1.Effect of Modified Xiangsha Liujunzitang on Hepatic Kupffer Cell Inflammation Mediated by Intestinal-derived LPS in Rats with Hyperlipidemia and Spleen Deficiency Syndrome
Mengzhu CHE ; Lianqun JIA ; Dongyu MIN ; Guoyuan SUI ; Qi ZHANG ; Guanlin YANG ; Yunhao CUI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):77-86
ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang (M-XSLJZ) on intestinal-derived lipopolysaccharide (LPS)-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups (n=10): blank control (CON), high-fat diet without spleen deficiency (HFD), high-fat diet with spleen deficiency (SD-HFD), M-XSLJZ low-, medium-, and high-dose groups (XS-L, XS-M, XS-H), and western medicine control (R). Spleen deficiency was induced in SD-HFD, XS-L, XS-M, XS-H, and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet, while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling, rats were treated for 8 weeks: M-XSLJZ was administered at 3.51, 7.02, 14.04 g·kg-1 in XS-L, XS-M, and XS-H groups, respectively. The R group received 9×10-4 g·kg-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin (HE) staining was used to evaluate the pathological conditions of the liver, and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS, portal vein serum LPS, LPS-binding protein (LBP), serum interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4, MyD88, NF-κB p65, and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6, TNF-α, and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the CON group, the SD-HFD group showed a decrease in D-xylose excretion (P<0.01). TC, TG, HDL-C, and LDL-C increased (P<0.05, P<0.01). A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS, portal LPS, and LBP increased (P<0.05, P<0.01). The levels of serum IL-6, TNF-α, and IL-1β increased (P<0.01). The expression of CD86 was upregulated (P<0.01), and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4, MyD88, and p-p65 in Kupffer cells increased (P<0.01). The mRNA and protein levels of IL-6, TNF-α, and IL-1β increased (P<0.05, P<0.01). Compared with the HFD group, the SD-HFD group exhibited decreased D-xylose excretion (P<0.01), higher HDL-C, LDL-C (P<0.05), increased portal LBP and LPS (P<0.05), increased serum IL-6 and TNF-α (P<0.01), upregulated CD86 (P<0.01), enhanced CD68/TLR4 co-expression, and higher TNF-α mRNA/protein (P<0.05). Compared with the SD-HFD group, all M-XSLJZ treatment groups showed reduced TC, TG, and LDL-C (P<0.05, P<0.01). XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS, portal LPS, and LBP levels (P<0.05, P<0.01). All M-XSLJZ treatment groups exhibited reduced serum IL-6, IL-1β, and TNF-α (P<0.01). The XS-H group showed downregulated CD86 (P<0.01) and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4, MyD88, and p-NF-κB p65 in Kupffer cells (P<0.01). XS-H and R groups showed lower IL-6, TNF-α, and IL-1β mRNA/protein (P<0.05, P<0.01). ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.
2.Electroencephalogram in the stage of temporal memory retrieval
Aili WANG ; Meixue JIA ; Li SUI
International Journal of Biomedical Engineering 2024;47(3):234-241
Objective:To explore the changes in behavioral indexes and electroencephalogram (EEG) in the stage of temporal memory retrieval under different extraction times.Methods:A total of 30 healthy subjects were randomly selected from Shanghai University of Science and Technology in November 2022. The reaction time and EEG of the subjects in the 1 500 ms stage of temporal memory retrieval were recorded by a reproduction method of time estimation task. The memory error rate, precision, accuracy, and low-frequency power of EEG were calculated, and time-frequency analysis and traceability analysis were carried out. Pearson correlation analysis was used to analyze the correlation between memory error rate, accuracy, θ rhythm, and β rhythm.Results:The main effects of time difference and memory precision between retrieval times were found [ F(3, 1 196) = 2.932, P = 0.033; F(3, 1 196) = 3.191, P = 0.026], and they increased with the extraction times. There was no main effect on memory accuracy, but as the number of extractions increases, the average accuracy increased. With the increase in memory retrieval times, the power of θ rhythm in the left frontal lobe gradually increased [ F(3, 116) = 2.668, P = 0.035], and the average power of β rhythm in the middle frontal lobe gradually decreased [ F(3, 116) = 2.810, P = 0.029]. The differences in current density distribution in the somatosensory cortex (BA7), dorsolateral prefrontal cortex (BA9), and premotor cortex (BA6) increased in the first and second, second and third, and third and fourth memory retrievals ( P < 0.01). The θ rhythm was positively correlated with memory accuracy ( r = 0.258, P < 0.05), and the β rhythm was negatively correlated with memory precision ( r = ? 0.404, P < 0.01). Conclusions:In the stage of temporal memory extraction, increasing the number of temporal memory extraction times can reduce the memory error rate and improve accuracy. Memory accuracy is related to the power of the θ rhythm in the left frontal lobe and the power of the β rhythm in the middle frontal lobe.
3.Applications of new approach methodologies in food toxicology research in China
Hui YANG ; Miaoying SHI ; Daoyuan YANG ; Haixia SUI ; Zhou YU ; Xudong JIA
Chinese Journal of Pharmacology and Toxicology 2024;38(10):734-741
Food toxicology plays a crucial role in supporting scientific and technical aspects of food safety risk assessment.However,traditional methods relying on animal testing are becoming increas-ingly inadequate for identifying and evaluating emerging foods and unknown risks.There is a strong push worldwide towards the development of new approach methodologies(NAMs)based on non-animal testing methods.Policies and regulations related to NAMs are being standardized gradually in the European Union,the United States,and China.Some progress has also been made in applying these methodologies in food toxicology research in China.For instance,within the"Food Toxicology Program"at the National Center for Food Safety Risk Assessment,high-content and high-throughput in vitro hazard identification models employing model organisms like human macrophages,hepatocytes,adipocytes,embryonic stem cells,and zebrafish,as well as Toxicological Thresholds of Concern and quantitative in vitro to in vivo extrapolation based on physiologically-based toxicokinetic models have been estab-lished and applied.Nonetheless,new toxicological hazard identification technologies still face challenges such as inadequate elucidation of toxic mechanisms,insufficient collaborative research efforts,and inef-ficient translation of these findings into practical applications.
4.Anti-inflammatory drugs in the treatment of diabetic nephropathy:a Meta-analysis
Yang ZHAO ; Qingqing WEI ; Xiangyu ZHAN ; Dongrui ZHANG ; Jia LIU ; Song XUE ; Yang ZHANG ; Jiahao DENG ; Hongyu SUI
China Pharmacist 2024;27(4):684-696
Objective To systematically review the efficacy of anti-inflammatory drugs in the treatment of diabetic nephropathy(DN).Methods Databases including PubMed,The Cochrane Library,EMbase,Web of Science,Scopus,Ovid,ProQuest,CBM,CNKI,WanFang Data,VIP and Duxiu data were electronically searched to collect randomized controlled trials(RCTs)of anti-inflammatory drugs for DN from inception to April 5,2022.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies.RevMan 5.4 software were then used to perform Meta-analysis.Results A total of 29 literature and 26 RCTs involving 4 095 patients were included.The results of Meta-analysis showed that compared with conventional treatment,conventional treatment combined with anti-inflammatory drugs could effectively reduce urinary albumin to creatinine ratio[SMD=-0.17,95%CI(-0.31,-0.03),P=0.02],urinary albumin excretion rate[SMD=-0.37,95%CI(-0.56,-0.18),P=0.000 1],urinary protein excretion rate[SMD=-0.97,95%CI(-1.29,-0.64),P=0.000 01],and glycosylated hemoglobin[SMD=-0.17,95%CI(-0.27,-0.08),P=0.000 4],while there was no significant difference in reducing serum creatinine[SMD=-0.04,95%CI(-0.19,0.1),P=0.57],urea nitrogen[MD=-0.23,95%CI(-0.50,0.04),P=0.09]and fasting blood glucose[SMD=-0.15,95%CI(-0.32,0.02),P=0.08].There was no statistically significant difference in changing glomerular filtration rate(GFR)[SMD=-0.04,95%CI(-0.15,0.07),P=0.47]with multiple drugs,except for a few drugs.Conclusion Conventional treatment combined with anti-inflammatory drugs can better improve the level of proteinuria in patients with DN,but the improvement of renal function is not obvious.Due to the limitations of the number of included studies and the duration of treatment,the above conclusion needs to be verified by more high-quality studies.
5.Application of excellence-performance management model in macro-quality management for occupational medical examination institutions
Runan LIAN ; Junmei JIN ; Yan JIA ; Qifen GUO ; Hongda ZHANG ; Xin SUI ; Fang JI ; Xingfu PAN
China Occupational Medicine 2024;51(6):713-716
Objective To analyze the status of occupational hazards in key positions of the small and micro book and newspaper printing enterprises in Beijing City. Methods A total of 16 small and micro printing enterprises in Beijing City were selected as the research subjects using the judgment sampling method. The status of occupational hazard was assessed using on-site occupational health investigations. The volatile chemical components in organic solvents such as inks and cleaning agents used in the workplace, the level of chemical hazardous agents in the air, and noise intensity were detected and analyzed. Results A total of 1 105 workers from 16 small and micro printing enterprises were included. The occupational hazard exposure rate was 22.2% (245/1 105), with chemical hazardous agents and noise exposure rates of 13.5% and 22.2%, respectively. The rate of compliance with occupational health training among the head of the enterprise and the occupational health management personnel, the regular detection rate of occupational hazards in last year, and the rate for the occupational health examination in last year were both 100.0%. The rate for annual update of occupational hazard project reporting was 93.8% (15/16). The usage rates of gas mask and noise-proof earplug were 68.8% (11/16) and 50.0% (8/16), respectively. The effectiveness rates of anti-toxic and noise-reduction facilities were 87.5% (14/16) and 62.5% (10/16). The sign setting rates of chemical hazardous agents and noise warning were 93.8% (15/16). Acetone and isopropanol were found in ink and cleaning agents in 15 printing enterprises, while toluene, xylene, and ethylbenzene were found in three, two, and one enterprise, respectively. Benzene, 1,2-dichloroethane, n-hexane, and trichloroethylene were not found in all 16 enterprises. Both the exposure concentration of short term and exposure concentration of time weighted average of the above chemical hazards were lower than the lower limit of quantitation of the detection method in the workplace and work site air among the 16 printing enterprises, and none of concentration was exceeded the national standard. A total of 240 noise work sites were detected, and the national noise-exceeding rate was 11.2%(27/240). Conclusion Noise hazards are prominent in the small and micro printing enterprises in Beijing City, and attention should be paid to the prevention and protection of noise-exposure. The usage rate of personal protective equipment is not high, and the training and on-site supervision management of protective equipment wearing in workers should be strengthened.
6.Clinical analysis of the correlation between the expression of soluble B cell maturation antigen and the efficacy of chimeric antigen receptor T cell targeting B cell maturation antigen in patients with multiple myeloma
Shuquan GAO ; Juan MU ; Xin LI ; Jia WANG ; Rui CUI ; Jingyi LI ; Tao SUI ; Qi DENG
Chinese Journal of Hematology 2024;45(4):378-382
Objective:The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) .Methods:This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared.Results:①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD ( P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ( R2=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion:sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.
7.Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture (version 2024)
Yun HAN ; Feifei JIA ; Qing LU ; Xingling XIAO ; Hua LIN ; Ying YING ; Junqin DING ; Min GUI ; Xiaojing SU ; Yaping CHEN ; Ping ZHANG ; Yun XU ; Tianwen HUANG ; Jiali CHEN ; Yi WANG ; Luo FAN ; Fanghui DONG ; Wenjuan ZHOU ; Wanxia LUO ; Xiaoyan XU ; Chunhua DENG ; Xiaohua CHEN ; Yuliu ZHENG ; Dekun YI ; Lin ZHANG ; Hanli PAN ; Jie CHEN ; Kaipeng ZHUANG ; Yang ZHOU ; Sui WENJIE ; Ning NING ; Songmei WU ; Jinli GUO ; Sanlian HU ; Lunlan LI ; Xiangyan KONG ; Hui YU ; Yifei ZHU ; Xifen YU ; Chen CHEN ; Shuixia LI ; Yuan GAO ; Xiuting LI ; Leling FENG
Chinese Journal of Trauma 2024;40(9):769-780
Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.
8.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
9.Discussion on the Scientific Connotation of Fortifying Spleen, Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein
Lianqun JIA ; Qige WANG ; Guoyuan SUI ; Nan SONG ; Huimin CAO ; Liang KONG ; Meijun LV ; Yuan CAO ; Ning YU ; Siyuan DING ; Guanlin YANG
Journal of Traditional Chinese Medicine 2024;65(2):128-133
The key pathogenesis of coronary heart disease (CHD) is spleen deficiency and phlegm stasis, and dysfunctional high-density lipoprotein (dys-HDL) may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein (HDL), it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL; and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways, namely, mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells, thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency, and spleen deficiency makes foundation for the production of dys-HDL; dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen, resolving phlegm, and dispelling stasis, is proposed as an important principle in the treatment of CHD by traditional Chinese medicine, which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL, thus revealing the scientific connotation of this method, and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.
10.Exploration of the effects of Huayu qutan formula on atherosclerosis in ApoE-/- mice based on EETs-mediated pyroptosis
Na ZHAO ; Guoyuan SUI ; Jiawei MENG ; Meijun LYU ; Lianqun JIA
China Pharmacy 2024;35(12):1437-1442
OBJECTIVE To explore the effects and mechanism of Huayu qutan formula on atherosclerosis (AS) in ApoE-/- mice. METHODS Thirty ApoE-/- mice were randomly divided into model group, Huayu qutan formula group [20 g/(kg·d)], rosuvastatin group [1.55 mg/(kg·d)], with 10 mice in each group. Another 10 C57BL/6J mice were selected as normal control group. ApoE-/- mice were given high-lipid diet for 12 weeks to induce AS model. After modeling, each group was given relevant medicine or normal saline intragastrically, once a day, for 4 consecutive weeks. After the last administration, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL- C), 5,6-epoxyeicosatrienoic acid (5, 6-EET), 8,9-EET, 11,12-EET, 14,15-EET, interleukin-1β (IL-1β) and IL-18 in serum were detected; mRNA expressions of inhibitor of nuclear factor κB (IκB), nuclear factor κB (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Caspase-1, IL-1β and IL-18 in the aortic tissue of mice were detected; protein expression levels of IκB, NF- κB, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in the aortic tissue of mice were detected. The morphological changes of the aortic tissue were observed. RESULTS Compared with model group, the serum levels of TC, TG, LDL-C, IL-1β and IL-18, the mRNA expressions of IκB, NF-κB, NLRP3, Caspase-1, IL-1β and IL-18 in aortic tissue, and the protein expressions of IκB, NF-κB, NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 were all decreased significantly in Huayu qutan formula group and rosuvastatin group (P<0.05), while the serum levels of 5,6-EET, 8,9-EET, 11,12-EET and 14,15-EET were increased significantly (P<0.05). The aortic atherosclerotic plaques were alleviated significantly. CONCLUSIONS Huayu qutan formula can play role of anti-AS through EETs-mediated pyroptosis.

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