1.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.
2.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.
3.Influence of repeated behavioral tests within a short term on cognitive and anxiety assessment in 3xTg-AD mice
Xiaoyue LI ; Fangzhao LIN ; Haijun CAO
Journal of Apoplexy and Nervous Diseases 2025;42(8):727-735
Objective To investigate the influence of repeated open field tests, novel object recognition tests, and Barnes maze behavioral tests within a short term on cognitive and anxiety assessment in 3xTg-AD mice.Methods Four groups of 3xTg-AD mice, aged 12 months, were obtained using different pretreatment regimens, and the mice in the experimental groups 1-3 were treated with different drugs, while those in the control group were treated with normal saline. The open field test, the novel object recognition test, and the Barnes maze test were performed on mice successively. A behavioral video analysis system was used to record the locomotor trajectories of the mice and analyze the parameters such as time spent in the central area, exploration time for novel versus familiar objects, and latency to reach the target hole. After one session of complete tests, three sessions were performed repeatedly, and all tests were completed within one month.Results With the increase in the number of repeated tests, there was a significant reduction in the time spent in the central area in the open field test (P<0.05); in the novel object recognition test, there was an increase in the coefficient of variation for object recognition index and a reduction in exploratory behavior towards both the new environment and the novel objects; in the Barnes maze test, there was no significant difference in the latency to reach the target hole across the four tests, suggesting good reproducibility.Conclusion Repeated tests within a short term can interfere with the evaluation of anxiety status in 3xTg-AD mice in the open field test and their preference for novel objects in the novel object recognition test, but it has no obvious influence on the latency to reach the target hole in the Barnes maze test. Whether behavioral tests can be performed repeatedly in 3xTg-AD mice should be determined based on different tests.
4.The Effects of Tai Chi Training on Bone Density,Bone Turnover Markers,and Heart Rate Variability in High-Risk Osteoporosis Population
Jiaming LIN ; Chao LI ; Wei ZHAO ; Jun ZHOU ; Xiaoying CHEN ; Xiangyu XI ; Haijun HE ; Baohong MI ; Yuefeng CHEN ; Weiheng CHEN
Journal of Traditional Chinese Medicine 2025;66(15):1566-1571
ObjectiveTo explore the effects of the Tai Chi training on bone density, bone turnover markers, and heart rate variability for people with high-risk osteoporosis, and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included, and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week, and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group, and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L1~L4 vertebrae, bilateral femoral necks and bilateral total hips in the two groups before and after the intervention; enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention, including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide (P1NP) and β-collagen type Ⅰ cross-linking carboxy-terminal peptide (β-CTX). Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor, they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each, and the heart rate variability (HRV) during exercise was collected, including time-domain indexes such as standard deviation of normal sinus intervals (SDNN), root-mean-square of the difference between adjacent RR intervals (RMSSD), frequency-domain metrics such as low-frequency power (LF), high-frequency power (HF), and low-frequency/high-frequency power ratio (LF/HF), as well as nonlinear metrics such as approximate entropy (ApEn), sample entropy (SampEn). ResultsFinally, 63 cases were included in the outcome analysis, including 30 cases in the intervention group and 33 cases in the control group. After the intervention, the differences of L1~L4 vertebrae, bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention (P>0.05), while the bone density of all parts of the control group decreased significantly compared with that before intervention (P<0.05), and the difference in the bone density of the L1~L4 vertebrae, bilateral femoral neck, and the right total hip before and after the intervention of the intervention group was smaller than that of the control group (P<0.05). The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant (P>0.05). Compared with walking exercise, LF decreased, HF increased and LF/HF decreased during Tai Chi exercise (P<0.05); the time domain indexes and non-linear indexes between groups had no statistically significant difference (P>0.05). ConclusionTai Chi exercise can maintain lumbar, hip, and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis, but cannot significantly improve bone turnover markers.
5.Desalination effect on FⅧ components: a compartive study among 5 desalination methods
Renjun PEI ; Xi DU ; Pan SUN ; Xiaoyue LI ; Peng JIANG ; Changqing LI ; Fangzhao LIN ; Haijun CAO
Chinese Journal of Blood Transfusion 2024;37(3):304-311
【Objective】 To compare the desalination effects of five desalination methods and their effects on the components for human coagulation factor Ⅷ(FⅧ), and provide reference for selection of protein desalination methods. 【Methods】 Sephadex G-25 Medium gel, Fractogel EMD BioSEC gel, ultrafiltration, room temperature dialysis and 4℃ dialysis were used to desalt human FⅧ. The desalination effect was evaluated by the removal rate of Na +, citrate ion and glycine. FⅧ protein recovery, FⅧ activity (FⅧ∶C), VWF antigen (VWF∶Ag), VWF activity(VWF∶Ac), VWF polymers and SDS-PAGE analysis before and after desalination were compared to evaluate the effect of desalination on FⅧ components. 【Results】 In terms of desalination effect, the removal rate of Na+ was the lowest in ultrafiltration desalination, while that of Fractogel EMD BioSEC gel was the highest [(97.90±0.06) % vs (99.82±0.07) %]. Except that there was no statistical significance between Sephadex G-25 Medium gel desalination and Fractogel EMD BioSEC gel desalination (P=0.90), the removal rates of the other four methods were statistically significant. The removal rate of glycine was the lowest in ultrafiltration desalination, wihle that of Fractogel EMD BioSEC gel desalination was the highest [(95.78±0.42) % vs (99.81±0.08) %]. Significant difference in glycine removal was noticed in ultrafiltration desalination, but not among the other four desalination methods. There was no significant difference in the removal rate of citrate ions among the five methods (P=0.85). For the effect of FⅧ components, FⅧ∶C, VWF∶Ag, VWF∶Ac and protein recovery rates of ultrafiltration desalination were the highest, with (18.34±1.99) IU/mL, (11.81±0.33) IU/mL, (12.26±0.58) IU/mL and (97.13±1.37) %, respectively. There was no significant change in VWF∶Ac/VWF∶Ag before and after desalination by the five methods. SDS-PAGE and VWF polymer analysis showed that different desalination methods had no significant impact on protein composition. 【Conclusion】 Although different desalination methods had no significant effect on the composition of FⅧ protein, the desalination effect was different. Moreover, different desalination methods had significant effects on protein recovery, FⅧ∶C, VWF∶Ag and VWF∶Ac. The selection of desalination methods should be more considered during protein processing,
6.Effect of Grain-sized Moxibustion on JAK2/ STAT3 Signaling Pathway in Colon Tissue of Ulcerative Colitis Mice
Tao ZHU ; Jie LI ; Hao YIN ; Yanting CHENG ; Yufang JI ; Haijun WANG ; Laixi JI
Journal of Traditional Chinese Medicine 2024;65(18):1925-1933
ObjectiveTo explore the effect of grain-sized moxibustion at "Zhongwan (RN12)" "Tianshu (ST25)" and "Shangjuxu (ST37)" on the colon tissue of mice with ulcerative colitis (UC), and to analyze the potential mechanism. MethodsForty C57BL/6 male mice were randomly divided into blank group, model group, moxibustion group and mesalazine group, with 10 mice in each group. In all the groups except for the blank group, UC mouse model was prepared by freely drinking 3% sodium dextran sulfate solution. After successful modeling, the moxibustion group was treated with grain-sized moxibustion at Zhongwan, Tianshu and Shangjuxu , 3 cones per acupoint, 30 s of each cone. The mesalazine group was given 300 mg/kg of mesalazine enteric-coated tablet solution by gavage. The blank group and the model group were only fixed by grasping without any intervention. Each group was intervened once a day for 7 consecutive days. The general condition of mice in each group was observed, and the disease activity index (DAI) score was evaluated. The colon length, intestinal weight and colon mucosal injury score were detected. The contents of serum intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The mRNA and protein expressions of non-receptor tyrosine protein kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) in colon tissue of mice were detected by real-time fluorescence quantitative PCR and immunohistochemistry, respectively. The mean fluorescence intensity of JAK2 and SOCS3 in colon tissue of mice was detected by immunofluorescence double staining. ResultsCompared to the blank group, the mice in the model group had unclean perianal area, unformed stool, destroyed colonic mucosal morphology, shortened body weight and colon length, increased DAI score, intestinal weight index, colonic mucosal injury and pathological score, serum ICAM-1, IL-6 and TNF-α levels, increased mRNA and protein expression of JAK2 and STAT3 in colon tissue, and decreased mRNA and protein expression of SOCS3 (P<0.01). Compared to those in the model group, the perianal area of mice in the moxibustion group and the mesalazine group was improved, and the colonic mucosal morphology was more complete; body weight and colon length increased, while DAI score, intestinal weight index, colonic mucosal injury and pathological score, serum ICAM-1, IL-6 and TNF-α levels decreased, with decreased mRNA and protein expression of JAK2 and STAT3 in colon tissue, and increased SOCS3 mRNA and protein expression ( P<0.01 or P<0.05 ). There was no significant difference in any index between the moxibustion group and the mesalazine group. ConclusionGrain-sized moxibustion at "Zhongwan", "Tianshu" and "Shangjuxu" can improve the damage of colon mucosa in UC model mice, and the mechanism may be related to the key factors regulating JAK2 / STAT3 signaling pathway based on SOCS3.
7.Predictive value of renal venous Doppler waveform pattern for 28-day renal dysfunction in critically ill patients
Haijun ZHI ; Jie CUI ; Mengwei YUAN ; Yaning ZHAO ; Xingwen ZHAO ; Tingting ZHU ; Chunmei JIA ; Yong LI
Chinese Journal of Emergency Medicine 2024;33(3):324-331
Objective:This study aimed to explore the performance of renal resistive index (RRI), semiquantitative power Doppler ultrasound (PDU) score, and renal venous Doppler waveform (RVDW) pattern in predicting 28-day renal dysfunction in critically ill patients and establish nomogram model.Methods:This was a prospective, observational study. Critically ill patients admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 2018 to October 2022 were included. Patients underwent renal ultrasound examination to obtain RRI, PDU score and RVDW pattern within 24 h after ICU admission. The following clinical variables were collected during the renal ultrasound examination session, including heart rate, mean arterial pressure, type and dose of vasoactive drugs, oxygen therapy parameters, and average urine volume per hour derived from a period of 6 h prior to the ultrasound examination. The data on duration of AKI and mortality were recorded on the 28th day of follow-up. Patients were divided into 28-day normal renal function group and 28-day renal dysfunction group according to 28-day renal dysfunction. 28-days of renal dysfunction was defined as failure to achieve renal function recovery within 28 days of ICU admission. The difference of each index between the two groups was compared. Associated factors for 28-day renal dysfunction were determined by univariate and multivariate COX regression analyses. A nomogram was developed based on the independently factors associated with 28-day renal dysfunction. Survival receiver operator characteristic (ROC) curves were plotted to assess diagnostic performance in predicting 28-day renal dysfunction. Delong’s test was used to compare area under the curves (AUC) between each predictor.Results:187 patients were enrolled for the final analysis: 97 with no AKI, 48 with AKI stage 1, 24 with AKI stage 2, and 18 with AKI stage 3 upon enrollment. At 28-day follow up, 16 patients had renal dysfunction and 2 required continuous renal replacement therapy (CRRT). The multivariate COX regression showed that RVDW and SCr upon enrollment were the independent risk predictors. Nomogram based on RVDW and SCr upon enrollment showed the best performance in predicting 14-day renal dysfunction (AUC = 0.918, 95% CI:0.871-0.964, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05). Nomogram also showed the best performance in predicting 28-day renal dysfunction (AUC = 0.924, 95% CI:0.865-0.983, P<0.05), and the AUC was statistically significantly higher than single index (all P<0.05) except for SCr upon enrollment. The optimal cutoff for nomogram in predicting 28-day renal dysfunction was ≤89.5 (sensitivity, 81.2%; specificity, 90.6%; Youden index, 0.719). Kaplan-Meier analysis showed that the median duration of renal dysfunction in the groups with total nomogram score >85.9 and ≤85.9 was 0 and 22 days (HR=0.220, 95% CI:0.129-0.376, P<0.001). Conclusions:SCr and RVDW pattern within 24 h from ICU admission were independent factors associated with 28-day renal dysfunction in critically ill patients. The value of the nomogram model based on these two factors in predicting 28-day renal dysfunction is superior to each single intrarenal Doppler spectrum indicator and clinical indicator.
8.XEN drainage tube implantation combined with mitomycin C for open angle glaucoma
Rumeng ZHAO ; Huiling CUI ; Jing REN ; Di WANG ; Haijun LI
International Eye Science 2024;24(6):965-969
AIM: To investigate the clinical efficacy and safety of XEN drainage tube implantation combined with mitomycin C(MMC)for open angle glaucoma(OAG).METHODS:A total of 37 OAG patients(37 eyes)were retrospectively included, grouped by anti-glaucoma surgical treatment as the first choice or not, with 17 patients(17 eyes)in the group with primary surgical treatment, and 20 patients(20 eyes)in the group with the numerous surgeries. The intraocular pressure(IOP), kinds of IOP-lowering drugs, and complications were collected and analyzed in 1 a follow-up postoperatively.RESULTS:Upon the one-year follow-up, IOP had decreased from 27.56±9.94, 28.43±14.18 mmHg to 15.16±3.65, 17.18±5.83 mmHg in both groups, respectively, representing a reduction of 55.01% and 60.43%, respectively(t=4.863, P<0.001; t=3.255, P=0.004). The IOP at various follow up points were lower than preoperative points in both groups(Ftime=6.876, Ptime<0.001; Fintergroup=0.242, Pintergroup=0.626; Ftime×intergroup=0.959, Ptime×intergroup=0.458). The complete success rate was 47% and 45%, the qualified success rate was 76% and 75%(Z=-0.115, P=0.909), respectively, and there was no significant difference in the cumulative survival rate between two groups(χ2=0.042, P=0.838; χ2=0.004, P=0.949). At the last follow up, IOP-lowering drugs were reduced from 3(2, 3)to 1(0, 2)in both groups(Z=-3.289, -3.796, all P<0.001), and no significant difference between groups(Z=-0.581, P=0.561). Hypotony is the most common short-term complications, anterior chamber haemorrhage followed, while, filtering bleb encapsulation is the most frequent long-term complication, no serious complications occurred, but with XEN drainage tube exposure in 1 eye and drop in 1 eye.CONCLUSION:Initial XEN drainage tube implantation combined with MMC and numerous glaucoma surgeries are both safe and effective treatment for OAG patients, while the incidence of filtering bleb encapsulation is high in those with numerous glaucoma surgeries.
9.Curcumin protects against liver cancer in a mouse model by down-regu-lating HO-1/NQO1
Haijun MOU ; Xingxing CHEN ; An'an LIU ; Li ZHANG ; Jiaxin ZHU ; Hai JIN
Chinese Journal of Pathophysiology 2024;40(3):438-443
AIM:To observe the effect of curcumin on a C57BL/6J mouse liver cancer model induced by N-ni-trosodiethylamine(DEN)combined with carbon tetrachloride(CCl4),and to explore its mechanism.METHODS:Forty young male C57BL/6J mice were intraperitoneally injected with DEN(25 mg/kg)14 d after birth and randomly divided in-to the following 4 groups at the 4th week(10 in each group):model control group and curcumin(100,200 and 400 mg/kg)groups.Ten male mice of the same age were used as normal control group.The mice in model group and curcumin groups were gavaged with 10%CCl4(5 mL/kg)twice a week from the 8th week on.At the same time,the mice in curcumin groups were gavaged with curcumin,and the mice in normal control group were gavaged with the same volume of distilled water once a day for 14 weeks.After administration,the mice were sacrificed,the liver surface was observed,and the number of tumor nodules was compared.The activity of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum was detected by an automatic biochemical instrument.The pathological changes of liver tissues were ob-served by HE staining.The mRNA expression levels of heme oxygenase-1(HO-1)and NAD(P)H-quinone oxidoreductase 1(NQO1)were detected by RT-qPCR,and the protein expression levels of HO-1,NQO1 and Ki67 were detected by Western blot and immunohistochemistry.RESULTS:Compared with normal control group,the body weight of the mice in model group was decreased significantly(P<0.01),the liver index was increased significantly(P<0.01),and the se-rum levels of ALT and AST were increased obviously(P<0.01).There was no significant difference in the mRNA expres-sion levels of HO-1 and NQO1(P>0.05),the protein levels of HO-1 and NQO1 were increased distinctly(P<0.05),and the positive expression rate of Ki67 was increased significantly(P<0.05).After curcumin treatment,the body weight of the mice was significantly increased(P<0.01),the liver index was not changed(P>0.05),and the number of tumor nodules in the liver was decreased significantly(P<0.05 or P<0.01).The serum level of AST was decreased significantly(P<0.01),the mRNA and protein expression levels of HO-1 and NQO1 were decreased significantly(P<0.05),and the posi-tive expression rate of Ki67 was decreased significantly(P<0.05).CONCLUSION:Curcumin significantly protects against liver cancer in a C57BL/6J mouse model induced by DEN combined with CCl4,and its mechanism may be related to the inhibition of HO-1 and NQO1 expression.
10.Efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases
Xinlian QI ; Xiao ZOU ; Haijun WANG ; Chunlin LI ; Sha ZHANG ; Xiansai MENG ; Yang LI ; Quanjin SI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):137-141
Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(<60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P<0.05,P<0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P>0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2%vs 3.0%vs 2.4%,P>0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P<0.05,P<0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P<0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2%vs 16.0%,P>0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

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