The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

The theory of constitution in traditional Chinese medicine （TCM） has emerged as a new discipline in recent years. Constitution plays a vital role in the onset，progression，transformation，and prognosis of diseases. At present，some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation"，in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology，onset，pathogenesis，syndrome differentiation，and treatment. Against this background，the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution，aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models，thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions，diseases，and syndromes，but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods，the study evaluates the model's validity，reliability，and practicality，with the aim of opening new avenues for future research in TCM and promoting the development of the field.

There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

Objective To evaluate the effectiveness and safety of Su Fei He Ji combined with anlotinib hydrochloride in the treatment of refractory advanced non-small cell lung cancer(NSCLC)patients presenting with phlegm stasis obstructing lung type.Methods Thirty-nine patients with advanced NSCLC were randomly assigned to either a control group(19 patients)or an experimental group(20 patients).The control group received treatment with anlotinib alone,while the experimental group received an additional oral administration of Su Fei He Ji.A comparative analysis was conducted between the two groups based on various parameters including short-term objective therapeutic efficacy,progression-free survival,TCM syndrome scores,KPS scores,weight changes,related tumor markers,incidence of adverse reactions,and variations in plasma concentrations of anlotinib.Results Following treatment,the objective response rate was 5%and the disease control rate was 85%in the experimental group,while the control group showed an objective response rate of 0%and a disease control rate of 78.95%.No statistically significant difference was observed in short-term objective efficacy between the two groups(P>0.05).Notably,the experimental group exhibited a significant improvement compared to the control group in various aspects,including TCM syndrome scores and KPS scores(P<0.05).Conversely,no significant differences were observed in weight changes or the reduction levels of other tumor markers(CEA,SCC,CA125,CA199,CYFRA21-1)(P>0.05).Moreover,the incidence of fatigue was notably lower in the experimental group(P<0.05),while no statistical difference was evident in the occurrence of other adverse reactions,such as hypertension,rash,and bleeding,between the two groups(P>0.05).It is important to highlight that there was no statistically significant variance in plasma concentrations between the groups(P>0.05),and no significant correlation was identified between plasma concentrations and the incidence of adverse reactions(P>0.05).Conclusion The combination of Su Fei He Ji and anlotinib hydrochloride effectively improves clinical symptoms and quality of life,and reduces adverse reactions in advanced NSCLC patients.This is achieved without affecting the plasma concentrations of anlotinib.

This article systematically analyzes the historical evolution of the name， origin， quality evaluation， harvesting， processing and other aspects of Picrorhizae Rhizoma by referring to the medical books， prescription books， and other documents of the past dynasties， combined with relevant modern research materials， in order to provide a basis for the development and utilization of famous classical formulas containing this medicinal herb. The research results indicate that Picrorhizae Rhizoma was first recorded in New Revised Materia Medica from the Tang dynasty. Throughout history， Huhuanglian has been used as its official name， and there are also aliases such as Gehu Luze， Jiahuanglian and Hulian. The main source of past dynasties is the the rhizomes of Picrorhiza kurrooa and P. scrophulariiflora. In ancient times， Picrorhizae Rhizoma was mainly imported by foreign traders via Guangzhou and other regions， and also produced in China， mainly in Xizang. In ancient times， it was harvested and dried in early August of the lunar calendar， while in modern times， it is mostly harvested from July to September， with the best quality being those with thick and crispy rhizomes without impurities， and bitter taste. Throughout history， Picrorhizae Rhizoma was collected， washed， sliced， and dried before being used as a raw material for medicine， it has a bitter and cold taste， mainly used to treat bone steaming， hot flashes， infantile chancre fever， and dysentery. There is no significant difference in taste and efficacy between ancient and modern times. Based on the research results， it is recommended that the rhizomes of P. scrophulariiflora in the 2020 edition of Chinese Pharmacopoeia， or the rhizomes of P. kurrooa， can be used in famous classical formulas containing this medicinal herb， which can be processed according to the processing requirements marked by the original formula. For those without clear processing requirements， the dried raw products are used as medicine.

Objective To evaluate the effectiveness and safety of Su Fei He Ji combined with anlotinib hydrochloride in the treatment of refractory advanced non-small cell lung cancer(NSCLC)patients presenting with phlegm stasis obstructing lung type.Methods Thirty-nine patients with advanced NSCLC were randomly assigned to either a control group(19 patients)or an experimental group(20 patients).The control group received treatment with anlotinib alone,while the experimental group received an additional oral administration of Su Fei He Ji.A comparative analysis was conducted between the two groups based on various parameters including short-term objective therapeutic efficacy,progression-free survival,TCM syndrome scores,KPS scores,weight changes,related tumor markers,incidence of adverse reactions,and variations in plasma concentrations of anlotinib.Results Following treatment,the objective response rate was 5%and the disease control rate was 85%in the experimental group,while the control group showed an objective response rate of 0%and a disease control rate of 78.95%.No statistically significant difference was observed in short-term objective efficacy between the two groups(P>0.05).Notably,the experimental group exhibited a significant improvement compared to the control group in various aspects,including TCM syndrome scores and KPS scores(P<0.05).Conversely,no significant differences were observed in weight changes or the reduction levels of other tumor markers(CEA,SCC,CA125,CA199,CYFRA21-1)(P>0.05).Moreover,the incidence of fatigue was notably lower in the experimental group(P<0.05),while no statistical difference was evident in the occurrence of other adverse reactions,such as hypertension,rash,and bleeding,between the two groups(P>0.05).It is important to highlight that there was no statistically significant variance in plasma concentrations between the groups(P>0.05),and no significant correlation was identified between plasma concentrations and the incidence of adverse reactions(P>0.05).Conclusion The combination of Su Fei He Ji and anlotinib hydrochloride effectively improves clinical symptoms and quality of life,and reduces adverse reactions in advanced NSCLC patients.This is achieved without affecting the plasma concentrations of anlotinib.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

Objective:To study the quality and stability of commercial ready-to-use tryptone soya agar(TSA)after storing at 2-25 ℃ for different storage duration under dark condition in order to discuss a determination method of validity period for medium.Methods:Three consecutive batches of ready-to-use TSA medium from two manufac-turers were selected and stored at 2-25 ℃ under dark conditions for 30,90 and 180 days,respectively.The appearance,pH,medium suitability and sterility of the medium were tested.Results:The results of appearance,pH,suitability and sterility of TSA medium from two manufacturers for each batch under different storage duration all met the requirements of the Chinese Pharmacopoeia 2020 Volume IV on the quality control of medium.Conclusion:The TSA medium from two manufacturers all met the requirements when stored for 180 days at 2-25 ℃ under dark condition,indicating that the validity period of TSA medium from two manufacturers can reach 180 days.

ObjectiveTo observe the effects and underlying mechanisms of Fagopyri Dibotryis Rhizoma extract on the proliferation， apoptosis， and autophagy of human colorectal cancer HCT-116 cells. MethodFirstly， cellular activity was detected by the cell proliferation and activity-8 （CCK-8） assay， and the half inhibition rate （IC₅₀） was calculated. Blank group and Fagopyri Dibotryis Rhizoma group （2， 4， 8 mg·L^-1） were set. The effect of Fagopyri Dibotryis Rhizoma on the proliferation of HCT-116 cells was observed by cloning experiments， and that of Fagopyri Dibotryis Rhizoma on apoptosis was observed by flow cytometry. The expressions of autophagy-related proteins， p38 mitogen-activated protein kinase （p38 MAPK）， extracellular signal-regulated kinase （ERK）， c-Jun amino-terminal kinase （JNK）， phosphorylated （p）-p38， p-ERK， p-JNK， and other proteins were detected by Western blot. Finally， flow cytometry instrumentation and fluorescence microscopy were used to analyze the changes in reactive oxygen species （ROS）， and a ROS scavenger （NAC） was adopted for verification. ResultCompared with the blank group， the activity of HCT-116 cells was significantly decreased in the Fagopyri Dibotryis Rhizoma group （P<0.05， P<0.01）. The apoptosis rate of HCT-116 cells in the Fagopyri Dibotryis Rhizoma group was significantly increased （P<0.01）. The expression of autophagy-related protein ubiquitin-binding protein （p62） was decreased， but that of autophagy-specific genes （Beclin1） and autophagic microtubule-associated protein 1 light-chain 3B （LC3B） was enhanced （P<0.05， P<0.01）. Compared with the Fagopyri Dibotryis Rhizoma group， the apoptosis rate of HCT-116 cells in the Fagopyri Dibotryis Rhizoma + NAC group was significantly reduced （P<0.01）. The expression of related autophagy protein Beclin1 was significantly reduced （P<0.01）， and that of LC3B protein was reduced （P<0.01）. In addition， the expression of MAPK pathway-related proteins ERK and JNK was decreased in the Fagopyri Dibotryis Rhizoma group （P<0.05， P<0.01）， and that of p-ERK and p-JNK was enhanced （P<0.05， P<0.01）. ConclusionFagopyri Dibotryis Rhizoma can inhibit the proliferation of HCT-116 cells and induce apoptosis and autophagy through the ROS/MAPK signaling pathway.