1.Sanren Runchang Formula Regulates Brain-gut Axis to Treat IBS-C: A Randomized Controlled Trial
Teng LI ; Xinrong FAN ; He YAN ; Zhuozhi GONG ; Mengxi YAO ; Na YANG ; Yuhan WANG ; Huikai HU ; Wei WEI ; Tao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):154-161
ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome (IBS-C) by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and substance P (SP). MethodsA randomized controlled design was adopted, and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups (36 cases).The observation group received Sanren Runchang formula granules twice daily, and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale (IBS-SSS), IBS Quality of Life Scale (IBS-QOL), and Bristol Stool Form Scale (BSFS) were used to assess clinical symptoms, and bowel movement frequency was recorded. The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT, VIP, and SP. ResultsThe total response rate in the observation group was 91.67% (33/36), which was higher than that (77.78%, 28/36) in the control group (χ2=4.50, P<0.05). After treatment, both groups showed increased defecation frequency and BSFS scores, decreased IBS-SSS total score, abdominal pain and bloating scores, IBS-QOL health anxiety, anxiety, food avoidance, and behavioral disorders scores, SAS and SDS scores, serum 5-HT and VIP levels, and increased SP levels (P<0.05, P<0.01). Moreover, the observation group showed more significant changes in the indicators above than the control group (P<0.05, P<0.01). The SP level showed no significant difference between the two groups. During the 4-week follow-up, the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group, and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients, with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP, suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However, its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.
2.Cost-utility analysis of anlotinib combined with penpulimab in first-line treatment of unresectable hepatocellular carcinoma
Wenying YAN ; Na YANG ; Ranran ZHANG ; Xinyue TAO ; Shengnan GAO ; Guoqiang LIU
China Pharmacy 2026;37(3):344-349
OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma (uHCC) from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study, a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year (QALY) was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio (ICER) of different treatment regimens. Using 3 times China’s per capita gross domestic product (GDP) in 2024 (287 247 yuan/QALY) as the willingness-to-pay (WTP) threshold, cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results; the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds (specifically, 1, 2, and 3 times China’s per capita GDP in 2024). RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY, which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab, the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%, 35%, and 13%, the ICER values were below the WTP threshold, which was 1, 2 and 3 times the per capita GDP of China in 2024, respectively. CONCLUSIONS From the perspective of China’s healthcare system, anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However, this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.
3.Comparison of clinical efficacy of evolocumab and probucol after PCI in patients with ultra-high-risk atherosclerotic cardiovascular disease
Yi YUAN ; Na LI ; Haiying SUN ; Jing SUN ; Yongqiang MA ; Yan WU ; Guohong YANG ; Junxiang LIU
China Pharmacy 2026;37(5):645-649
OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI). METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1, 2023 and December 31, 2024. According to the lipid-lowering regimen, the patients were categorized into evolocumab group ( n =86) and probucol group ( n =70). Changes in lipid parameters [total cholesterol (TC), low-density lipoprot ein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, lipoprotein (a), and lipid goal achievement rate ] , inflammatory markers [interleukin-6 (IL-6) and C-reactive protein (CRP) ] , and cardiac function indices (left ventricular ejection fraction, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and N-terminal pro-B-type natriuretic peptide) were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment, including acute myocardial infarction, in-stent restenosis, acute heart failure, cerebral hemorrhage, and stroke, was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline ( P >0.05). After 6 months of treatment, both groups demonstrated significant improvements in lipid profiles (except HDL-C) and inflammatory markers compared to those at baseline ( P <0.05). The evolocumab group exhibited greater reductions in TC, LDL-C, IL-6, and CRP, along with a higher lipid target achievement rate, compared with the probucol group ( P <0.05). There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups, nor in the incidence of adverse events during the treatment ( P >0.05). CONCLUSIONS For ultra-high-risk ASCVD patients after PCI, both of the above treatment options are associated with improvements in blood lipid and inflammatory response, with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC, LDL-C and inflammatory markers reduction and lipid target achievement, compared to probucol.
4.Predictive modle for violence risk in hospitalized schizophrenia patients based on support vector machine
Huan LIU ; Peifang SHI ; Kun ZHANG ; Li KANG ; Yan ZHANG ; Long NA ; Binhong WANG ; Meiqing HE
Sichuan Mental Health 2026;39(1):27-35
BackgroundThe violent aggressive behaviors of patients with schizophrenia usually have the characteristics of suddenness, unpredictability, high severity, and great difficulty in prevention. Early identification and accurate assessment of their risk of violent aggression have significant clinical significance. ObjectiveTo construct a predictive model for the violence risk in hospitalized patients with schizophrenia, to identify the key factors influencing the occurrence of violent behavior in these patients, so as to provide references for clinical precise quantitative assessment and early intervention. MethodsA total of 200 patients with schizophrenia who were hospitalized at Taiyuan Psychiatric Hospital from March 2022 to September 2024 and met the diagnostic criteria of the International Classification of Diseases, eleventh edition (ICD-11) were collected to form the modeling cohort. They were randomly divided into a training set (n=140) and a test set (n=60) at a ratio of 7∶3. Based on the least absolute shrinkage and selection operator (LASSO) regression algorithm, the feature variables were screened and dimension-reduced. The support vector machine (SVM) from machine learning was selected for model training and prediction. The discrimination efficacy of the model was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC), accuracy, precision, sensitivity, specificity, F1 value, and Brier value. ResultsLASSO regression screening identified 16 feature variables. Pearson correlation analysis revealed a positive correlation between prior violent behavior frequency and clinical psychiatric symptom scores (r=0.580, P<0.01), a positive correlation between hospitalization compliance and current disease status (r=0.550, P=0.003), and a positive correlation between educational level and family per capita monthly income (r=0.367, P<0.01). The SVM model achieved an AUC of 0.853, accuracy of 0.800, precision of 0.810, sensitivity of 0.895, specificity of 0.636, F1 value of 0.850, and Brier value of 0.168. ConclusionThe SVM model has a relatively high level of applicability and overall predictive performance in the assessment of violent risk in schizophrenia patients, which is helpful for the early identification of violent risks in such patients. [Funded by Specialized Research Project for Enhancing the Competence of Health Professionals in Taiyuan City (number, Y2023006)]
5.Palpitations, Shortness of Breath, Weakness in Limbs, Edema, and Dyspnea: A Rare Inflammatory Myopathy with Positive Aniti-mitochondrial Antibodies and Cardiac Involvement
Chunsu LIANG ; Xuchang ZHANG ; Ning ZHANG ; Lin KANG ; Xiaohong LIU ; Jiaqi YU ; Yingxian LIU ; Lin QIAO ; Yanli YANG ; Xiaoyi ZHAO ; Ruijie ZHAO ; Na NIU ; Xuelian YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):248-255
This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.
6.Multidimensional optimization strategies and practical effects of prescription pre-review system
Guangming GAO ; Tianjiao LIU ; Na XU ; Jing LIANG ; Xiangju SUN ; Zhanguo ZHU ; Hong YAN
China Pharmacy 2025;36(14):1797-1801
OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system, optimization measures were taken, including improving the content of the rule base, adjusting the interception level and prompt mode, refining the working model of prescription review pharmacists, and strengthening clinical communication. A retrospective cohort study was conducted, with prescription data from June to December 2023 (before optimization) as the control group and June to December 2024 (after optimization) as the observation group. Through inter group comparative analysis, the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from (82.51± 4.04)% before optimization to (90.98±1.55)% after optimization; the false positive rate decreased from (20.87±1.64)% before optimization to (7.41±2.04)% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%, and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%, the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital, its prescription review efficiency has been significantly enhanced, the quality of prescriptions has steadily improved, and the accuracy of reviews has notably improved.
7.Mechanism of Quanduzhong Capsules in treating knee osteoarthritis from perspective of spatial heterogeneity.
Zhao-Chen MA ; Zi-Qing XIAO ; Chu ZHANG ; Yu-Dong LIU ; Ming-Zhu XU ; Xiao-Feng LI ; Zhi-Ping WU ; Wei-Jie LI ; Yi-Xin YANG ; Na LIN ; Yan-Qiong ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2209-2216
This study aims to systematically characterize the targeted effects of Quanduzhong Capsules on cartilage lesions in knee osteoarthritis by integrating spatial transcriptomics data mining and animal experiments validation, thereby elucidating the related molecular mechanisms. A knee osteoarthritis model was established using Sprague-Dawley(SD) rats, via a modified Hulth method. Hematoxylin and eosin(HE) staining was employed to detect knee osteoarthritis-associated pathological changes in knee cartilage. Candidate targets of Quanduzhong Capsules were collected from the HIT 2.0 database, followed by bioinformatics analysis of spatial transcriptomics datasets(GSE254844) from cartilage tissues in clinical knee osteoarthritis patients to identify spatially specific disease genes. Furthermore, a "formula candidate targets-spatially specific genes in cartilage lesions" interaction network was constructed to explore the effects and major mechanisms of Quanduzhong Capsules in distinct cartilage regions. Experimental validation was conducted through immunohistochemistry using animal-derived biospecimens. The results indicated that Quanduzhong Capsules effectively inhibited the degenerative changes in the cartilage of affected joints in rats, which was associated with the regulation of Quanduzhong Capsules on the thioredoxin-interacting protein(TXNIP)-NOD-like receptor family pyrin domain containing 3(NLRP3)-bone morphogenetic protein receptor type 2(BMPR2)-fibronectin 1(FN1)-matrix metallopeptidase 2(MMP2) signal axis in the articular cartilage surface and superficial zones, subsequently inhibiting cartilage matrix degradation leading to oxidative stress and inflammatory diffusion. In summary, this study clarifies the spatially specific targeted effects and protective mechanisms of Quanduzhong Capsules within pathological cartilage regions in knee osteoarthritis, providing theoretical and experimental support for the clinical application of this drug in the targeted therapy on the inflamed cartilage.
Animals
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Osteoarthritis, Knee/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Rats, Sprague-Dawley
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Rats
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Male
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Humans
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Capsules
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Female
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Disease Models, Animal
8.Effects and mechanisms of Yuxuebi Tablets combined with ibuprofen in treating chronic musculoskeletal pain through "integrated regulation of inflammation and pain-related oxylipins".
Ao-Qing HUANG ; Wen-Li WANG ; Guo-Xin ZHANG ; Ying LIU ; Na LIN ; Chun-Yan ZHU
China Journal of Chinese Materia Medica 2025;50(13):3763-3777
This study adopted a three-dimensional "effect-dose-mechanism" evaluation system to screen the optimal regimen of Yuxuebi Tablets(YXB) combined with ibuprofen(IBU) for chronic musculoskeletal pain(CMP) intervention and elucidate its pharmacological mechanism, so as to provide a scientific basis for the clinical application of the regimen. The experiments were conducted using 8-week-old ICR mice, which were randomly divided into sham operation(sham) group, model(CFA) group, IBU group, YXB group, stasis paralysis tablets combined with ibuprofen low-dose group(IBU-L-YXB), stasis paralysis combined with ibuprofen high-dose group(IBU-H-YXB), stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen discontinuation on the 10th day of administration(IBU-10-YXB), and stasis paralysis tablets combined with ibuprofen high-dose with ibuprofen halving on the 10th day of administration(IBU-1/2-YXB) group. An animal model was established using the CFA plantar injection method. On D0(the second day post-modeling), the success of model establishment was assessed, followed by continuous drug administration for 18 consecutive days from D1 to D18. During this period, mechanical pain threshold was measured by the Von Frey test; thermal hyperalgesia was detected by the hot plate test, and depression-like behavior was observed by the tail suspension test. After treatment, peripheral blood was collected from all groups for complete blood biochemical analysis, and the injected feet of the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups were subjected to oxylipin metabolomics analysis. Immunofluorescence double staining was further performed to detect the co-expression of key oxylipin metabolic enzymes(COX2, LTA4H, and 5/12/15-LOX) and macrophage marker CD68 in the sham, CFA, IBU, and YXB-L/M/H groups. Subsequently, confirmatory analysis of positive indicators was conducted in the sham, CFA, IBU, YXB, IBU-YXB, and IBU-10-YXB groups. On D6(acute phase), mechanical pain sensitivity data showed that compared with the CFA group, only the three combination groups(IBU-YXB, IBU-10-YXB, and IBU-1/2-YXB) exhibited significantly increased paw withdrawal thresholds. On D17(chronic phase), only the IBU-10-YXB group showed a mechanical pain threshold significantly higher than all other monotherapy and combination groups. On D17, thermal pain data showed that compared with the CFA group, all groups except IBU-1/2-YXB had significantly prolonged paw withdrawal latency. On D18, tail suspension data showed that compared with the CFA group, the YXB, IBU-YXB, and IBU-10-YXB groups had significantly reduced immobility time. In summary, IBU-10-YXB stably improved the core symptoms of acute and chronic inflammatory pain. Complete blood count data showed that compared with the sham group, the CFA group had significantly increased mean platelet volume(MPV), while compared with the CFA group, the IBU-YXB and IBU-10-YXB groups had significantly reduced MPV. Moreover, the platelet distribution width(PDW) of the IBU-10-YXB group was further reduced compared with the CFA group. These data suggest that the IBU-10-YXB combination regimen has superior effects on inflammation and blood circulation improvement compared with other treatment groups. At the mechanistic level, each treatment group differentially regulated pro-inflammatory and pro-resolving oxylipin(SPM). Specifically, compared with the CFA group, the IBU and IBU-YXB groups significantly inhibited the synthesis of the prostaglandin family downstream of COX2, reducing pro-inflammatory oxylipins PGD2 and 6-keto-PGF1α but inhibiting PGE1 and PGE2, which played positive roles in peripheral circulation, vasodilation, and inflammation resolution. Compared with the CFA group, the YXB group tended to inhibit the pro-inflammatory oxylipin LTB4 downstream of LTA4H and increase SPMs such as LXA4. The IBU-10-YXB group bidirectionally regulated pro-inflammatory oxylipins and SPMs. Compared with IBU, IBU-10-YXB significantly inhibited the pro-inflammatory mediator 5-HETE. Meanwhile, IBU-10-YXB broadly upregulated SPMs, as evidenced by significant upregulation of LXA4 compared with the CFA group, significant upregulation of LXA5 compared with the IBU and IBU-YXB groups, significant upregulation of RvD1 compared with the CFA group and all other treatment groups, and significant upregulation of RvD5 compared with the sham group. Immunofluorescence double staining results were as follows: compared with the CFA group, the IBU group specifically inhibited the oxylipin metabolic enzyme COX2. In the YXB group, COX2, LTA4H, and 5/12-LOX were significantly inhibited. Within the optimal analgesic dose range, YXB's inhibitory effects on COX2 and LTA4H were dose-dependent, while its inhibitory effects on 5/12-LOX were inversely dose-dependent. The two combination groups(IBU-YXB and IBU-10-YXB) inhibited COX2 and LTA4H without significantly affecting 5-LOX, while IBU-10-YXB further significantly inhibited 12-LOX. These results suggest that the IBU-10-YXB combination regimen effectively maintains stable inhibition of COX2, LTA4H, and 12-LOX while enhancing 5-LOX expression. This combinatorial strategy effectively suppresses pro-inflammatory oxylipins and promotes SPM biosynthesis, overcoming IBU's analgesic ceiling effect and its blockade of pain resolution pathways while compensating for YXB's inability to effectively intervene in acute pain and inflammation. Therefore, it achieves more stable anti-inflammatory, analgesic, and antidepressant effects.
Animals
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Ibuprofen/administration & dosage*
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Mice
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Mice, Inbred ICR
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Musculoskeletal Pain/immunology*
;
Tablets
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Humans
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Chronic Pain/metabolism*
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Drug Therapy, Combination
;
Disease Models, Animal
9.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.
10.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.

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