1.Construction of Risk Prediction Model for Frequent Acute Exacerbations of Chronic Obstructive Pulmonary Disease Under Disease-syndrome Combination
Jing ZHOU ; Gang TENG ; Nianzhi ZHANG ; Yuanyuan WANG ; Qianqian ZHANG ; He HUANG ; Ling LIU ; Mei DONG ; Juan JI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):143-151
ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease (COPD) under disease-syndrome combination, thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations (≥2 times/year) and infrequent acute exacerbations (<2 times/year) according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression, and a nomogram model was constructed. The model performance was assessed based on the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). ResultsThe differences in baseline characteristics between the frequent acute exacerbations group (1 196 cases) and infrequent acute exacerbations group (833 cases) were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors: body mass index (BMI), hospitalization days, number of smoking years, place of residence, use of noninvasive ventilators, oxygen-demanding therapy, liver cirrhosis, use of systemic glucocorticosteroids, and traditional Chinese medicine syndrome (phlegm and stasis obstructing the lung). The nomogram model showed good discrimination and calibration in both the training set (AUC=0.748) and validation set (AUC=0.774). ConclusionThe risk prediction model for frequent acute exacerbations of COPD, integrating traditional Chinese medicine syndrome, constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.
2.Evaluation of CARIFS Score and Negative Antigen Conversion Rate of Qingxuan Daozhi Formula in Treatment of Influenza in Children (Heat Accumulation in Lung and Stomach Syndrome):A Multi-center Randomized Controlled Clinical Study
Jing WANG ; Liqun WU ; Tiegang LIU ; Yongning CAO ; Jing QIU ; Jing LI ; Huaqing TAN ; Ying ZHANG ; Xulei GOU ; Jia WANG ; Jing LI ; Haipeng CHEN ; Xueying QIN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Lin JIANG ; Yingqi XU ; Jianping LIU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):188-196
ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome). MethodsThrough a multi-center randomized controlled methodology design,confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals,such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days,and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale (CARIFS) and the incidence of complications,severe cases, and critical cases. Follow-up observation was conducted on the day of enrollment,48 hours after medication,72 hours after medication, and (6+1) d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group (90 cases) or the control group (90 cases). All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was (5.29±1.25) d,and that in the control group was (5.40±1.68) d,without a statistically significant difference. After five days of intervention,52 cases in the experimental group and 51 cases in the control group converted to negative,without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention,there were statistically significant differences between the experimental group and the control group in three dimensions, including headache,muscle soreness, and the need for extra care (P<0.05). On the (6+1) days after the intervention,the differences in both the experimental group and the control group were statistically significant in 10 dimensions, including sore throat,bad sleep,uncomfortable feeling,poor spirit and fatigue,crying more than usual,the need for extra care,symptom,function,influence on parents,and total score (P<0.05). The comparison results within the group in the dimensional scores of symptom, function, and influence on parents,as well as the CARIFS total score showed that with the delay of follow-up time,scores of both groups decreased significantly,with a statistically significant difference (P<0.01). Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention,the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up,the mean score of the experimental group was lower than that of the control group,with no statistically significant difference. In terms of the incidence of complications,severe cases, and critical cases, there were no complications,severe cases, and critical cases in the two groups,without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome) are not inferior to Oseltamivir Phosphate granules, and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children (heat accumulation in the lung and stomach syndrome).
3.PD-L1 and TGF-β cooperatively regulate tumor immune escape: mechanisms and advances in dual-targeting therapy
Qianqian HE ; Yanli YANG ; Han ZHANG ; Zheyu CHEN ; Puzhong JI
Chinese Journal of Clinical Medicine 2026;33(3):533-543
While programmed cell death ligand 1 (PD-L1) inhibitors have yielded breakthroughs in tumor therapy, their efficacy is constrained by the heterogeneity of the tumor microenvironment and multiple immunosuppressive pathways. In recent years, research has revealed that transforming growth factor-β (TGF-β) synergistically drives tumor cell immune escape with PD-L1 via pathways such as metabolic reprogramming, epithelial-mesenchymal transition, and SOX family factors. Currently, various PD-L1/TGF-β bispecific antibodies (bsAbs) have exhibited promising therapeutic potential in early-phase clinical trials, yet they still confront challenges related to toxicity and drug resistance. This article systematically reviews the mechanisms by which PD-L1 and TGF-β synergistically regulate tumor immune escape, summarizes the clinical research progress of bsAbs, and discusses strategies for novel drug design and biomarker development, with the aim of offering new insights for the development of combined tumor immunotherapy strategies.
4.Randomized Controlled Study on Wenshen Yangxue Decoction Plus Endometrial Microstimulation for Polycystic Ovary Syndrome (PCOS) Infertility with Syndrome of Kidney-Yang Deficiency and Blood Stasis
Qianqian HUANG ; Qian HAN ; Mingwei XIN ; Junqin HE ; Jingshang WANG ; Xiaodan YIN ; Mengyuan LI ; Yanxiao YI ; Yanli TANG ; Yiting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):181-190
ObjectiveTo evaluate the clinical efficacy and safety of Wenshen Yangxue decoction combined with endometrial microstimulation in the treatment of infertile patients with polycystic ovary syndrome (PCOS, syndrome of kidney-Yang deficiency and blood stasis). MethodsA randomized, positive-drug parallel-controlled, open-label clinical study was conducted. A total of 240 infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis who met the inclusion and exclusion criteria were randomly assigned into 4 groups, with 60 patients in each group. The control group was treated with clomiphene citrate (50-100 mg·d-¹, orally for 5-10 consecutive days) for ovulation induction. On the basis of the therapy in the control group, the Wenshen group was additionally treated with Wenshen Yangxue decoction (250 mL, warm oral administration, twice daily, in the morning and evening), and the stimulation group received endometrial microstimulation during the early follicular phase. The combined group was treated with clomiphene citrate plus Wenshen Yangxue decoction (at the same dosages as aforementioned) and endometrial microstimulation. The course of treatment for all the groups was 3 menstrual cycles. The pregnancy rate, ovulation status, sex hormone levels, glucose metabolism indicators, coagulation function, endometrial thickness, traditional Chinese medicine (TCM) symptom scores, and adverse reactions were observed in each group. ResultsA total of 239 patients were included in the final analysis, with 59 patients in the Wenshen group and 60 patients in each of the other three groups. The pregnancy rates were 43.3%(26/60) in the combined group and 32.2%(19/60) in the Wenshen group, both significantly higher than that (10%) in the control group (χ2=17.56,P<0.01). Compared with the control group, the combined and Wenshen groups had increased mature follicle rates (P<0.01), while the Wenshen group showed a decreased luteinization rate (P<0.05). All the groups exhibited significant reductions in TCM symptom scores after treatment, and the Wenshen and combined groups had lower scores than the control group (P<0.01). No statistically significant difference was found in the incidence of adverse events among the four groups, and all the adverse events were mild. ConclusionWenshen Yangxue decoction combined with endometrial microstimulation can alleviate the TCM symptoms of infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis, promote follicular maturation and ovulation, increase the cumulative pregnancy rate, and has good safety. It can provide new clinical evidence for the integrated traditional Chinese and Western medicine treatment of PCOS infertility.
5.Randomized Controlled Study on Wenshen Yangxue Decoction Plus Endometrial Microstimulation for Polycystic Ovary Syndrome (PCOS) Infertility with Syndrome of Kidney-Yang Deficiency and Blood Stasis
Qianqian HUANG ; Qian HAN ; Mingwei XIN ; Junqin HE ; Jingshang WANG ; Xiaodan YIN ; Mengyuan LI ; Yanxiao YI ; Yanli TANG ; Yiting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):181-190
ObjectiveTo evaluate the clinical efficacy and safety of Wenshen Yangxue decoction combined with endometrial microstimulation in the treatment of infertile patients with polycystic ovary syndrome (PCOS, syndrome of kidney-Yang deficiency and blood stasis). MethodsA randomized, positive-drug parallel-controlled, open-label clinical study was conducted. A total of 240 infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis who met the inclusion and exclusion criteria were randomly assigned into 4 groups, with 60 patients in each group. The control group was treated with clomiphene citrate (50-100 mg·d-¹, orally for 5-10 consecutive days) for ovulation induction. On the basis of the therapy in the control group, the Wenshen group was additionally treated with Wenshen Yangxue decoction (250 mL, warm oral administration, twice daily, in the morning and evening), and the stimulation group received endometrial microstimulation during the early follicular phase. The combined group was treated with clomiphene citrate plus Wenshen Yangxue decoction (at the same dosages as aforementioned) and endometrial microstimulation. The course of treatment for all the groups was 3 menstrual cycles. The pregnancy rate, ovulation status, sex hormone levels, glucose metabolism indicators, coagulation function, endometrial thickness, traditional Chinese medicine (TCM) symptom scores, and adverse reactions were observed in each group. ResultsA total of 239 patients were included in the final analysis, with 59 patients in the Wenshen group and 60 patients in each of the other three groups. The pregnancy rates were 43.3%(26/60) in the combined group and 32.2%(19/60) in the Wenshen group, both significantly higher than that (10%) in the control group (χ2=17.56,P<0.01). Compared with the control group, the combined and Wenshen groups had increased mature follicle rates (P<0.01), while the Wenshen group showed a decreased luteinization rate (P<0.05). All the groups exhibited significant reductions in TCM symptom scores after treatment, and the Wenshen and combined groups had lower scores than the control group (P<0.01). No statistically significant difference was found in the incidence of adverse events among the four groups, and all the adverse events were mild. ConclusionWenshen Yangxue decoction combined with endometrial microstimulation can alleviate the TCM symptoms of infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis, promote follicular maturation and ovulation, increase the cumulative pregnancy rate, and has good safety. It can provide new clinical evidence for the integrated traditional Chinese and Western medicine treatment of PCOS infertility.
6.Effect and mechanisms of highly active umbilical cord mesenchymal stem cells on aging spleen in elderly tree shrews
Li YE ; Chuan TIAN ; Xiaojuan ZHAO ; Mengdie CHEN ; Qianqian YE ; Qiang LI ; Zhuyin LIAO ; Ye LI ; Xiangqing ZHU ; Guangping RUAN ; Zhixu HE ; Liping SHU ; Xinghua PAN
Chinese Journal of Tissue Engineering Research 2025;29(19):4000-4010
BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.
7.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
8.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
9.Effect of cholesterol on distribution,cell uptake,and protein corona of lipid microspheres at sites of cardiovascular inflammatory injury
Lingyan LI ; Xingjie WU ; Qianqian GUO ; Yu'e WANG ; Zhiyong HE ; Guangqiong ZHANG ; Shaobo LIU ; Liping SHU ; Babu GAJENDRAN ; Ying CHEN ; Xiangchun SHEN ; Ling TAO
Journal of Pharmaceutical Analysis 2025;15(7):1542-1564
Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.
10.Experimental animal models for rheumatoid arthritis-associated interstitial lung disease
Qianqian YAN ; Lianhua HE ; Lili WANG ; Liting XU ; Aimin ZHOU ; Chunfang LIU ; Na LIN
Science of Traditional Chinese Medicine 2025;3(2):124-136
Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease primarily affecting the joints of the limbs. As the disease progresses, it can involve multiple organ systems. Interstitial lung disease (ILD) is the most common pulmonary manifestation of RA. Reported animal models of RA-ILD include adjuvant-induced arthritis (AA), collagen-induced arthritis (CIA), and transgenic mouse arthritis. However, the establishment criteria and evaluation methods for these models lack uniform standards, and they fail to fully replicate the clinicopathological characteristics of RA-ILD. This limitation significantly hinders research into the pathogenesis and development of therapeutic drugs for RA-ILD. Objective: The aim of the study was to review literature in China and abroad on RA-ILD animal models, analyze current research progress, identify existing issues, and propose research recommendations. Methods: Literature searches were conducted using the English keywords “rheumatoid arthritis, interstitial lung disease, model” and the Chinese keywords “(rheumatoid arthritis), (interstitial lung disease), (model)” or “(rheumatoid arthritis), (lung interstitial lesions), (model).” The search was performed in PubMed, Web of Science, CNKI, Wanfang Data, and VIP (China Science and Technology Journal Database) for articles published before November 2024. A total of 41 articles were included. Results and conclusions: The CIA model and the CIA model combined with bleomycin are commonly used due to their similarities to the histopathology and disease manifestations of human RA-ILD. Additionally, these models have appropriate cost and modeling duration, along with a high success rate, making them preferable choices. Transgenic animal models exhibit pathological features similar to the nonspecific interstitial pneumonia subtype of human RA-ILD and are useful for studying the genetic effects on RA-ILD. However, they have drawbacks such as high economic costs, long modeling durations, and a low success rate in some cases. The AA model is easy to establish, requires a short modeling period, and has low experimental costs. However, it lacks the chronic pathological development characteristic of human RA and exhibits a degree of self-limitation in lesion progression. Among other models, the comprehensive HLA-DQ8 transgenic mouse model can be used to study the combined effects of genetic and environmental factors on RA-ILD. The collagen autoantibody-induced arthritis model combined with bleomycin has a short modeling period, but it does not align well with the disease course of RA-ILD. These established animal models provide valuable insights into the pathogenesis of RA-ILD, the identification of novel biomarkers, and the development of new therapeutic approaches. Future research should focus on identifying an animal model that better replicates the physiological and pathological changes of clinical RA-ILD while being more convenient, cost-effective, and comprehensive in reflecting disease progression.

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