1.Effect of Modified Duhuo Jisheng Mixture Regulating PI3K/Akt/mTOR Signaling Pathway on Synoviocyte Pyroptosis in Rabbit Models of Knee Osteoarthritis
Zifeng YE ; Yiwei YUAN ; Liguo QIU ; Xuyi TAN ; Liang OU ; Gaoyan KUANG ; Min LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):170-179
ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture (JDJM) in treating synovial lesions in knee osteoarthritis (KOA). MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group (n=8) and a model group (n=35). The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage, with a modeling period of 6 weeks, resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group, celecoxib group, JDJM group and JDJM+740Y-P group, each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg-1, while the JDJM was administered a single dose of 6.8 mL·kg-1 (4.515 2 g·kg-1) of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway activator + JDJM group received 4.515 2 g·kg-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg-1 740Y-P. For a period of 6 weeks, the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period, the knee joint pain threshold and circumference were measured, and hematoxylin-eosin (HE) staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay (ELISA) measured the levels of interleukin-1β (IL-1β), interleukin-6 (IL-18) and tumor necrosis factor-α (TNF-α) in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, NOD-like receptor protein 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1) and gasdermin D (GSDMD) in the synovial tissues. Immunohistochemical (IHC) assay was performed to assess the protein expression of NLRP3, Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD. ResultsCompared to the blank group, the model group showed a significant increase in knee joint circumference and decrease in pain threshold, the synovial tissue pathology score was higher (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid significantly increased (P<0.01). PI3K, Akt, mTOR phosphorylation as well as mRNA and protein expression increased (P<0.01), while the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD also significantly increased (P<0.01). Compared to the model group, the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold, the synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid decreased (P<0.01). The mRNA and protein expression of p-PI3K, p-Akt, p-mTOR, NLRP3, Caspase-1 and GSDMD were reduced (P<0.01). Compared to the JDJM group, the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions, an increase in knee joint circumference, and a decrease in pain threshold. The synovial tissue pathology score was lower (P<0.05), and the levels of IL-1β, IL-18, and TNF-α in the joint fluid were higher (P<0.01). The mRNA and protein expression of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, NLRP3, Caspase-1 and GSDMD increased (P<0.01). ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues, inhibiting pyroptosis, reducing inflammatory factor release, and protecting bony structures.
2.Research progress on the chemical composition and antidepressant mechanism of volatile oils of traditional Chinese medicine
Yifei ZHANG ; Lu CHENG ; Mingshi REN ; Dao GUO ; Fengjiao KUANG ; Zonghua KANG ; Jianguang LUO ; Feihua WU
Journal of China Pharmaceutical University 2025;56(1):22-30
Depressive disorder is a mental illness characterized by poor mood and cognitive dysfunction caused by a range of complicated factors. Antidepressants have strong short-term efficacy in clinical application, yet with significant adverse effects and resistance in long-term use. Essential oils are small molecular compounds mainly composed of monoterpenes and sesquiterpenes, most of which are characterized by aromatic odors, easy permeability through the blood-brain barrier, and low toxic side effects. Volatile oil from traditional Chinese medicine can regulate neurotransmitter monoamine, hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, neuroinflammation and oxidative stress, and intestinal microbiota-gut-brain axis to exert an antidepressant effect through multiple pathways and targets. This review summarizes the main antidepressant chemical components of essential oil of traditional Chinese medicine, their pharmacological mechanisms and clinical application, aiming to provide some reference for further development and clinical application of essential oil of traditional Chinese medicine.
3.Association between maternal lipids during pregnancy and risk of offspring s overweight and obesity at 3 years of age
Chinese Journal of School Health 2025;46(8):1074-1078
Objective:
To explore the association between maternal lipid levels during pregnancy and the risk of overweight and obesity in offspring at 3 years of age, providing scientific evidences for the prevention and control of childhood obesity.
Methods:
A total of 2 432 mother-child pairs with maternal lipid tests during pregnancy and offspring s physical growth data at 3 years of age were included from the Borin in Guangzhou Cohort Study up to September 2021. Lipid indicators, including high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), triglycerides (TG), and total cholesterol (TC), were measured at 13-19 +6 weeks (mid pregnancy) and 32-39 +6 weeks (late pregnancy). Children s body mass index (BMI) Z score were calculated according to the World Health Organization s growth standards for children under 5 years old. The lipid Z score were divided into four quartiles: Q 1, Q 2, Q 3 and Q 4. Linear regression was used to analyze the relationship between maternal lipid levels during pregnancy and offspring’s BMI Z score at 3 years of age. Poisson regression with a robust error variance was employed to evaluate the association between maternal lipid levels during pregnancy and the at risk of overweight and obesity in offspring at 3 years of age, after adjusting for maternal age at conception, education level, parity, pre pregnancy BMI and gestational diabetes mellitus.
Results:
There was a statistically significnt difference in the detection rate of overweight and obesity risk among children with different mothers s pre pregnancy BMI ( χ 2=22.85, P <0.05). Linear regression analysis showed that TG levels in late pregnancy were positively related to BMI Z score ( β=0.10, 95%CI=0.02-0.18, P <0.05). Poisson regression with a robust error variance indicated that, compared with the Q 1 group of TC, the Q 4 group of TC in mid pregnancy was associated with an increased risk of overweight and obesity in offspring at 3 years of age ( RR=1.59, 95%CI =1.04-2.44); compared with the Q 1 group of TG, the Q 4 group of TG during late pregnancy increased the risk of overweight and obesity in offspring at 3 years of age ( RR=1.79, 95%CI =1.02-3.12) (both P <0.05).
Conclusions
Maternal serum TC level during mid pregnancy can increase the risk of overweight and obesity in offspring at 3 years of age. Maternal serum TG levels during late pregnancy is positively correlated with BMI and the risk of overweight and obesity in offspring at 3 years of age.
4.HDAC1 overexpression inhibits steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells by inducing SP1 deacetylation.
Shenyao ZHANG ; Min LU ; Gaoyan KUANG ; Xiaotong XU ; Jun FU ; Churan ZENG
Journal of Southern Medical University 2025;45(1):10-17
OBJECTIVES:
To explore the mechanism by which histone deacetylase 1 (HDAC1) regulates steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells.
METHODS:
MLY-O4 cells were treated with 400 nmol/L trichostatin A (TSA) or 1 mmol/L dexamethasone for 24 h or transfected with a HDAC1-overexpressing vector prior to TSA or dexamethasone treatment. The changes in the expressions of HDAC1, SP1, cleaved caspase-3 and Bax, SP1 acetylation level, cell proliferation, and cell apoptosis were examined. The interaction between HDAC1 and SP1 was determined with immunoprecipitation assay and Western blotting.
RESULTS:
Treatment with dexamethasone significantly increased cell apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, reduced HDAC1 expression, and suppressed proliferation of MLO-Y4 cells. Both TSA and dexamethasone obviously increased SP1 acetylation level and the expression of SP1 in MLO-Y4 cells. HDAC1 overexpression in the cells significantly attenuated the effect of TSA and dexamethasone, promoted cell proliferation, lowered the expressions of SP1, cleaved caspase-3 and Bax, and inhibited dexamethasone-induced cell apoptosis. Immunoprecipitation assay and Western blotting demonstrated the interaction between HDAC1 and SP1 in the cells.
CONCLUSIONS
HDAC1 inhibits dexamethasone-induced apoptosis and promotes proliferation of cultured mouse osteocytes by suppressing SP1 expression via promoting its deacetylation.
Animals
;
Apoptosis/drug effects*
;
Mice
;
Histone Deacetylase 1/genetics*
;
Osteocytes/drug effects*
;
Sp1 Transcription Factor/metabolism*
;
Acetylation
;
Dexamethasone/pharmacology*
;
Cell Proliferation/drug effects*
;
Caspase 3/metabolism*
;
Cell Line
;
Hydroxamic Acids/pharmacology*
;
bcl-2-Associated X Protein/metabolism*
5.Construction of SPHK1 overexpression lentiviral vectors and establishment of stable transfected SKOV3 cell lines
Qiuyuan SU ; Ling ZHAO ; Jiajia TAN ; Shien MO ; Haiqin ZHOU ; Fangfang LU ; Yi WEI ; Yang ZHOU ; Yan KUANG
Journal of Jilin University(Medicine Edition) 2025;51(6):1709-1716
Objective:To construct the sphingosine kinase 1(SPHK1)overexpression lentiviral vector,and to establish the SKOV3 lentiviral stable transfection cell line.Methods:According to the SPHK1 data information provided by the National Center for Biotechnology Information(NCBI)database,the primers were designed and synthesized,the target gene was amplified,and connected to the GV492 plasmid treated with Bam HⅠ and AgeⅠ restriction enzymes to construct the SPHK1 overexpression lentiviral vector;the positive clones were selected for PCR and sequencing identification;the lentiviral plasmid and the lentiviral packaging auxiliary plasmid were co-transfected into the HEK-293T cells for packaging and titer determination;according to the measured optimal multiplicity of infection(MOI)of 10,the corresponding lentiviral amounts in various groups were transfected into the SKOV3 cells,and the SKOV3 cells were divided into blank group(without treatment),GV492 control group(GV492 control lentivirus infected SKOV3 cells),and GV492-SPHK1 overexpression group(GV492-SPHK1 overexpression lentivirus infected SKOV3 cells,ov-SPHK1 group);the optimal concentration of 2 mg·L-1 puromycin was used to screen the stably transfected SKOV3 cell line;after 48 h,the medium was changed and replaced with 1 mg·L-1 puromycin for screening for 14 d;the morphology and fluorescence expression of the cells were observed under fluorescence microscope;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of SPHK1 mRNA in the SKOV3 cells in various groups;Western blotting method was used to detect the expression level of SPHK1 protein in the SKOV3 cells in various groups.Results:The PCR sequencing results showed that the gene sequence of the SPHK1 overexpression lentiviral vector was completely consistent with the target sequence,and the SPHK1 overexpression lentiviral vector was successfully constructed;the titer determination results showed that the lentiviral titers in GV492 control group and ov-SPHK1 group were 5×1011 and 8×1011 TU·L?1,respectively;the SKOV3 cells in GV492 control group and ov-SPHK1 group were in good state and showed strong fluorescence expression,suggesting that the SKOV3 stable transfection cell line overexpressing SPHK1 was successfully established;the RT-qPCR results showed that compared with blank group and GV492 control group,the expression level of SPHK1 mRNA in the SKOV3 cells in ov-SPHK1 group was significantly increased(P<0.01);the Western blotting results showed that compared with blank group and GV492 control group,the expression level of SPHK1 protein in the SKOV3 cells in ov-SPHK1 group was significantly increased(P<0.01).Conclusion:The SPHK1 overexpression lentiviral vector is successfully constructed,and the SKOV3 stable transfection cell line is established.
6.The role of H-type vessels as a mediator of subchondral bone remodeling and cartilage degeneration in the pathogenesis of knee osteoarthritis
Zifeng YE ; Yiwei YUAN ; Liguo QIU ; Gaoyan KUANG ; Min LU
Journal of Chongqing Medical University 2025;50(9):1247-1252
There is a close relationship between subchondral bone remodeling and angiogenesis in knee osteoarthritis(KOA).Type H vessels,a newly identified subtype of bone vasculature,play a pivotal role in linking angiogenesis with osteogenesis by mediating signals through various cytokines,thereby regulating bone growth and homeostasis.During KOA development,mechanical loads and factors like transforming growth factor-β1(TGF-β1),platelet-derived growth factor-BB(PDGF-BB),vascular endothelial growth factor(VEGF)cause abnormal H-type vessel growth in subchondral bone and cartilage.This suggests that H-type vessel regulation might be a potential KOA treatment mechanism.This article explores the role of H-type vessels in subchondral bone remodeling and cartilage degeneration and the factors driving their abnormal growth,which provides a theoretical basis for further research and high-lights the potential of targeting H-type vessels for KOA treatment.
7.Construction and Validation of Prediction Model of Gestational Diabetes Mellitus Based on Multivariate Regression Analysis in the First Trimester of Pregnancy
Menghua KUANG ; Cong LU ; Mengjiao KUANG
Journal of Modern Laboratory Medicine 2024;39(1):158-161,204
Objective To explore the risk factors of gestational diabetes mellitus(GDM)in the first trimester(12~13+6 weeks)of pregnancy,build a prediction model and verify it.Methods 433 singleton pregnant women delivered in the First People's Hospital of Shanghai from January 2020 to December 2020 were selected.They were divided into GDM group(n=188)pregnant women and non-GDM group(n=245)pregnant women according to a 75g glucose tolerance test results at 24~28 weeks of gestation.The electrochemiluminescence method measured serum biochemical indexes in early pregnancy,and glycosylated hemoglobinAlc was measured by ion exchange high-performance liquid chromatography.Using logistic regression analysis to screen the risk factors of GDM and construct a predictive model,draw the subject's work characteristic curve to analyze the model's predictive value.Ninety-five pregnant women who underwent prenatal examinations at Shanghai First People's Hospital from January 2021 to June 2021 were selected to validate the model's effectiveness.Results Compared with the non-GDM group,the level of body mass index(BMI)(23.41±11.17 kg/m2 vs 21.18±2.88 kg/m2),gamma-glutamyl transpeptidase(γ-GGT)(16.61±10.62 U/L vs 14.00±8.35 U/L),triacylglycerol(TG)(1.90±0.58 mmol/L vs 1.57±0.55 mmol/L),glycosylated hemoglobinAlc(HbAlc)(5.25%±0.47%vs 5.07±0.34%),fasting blood glucose(FBG)(4.68±0.47 mmol/L vs 4.36±0.36 mmol/L),LDL/HDL(1.53±0.49 vs 1.41±0.50),TG/HDL(2.93±0.59 vs 2.71±0.58),and TC/HDL(1.19±0.49 vs 0.95±0.45)in GDM group was increased,and the level of highdensity lipoprotein-cholesterol(HDL)(1.69±0.39 mmol/L vs 1.77±0.41 mmol/L)was decreased,the differences were statistically significant(t=2.613,2.818,5.874,4.582,17.701,2.458,3.815,5.310,-2.187,all P<0.05).Logistic regression analysis showed that pre-pregnancy BMI,FBG,HbAlc,TG,and TC/HDL were all independent risk factors for predicting gestational diabetes(Waldχ2=4.48~35.549,all P<0.05).The prediction model constructed based on the selected risk factors was as follows:Logit(P)=-20.562+0.085(BMI)+1.921(FBG)+1.57(HbAlc)+2.248(TG)-2.302(TC/HDL).The model predicts that the area under the curve of GDM was 0.800(95%CI:0.757~0.842),the optimal cutoff value was 0.352,and the sensitivity and specificity were 80.00%and 66.00%,respectively.Ninety-five pregnant women validated the model,and its sensitivity,specificity,and accuracy were 84.50%,91.00%,and 85.30%,respectively.Conclusion The prediction model constructed by BMI combined with FBG,HbAlc,TG and TC/HDL in the first trimester(12~13+6 weeks)of pregnancy has a high predictive value for GDM.
8.Current status and thinking of data management of human genetic resources
Na LI ; Yang LU ; Ting HU ; Miao KUANG ; Jianjun FAN
Chinese Journal of Medical Science Research Management 2024;37(1):7-13
Objective:To analysis the laws and regulations related to human genetic resources, this study analyzed the current management status and trends at home and abroad, explored the related issues of human genetic resources data management, and provided reference for further promoting and standardizing the management of human genetic resources data in my country.Methods:This article analyzed the current management status of human genetic resources data from three levels: relevant policies, management frameworks, data platforms and sample databases through literature review and expert consultation and policy research.Results:Countries paid more and more attention to human genetic resources, and the construction of my country′s human genetic resources management system is constantly advancing and improving. In the data era, the management of human genetic resources was facing new problems and challenges, requiring further strengthening the research and management of relevant data.Conclusions:At present, the management of human genetic resource data in my country needs to be strengthened. On the one hand, it is necessary to promote the implementation and coordinated management of specific systems on human genetic resources data. On the other hand, it is necessary to strengthen the effective protection and sharing of human genetic resource data.
9.Accuracy evaluation of bioelectrical impedance analysis in assessment of appendicular skeletal muscle mass in adults aged 18-42 years
Yiying ZHENG ; Hong CHENG ; Yuxian KUANG ; Zhenxin MA ; Weiye CHEN ; Keyuan LU ; Jie MI ; Li LIU
The Journal of Practical Medicine 2024;40(4):549-553
Objective To evaluate the accuracy of bioelectrical impedance analysis(BIA)in measurement of appendicular skeletal muscle mass(ASM)of adults.Methods A total of 836 adults aged 18-42 years were recruited in Guangzhou using a convenient sampling method from April 2021 to September 2022.ASM was measured using BIA and Dual-energy X-ray absorptiometry(DXA).Using DXA as the standard method,the consistency between the BIA and DXA measurements was evaluated by intra-class correlation coefficients(ICCs)and Bland-Altman analysis in logarithmically transformed data,in order to evaluate the accuracy of BIA in ASM measurement.Receiver operating characteristic curve was plotted to evaluate the diagnostic value of BIA for screening low muscle mass.Results A total of 774 individuals were included for analysis finally.ICCs for ASM measured by BIA and DXA were 0.774 and 0.667 in males and females,respectively.Mean ratios(limits of Agreement)of ASM were 0.94(0.80-1.10)and 0.91(0.78-1.05)in males and females,respectively.Area under curve of BIA for screening low muscle mass were 0.91 and 0.94 in males and females,respectively.The optimal cut-off values of Z-score by BIA for males and females were-0.57 and-0.66,respectively.Sensitivity and specificity for males were 82.5%and 86.0%,while being 86.8%and 93.8%,for females.Conclusion BIA shows a moderate consistency with DXA for measuring ASM in adults.Furthermore,BIA yields a good diagnostic value in identifying low muscle mass in adults aged 18-42 years.
10.Individual monitoring of occupational external radiation in radiation workers of medical institutions in Jing’an District, Shanghai
Yujie KUANG ; Hong XIAO ; Linfeng GAO ; Bin WANG ; Shunqi LU
Shanghai Journal of Preventive Medicine 2024;36(11):1076-1081
ObjectiveTo analyze the individual monitoring results of the radiation workers in Shanghai’s Jing’an District from 2017 to 2023, to assess the occupational protection status as well as to offer scientific references for enhancing occupational health and radiation safety, and to provide support for health education initiatives targeting radiation workers. MethodsRadiation workers from several medical institutions in Jing’an District from 2017 to 2023 were selected as the subjects for this study. The individual dose of occupational external radiation exposure was monitored by using thermoluminescence dosimeters. Continuous data of seven years were statistically analyzed using SPSS 20.0. ResultsFrom 2017 to 2023, the annual collective effective dose for radiation workers in Jing’an District was 329.53 person·mSv, with an average individual annual effective dose of 0.17 mSv, and the median individual annual effective dose was 0.12 mSv. There were statistically significant differences in the individual annual effective doses across different years (H=277.131, P<0.05). The individual doses varied significantly among different levels of medical institutions (H=46.097, P<0.05), with tertiary institutions having the lowest median individual dose of 0.09 mSv, which was significantly lower than those at primary, secondary, and ungraded institutions (P<0.05). The median annual effective dose in males was lower than that in females, showing a statistically significant difference (Z=-3.438, P<0.05). There were significant differences in the individual annual effective doses among different occupational categories (H=150.727, P<0.05), with nuclear medicine workers experiencing the highest median annual dose of 0.56 mSv. ConclusionFrom 2017 to 2023, the individual dose of radiation workers in medical institutions in Jing’an District of Shanghai remained at a low level, reflecting the effective measures of radiation protection facilities in workplaces in Jing’an District, but particular attention should be given to radiological workers in nuclear medicine and workers in primary medical institutions.


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