.
Echinococcosis/genetics* ; Gene Expression Profiling ; Humans ; MicroRNAs/metabolism* ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; T-Lymphocytes, Regulatory ; TOR Serine-Threonine Kinases/genetics* ; Th17 Cells ; Transcription Factors/genetics*

Background: Based on the theory of"five Zang-organs corresponding to the seasons"in traditional Chinese medicine (TCM), physiological functions including emotions vary with the seasons. We aimed to investigate the seasonal photoperiod effects of melatonin (MT) released from the pineal gland on the MT receptor (MTR)-Gs/Gi-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in the hippocampus.Methods: Rats were divided into three groups: control, operation (surgery with pineal gland removal), and pseudo-operation groups (same surgery as operation group but without removing pineal gland), and fed at specific time across the four seasons. The levels of MTR, adenylate cyclase (AC), cAMP, PKA, and CREB in the hippocampus were analyzed using ELISA. The concentrations of Gs and Gi were analyzed using Western blot. The expression of CREB mRNA was detected by PCR. Results: For intragroup comparisons, compared with spring, the levels of Gs/Gi in the control group were higher in summer, autumn, and winter (P=.009 in summer;P<.001 in autumn and winter);the levels of MTR, cAMP, PKA, and CREB in the control group were significantly higher in autumn and winter than in spring (all P<.001). The levels of MTR, cAMP, PKA, and CREB in each season were significantly lower in the operation group than in the control group (all P < .05). Significant differences were noted in Gs/Gi levels between the operation group and control group in spring, autumn, and winter (all P<.05). Conclusion: Our findings suggest that MTR-Gs/Gi-cAMP-PKA-CREB signaling pathway is involved in the seasonal photoperiod effects of the pineal gland on the hippocampus and may underpin seasonal changes in emotions. It can support the prevention and treatment of the seasonal onset of mental dis-orders, and enrich the theory of"five Zang-organs corresponding to the seasons".

Objective: To evaluate the value of cardiac MR imaging in chronic ischemie mitral regurgitation (IMR) in patients with myocardial infarction. Methods: All patients clinically diagnosed with coronary heart disease and myocardial infarction in our hospital from January 2016 to September 2018 were retrospectively selected, myocardial infarction time more than 3 months and confirmed to have necrotic myocardium by cardiac magnetic resonance examination. All patients underwent echocardiography at the same time. Based on the results of echocardiography, patients were divided into the myocardial infarction group without IMR (40 cases), the mild IMR group (39 cases) and the moderate to severe IMR group (51 cases). Cardiac MR and delayed enhancement (LGE) scan images were analyzed. Cardiac function indexes were measured and left ventricular LGE positive segments were recorded. The indexes of myocardial global longitudinal strain (GLS), global peripheral strain (GCS) and global radial strain (GRS) of left ventricle of IMR patients were measured by feature tracking(FT). Cardiovascular history, coronary artery stenosis and location of myocardial infarction were compared by chi-square test between the without IMR, mild IMR and moderate to severe IMR groups.Univariate analysis of variance was used to compare the measurement data of left ventricular myocardial infarction volume, left heart function and left ventricular myocardial globle strain, and LSD test was used for pair-wise comparison. Results: There was no difference in age, sex and cardiovascular history among the three groups. Comparison of myocardial infarction patients in the three groups: (1) There was no statistically significant difference in the myocardial infarction volume between the three groups (P=0.052), while the myocardial infarction volume tended to increase as the grade of mitral regurgitation increased. The number of patients with myocardial infarction in the inferior wall and the inferolateral wall in the moderate to severe IMR group were significantly higher than those of the other two groups (P<0.05), and there was no significant difference in the volume of myocardial infarction between the without IMR group and mild IMR group, and no difference in the number of patients with inferior wall and inferolateral wall. (2) Cardiac function measured by CMR: ejection fraction (EF) was significantly reduced in the moderate to severe IMR group compared with the without IMR group and the mild IMR group (P<0.05), the end diastolic volume (EDV) increased significantly and the end systolic volume (ESV) increased significantly (P<0.05). Mass of myocardium increased significantly (P<0.05); Stroke volume (SV) and cardiac output (CO) there was no significant difference among the three groups. (3) Comparison of the moderate to severe IMR group to the without IMR group and the mild IMR group respectively: left ventricular GLS and GRS decreased (P<0.05), the difference of the GCS was no statistically significant. There was no statistical difference in the three strain values between the without IMR group and the mild IMR group. Conclusion The globe myocardial strain of the left ventricle in myocardial infarction patients with chronic moderate to severe IMR was significantly impaired, the myocardial infarction in the inferior wall and the inferolateral wall in the level of the papillary muscle may be correlated with chronic moderate to severe IMR, and the myocardial infarction volume of the left ventricle may also be related.

Objective To evaluate the value of cardiac MR imaging in chronic ischemie mitral regurgitation (IMR) in patients with myocardial infarction. Methods All patients clinically diagnosed with coronary heart disease and myocardial infarction in our hospital from January 2016 to September 2018 were retrospectively selected, myocardial infarction time more than 3 months and confirmed to have necrotic myocardium by cardiac magnetic resonance examination. All patients underwent echocardiography at the same time. Based on the results of echocardiography, patients were divided into the myocardial infarction group without IMR (40 cases), the mild IMR group (39 cases) and the moderate to severe IMR group (51 cases). Cardiac MR and delayed enhancement (LGE) scan images were analyzed. Cardiac function indexes were measured and left ventricular LGE positive segments were recorded. The indexes of myocardial global longitudinal strain (GLS), global peripheral strain (GCS) and global radial strain (GRS) of left ventricle of IMR patients were measured by feature tracking(FT). Cardiovascular history, coronary artery stenosis and location of myocardial infarction were compared by chi?square test between the without IMR, mild IMR and moderate to severe IMR groups.Univariate analysis of variance was used to compare the measurement data of left ventricular myocardial infarction volume, left heart function and left ventricular myocardial globle strain, and LSD test was used for pair?wise comparison. Results There was no difference in age, sex and cardiovascular history among the three groups. Comparison of myocardial infarction patients in the three groups: (1) There was no statistically significant difference in the myocardial infarction volume between the three groups (P=0.052), while the myocardial infarction volume tended to increase as the grade of mitral regurgitation increased. The number of patients with myocardial infarction in the inferior wall and the inferolateral wall in the moderate to severe IMR group were significantly higher than those of the other two groups (P<0.05), and there was no significant difference in the volume of myocardial infarction between the without IMR group and mild IMR group, and no difference in the number of patients with inferior wall and inferolateral wall. (2) Cardiac function measured by CMR: ejection fraction (EF) was significantly reduced in the moderate to severe IMR group compared with the without IMR group and the mild IMR group (P<0.05), the end diastolic volume (EDV) increased significantly and the end systolic volume (ESV) increased significantly (P<0.05). Mass of myocardium increased significantly (P<0.05); Stroke volume (SV) and cardiac output (CO) there was no significant difference among the three groups. (3) Comparison of the moderate to severe IMR group to the without IMR group and the mild IMR group respectively: left ventricular GLS and GRS decreased (P<0.05), the difference of the GCS was no statistically significant. There was no statistical difference in the three strain values between the without IMR group and the mild IMR group. Conclusion The globe myocardial strain of the left ventricle in myocardial infarction patients with chronic moderate to severe IMR was significantly impaired, the myocardial infarction in the inferior wall and the inferolateral wall in the level of the papillary muscle may be correlated with chronic moderate to severe IMR, and the myocardial infarction volume of the left ventricle may also be related.

Objective: To investigate the effect of incisor retraction on three-dimensional morphology of upper airway and fluid dynamics in class Ⅰ adult patients with bimaxillary protrusion. Methods: Thirty class Ⅰ patients with bimaxillary protrusion that received fixed orthodontic treatment in Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University from January 2011 to September 2014 were selected using random number table. All the patients were treated with extraction of four first premolars and retraction of anterior teeth using implant anchorage. Cone-beam CT (CBCT) scans were performed before and after incisor retraction for all patients. The CBCT data of the upper airway were constructed using Mimics 16.0, and the flow field characteristics inside the upper airway were simulated using Ansys 14.0. The changes of volume (V), mean cross-sectional area (mCSA), maximum lateral diameters/maximum anteroposterior diameters (LP/AP) of cross section, the maximum pressure of airflow (P_max), the minimum pressure of airflow (P_min) and pressure drop (△P) of nasopharynx, oropharynx and hypopharynx before and after incisor retraction were measured and compared using paired t test. The correlation between the variation of △P in the most significant pharyngeal part and the morphological variables after incisor retraction was analyzed using Pearson correlation test. Results: No statistical differences were observed in the morphology and flow field in nasopharynx before and after incisor retraction (P>0.05). Before incisor retraction, the oropharyngeal volume and mCSA were (7 580±622) mm³ and (217±40) mm², respectively, and the hypopharyngeal volume and mCSA were (2 564±162) mm³, and (239±43) mm², respectively. After incisor retraction, the volumes of oropharynx and hypopharynx were (6 885±601) mm³ and (2 535±156) mm³, respectively, and mCSA of oropharynx and hypopharynx were (197±37) mm² and (236±42) mm², respectively. The volume and mCSA of oropharynx and hypopharynx were significantly decreased after incisor retraction (P<0.05). The greatest changes in pharyngeal volume and mCSA occurred in the oropharynx. In addition, the LP/AP of oropharynx after incisor retraction was changed from 1.9±0.6 to 2.1±0.7, which was significantly increased compared with the levels before incisor retraction (P<0.05). After simulation of pharyngeal airflow, the oropharyngeal P_min, hypopharyngeal P_max and P_min were (-13.7±4.3), (-8.3±3.8) and (-42.8±9.5) Pa, respectively, whereas the values turned to (-16.4±6.5), (-11.9±3.6) and (-46.0±11.0) Pa, respectively after incisor retraction, which was significantly reduced (P<0.05). △P of oropharynx was significantly increased from (42.7±10.1) Pa to (45.2±13.0) Pa after incisor retraction (P<0.05) and the variation of oropharyngeal △P was negatively correlated with the variation of V and mCSA in oropharynx before and after incisor retraction (r=-0.681, P=0.001; r=-0.844, P=0.000). Conclusions The oropharynx was constricted and the pharyngeal resistance was increased after incisor retraction in adult class Ⅰ patients with bimaxillary protrusion. A comprehensive and systematic evaluation of the pharyngeal morphology and ventilatory function were very important for making a scientific and rational clinical treatment plan.