1.Study on the effect of chlorogenic acid in ameliorating atherosclerosis in ApoE-/- mice
Yunyang ZHANG ; Tianshu XU ; Wangjing CHAI ; Lili WANG ; Bin LIU ; Dongwei ZHANG ; Shuzhen GUO
Clinical Medicine of China 2025;41(3):189-194
Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.
2.Clinical observation on the efficacy and safety of intravenous thrombolysis in the treatment of acute mild non-disabling ischemic stroke:a single-center retrospective observational study
Meng ZHANG ; Yongxin MA ; Qiong JIA ; Dongwei ZHANG ; Xinhong ZHANG ; Yaoming XU
Journal of Capital Medical University 2025;46(1):56-62
Objective To explore the clinical efficacy and safety of intravenous thrombolysis and dual antiplatelet therapy in the treatment of acute mild non-disabling ischemic stroke.Methods A retrospective cohort study was conducted,including 138 patients with acute mild non-disabling ischemic stroke[National Institutes of Health Stroke Scale(NIHSS)score≤5]from January 2022 to March 2024,within 6 h of onset.Patients were divided into an intravenous thrombolysis group(66 cases)and a dual antiplatelet group(72 cases).Propensity score matching was used to match patients 1∶1,resulting in 44 patients in each group after matching.Demographic data,clinical data,clinical outcome indicators,and adverse events were collected.The primary outcome was defined as a good functional outcome[modified Rankin Scale(mRS)score 0-2]at 90 d post-onset.Secondary outcomes included NIHSS scores at 24 h,72 h,and 7 d post-onset;the proportion of early neurological deterioration;intracranial and systemic hemorrhagic events within 90 d post-onset;and death within 90 d.Results ①Before matching,the intravenous thrombolysis group had a lower age and admission mRS score than that of the dual antiplatelet group,with statistically significant differences(all P<0.05).After matching,there were no statistically significant differences between the two groups in terms of age,gender,hypertension,diabetes,cardiac disease,atrial fibrillation,hyper low density lipoprotein-cholesterol(LDL-C),hyperhomocysteinemia,prior stroke,prior smoking,admission NIHSS score,admission mRS score,location of stroke and TOAST classification(all P>0.05);②There was no statistically significant difference in the proportion of patients with a good functional outcome at 90 d post-onset and the mRS score at 90 d between the intravenous thrombolysis group and the dual antiplatelet group[88.6%(39/44)vs 93.2%(41/44),P=0.458,P=0.308];③ The intravenous thrombolysis group had significantly lower median NIHSS scores at 24 h and 72 h post-onset compared to the dual antiplatelet group,with statistically significant differences[1 vs 2.5,1 vs 2,P=0.018,0.043].There were no statistically significant differences in the other efficacy and safety outcomes.Conclusions Intravenous thrombolysis therapy can bring significant short-term benefits to patients with acute mild non-disabling ischemic stroke,helping to shorten the time to recovery to a good neurological functional outcome,and does not increase the risk of bleeding and mortality.However,in terms of good functional outcomes at 90 d post-onset,its effects are similar to those of dual antiplatelet therapy.Nevertheless,there is an urgent need for larger sample,higher quality clinical studies to further validate these findings.
3.Current status and suggestions on regulation of traditional Chinese medicine raw materials and preparations under regulatory system of drugs.
Li-Ping QU ; Yong-Dan XU ; Wei-Jing HE ; Ding-Kun ZHANG ; Nan YANG ; Min-Xian SONG ; Zhi-Qiang MIN ; Ting-Mo ZHANG
China Journal of Chinese Materia Medica 2025;50(3):824-832
At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics*
;
Medicine, Chinese Traditional/standards*
;
China
;
Quality Control
;
Humans
;
Plants, Medicinal/chemistry*
4.Mendelian randomization study on hyperthyroidism and systemic lupus erythematosus
Shengfei YANG ; Yunda ZHANG ; Mengling WEI ; Dongwei LI
Chongqing Medicine 2025;54(2):441-445
Objective To investigate the causal relationship between hyperthyroidism and systemic lu-pus erythematosus(SLE).Methods According to the current summary data of genome-wide association studies(GWAS),the screened single nucleotide polymorphism(SNP)was selected as the instrumental varia-bles,hyperthyroidism served as the exposure factor and SLE as the outcome variable,and the Mendelian ran-domization analysis(MR)analysis method was used for conducting the study.Among them,the inverse vari-ance weighting(IVW)was the main MR analysis method,the MR-Egger regression method was used to the test for horizontal pleiotropy,and the sensitivity adopted the leave-one-method test,and the MR results con-ducted the visualized analysis by scatter plot,forest plot and funnel plot.Results Ten valid SNP were screened.In the MR analysis,IVW supported a causal relationship between hyperthyroidism and SLE(OR=1.838,95%CI:1.302-2.593,P<0.001);the MR-egger regression method supported the relationship be-tween hyperthyroidism and SLE(OR=4.070,95%CI:1.961-8.449,P=0.003);in addition,the weighted median method also supported the relationship between hyperthyroidism and SLE(OR=1.685,95%CI:1.238-2.294,P<0.001).Conclusion There appears to be a causal relationship between hyperthyroidism and SLE.
5.Clinical observation on the efficacy and safety of intravenous thrombolysis in the treatment of acute mild non-disabling ischemic stroke:a single-center retrospective observational study
Meng ZHANG ; Yongxin MA ; Qiong JIA ; Dongwei ZHANG ; Xinhong ZHANG ; Yaoming XU
Journal of Capital Medical University 2025;46(1):56-62
Objective To explore the clinical efficacy and safety of intravenous thrombolysis and dual antiplatelet therapy in the treatment of acute mild non-disabling ischemic stroke.Methods A retrospective cohort study was conducted,including 138 patients with acute mild non-disabling ischemic stroke[National Institutes of Health Stroke Scale(NIHSS)score≤5]from January 2022 to March 2024,within 6 h of onset.Patients were divided into an intravenous thrombolysis group(66 cases)and a dual antiplatelet group(72 cases).Propensity score matching was used to match patients 1∶1,resulting in 44 patients in each group after matching.Demographic data,clinical data,clinical outcome indicators,and adverse events were collected.The primary outcome was defined as a good functional outcome[modified Rankin Scale(mRS)score 0-2]at 90 d post-onset.Secondary outcomes included NIHSS scores at 24 h,72 h,and 7 d post-onset;the proportion of early neurological deterioration;intracranial and systemic hemorrhagic events within 90 d post-onset;and death within 90 d.Results ①Before matching,the intravenous thrombolysis group had a lower age and admission mRS score than that of the dual antiplatelet group,with statistically significant differences(all P<0.05).After matching,there were no statistically significant differences between the two groups in terms of age,gender,hypertension,diabetes,cardiac disease,atrial fibrillation,hyper low density lipoprotein-cholesterol(LDL-C),hyperhomocysteinemia,prior stroke,prior smoking,admission NIHSS score,admission mRS score,location of stroke and TOAST classification(all P>0.05);②There was no statistically significant difference in the proportion of patients with a good functional outcome at 90 d post-onset and the mRS score at 90 d between the intravenous thrombolysis group and the dual antiplatelet group[88.6%(39/44)vs 93.2%(41/44),P=0.458,P=0.308];③ The intravenous thrombolysis group had significantly lower median NIHSS scores at 24 h and 72 h post-onset compared to the dual antiplatelet group,with statistically significant differences[1 vs 2.5,1 vs 2,P=0.018,0.043].There were no statistically significant differences in the other efficacy and safety outcomes.Conclusions Intravenous thrombolysis therapy can bring significant short-term benefits to patients with acute mild non-disabling ischemic stroke,helping to shorten the time to recovery to a good neurological functional outcome,and does not increase the risk of bleeding and mortality.However,in terms of good functional outcomes at 90 d post-onset,its effects are similar to those of dual antiplatelet therapy.Nevertheless,there is an urgent need for larger sample,higher quality clinical studies to further validate these findings.
6.Study on the effect of chlorogenic acid in ameliorating atherosclerosis in ApoE-/- mice
Yunyang ZHANG ; Tianshu XU ; Wangjing CHAI ; Lili WANG ; Bin LIU ; Dongwei ZHANG ; Shuzhen GUO
Clinical Medicine of China 2025;41(3):189-194
Objective:To investigate the effect of chlorogenic acid on atherosclerosis (AS) in a mouse model.Methods:Twenty-four specific pathogen-free male ApoE-/- mice were adaptively fed for 1 week and then randomly divided into three groups ( n=8 per group): The model group, the atorvastatin group, and the chlorogenic acid group. All three groups were fed with a high-fat diet. Eight male C57BL/6N wild-type mice served as the control group and were fed with a standard diet. After 8 weeks, the atorvastatin group received intragastric administration of a solution containing 0.9% sodium chloride +2.6 mg/kg atorvastatin at 10 mL/kg, while the chlorogenic acid group received 0.9% sodium chloride +200 mg/kg chlorogenic acid at 10 mL/kg. The control and model groups were given an equal volume of 0.9% sodium chloride once a day. After 9 weeks of continuous treatment, the mice were anesthetized, and the aortas were collected for Oil Red O staining. Image J was used to measure plaque area and total vascular area, and the percentage was calculated. Liver tissues were subjected to hematoxylin-eosin (H&E) staining to observe pathological changes. Blood samples from the abdominal aorta were collected to measure lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function markers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)], and inflammatory cytokines [interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α)]. Non-HDL-C levels were calculated as TC minus HDL-C. Results:Aortic lipid plaque area: The model group exhibited a significantly higher plaque area than the control group [(44.91±1.91)% vs. (0.21±0.11)%]. Both the atorvastatin group [(15.00±1.29)%] and the chlorogenic acid group [(26.13±2.16)%] showed reduced plaque areas compared to the model group ( P<0.05). Liver pathology: The control group displayed intact hepatocyte structure with regular morphology, whereas the model group exhibited significant steatosis. Both the atorvastatin and chlorogenic acid groups showed alleviated liver damage compared to the model group. Blood lipid levels: The model group had higher TC, TG, HDL-C, LDL-C, and non-HDL-C levels than the control group [(30.3±4.0) mmol/L vs. (2.8±0.3) mmol/L, (1.26±0.32) mmol/L vs. (0.52±0.12) mmol/L, (3.02±0.39) mmol/L vs. (2.00±0.17) mmol/L, (14.87±5.23) mmol/L vs. (0.39±0.09) mmol/L, (27.3±4.0) mmol/L vs. (0.8±0.3) mmol/L, respectively]. Both the atorvastatin group [(24.0±3.1), (0.64±0.08), (2.04±0.41), (8.55±1.15), (22.0±3.2) mmol/L] and the chlorogenic acid group [(23.3±2.5), (0.88±0.14), (2.28±0.18), (8.90±0.29), (21.0±2.5) mmol/L] showed lower levels than the model group ( P<0.05). The model group had higher ALT, AST, and ALP levels than the control group [(274±43) U/L vs. (99±14) U/L, (130±66) U/L vs. (38±4) U/L, (86±15) U/L vs. (60±5) U/L, respectively]. Both the atorvastatin group [(139±12), (58±16), (69±5) U/L] and the chlorogenic acid group [(138±11), (55±16), (54±5) U/L] exhibited lower levels than the model group ( P<0.05). Inflammatory cytokines: The model group had higher IL-6, IL-1β, and TNF-α levels than the control group [(238±15) ng/L vs. (202±7) ng/L, (211±6) ng/L vs. (174±6) ng/L, (1 325±75) ng/L vs. (1 036±75) ng/L, respectively]. Both the atorvastatin group [(215±9), (191±4), (1 163±78) ng/L] and the chlorogenic acid group [(220±13), (195±7), (1 197±53) ng/L] showed reduced levels compared to the model group (all P<0.05). Conclusion:Chlorogenic acid may inhibit aortic lipid plaque deposition and ameliorate AS in mice by improving lipid metabolism and suppressing inflammatory responses.
7.Clinical evaluation of anlotinib in third-line treatment for advanced non-small cell lung cancer based on real-world data
Jian WU ; Peipei LI ; Yongfu ZHU ; Dongwei ZHANG ; Yongzhong WANG ; Hao CHEN
China Pharmacy 2025;36(12):1488-1494
OBJECTIVE To evaluate the clinical value of anlotinib in third-line treatment for patients with advanced non-small cell lung cancer(NSCLC)through real-world data.METHODS Clinical data of patients with advanced NSCLC who received treatment at the First Affiliated Hospital of Anhui University of Chinese Medicine from February 2021 to December 2024 were retrospectively collected.They were divided into anlotinib group(27 cases,receiving anlotinib therapy)and immunotherapy group(22 cases,receiving immunotherapy agents alone or in combination with chemotherapy drugs)according to treatment regimens.The progression-free survival(PFS)and overall survival(OS)of patients were compared between the two groups,and the occurrence of adverse drug reactions during the treatment period was recorded.Using a partitioned survival model,an economic evaluation of the two treatment regimens was conducted with a cost-utility analysis approach from the perspective of the healthcare system.RESULTS The median PFS and OS of patients in the anlotinib group were 5.93 months and 11.27 months,respectively;the median PFS and OS of patients in the immunotherapy group were 5.33 months and 9.77 months,respectively;the difference was not statistically significant(P>0.05).There was no statistical difference in the total incidence of adverse drug reactions and grade 3-4 serious adverse drug reactions between the two groups(P>0.05).Compared with the immunotherapy group,the incremental cost-effectiveness ratio of the anlotinib group was 1 806 724.60 yuan/quality-adjusted life year(QALY),which was significantly higher than three times China's per capita gross domestic product in 2024(287 247 yuan/QALY).CONCLUSIONS For third-line treatment of advanced NSCLC patients,the efficacy of anlotinib is no worse than that of immunotherapy alone or in combination with chemotherapy drugs,and the safety of the two groups is comparable.However,anlotinib is not cost-effective.
8.Effect and mechanism of compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis in T2DM insulin resistance rats
Shuang WEI ; Feng HAO ; Wenchun ZHANG ; Zhangyang ZHAO ; Ji LI ; Dongwei HAN ; Huan XING
China Pharmacy 2025;36(1):57-63
OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus (T2DM) insulin resistance (IR) rats.METHODS Sixty male SD rats were randomly divided into control group (12 rats) and modeling group (48 rats).The modeling group was fed with a high-fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model.The model rats were randomly divided into model group,the compatibility of Astragali Radix-Puerariae Lobatae Radix group[QG group,4.05 g/(kg·d),intragastric administration],ferroptosis inhibitor ferrostatin-1 group[Fer-1 group,5 mg/kg by intraperitoneal injection,once every other day],the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group[QG+erastin group,4.05 g/(kg·d) by intragastric administration+erastin 10 mg/(kg·d),intraperitoneal injection].After 4 weeks of intervention,serum fasting blood glucose (FBG) and fasting insulin (FINS) were measured in each group of rats,and homeostasis model assessment of insulin resistance (HOMA-IR) and the natural logarithm of insulin action index(IAI) were calculated;the serum levels of total cholesterol (TC),triglyceride (TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C),aspartate transaminase (AST) and alanine transaminase (ALT),Fe2+and Fe content,glutathione (GSH),malondialdehyde (MDA) and superoxide dismutase (SOD) levels,NADP+/NADPH ratio and reactive oxygen species (ROS) were determined.The pathological morphology of its liver tissue was observed;the protein expressions of glutathione peroxidase 4 (GPX4),ferritin heavy chain 1 (FTH1),long-chain acyl-CoA synthetase 3 (ACSL3),ACSL4,ferritin mitochondrial (FTMT),and cystine/glutamate anti-porter (xCT) in the liver tissue of rats were detected.RESULTS Compared with control group,the liver cells in the model group of rats showed disordered arrangement,swelling,deepened nuclear staining,and more infiltration of inflammatory cells,as well as a large number of hepatocyte vacuoles and steatosis;FBG (after medication),the levels of TC,TG,LDL-C,AST,ALT,FINS,MDA and ROS,HOMA-IR,Fe2+and Fe content,NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated,while the levels of HDL-C,GSH and SOD,IAI,protein expressions of GPX4,FTH1,ACSL3,FTMT and xCT were significantly reduced or down-regulated (P<0.01).Compared with the model group,both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators,the differences in the changes of most indicators were statistically significant (P<0.01 or P<0.05).Compared with QG group,the improvement of the above indexes of QG+erastin group had been reversed significantly (P<0.01).CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats,and alleviate IR degree,ion overload and pathological damage of liver tissue.The above effects are related to the inhibition of ferroptosis.
9.Effects of advanced bone flap versus no bone flap on the healing of osteotomy gap in high tibial osteotomy
Jiahao YU ; Dongwei WU ; Yanbin ZHU ; Yingze ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(2):96-102
To compare the effects of advanced bone flap and no bone flap on the healing of osteotomy gap in open-wedge high tibial osteotomy (OW-HTO) for the treatment of medial compartment osteoarthritis and knee inversion.Methods:A retrospective study was conducted to analyze the 85 patients who had undergone OW-HTO from March 2021 to December 2021 at Trauma Emergency Centre, The Third Hospital of Hebei Medical University for medial compartment osteoarthritis and knee inversion. The patients were divided into 2 groups according to whether bone flap was grafted. In group A of 42 patients who received advanced bone flap intraoperatively, there were 32 females and 10 males with an age of (63.7±6.6) years; in group B of 43 patients who received no advanced bone flap intraoperatively, there were 31 females and 12 males with an age of (63.2±9.4) years. The measures recorded and compared between the 2 groups included: osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS) for pain, and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 18 months postoperatively; medial proximal tibial angle (MPTA) and femorotibial angle at immediate postoperation and 18 months postoperation; postoperative complications.Results:The differences in preoperative general information between the 2 groups were not statistically significant, showing comparability ( P>0.05). The osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively in group A were significantly higher than those in group B ( P<0.05). The WOMAC (26.1±5.9), VAS (4.1±1.4), and KOOS (47.0±9.7) scores at 6 months postoperatively in group A were significantly lower than those in group B (31.3±8.3, 4.8±1.6, and 56.1±11.9) ( P<0.05), but the differences in the above indicators between the 2 groups at 18 months postoperatively were not statistically significant ( P>0.05). There was no statistically significant difference in MPTA or femorotibial angle at immediate postoperation between the 2 groups ( P>0.05). At 18 months postoperatively, the MPTA in group A (88.7°±1.1°) was significantly better than that in group B (87.7°±1.5°) ( P<0.05). The total complication rate in group B [27.9% (12/43)] was signifcantly higher than that in group A [2.4% (1/42)]( P<0.05). Conclusions:In the OW-HTO treatment of the patients with medial compartment osteoarthritis and knee inversion, application of an advanced bone flap to fill the osteotomy gap can accelerate the gap healing and reduces occurrence of delayed healing or non-healing of the osteotomy gap.
10.Mechanism of Si Junzitang in Inhibiting Hepatocellular Carcinoma Progression Through Regulating O-GlcNAcylation of NF-κB p65 in Paracancerous Tissues
Mingzhe LI ; Zhaoqin FANG ; Weifei ZHANG ; Peike PENG ; Dongwei JIA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):21-28
ObjectiveTo investigate the molecular mechanism by which Si Junzitang in intervening in the development of hepatocellular carcinoma (HCC) by regulating the O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) of nuclear factor kappa-B (NF-κB) p65 in the paracancerous tissues. MethodThe orthotopic liver cancer mouse model was established. Twenty-four C57BL/6 mice were randomly divided into four groups: Normal group, model group, Si Junzitang low-dose group (10 g·kg-1), and Si Junzitang high-dose group (25 g·kg-1), with 6 mice in each group. The O-GlcNAcylation level and phosphorylation modification level of p65 in the paracancerous tissues were detected using Western blot. The O-GlcNAcylation of p65 was assessed using immunoprecipitation (IP). The mRNA expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) in the paracancerous tissues was detected using real-time quantitative polymerase chain reaction (Real-time PCR). The tumor number, liver weight, locomotor activity, grip strength, and Qi status of the mice were observed and analyzed. ResultCompared with the normal group, the model group showed a significant decrease in O-GlcNAcylation in the paracancerous tissues (P<0.01), a significant decrease in p65 O-GlcNAcylation (P<0.01), a significant increase in p65 phosphorylation (P<0.01), significantly elevated mRNA levels of cytokines IL-6, TNF-α, TGF-β1, VEGFA, MMP-2, and MMP-9 (P<0.01), significantly increased liver weight (P<0.01), significantly declined grip strength, number of grid crossings, and number of vertical stand-ups (P<0.01), and significantly dwindled Qi status (P<0.01). Compared with model group, the Si Junzitang low-dose and high-dose groups showed significantly increased levels of O-GlcNAcylation in the paracancerous tissues (P<0.05, P<0.01), significantly upregulated p65 O-GlcNAcylation levels (P<0.05, P<0.01), and significantly decreased p65 phosphorylation levels (P<0.01). In the Si Junzitang low-dose group, the mRNA levels of IL-6, TGF-β1, and VEGFA significantly decreased (P<0.05, P<0.01). In the Si Junzitang high-dose group, the mRNA levels of IL-6, TNF-α, TGF-β1, VEGFA, MMP-2, and MMP-9 significantly decreased (P<0.01), the number of tumors larger than 3 mm in diameter significantly decreased (P<0.01), and liver weight significantly decreased (P<0.05). Additionally, grip strength, number of grid crossings, and number of vertical stand-ups significantly increased (P<0.05, P<0.01), along with a significant increase in qi status (P<0.01). ConclusionSi Junzitang can inhibit the progression of orthotopic HCC in mice, which may be achieved by increasing the O-GlcNAcylation level in the paracancerous tissues, enhancing the O-GlcNAcylation of p65, inhibiting the phosphorylation modification of p65, and ultimately suppressing the expression of downstream IL-6, TNF-α, TGF-β1, VEGFA, MMP-2, and MMP-9.

Result Analysis
Print
Save
E-mail