Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200 μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1α related to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

Objective To investigate mutations in OTU domain-containing protein 3(OTUD3)and their functional mechanisms in the initiation and progression of colorectal cancer(CRC).Methods Gene expression profiling interactive analysis(GEPIA2)and the human protein atlas database(THPA)were used to analyze gene transcription and protein expressions.Samples from 32 patients with CRC were collected to identify OTUD3 mutants.Based on the information about mutation sitesof OTUD3 in an existing database,a plasmid vector containing the OTUD3 gene mutant was constructed.Plasmid vectors containing the phosphatase and tensin homolog deleted on chromosome 10(PTEN)and the OTUD3 gene mutant were co-transfected into HCT116 cells.Western blotting,half-life,immunoprecipitation,ubiquitination,and hybrid algorithm molecular docking(H-DOCK)assays were employed to find out whether and why the OTUD3 mutants affected PTEN protein levels.Functional alterations in CRC cells after OTUD3 mutation were verified by CCK-8 cell proliferation,transwell cell invasion,scratch,and clonal formation assays.Results OTUD3 mutations were highly frequent in CRC.OTUD3 mutants R178W and N321S resulted in the loss of function of the stable PTEN protein,leading to enhanced proliferation,invasion,migration,and survival of CRC.Conclusion In CRC,OTUD3 mutation reduces the ability to stabilize PTEN and promotes the occurrence and development of CRC.

Mitochondrial diabetes mellitus(MDM)is a genetically heterogeneous disorder caused by mitochondrial DNA(mtDNA)or nuclear DNA mutations,characterized by multi-system involvement and diverse clinical phenotypes.We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus.Systematic evaluation revealed concurrent bilateral sensorineural hearing loss,bilateral basal ganglia calcification,and electroencephalographic abnormalities.A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion.Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084.This case re-port is complemented by a literature review focusing on the pathogenesis,genetic characteristics,and therapeu-tic approaches of mitochondrial diabetes,with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations.Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

ObjectiveTo investigate the potential mechanism of Renshen Yangrongtang in alleviating myelosuppression by regulating the expression of reactive oxygen species （ROS）， myeloperoxidase （MPO）， and neutrophil extracellular traps （NETs）. MethodsK562 cells were divided into blank group， etoposide group （40 μmol·L^-1）， and etoposide+Renshen Yangrongtang freeze-dried powder groups with low-， medium-， and high-dose （2， 4， 8 g·L^-1）. Liquid chromatography-mass spectrometry （LC-MS） was used to determine the freeze-dried powder of Renshen Yangrongtang. Enzyme-Linked Immunosorbent Assay （ELISA） was used to detect ROS， MPO， and NETs expression in each group. Western blot analysis was performed to assess intracellular MPO and NE expressions. Twenty 8-week-old male mice were randomly divided into blank group， etoposide group （100 mg·kg^-1）， and etoposide + Renshen Yangrongtang groups with low-， medium-， and high-dose （0.1， 0.5， 2.0 g·kg^-1）. Except for the blank group that received PBS via gavage at room temperature， and the etoposide group that received an intraperitoneal injection for 3 days， the remaining groups received gavage of Renshen Yangrongtang for 14 consecutive days after 3 days of etoposide administration. The peripheral blood related indicators were detected through an automated hematology analyzer； Western blot analysis was performed to assess MPO and neutrophil elastase （NE） expression changes in the marrow cells of mice. Enzyme-linked immunosorbent assay （ELISA） was used to detect ROS， MPO， and NETs changes in the marrow cells of mice. MPO and NE on femur bones were stained through immunohistochemistry. Scanning electron microscopy was used to analyze the structural changes of NETs in the marrow cells of mice after drug administration. ResultsLC-MS results showed that the freeze-dried powder of Renshen Yangrongtang contained complete technical materials such as Chinese angelica， Astragalus mongholicus， and ginseng. In K562 cells， compared with the etoposide group， ELISA results indicated that the concentrations of MPO， ROS， and NETs in the etoposide + Renshen Yangrongtang medium and high-dose groups were decreased （P<0.05， P<0.01）， and Western blot data showed that the etoposide high-dose group significantly reduced the expression of MPO and NE protein in K562 cells （P<0.05， P<0.01）. In vivo， compared with the etoposide group， the number of RBC， WBC， and PLT in the etoposide+Renshen Yangrongtang high-dose group increased significantly （P<0.05）. ELISA results suggested that in the etoposide+Renshen Yangrongtang low-， medium-， and high-dose groups， the concentration of mice ROS， MPO， and NETs significantly decreased （P<0.05， P<0.01）. Western blot results revealed that compared with the etoposide group， the expressions of MPO and NE in the marrow cells of mice in the etoposide + Renshen Yangrongtang low-， medium- and high-dose groups were significantly decreased （P<0.05， P<0.01）. Scanning electron microscopy observations revealed that Renshen Yangrongtang reduced the NETs structure generation in the marrow cells of mice after the influence of etoposide. ConclusionRenshen Yangrongtang can alleviate etoposide-induced myelosuppression by inhibiting ROS/MPO and reducing the formation of intracellular NETs.

Objuective To analyze the evaluation indicators of TCM syndrome efficacy in patients with angina pectoris at a clinical research center,and to preliminarily form a pool of items to evaluate the efficacy of TCM syndromes in angina pectoris,with the aim of providing a reference for evaluating the efficacy of TCM syndromes in angina pectoris.Metods By searching the literature on the clinical efficacy of angina pectoris published from January 1,2008,to December 31,2023,in the China National Knowledge Infrastructure(CNKI),VIP database(VIP),and Wanfang database(WF),the eligible literature was sorted and summarized,and items such as syndrome type,symptoms,and physical signs were recorded one by one in Excel to establish a database.SPSS Modeler 18.0 was used to perform Bayesian network model and association rule analysis on the evaluation items.The items that met both the Bayesian network model and association rule conditions were combined to preliminarily form a pool of items to evaluate the efficacy of TCM in angina pectoris.Results A total of 94 qualified articles were included,containing 21 types of differential diagnoses,with a total frequency of 100.Except for qi deficiency and blood stasis syndrome(28 times,28%),phlegm and blood stasis syndrome(14 times,14%),blood flow stasis obstruction syndrome(14 times,14%),and qi stagnation and blood stasis syndrome(10 times,10%),the frequency of other syndromes was relatively low,so only the first four syndromes were data mined.There were a total of 38 types of symptoms and physical signs for clinical efficacy evaluation,with a total frequency of 599 times.A preliminary pool of items for evaluating the efficacy of TCM in four types of angina pectoris was formed:① Qi deficiency and blood stasis syndrome main items included chest pain(contribution rate 0.96);secondary items included chest tightness(contribution rate 0.93),palpitations(contribution rate 0.77),dark purple(light purple)tongue or ecchymosis(contribution rate 0.77),and shortness of breath(contribution rate 0.83).② Phlegm and blood stasis syndrome main items included chest pain(contribution rate:0.94);secondary items included chest tightness(contribution rate:0.94)and palpitations(contribution rate:0.69).③ Blood flow stasis obstruction syndrome,main items include chest pain(contribution rate 0.94);secondary items include chest tightness(contribution rate 0.81),palpitations(contribution rate 0.69),purple dark(light purple)tongue or ecchymosis(contribution rate 0.94),rough pulse(contribution rate 0.81),fixed pain location,refusal to press,and aggravation at night(contribution rate 0.81).④ Qi stagnation and blood stasis syndrome,main items include chest pain(contribution rate 0.92);secondary items include chest tightness(contribution rate 0.92),palpitations(contribution rate 0.83),purple dark(light purple)tongue or ecchymosis(contribution rate 0.75),rough pulse(contribution rate 0.67),costal pain(contribution rate 0.75).Conclusion The pool of evaluation indicators for the efficacy of TCM syndromes in patients with angina pectoris can provide a reference for conducting scientific and standardized evaluations of the efficacy of TCM syndromes,provide a basis for selecting core indicators,and lay the foundation for further building a core indicator set(COS).

The management of chronic diseases at the county-level faces the problems of low degree of standardized manage-ment,weak management capacity of chronic diseases at the grassroots level,and shedding management of chronic disease patients.The"county-level chronic disease management center"proposed in the"Thousand Counties Project"can promote the county-town-ship-village medical institutions to jointly provide integrated and continuous chronic disease management services for county resi-dents.The study conducted in-depth interviews and analyses on the construction of the centers in 10 county(district)hospitals.Con-clusion:Firstly,the construction of the centers is in its infancy,and the support of government investment,performance incen-tives,and informatization construction is insufficient;secondly,the service content of the current centers is not clear enough,and the collaborative management model of chronic diseases in counties and villages is not stable.Enlightenment:The county-level med-ical community has built an effective path for the centers and the construction of chronic disease management centers needs to be fur-ther strengthened in terms of finance,medical insurance,interest mechanism,informatization construction and awareness of chronic diseases.

Objuective To analyze the evaluation indicators of TCM syndrome efficacy in patients with angina pectoris at a clinical research center,and to preliminarily form a pool of items to evaluate the efficacy of TCM syndromes in angina pectoris,with the aim of providing a reference for evaluating the efficacy of TCM syndromes in angina pectoris.Metods By searching the literature on the clinical efficacy of angina pectoris published from January 1,2008,to December 31,2023,in the China National Knowledge Infrastructure(CNKI),VIP database(VIP),and Wanfang database(WF),the eligible literature was sorted and summarized,and items such as syndrome type,symptoms,and physical signs were recorded one by one in Excel to establish a database.SPSS Modeler 18.0 was used to perform Bayesian network model and association rule analysis on the evaluation items.The items that met both the Bayesian network model and association rule conditions were combined to preliminarily form a pool of items to evaluate the efficacy of TCM in angina pectoris.Results A total of 94 qualified articles were included,containing 21 types of differential diagnoses,with a total frequency of 100.Except for qi deficiency and blood stasis syndrome(28 times,28%),phlegm and blood stasis syndrome(14 times,14%),blood flow stasis obstruction syndrome(14 times,14%),and qi stagnation and blood stasis syndrome(10 times,10%),the frequency of other syndromes was relatively low,so only the first four syndromes were data mined.There were a total of 38 types of symptoms and physical signs for clinical efficacy evaluation,with a total frequency of 599 times.A preliminary pool of items for evaluating the efficacy of TCM in four types of angina pectoris was formed:① Qi deficiency and blood stasis syndrome main items included chest pain(contribution rate 0.96);secondary items included chest tightness(contribution rate 0.93),palpitations(contribution rate 0.77),dark purple(light purple)tongue or ecchymosis(contribution rate 0.77),and shortness of breath(contribution rate 0.83).② Phlegm and blood stasis syndrome main items included chest pain(contribution rate:0.94);secondary items included chest tightness(contribution rate:0.94)and palpitations(contribution rate:0.69).③ Blood flow stasis obstruction syndrome,main items include chest pain(contribution rate 0.94);secondary items include chest tightness(contribution rate 0.81),palpitations(contribution rate 0.69),purple dark(light purple)tongue or ecchymosis(contribution rate 0.94),rough pulse(contribution rate 0.81),fixed pain location,refusal to press,and aggravation at night(contribution rate 0.81).④ Qi stagnation and blood stasis syndrome,main items include chest pain(contribution rate 0.92);secondary items include chest tightness(contribution rate 0.92),palpitations(contribution rate 0.83),purple dark(light purple)tongue or ecchymosis(contribution rate 0.75),rough pulse(contribution rate 0.67),costal pain(contribution rate 0.75).Conclusion The pool of evaluation indicators for the efficacy of TCM syndromes in patients with angina pectoris can provide a reference for conducting scientific and standardized evaluations of the efficacy of TCM syndromes,provide a basis for selecting core indicators,and lay the foundation for further building a core indicator set(COS).

The management of chronic diseases at the county-level faces the problems of low degree of standardized manage-ment,weak management capacity of chronic diseases at the grassroots level,and shedding management of chronic disease patients.The"county-level chronic disease management center"proposed in the"Thousand Counties Project"can promote the county-town-ship-village medical institutions to jointly provide integrated and continuous chronic disease management services for county resi-dents.The study conducted in-depth interviews and analyses on the construction of the centers in 10 county(district)hospitals.Con-clusion:Firstly,the construction of the centers is in its infancy,and the support of government investment,performance incen-tives,and informatization construction is insufficient;secondly,the service content of the current centers is not clear enough,and the collaborative management model of chronic diseases in counties and villages is not stable.Enlightenment:The county-level med-ical community has built an effective path for the centers and the construction of chronic disease management centers needs to be fur-ther strengthened in terms of finance,medical insurance,interest mechanism,informatization construction and awareness of chronic diseases.

Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200 μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1α related to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome.METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3,apoptosis-associated speck-like protein containing a CARD (ASC),and caspase-1 precursor (pro-caspase-1) were predicted by molecular docking.Sixty 1-day-old pregnant rats were randomly divided into normal group,model group,dexamethasone group (0.002 g/kg),and Pangshi antai zhixue decoction low-,medium-,and high-dose groups (11.025,22.05,44.10 g/kg),with 10 rats in each group.Each group was given distilled water/corresponding medicinal solution intragastrically,once a day,for 12 consecutive days.Except for normal group,other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome.24 h after the last medication,serum levels of triiodothyronine (T3),thyroxine (T4),interleukin-2 (IL-2),IL-4,IL-6,IL-10,and interferon-γ (IFN-γ) were all detected;the abortion rate and uterine coefficient were calculated;the pathological morphology of the pregnant uterus was observed;protein expressions of NLRP3,ASC and caspase-1 were detected.RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3,ASC,and pro-caspase-1 were all less than-5 kJ/moL.The animal experiment results showed that compared with normal group,the uterine coefficient and serum levels of IL-4,IL-6 and IL-10 were decreased significantly in model group (P<0.05);the abortion rate and serum levels of T3,T4,IL-2 and IFN-γ as well as protein expressions of NLRP3,ASC and caspase-1 were increased significantly (P<0.05);there were abortion lesions in the pregnant endometrium.Compared with the model group,most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups (P<0.05),and the endometrial miscarriage lesions in pregnancy were improved to varying degrees.CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome,down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2,and up-regulating anti-inflammatory cytokines such as IL-4,IL-6 and IL-10,thereby improving spontaneous abortion with heat syndrome.