ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective To investigate the effects of different components of short-chain fatty acids (SCFAs) on depression-like behaviors and intestinal flora in chronic unpredictable mild stress (CUMS)-induced depressive rats. Methods Seventy-six healthy male rats were randomly divided into six groups. Rats in the acetate group (n=12),propionate group (n=15) and butyrate group (n=14) were given intraperitoneal injection (i.p.) of 50 mg/kg sodium acetate,100 mg/kg sodium propionate and 50 mg/kg sodium butyrate,respectively. Rats in the SCFAs group (n=12) were given i.p of 1∶1∶1 sodium acetate,sodium propionate and sodium butyrate mixed solution. Rats in the CUMS group (n=13) were given i.p of 1 mL/100 g saline. Rats in the control group (n=10) did not receive any treatment. Besides the control group,other groups were subjected to CUMS and intraperitoneal injection before stress for 28 days. The depression-like behaviors were assessed by sucrose preference test,forced swimming test,open field test,and then cecal fecal samples were collected to examine the composition of intestinal flora by 16S rRNA sequencing. Results Compared with the control group,the body weight of rats and the sugar preference coefficient decreased and the immobility time increased in the CUMS group (P<0.05). The butyrate group reversed the alterations in change of the sugar preference coefficient and the immobility time (P<0.05). Additionally,the sugar preference coefficient was elevated in the SCFAs group (P<0.05). The community structure of intestinal flora was changed in the CUMS group compared to the control group and was partially improved in the acetate group. The number of unique species reduced in the CUMS group but increased in the acetate group,propionate group,butyrate group and SCFAs group. LEfSe found the enrichment of Bifidobacterium in the propionate group and the enrichment of Collinsella in the SCFAs group. Conclusions Sodium butyrate significantly improves depressive-like behaviors of the CUMS-induced rats. Sodium acetate,sodium propionate,and short-chain fatty acid mixture can influence the composition of intestinal flora. However,their antidepressant effect is not significant. Sodium butyrate may be a better alternative for supplementing short-chain fatty acids in depression.

Objective To investigate the effects of different components of short-chain fatty acids (SCFAs) on depression-like behaviors and intestinal flora in chronic unpredictable mild stress (CUMS)-induced depressive rats. Methods Seventy-six healthy male rats were randomly divided into six groups. Rats in the acetate group (n=12),propionate group (n=15) and butyrate group (n=14) were given intraperitoneal injection (i.p.) of 50 mg/kg sodium acetate,100 mg/kg sodium propionate and 50 mg/kg sodium butyrate,respectively. Rats in the SCFAs group (n=12) were given i.p of 1∶1∶1 sodium acetate,sodium propionate and sodium butyrate mixed solution. Rats in the CUMS group (n=13) were given i.p of 1 mL/100 g saline. Rats in the control group (n=10) did not receive any treatment. Besides the control group,other groups were subjected to CUMS and intraperitoneal injection before stress for 28 days. The depression-like behaviors were assessed by sucrose preference test,forced swimming test,open field test,and then cecal fecal samples were collected to examine the composition of intestinal flora by 16S rRNA sequencing. Results Compared with the control group,the body weight of rats and the sugar preference coefficient decreased and the immobility time increased in the CUMS group (P<0.05). The butyrate group reversed the alterations in change of the sugar preference coefficient and the immobility time (P<0.05). Additionally,the sugar preference coefficient was elevated in the SCFAs group (P<0.05). The community structure of intestinal flora was changed in the CUMS group compared to the control group and was partially improved in the acetate group. The number of unique species reduced in the CUMS group but increased in the acetate group,propionate group,butyrate group and SCFAs group. LEfSe found the enrichment of Bifidobacterium in the propionate group and the enrichment of Collinsella in the SCFAs group. Conclusions Sodium butyrate significantly improves depressive-like behaviors of the CUMS-induced rats. Sodium acetate,sodium propionate,and short-chain fatty acid mixture can influence the composition of intestinal flora. However,their antidepressant effect is not significant. Sodium butyrate may be a better alternative for supplementing short-chain fatty acids in depression.

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

In this study,a functionalized covalent-organic framework(COF)was first synthesized using porphyrin as the fabrication unit and showed an edge-curled,petal-like and well-ordered structure.The synthesized COF was then introduced to prepare porous organic polymer monolithic materials(POPMs).Two com-posite POPM/COF monolithic materials with rod shapes,referred to as sorbent A and sorbent B,were prepared in stainless steel tubes using different monomers.Sorbents A and B exhibited relatively uniform porous structures and enhanced specific surface areas of 153.14 m2/g and 80.01 m2/g,respectively.The prepared composite monoliths were used as in-tube solid-phase extraction(SPE)sorbents combined with HPLC for the on-line extraction and quantitative analytical systems.Indole alkaloids(from Catharanthus roseus G.Don and Uncaria rhynchophylla(Miq.)Miq.Ex Havil.)contained in mouse plasma were extracted and quantitatively analyzed using the online system.The two composite multifunctional monoliths showed excellent clean-up ability for complex biological matrices,as well as superior selec-tivity for target indole alkaloids.Method validation showed that the RSD values of the repeatability(n=6)were≤3.46％,and the accuracy expressed by the spiked recoveries was in the ranges of 99.38％-100.91％and 96.39％-103.50％for vinca alkaloids and Uncaria alkaloids,respectively.Furthermore,sorbents A and B exhibited strong reusability,with RSD values≤5.32％,which were based on the peak area of the corresponding alkaloids with more than 100 injections.These results indicate that the composite POPM/COF rod-shaped monoliths are promising media as SPE sorbents for extracting trace compounds in complex biological samples.

Objective To explore the application and method of World Health Organization Rehabilitation Competency Framework (RCF) in rehabilitation human resource management, and provide theoretical and practical reference for rehabilitation human resource management.Methods Based on the International Standard Classification of Occupations issued by the International Labour Organization, the application scope of RCF was systematically analyzed. The theoretical framework of rehabilitation human resource management based on RCF was constructed in combination with competency-based human resource management framework. On this basis, taking rehabilitation nurses as an example, the corresponding management methods and paths are proposed from four aspects of human resource management, including career management, recruitment and selection, training and development, and performance appraisal and salary management.Results Based on RCF, the theoretical framework of human resource management for rehabilitation nursing positions was constructed, and the main contents and processes of human resource management based on RCF were clarified from four aspects: recruitment and selection, training and development, performance appraisal and salary management, and career management. Occupational competency of rehabilitation professionals in International Standard Classification of Occupations was analyzed by RCF.Conclusion The rehabilitation competency framework constructed by WHO can be used to supplement the responsibilities of rehabilitation-related professionals in the International Standard Classification of Occupations issued by the International Labour Organization. RCF serves as a tool for practice managers and rehabilitation professionals in identifying selection criteria, learning objectives, and professional title assessment criteria. It can also be used in recruitment and selection, training and development, performance appraisal, salary management and career management in the field of rehabilitation human resource management.

Objective To explore the theory and method of performance evaluation for rehabilitation workers based on the World Health Organization Rehabilitation Competency Framework (RCF).Methods Using the theoretical framework and methods of the RCF, we analyzed rehabilitation workers' related competencies from the five dimensions, namely practice, professionalism, learning and development, management and leadership, and research, integrating core values and beliefs, competencies and behaviors, activities and tasks, and knowledge and skills, to construct a comprehensive evaluation method and pathway for rehabilitation workers' performance.Results Based on the RCF, which confirms the job competency requirements for rehabilitation workers, a multi-dimensional, multi-level and standardized performance evaluation index framework was formed. For example, performance evaluation system of physical therapists was consisted of five primary indicators and 26 secondary indicators from the combination of RCF and job standards.Conclusion The rehabilitation worker performance evaluation based on the RCF can evaluate the performance of rehabilitation workers in a scientific, standardized and comprehensive way. It analyzes the performance of rehabilitation workers in a multi-dimensional and systematic manner with the competence of rehabilitation workers as the center, and evaluates the quality and effectiveness of the performance of rehabilitation workers at different levels of proficiency, which makes the performance evaluation of rehabilitation workers more scientific and comprehensive, and enables rehabilitation workers to understand proficiency and clarify the gap, to promote rehabilitation workers to continuously improve their own level and enhance the quality of rehabilitation services.