From the theoretical perspective of "body fluids and blood stasis mixing"， environmental microplastics （MPs） are conceptualized as a "novel turbid-toxin". This study aims to elucidate the complete pathogenic pathway through which MPs act as a key driving force （the "crucible" of pathogenesis） in the initiation and progression of atherosclerosis （AS）. By tracing the classical theories in the Chapter The Occurrence of All Diseases of Miraculous Pivot （Ling Shu）， this paper clarifies the core connotations of "body fluids"-it not only refers to endogenous pathological fluids and lipid turbidity but also provides a theoretical basis for incorporating "exogenous turbid fluids"， thereby laying a logical foundation for conceptualizing MPs as a "novel turbid-toxin". Meanwhile， the implications of "blood" （encompassing both blood quality abnormalities and blood stasis） and the dynamic process of "mixing" are elucidated. Drawing upon modern toxicological evidence， this paper demonstrates the high homology between MPs and "exogenous turbid-fluids" from three aspects： Morphology， toxicity， and invasion routes. The micro/nano-scale particle morphology of MPs enables mobility within the bloodstream. The multiple exposure pathways of MPs correspond to the traditional Chinese medicine understanding of pathogens invading through the mouth， nose， and skin. The characteristics of accumulating in vivo while inducing oxidative stress and inflammatory responses of MPs fully embody the pathogenic features-adhesion， binding， and vessel damage-of "turbid-toxin". On this basis， the dynamic pathogenesis of MP-induced AS is systematically interpreted. Initially， MPs with the "turbid-toxin" nature impair nutrient-defense harmony and cause endothelial dysfunction. Subsequently， as the core of "mixing"， they interact with blood lipids and immune cells， generating heat and phlegm to form a major pathological hub of chronic inflammation. Ultimately， this process drives the coalescence of phlegm， stasis， and turbid-toxin into tangible plaques， evolving from stable lesions to vulnerable masses and accumulations. By integrating classical pathogenic model with contemporary environmental medicine， this study establishes an analytical framework that bridges macro-theory and micro-mechanisms for understanding the cardiovascular risks of MPs through an integrative Chinese-Western medicine lens.

Synovium is the target organ of rheumatoid arthritis.The excessive proliferation of synovial cells and insufficient apoptosis lead to synovial hyperplasia,which in turn causes damage to the surrounding tissues of the joint and bone destruction."Yang transforming qi and yin forming elements"is derived from Su Wen and is a highly summarized description of the functions of yin and yang,which runs through the entire course of the disease.This article elucidated the theoretical connotation of"yang transforming qi and yin forming elements"and its connection with synovial hyperplasia,proposing that the insufficiency of"yang transforming qi"is the root of synovial hyperplasia,while the excess of"yin forming elements"is the manifestation of synovial hyperplasia.Based on this,it put forward that"assisting yang qi as the priority,and according to the bias of pathogenic factors of yin,supplementing the method of reducing yin forming elements"is an important principle for treating this disease,which could provide new ideas for the treatment of the disease.

OBJECTIVE To investigate the time-effect relationship of ginger-partitioned moxibustion in treating fecal inconti-nence in patients with mild to moderate active Crohn's disease so as to optimize moxibustion duration and provide a basis for clinical application.METHODS A total of 128 patients with Crohn's disease complicated by fecal incontinence who met the inclusion crite-ria were selected as the study subjects.They were divided into a control group and three experimental groups(experimental group Ⅰ,Ⅱ,and Ⅲ)of 32 patients each using a stratified random method(with 1 dropout in experimental group Ⅰ).Patients in the control group received routine anti-tumor necrosis factor-α monoclonal antibody(adalimumab)treatment,while patients in the experimental groups received ginger moxibustion therapy in addition to the treatment provided to the control group.Among them,experimental groupⅠ received treatment for 20 minutes,experimental group Ⅱ for 40 minutes,and experimental group Ⅲ for 60 minutes.The course of treatment for all four groups was 3 months.Changes in TCM syndrome scores were compared before and after treatment in the four groups to assess clinical efficacy.The cleveland clinic incontinence score(CCIS)was used to assess the severity of fecal incontinence,the Crohn's disease activity index(CDAI)was used to assess the degree of disease activity,and the inflammatory bowel disease ques-tionnaire(IBDQ)was used to evaluate the quality of life.Anal pressure index and peripheral blood CRP and ESR levels were mea-sured,and the relationship between moxibustion time and effect was analyzed.RESULTS After 3 months of treatment,the total TCM syndrome scores of all four groups improved to varying degrees(P<0.05,P<0.01).The total scores of groups Ⅰ,Ⅱ,and Ⅲ were supe-rior to those of the control group(P<0.05,P<0.01),while group Ⅱ had the lowest total TCM syndrome score.Group Ⅱ had the high-est overall clinical effective rate,significantly better than both the control and group Ⅰ(P<0.05,P<0.01).CCIS scores,IBDQ scores and total scores,and peripheral blood ESR levels were significantly reduced in all four groups(P<0.01),with group Ⅱ having the low-est score,lower than both the control and group Ⅰ(P<0.05,P<0.01).CRP levels were significantly reduced in groups Ⅱ and Ⅲ(P<0.05,P<0.01),both lower than the control group(P<0.05,P<0.01),with group Ⅱ lower than group Ⅰ(P<0.01).Intestinal symptom scores in the IBDQ of groups Ⅱ and Ⅲ were significantly higher than those in the control group and group Ⅰ(P<0.05,P<0.01).The maximum resting pressure of the anal canal,rectal defecation threshold,and maximum tolerance capacity all increased significantly in the four groups(P<0.05,P<0.01),but there were no significant differences among the groups(P>0.05).During the treatment,two cases of mild skin redness occurred in group Ⅲ,which resolved after treatment,with no serious adverse reactions.CONCLUSION Ginger moxibustion in the treatment of Crohn's disease complicated by fecal incontinence exhibits a time-effect relationship,with 40 minutes as the optimal duration.It can effectively improve symptoms,control inflammation,enhance quality of life,and has good safety.

Objective To explore the mechanism of Quhan Zhufeng Mixture on proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocyte(RA-FLS)based on NDRG2/JAK2/STAT3 signaling pathway.Methods RA-FLS cells were cultured in vitro,and were divided into ① blank serum group,methotrexate group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups;② blank serum group,AG490 group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups.Different concentrations of drug-containing serum were used to intervene cells.Cell proliferation was detected by CCK-8 method,apoptosis was detected by flow cytometry,and mRNA expressions of Bax,Bcl-2,Caspace-3,Caspace-9,N-myc downstream regulatory gene 2(NDRG2),Janus kinase 2(JAK2)and signal transduction and transcription activator 3(STAT3)were detected by RT-qPCR,Western blot was used to detect the protein expressions of Bax,Bcl-2,Caspace-3,Caspace-9,NDRG2,JAK2,STAT3,p-JAK2 and p-STAT3 in cells.Results Compared with the blank serum group,cell survival rate in methotrexate group,Quhan Zhufeng Mixture all dosage groups significantly decreased(P<0.01),the apoptosis rate significantly increased(P<0.01),the mRNA and protein expressions of Bax and Caspase-9 significantly increased(P<0.05,P<0.01),while the mRNA and protein expression of Bcl-2 significantly decreased(P<0.01),and Caspase-3 mRNA and protein expression in methotrexate group and Quhan Zhufeng Mixture medium-and high-dosage groups significantly increased(P<0.01).Compared with the blank serum group,the mRNA and protein expression of NDRG2 significantly increased in Quhan Zhufeng Mixture all dosage groups(P<0.05,P<0.01),the mRNA and protein expressions of JAK2 and STAT3 were significantly reduced in AG490 group and Quhan Zhufeng Mixture medium-and high-dosage groups(P<0.05,P<0.01),and the expressions of p-JAK2 and p-STAT3 proteins were significantly reduced(P<0.01).Conclusion Quhan Zhufeng Mixture can regulate the proliferation and apoptosis of RA-FLS by regulating the activity of NDRG2/JAK2/STAT3 signaling pathway,playing a role in treating rheumatoid arthritis.

Objective To investigate the expression levels and clinical significance of serum and placental microRNA(miR)-1227-3p and miR-212-3p in puerperas with fetal growth restriction(FGR).Methods A total of 120 puerperas diagnosed with FGR and completed delivery in our hospital were included as the study group.Patients were assigned into the mild group(n=72)and the severe group(n=48)according to the severity of their condition.Another 120 healthy puerperas who underwent prenatal check ups and delivered during the same period in our hospital were included as the control group.QRT-PCR was used to detect serum and placental miR-1227-3p and miR-212-3p.The pregnancy outcomes of both groups were recorded,including neonatal weight,1min Apgar score,placental weight and placental volume.Results Serum and placental miR-1227-3p expression levels,neonatal weight,1 min Apgar score,placental weight and placental volume were significantly lower in the study group than those of the control group(P＜0.05),while serum and placental miR-212-3p expression levels were significantly higher than those of the control group(P＜0.05).The expression levels of miR-1227-3p in serum and placenta of the severe group were obviously lower than those of the mild group(P＜0.05),while the expression level of miR-212-3p was obviously higher than those of the mild group(P＜0.05).The expression levels of miR-1227-3p in serum and placenta were positively correlated with neonatal weight,1 min Apgar score,placental weight and placental volume,and the expression levels of miR-212-3p in serum and placenta were negatively correlated with the above indicators(P＜0.05).Multivariate Logistic regression analysis revealed that elevated serum and placental miR-212-3p levels were risk factors for FGR(P＜0.05),and increased serum and placental miR-1227-3p,neonatal weight,1 min Apgar,placental weight and placental volume were protective factors(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the diagnostic value of combined detection of serum and placenta miR-1227-3p and miR-212-3p levels for FGR was better than that of single diagnosis.Conclusion The combined detection of miR-1227-3p and miR-212-3p in serum and placenta of FGR puerperas has certain value in the clinical diagnosis of FGR.

Objective To explore the mechanism of Quhan Zhufeng Mixture on proliferation and apoptosis of rheumatoid arthritis fibroblast-like synoviocyte(RA-FLS)based on NDRG2/JAK2/STAT3 signaling pathway.Methods RA-FLS cells were cultured in vitro,and were divided into ① blank serum group,methotrexate group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups;② blank serum group,AG490 group,Quhan Zhufeng Mixture low-,medium-and high-dosage groups.Different concentrations of drug-containing serum were used to intervene cells.Cell proliferation was detected by CCK-8 method,apoptosis was detected by flow cytometry,and mRNA expressions of Bax,Bcl-2,Caspace-3,Caspace-9,N-myc downstream regulatory gene 2(NDRG2),Janus kinase 2(JAK2)and signal transduction and transcription activator 3(STAT3)were detected by RT-qPCR,Western blot was used to detect the protein expressions of Bax,Bcl-2,Caspace-3,Caspace-9,NDRG2,JAK2,STAT3,p-JAK2 and p-STAT3 in cells.Results Compared with the blank serum group,cell survival rate in methotrexate group,Quhan Zhufeng Mixture all dosage groups significantly decreased(P<0.01),the apoptosis rate significantly increased(P<0.01),the mRNA and protein expressions of Bax and Caspase-9 significantly increased(P<0.05,P<0.01),while the mRNA and protein expression of Bcl-2 significantly decreased(P<0.01),and Caspase-3 mRNA and protein expression in methotrexate group and Quhan Zhufeng Mixture medium-and high-dosage groups significantly increased(P<0.01).Compared with the blank serum group,the mRNA and protein expression of NDRG2 significantly increased in Quhan Zhufeng Mixture all dosage groups(P<0.05,P<0.01),the mRNA and protein expressions of JAK2 and STAT3 were significantly reduced in AG490 group and Quhan Zhufeng Mixture medium-and high-dosage groups(P<0.05,P<0.01),and the expressions of p-JAK2 and p-STAT3 proteins were significantly reduced(P<0.01).Conclusion Quhan Zhufeng Mixture can regulate the proliferation and apoptosis of RA-FLS by regulating the activity of NDRG2/JAK2/STAT3 signaling pathway,playing a role in treating rheumatoid arthritis.

Objective To analyse the mediating effect of the pain beliefs on pain and fear of disease progression in patients with trigeminal neuralgia.Methods A convenience sampling method was employed to select hospitalised 220 patients with trigeminal neuralgia as research objects from 3 Grade IIIA hospitals.The selected study subjects were surveyed with a general information questionnaire,the numeric pain rating scale,pain beliefs and perceptions scale,and fear of disease progression short form.Structural equation model was used to verify the pathways that affected the pain and pain beliefs on fear of disease progression in patients with trigeminal neuralgia.Results A total of 214 patients with trigeminal neuralgia completed the survey.The mean score of fear of disease progression was 33.38±8.47,the mean score of pain was 8.25±1.44,and the mean score of pain beliefs was-2(-9,8).Spearman correlation analysis showed that fear of disease progression was positively correlated with the pain beliefs(r=0.746,P<0.01)and pain(r=0.838,P<0.01),and the pain beliefs were positively correlated with pain intensity(r=0.704,P<0.01).Pain beliefs partially mediated between the pain and fear of disease progression in patients with trigeminal neuralgia,with a mediating effect of 0.442,a direct effect of 0.482,and a total effect of 0.924.The mediating effect accounted for 47.84%of the total effect.Conclusion Patients with trigeminal neuralgia generally have a critical state of psychologicol disfunction of fear of disease progression,with a moderate to severe pain,and moderate pain beliefs.Pain intensity in patients with trigeminal neuralgia not only directly affects fear of disease progression but also indirectly affects it through pain beliefs.

Objective To analyse the mediating effect of the pain beliefs on pain and fear of disease progression in patients with trigeminal neuralgia.Methods A convenience sampling method was employed to select hospitalised 220 patients with trigeminal neuralgia as research objects from 3 Grade IIIA hospitals.The selected study subjects were surveyed with a general information questionnaire,the numeric pain rating scale,pain beliefs and perceptions scale,and fear of disease progression short form.Structural equation model was used to verify the pathways that affected the pain and pain beliefs on fear of disease progression in patients with trigeminal neuralgia.Results A total of 214 patients with trigeminal neuralgia completed the survey.The mean score of fear of disease progression was 33.38±8.47,the mean score of pain was 8.25±1.44,and the mean score of pain beliefs was-2(-9,8).Spearman correlation analysis showed that fear of disease progression was positively correlated with the pain beliefs(r=0.746,P<0.01)and pain(r=0.838,P<0.01),and the pain beliefs were positively correlated with pain intensity(r=0.704,P<0.01).Pain beliefs partially mediated between the pain and fear of disease progression in patients with trigeminal neuralgia,with a mediating effect of 0.442,a direct effect of 0.482,and a total effect of 0.924.The mediating effect accounted for 47.84%of the total effect.Conclusion Patients with trigeminal neuralgia generally have a critical state of psychologicol disfunction of fear of disease progression,with a moderate to severe pain,and moderate pain beliefs.Pain intensity in patients with trigeminal neuralgia not only directly affects fear of disease progression but also indirectly affects it through pain beliefs.

Synovium is the target organ of rheumatoid arthritis.The excessive proliferation of synovial cells and insufficient apoptosis lead to synovial hyperplasia,which in turn causes damage to the surrounding tissues of the joint and bone destruction."Yang transforming qi and yin forming elements"is derived from Su Wen and is a highly summarized description of the functions of yin and yang,which runs through the entire course of the disease.This article elucidated the theoretical connotation of"yang transforming qi and yin forming elements"and its connection with synovial hyperplasia,proposing that the insufficiency of"yang transforming qi"is the root of synovial hyperplasia,while the excess of"yin forming elements"is the manifestation of synovial hyperplasia.Based on this,it put forward that"assisting yang qi as the priority,and according to the bias of pathogenic factors of yin,supplementing the method of reducing yin forming elements"is an important principle for treating this disease,which could provide new ideas for the treatment of the disease.

The study aims to explore the herb-drug interaction between Xuefu Zhuyu Decoction(XFZY) and atorvastatin(AT). Reverse transcription polymerase chain reaction(RT-PCR) was used to analyze the transcription levels of proteins related to drug metabolism and transport in LS174T cells, detect the intracellular drug uptake under various substrate concentrations and incubation time, and optimize the model reaction conditions of transporter multidrug resistance protein 1(MDR1)-specific probe Rhodamine 123 and AT to establish a cell model for investigating the human intestinal drug interaction. The cell counting kit-8(CCK-8) method was adopted to evaluate the cytotoxicity of XFZY on LS174T cells. After a single and continuous 48 h culture with XFZY, AT or Rhodamine 123 was added for co-incubation. The effect and mechanism of XFZY on human intestinal absorption of AT were analyzed by measuring the intracellular drug concentrations and transcription levels of related transporters and metabolic enzymes. The results of in vitro experiments show that a single co-culture with a high concentration of XFZY significantly increases the intracellular concentrations of Rhodamine 123 and AT. A high concentration of XFZY co-culture for 48 h increases the AT uptake level, significantly induces the CYP3A4 and UGT1A1 gene expression levels, and inhibits the OATP2B1 gene expression level. To compare with the evaluation results of the in vitro human cell model, the pharmacokinetic experiment of XFZY combined with AT was carried out in rats. Sprague-Dawley(SD) rats were randomly divided into a blank control group and an XFZY group. After 14 days of continuous intragastric administration, AT was given in combination. The liquid chromatography-mass spectrometry(LC-MS)/MS method was used to detect the concentrations of AT and metabolites 2-hydroxyatorvastatin acid(2-HAT), 4-hydroxyatorvastatin acid(4-HAT), atorvastatin lactone(ATL), 2-hydroxyatorvastatin lactone(2-HATL), and 4-hydroxyatorvastatin lactone(4-HATL) in plasma samples, and the pharmacokinetic parameters were calculated. Pharmacokinetic analysis in rats shows that continuous administration of XFZY does not significantly change the pharmacokinetic characteristics of AT in rats, but the AUC_(0-6 h) values of AT and metabolites 2-HAT, 4-HAT, and 2-HATL increase by 21.37%, 14.94%, 12.42%, and 6.68%, respectively. The metabolic rate of the main metabolites shows a downward trend. The study indicates that administration combined with XFZY can significantly increase the uptake level of AT in human intestinal cells and increase the exposure level of AT and main metabolites in rats to varying degrees. The mechanism may be mainly due to the inhibition of intestinal MDR1 transport activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atorvastatin/administration & dosage* ; Humans ; Rats ; Rats, Sprague-Dawley ; Male ; Intestines/cytology* ; Intestinal Mucosa/metabolism* ; Herb-Drug Interactions ; Cytochrome P-450 CYP3A/metabolism* ; Intestinal Absorption/drug effects*