1.Study on Mechanism of Hot Compress with Sangzhi Shengjiang Decoction in Relieving Pain and Improving Hemorheology of Patients with Femoral Head Necrosis
Xin ZHANG ; Meng ZHANG ; Jian LIU ; Haijun HE
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(2):315-321
Objective To explore the therapeutic mechanism of hot compress with Sangzhi Shengjiang Decoction(manily composed of Zingiberis Rhizoma Recens,Mori Ramulus,Cinnamomi Ramulus,Speranskiae Tuberculatae Herba,and Cervi Cornus Colla)in relieving pain and improving hemorheology of patients with femoral head necrosis(FHN).Methods A total of 104 patients with FHN who admitted to Guang'anmen Hospital Baoding,China Academy of Chinese Medical Sciences from May 2022 to May 2024 were randomly divided into the control group and the treatment group according to the random number table method,with 52 cases in each group.The control group was treated with Alendronate Sodium orally,and the treatment group was given hot compress with Sangzhi Shengjiang Decoction on the basis of treatment for the control group.The course of treatment for the two groups covered three months.Before and after the treatment,the traditional Chinese medicine(TCM)syndrome score,Harris score of joint function,Visual Analogue Scale(VAS)score for pain,and the levels of hemorheology indicators,bone metabolism indicators,and bone mineral density(BMD)of proximal femur and lumbar trabecular bone in the two groups were observed.After treatment,the clinical efficacy of patients in the two groups was evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 92.31%(48/52)and that of the control group was 71.15%(37/52),and the intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the treatment group was significantly superior to that of the control group(P<0.01).(2)After treatment,the scores of TCM symptoms such as soreness and weakness in the waist and knee,claudication,restlessness and insomnia,and soreness and heaviness of lower limbs in the two groups were decreased compared with those before treatment(P<0.05),and the decreases in the treatment group were significantly superior to that in the control group(P<0.01).(3)After treatment,the Harris scores of joint function in the two groups were increased(P<0.05)and the VAS scores for pain were decreased compared with those before treatment(P<0.05),and the increase of Harris scores and the decrease of VAS scores in the treatment group were significantly superior to those in the control group(P<0.01).(4)After treatment,the levels of hemorheology indicators such as erythrocyte sedimentation rate(ESR),whole blood low-shear viscosity(LBV),and whole blood high-shear viscosity(HBV)in the two groups were improved compared with those before treatment(P<0.05),and the improvement in the treatment group was significantly superior to that in the control group(P<0.01).(5)After treatment,the levels of bone metabolism indicators such as serum N-terminal mid-fragment of osteocalcin(N-MID)β-C-terminal telopeptide of type Ⅰ collagen(β-CTX)and total procollagen type Ⅰ N-terminal propeptide(T-PINP)levels of patients in the two groups were decreased compared with those before treatment(P<0.05),and serum 25-hydroxy vitamin D[25-(OH)D]level was increased compared with that before treatment(P<0.05).The decrease of serum N-MID,β-CTX and T-PINP levels and the increase of serum 25-(OH)D level in the treatment group were significantly superior to those in the control group(P<0.01).(6)After treatment,BMD of proximal femur and lumbar trabecular bone in the two groups was increased compared with that before treatment(P<0.05),and the increase in the treatment group was significantly superior to that in the control group(P<0.01).Conclusion Hot compress with Sangzhi Shengjiang Decoction exerts certain efficacy for the treatment of patients with FHN.The therapy is effective on reducing the scores of TCM syndrome,relieving pain,improving joint function,regulating bone metabolism and bone density,improving hemorheology indicators,and presenting remarkable therapeutic effect.
2.Therapeutic Mechanism of Taohong Siwu Decoction in Recovering Joint Muscle Strength and Bone Mineral Density of Patients After Hip Preservation Surgery for Osteonecrosis of the Femoral Head
Xin ZHANG ; Meng ZHANG ; Jian LIU ; Haijun HE
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(8):1890-1897
Objective To explore the mechanism of Taohong Siwu Decoction in recovering joint muscle strength and bone mineral density(BMD)in patients after hip preservation surgery for osteonecrosis of the femoral head(ONFH).Methods A total of 110 ONFH patients admitted to Guang'anmen Hospital Baoding Branch,China Academy of Chinese Medical Sciences from April 2022 to April 2024 were enrolled.The patients were equally randomized into a control group and a study group using a random number table,with 55 cases in each group.All patients underwent core decompression surgery and then were given postoperative conventional western medical treatment,and the study group received additional modified Taohong Siwu Decoction.The course of treatment lasted for 8 weeks.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,Visual Analogue Scale(VAS)score for pain,Harris hip score,joint muscle strength,bone mineral density(BMD),hemorheological parameters(including plasma viscosity,whole blood high-shear viscosity,and whole blood low-shear viscosity),and bone metabolism markers[including alkaline phosphatase(ALP),osteocalcin(BGP),and bone morphogenetic protein 2(BMP-2)].After treatment,the clinical efficacy was evaluated between groups.Results(1)After 8 weeks of treatment,the total effective rate in the study group was 92.73%(51/55),which was significantly higher than that in the control group(72.73%,40/55).The intergroup comparison showed a statistically significant difference(χ2=7.698,P<0.01).(2)After treatment,scores for hip pain,soreness and weakness of the lower back and knees,mental fatigue,and deep-thin-choppy pulse decreased in both groups compared with those before treatment(P<0.05).Moreover,the magnitude of reduction in all these scores was significantly greater in the study group than that in the control group(P<0.01).(3)After treatment,the VAS scores for pain severity decreased in both groups compared with baseline(P<0.05),while the Harris scores for joint function increased in both groups(P<0.05).Furthermore,the magnitude of reduction in VAS scores and the magnitude of improvement in Harris scores were both significantly greater in the study group than those in the control group(P<0.01).(4)After treatment,plasma viscosity,high-shear whole blood viscosity,and low-shear whole blood viscosity decreased in both groups compared with those before treatment(P<0.05).Additionally,the reductions in all these parameters were significantly more pronounced in the study group than in the control group(P<0.01).(5)After treatment,serum alkaline phosphatase(ALP)levels decreased in both groups(P<0.05),while serum osteocalcin(BGP)and bone morphogenetic protein-2(BMP-2)levels increased in both groups(P<0.05).Crucially,the magnitude of reduction in serum ALP levels and the magnitude of elevation in serum BGP and BMP-2 levels were all significantly greater in the study group than those in the control group(P<0.01).(6)After treatment,in the study group,the number of patients with Grade 3 muscle strength significantly decreased while the number with Grade 4 muscle strength significantly increased compared with those before treatment(P<0.05).In contrast,although the control group showed some improvement in joint muscle strength,the changes were not statistically significant(P>0.05).After treatment,the intergroup comparisons showed that the study group had a significantly smaller number of patients with Grade 3 muscle strength and a significantly larger number with Grade 4 muscle strength than the control group(P<0.01).(7)After treatment,both local femoral head BMD and average BMD increased in both groups compared with those before treatment(P<0.05).The magnitude of increase in both local and average BMD was significantly greater in the study group than that in the control group(P<0.01).Conclusion The application of Taohong Siwu Decoction in the treatment of in patients after hip preservation surgery for ONFH is effective on reducing TCM syndrome scores,alleviating pain,improving joint function and hemorheology,and restoring BMD and bone metabolism indicators,which enhances the overall clinical efficacy for the patients.
3.Effect of practicing Traditional Chinese Medicine guidance on health status in weightless conditions
Xiaorui WU ; Haijun HAN ; Junlian LIU ; Quanchun FAN ; Liguo GUO ; Yu LIU ; Jiaping WANG ; Jihong SHEN ; Xining CHEN
Space Medicine & Medical Engineering 2025;36(4):385-388
Objective To study the effect of practicing traditional Chinese medicine(TCM)guidance on the health in weightless conditions based on the examination results of the TCM diagnostic instrument.Methods 6 subjects in weightless conditions practiced TCM guidance for 14 consecutive days,once a day for 8 minutes each time.The Digital TCM Diagnostic Instrument and TCM Syndrome Diagnosis Scale were used to collect information before and after their practice of TCM guidance through diagnostic methods of observation,palpation and inquiry according to TCM theory.The data such as the degree of virtual-reality,pulse rate,and characteristic parameters of pulse diagrams h3/h1,h4/h1,t1,h1/t1 were processed and analyzed,and the changes before and after the practice were compared.Results Compared with before the practice,the degree of deficiency syndrome was significantly reduced after practicing TCM guidance(P<0.05),the pulse rate was significantly decreased(P<0.01),and the pulse diagnosis parameters h3/h1 and t1 were significantly decreased(P<0.05),while h4/h1 and h1/t1 showed no significant changes.Conclusion Practicing TCM guidance in weightless conditions is helpful for enhance cardiovascular regulatory function,correcting symptom bias,adjusting the body's balance state,and has a positive effect on health.
4.Advances in the use of human respiratory stem cells in the treatment of respiratory tract infections
Xuan LIU ; Wenyan TIAN ; Ze CHEN ; Yingli QU ; Jin CAO ; Chenxi ZHANG ; Qi WEN ; Qin LUO ; Qiangqiang SHI ; Lifeng ZHANG ; Guoyong MEI ; Haijun DU ; Zhiqiang XIA ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2025;39(1):128-132
Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.
5.Efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy: a multicenter, non-inferiority, randomized controlled trial
Qian HU ; Jian GUO ; Haijun YUAN ; Weiping LEI ; Haipeng LIU ; Chen YONG ; Yanhui HU ; Junping CHEN ; Jianliang SUN ; Zhijian LAN ; Jianhong XU ; Xin YU ; Gang CHEN
Chinese Journal of Anesthesiology 2025;45(6):720-725
Objective:To evaluate the efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy.Methods:In this multicenter, non-inferiority, randomized controlled trial, 300 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-60 yr, with body mass index of 18-28 kg/m 2, who underwent daytime laparoscopic cholecystectomy under general anesthesia with tracheal intubation at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou First People′s Hospital Affiliated to Westlake University School of Medicine, Ningbo No. 2 Hospital, and the Second Affiliated Hospital of Nanchang University from August 2021 to August 2023, were selected and divided into 2 groups ( n=150 each) using a random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced as follows: Sufentanil was intravenously injected at a rate of 0.5 μg/kg, remimazolam was intravenously injected at a rate of 0.3 mg/kg in group R, propofol was intravenously injected at a rate of 2.0-2.5 mg/kg in group P, and cisatracurium besilate was intravenously injected at a rate of 0.2 mg/kg after loss of consciousness in two groups. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained as follows: Remimazolam was intravenously injected at a rate of 0.5-1.0 mg·kg -1·h -1 in group R, propofol was intravenously injected at a rate of 4-10 mg·kg -1·h -1 in group P, and remifentanil was intravenously infused at a rate of 0.25-2.00 μg·kg -1·min -1, maintaining intraoperative bispectral index value of 40-60. The success rate of sedation was recorded, and non-inferiority tests were conducted. The time to loss of consciousness, emergence time, extubation time, recovery time of orientation, time of stay in post-anesthesia care unit and occurrence of delayed emergence were recorded. Liver function and renal function were measured before operation and within 24 h after operation. The occurrence of abnormal alanine transaminase, abnormal aspartate transaminase, abnormal creatinine and abnormal urea was recorded. The occurrence of adverse reactions during and after operation was recorded. Results:The success rates of sedation were 98.6% and 99.3% in group R and group P, respectively, there was no statistically significant difference in the success rate of sedation between the two groups ( P>0.05), and the difference in the success rates of sedation between the two groups was -0.007 (95% confidence interval-0.0301-0.0161), which met the pre-set non-inferiority criteria(95% confidence interval >-0.055). Compared with group P, the time to loss of consciousness and recovery time of orientation were significantly prolonged, and the incidence of delayed emergence was increased ( P<0.05), and no statistically significant changes were found in the emergence time, extubation time, time of stay in post-anesthesia care unit and severity of postoperative nausea and vomiting in group R ( P>0.05). There was no statistically significant difference in the abnormal rates of alanine transaminase, aspartate transaminase, creatinine and urea before and after operation between the two groups ( P>0.05). Conclusions:The efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy is not inferior to that of propofol-based anesthesia.
6.Research status of reversing chemoresistance of osteosarcoma by traditional Chinese medicine ingredients
Danting XIAO ; Haijun TANG ; Kai LUO ; Hongcai TENG ; Hening LI ; Wei DAI ; Yun LIU
Tumor 2025;45(2):170-183
Osteosarcoma is the most common primary malignant bone tumor,typically treated with a combination of surgery and chemotherapy in clinical practice.However,the increasing prevalence of chemotherapy resistance poses a significant challenge.Chemotherapy resistance can lead to a sharp decline in patients'survival rates.Traditional Chinese medicine,known for its low cost,wide-ranging efficacy,and diverse varieties,has attracted significant attention from researchers.Their attempts to investigate the sensitizing effect of extracted ingredients on osteosarcoma chemoresistance both in vitro and in vivo have yielded promising results.This review has summarized the studies of single traditional Chinese medicine ingredients on reversing osteosarcoma chemoresistance by the mechanisms of chemoresistance,and found that the current research of the clinical mechanism of traditional Chinese medicine ingredients in reversing osteosarcoma chemoresistance is still lacking,indicating significant potential for future development.Utilizing the theory of herbal medicine properties as the theoretical basis for ingredient development may provide novel strategies for the development of new therapeutic approaches.
7.Correlation between terminal soft tissue infection of the diabetic foot and glycolipid metabolism as well as inflammatory factors
Weixian JU ; Lili ZHANG ; Jianjian LIU ; Jianhui SUN ; Haijun SUN ; Minghua YANG
Chinese Journal of Laboratory Medicine 2025;48(7):902-907
Objective:To investigate the relationship between terminal soft tissue infection of the diabetic foot and glucose and lipid metabolism as well as inflammatory factors.Methods:A total of 126 patients with diabetes mellitus combined with foot-soft tissue infections, who hospitalized in our hospital from March 2018 to February 2023 were divided into mild group (46 cases), moderate group (43 cases) and severe infections group (37 cases) according to the degree of foot-soft tissue infection before treatment. The glucose and lipid metabolism and inflammatory factors of patients among the different groups were compared, and the effects of glycolysis and lipid metabolism and inflammatory factors on the soft tissue infection at the end of diabetic foot were analyzed by logistic regression analysis. Patients were treated with antimicrobial therapy and other treatments. After 2 weeks of anti-infective treatment, if three consecutive cultures of secretions were negative for bacteria, antibiotic therapy was discontinued and glucose-lipid metabolism and inflammatory factors after treatment were compared. Patients were followed up for 1 year, and the changes in glucose-lipid metabolism and inflammatory factors were observed in toe or limb amputations group ( n=38) and non-toe or limb amputations group ( n=88). Results:Before treatment, the levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin typeA1c (HbA 1c), vascular cell adhesion molecule-1 (VCAM-1), C reactive protein (CRP,) tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the mild group were significantly lower than those in the moderate and severe group, and the adiponectin (APN) level was significantly higher than that in the moderate and severe group (all P<0.05). Logistic regression analysis showed that FFA, FPG, FINS, APN, VCAM-1, CRP, TNF-α and IL-6 were risk factors of terminal soft tissue infection ( P<0.05). After treatment, the levels of TC, LDL-C, FFA, FPG, FINS, HbA1c, VCAM-1, CRP, TNF-α and IL-6 were significantly decreased, and the APN was significantly increased (all P<0.05). The levels of TC, LDL-C, FFA, FPG, FINS, HbA1c, VCAM-1, CRP, TNF-α, and IL-6 were significantly higher in the toe/limb amputation group than in the non-toe/limb amputation group, and the APN levels were significantly lower in the toe/limb amputation group than in the non-toe/limb amputation group (all P<0.05). Conclusion:There is a close relationship between glucose and lipid metabolism, inflammatory factors and terminal soft tissue infection of the diabetic foot.
8.Distribution characteristics of current patients with Kashin-Beck disease in Molidawa Daur Autonomous Banner, Inner Mongolia Autonomous Region
Haijun WANG ; Shuyan WU ; Jinming LIU ; Zhongmin LIU ; Peng DU ; Jinguang GUO ; Zhanfeng ZHAO ; Mingming WANG ; Guangyu YU ; Xinxin CUI ; Jianping AO ; Baolong LIU
Chinese Journal of Endemiology 2025;44(9):737-740
Objective:To study the distribution characteristics of current patients with Kashin-Beck disease (KBD) in Molidawa Daur Autonomous Banner (referred to as Morin Banner), and provide suggestions for service management.Methods:Information of KBD current patients in Morin Banner was collected from January 1, 2018 to June 30, 2024 using the "KBD Current Patient Survey System" provided by the Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention. A descriptive study method was used to analyze the basic information and clinical data of current patients.Results:As of June 30, 2024, a total of 6 223 KBD current patients were reported in Morin Banner, and the patients were distributed in 15 townships (towns). There was a statistically significant difference in the prevalence rate of KBD among different townships (towns, χ 2 = 3 069.01, P < 0.001). The minimum age of the KBD current patients was 27 years old, and the maximum was 98 years old, mainly concentrated in the age range of 45 - 74 years old, accounting for 95.7% (5 954/6 223). There was a significant difference in the prevalence rate of KBD among different age groups (χ 2 = 5 912.76, P < 0.001). The male to female ratio was 1.00∶1.14 (2 910 ∶ 3 313), and there was a statistically significant difference in prevalence rate of KBD between genders(χ 2 = 44.38, P < 0.001). The KBD current patients mainly had a primary school education, married, and farmers, accounting for 59.2% (3 685/6 223), 89.8% (5 590/6 223), 93.2% (5 802/6 223), respectively; and the clinical grading of patients is mainly degree Ⅰ. There was a statistically significant difference in the rate of limb disability among patients with different clinical grades (χ 2 = 64.26, P < 0.001). The rate of limb disability in males was higher than that in females (χ 2 = 10.36, P = 0.001). Conclusions:The KBD current patients in Morin Banner are distributed in various township (town), with middle-aged and elderly famers being the main ones. It is necessary to strengthen monitoring of KBD, and pay attention to personalized treatment and management of KBD current patients.
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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