1.Causal relationship between circulating inflammatory cytokines and bone mineral density based on two-sample Mendelian randomization
Shuai CHEN ; Jie JIN ; Huawei HAN ; Ningsheng TIAN ; Zhiwei LI
Chinese Journal of Tissue Engineering Research 2025;29(8):1556-1564
BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.
2.Effect of geniposidic acid on SHP-LRH-1 signaling pathway in cholestasis rats.
Hao CHEN ; Xuan GAO ; Wei ZHAO ; Hao YU ; Ningsheng WANG ; Suiqing MI
Journal of Central South University(Medical Sciences) 2019;44(6):605-613
To explore the effect of geniposidic acid (GPA) on the signal pathway of small heterodimer dimer receptor (SHP) and liver receptor homologue 1 (LRH-1) in cholestasis rats induced by alpha-naphthalene isothiocyanate (ANIT).
Methods: Fifty SD rats were randomly divided into five groups: a blank group, an ANIT group, an ANIT+GPA (100 mg/kg) group, an ANIT+GPA (50 mg/kg) group, and an ANIT+GPA (25 mg/kg) group (n=10 in each group). The GPA were intragastrically given to rats for 10 days, and the control group and the ANIT group were given normal saline. At the eighth day of administration, all rats except the blank group were given 65 mg/kg ANIT once until the tenth day. After the last administration, serum total cholesterol (TC), triglyceride (TG) and total bile acids (TBA) were measured. The primary hepatocytes (RPH) were isolated from normal rats and cultured. The cells were divided into a blank group, an ANIT (40 μmol/L) group, an ANIT (40 μmol/L)+GPA (4.00 mmol/L) group (A4.00G group), an ANIT (40 μmol/L)+GPA (1.00 mmol/L) group (A1.00G group), and an ANIT (40 μmol/L)+GPA (0.25 mmol/L) group (A0.25G group). The mRNA transcription levels of SHP and cholesterol 7 alpha hydroxylase (CYP7A1) in RPH were detected by real-time-PCR, and the protein levels of SHP and CYP7a1 were detected by Western blotting. In the LRH-1 silence experiment, the RPH were divided into a blank group, a negative transfection group, a siRNA-LRH group (ZR group), a siRNA-LRH+GPA (4.00 mmol/L) group (ZR4.00G group), a siRNA-LRH+GPA (1.00 mmol/L) group (ZR1.00G group) and a siRNA-LRH+GPA (0.25 mmol/L) group (ZR0.25G group). The protein and mRNA levels of SHP, CYP7a1, LRH-1 were detected. In the over-expression experiment, the RPH were also divided into a blank group, a negative transfection group, a LRH-1 over-expression plasmid group (OE group), a LRH-1 over-expression plasmid+GPA (4.00 mmol/L) group (OE4.00G group), a LRH-1 over-expression plasmid+GPA (1.00 mmol/L) group (OE1.00G group), and a LRH-1 over-expression plasmid+GPA (0.25 mmol/L) group (OE0.25G group). The protein and mRNA levels of SHP, CYP7a1 and LRH-1 were detected.
Results: Compared with the blank control group, TC and TBA were significantly increased (both P<0.01) in the ANIT group, but there was no difference in TG; compared with the ANIT group, the contents of TC and TBA in the AG100 and AG50 groups were significantly reduced (all P<0.01). Compared with the blank control group, the proteins and mRNA levels of SHP were significantly decreased (P<0.01), while CYP7a1 were dramatically increased (P<0.01) in the ANIT group; compared with the ANIT group, the proteins and mRNA levels of SHP in the A4.00G group and the A1.00G group were significantly increased (both P<0.01), while the levels of CYP7a1 proteins and mRNA levels were evidently decreased in the A4.00G and A1.00G groups (both P<0.01). Compared with the negative transfection group, the proteins and mRNA levels of CYP7a1 and LRH-1 were dramatically restrained (all P<0.01), while there was no change in SHP in the ZR group; compared with the ZR group, the proteins and mRNA levels of SHP were significantly increased (all P<0.01), while LRH-1 and CYP7a1 were not changed in the ZR4.00G, ZR1.00G and ZR0.25G groups. Compared with the negative transfection group, the protein and mRNA levels of CYP7a1 and LRH-1 were significantly suppressed in the OE group (all P<0.01). Compared with the OE group, the protein and mRNA levels of SHP were evidently increased in the OE4G and OE1G groups (all P<0.01), while LRH-1 and CYP7a1 were not changed in the OE4G, OE1G and OE0.25G groups.
Conclusion: The over-expression of LRH-1 in RPH can up-regulate the mRNA and protein levels of CYP7a1. GPA can improve the biochemical and liver pathology of ANIT-induced cholestasis rats, which may be related to the decrease of CYP7a1 by activating SHP through LRH-1 in RPH.
Animals
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Cholestasis
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Iridoid Glucosides
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear
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Signal Transduction
3.Tibial eminence avulsion fracture of the anterior cruciate ligament fixed with arthroscopic double-steel wire clip
Jingrui XIE ; Bin CHEN ; Ningsheng ZHANG ; Xiaoreng FENG ; Kun LIN
Chinese Journal of Tissue Engineering Research 2015;(29):4742-4746
BACKGROUND:Conventional surgical repair can cause large traumas in patients with knee injuries, and patients often recover slowly after implant fixation, most of whom can appear to have poor recovery of knee function. OBJECTIVE: To explore the folow-up effect of arthroscopic double-steel wire clip fixation on tibial eminence avulsion fracture of anterior cruciate ligament. METHODS: A retrospective analysis was performed on the clinical data of 23 patients with tibial eminence avulsion fractures, who were given arthroscopic double-steel wire clip fixation. The patients were folowed up for 1-6 months. Short- and middle-term therapeutic effect as wel as IKDC and Lysholm scores before and after treatment were observed and analyzed. RESULTS AND CONCLUSION:The operation time was 35-65 minutes, and no complications, such as blood, nerve and anterior cruciate ligament injuries occurred. Moreover, no infection and other poor biocompatible reactions occurred after internation fixation. Al patients were folowed up for 1-6 months. The excelent and good rate was 87% at 1 month after treatment and 96% at 6 months after treatment. Al the patients had improved IKDC score and Lysholm score after treatment (P < 0.05), indicating that the knee function of patients was improved significantly.
4.Study on medical postraduate training quality monitor system
Ningsheng DAI ; Tong ZOU ; Qiaoyan WANG ; Gaiqing CHEN ; Ping WU
Chinese Journal of Medical Education Research 2006;0(10):-
The paper set up a set of quality monitor measures from training important tache, beginning thesis, imposing advantage resource to strengthening practice ability to build a scientific quality monitor system for postgraduate training and ensure steadily improvement of the postgraduate training quality.
5.Residue Determination of Six Kinds of Heavy Metal in Rhizoma Curcumae Longae
Jinhong CHEN ; Yishan TANG ; Dawei LIU ; Ningsheng WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2000;0(05):-
Objective To determine the content of six heavy metal elements of arsenicum(As),mercury(Hg),cuprum(Cu),plumbum(Pb),cadmium(Cd) and chromium(Cr) in Rhizoma Curcumae Longae.Methods Samples were digested with microwave digestion system,and the contents of Cu,Pb,Cd and Cr were determined by graphite furnace atomic absorption spectrometry(GFAAS);the contents of As and Hg were determined by atomic fluorescence spectrometry(AFS),and the reproducibility and recovery of the method were also examined.Results As and Hg contents in most of the products were below the limit.Only Cu,Pb and Cd contents exceed the limit.The recovery was 86.3 %~113.4 %and RSD was 10.4 %.Conclusions The method is simple and accurate,and can be used for the determination of heavy metal in Chinese herbs.
6.Determination of Trace Formaldehyde in Textiles by Discoloring Kinetic Spectrophotometry
Ningsheng CHEN ; Xinyuan GUO ; Haiqing LUO
Journal of Environment and Health 1993;0(03):-
Objective To establish a discoloring kinetic analysis method for determination of trace formaldehyde in textiles. Methods Based on the catalysis of formaldehyde on the discoloring reaction of bromophenol blue oxidized by potassium bromated in phosphoric acid medium,the contents of formaldehyde in textiles were determinated by spectrophotometry. The optimum condition and kinetic parammeters of the reaction were studied in detail. Results The optimum required volumes of reagents were 2.0,3.0,1.0 ml for H3PO4,KBrO3 and bromophenol blue respectively.The reaction was optimized at 85 ℃ for10 min.At working wave length of 430 nm,the linear range was 0.05-0.40 ?g/ml,the detection limit was 0.006 9 ?g/ml ,the recovery rate and RSD were 96%-106% and 2.9%-3.2% respectively. Conclusion This method was easy ,rapid and sensitive for the determination of trace formaldehyde in textiles.
7.Determination of Trace Resorcin in Waste Water by Kinetic Spectrophotometry
Journal of Environment and Health 1993;0(01):-
Objective To establish a new spectrophotometry for determination of trace resorcin. Methods Resorcin can inhibit discolouring reaction of bromophenol red induced by H2O2 ,which is catalyzed by Fe(Ⅲ) in NH3-NH4Cl medium. Results The detection limit of this method was 0.054 ?g/ml, linear range was 0.16-2.6 ?g/ml, the optimum reaction temperature was 75℃ and the optimum reaction time was 4 min. Conclusion The present method is simple, accurate and can be used to determine trace resorcin in waste water.
8.Determination of Formaldehyde in Water Sample by Kinetic Spectrophotometry
Ningsheng CHEN ; Lei ZHANG ; Pengcheng YIN
Journal of Environment and Health 1993;0(03):-
Objective To establish a new kinetic spectrophotometry for determination of formaldehyde in water sample. Methods Micro formaldehyde could sensitively catalyze the discoloring reaction of methyl orange oxidized by potassium bromated in dilute H3PO4 medium, the relationship between the reaction speed and the content of formaldehyde could be determinated by spectrophotometry, then the content of formaldehyde could be determinated. Results The optimum condition and kinetic paramneters were investigated and showed in the present paper in detail. The calibration curve showed linearity in the range of 0.13-3.0 ?g/ml and the limit of detection was 4.7?10-5 mg/ml. The RSDs ranged from 1.5% to 3.3%.The recovery rates ranged from 97.3% to 102.0%. Conclusion The mothed was simple, rapid and more sensitive, can be used for the determination of micro amounts of formaldehyde in water sample with satisfied results.
9.Determination of Micro 2,4-Dinitrotoluene in Wastewater by Kinetic Spectrophotometry
Ningsheng CHEN ; Xinyuan GUO ; Moxin YU
Journal of Environment and Health 1992;0(05):-
Objective To establish an easy, rapid and sensitive method for determination of micro 2,4-dinitrotoluene in waste water. Methods Based on the fact that micro 2,4-dinitrotoluene could inhibit the discoloring oxidation reaction of methylene blue by KIO4 in the HC1 solution, micro 2,4-dinitrotoluene was determined using kinetic spectrophotometric method. Results A new kinetic spectrophotometric method for determination of micro 2,4-dinitrotoluene was established. The linear range of the method was 0.20?10~(-5)-1.8?10~(-5) mg/L, the detection limit was 1.7xlO'7 mg/L. When the method was applied to the determination of the 2,4-dinitrotoluene in waste water, its recovery rates in standard addition method were 95.6%-99.1% and the RSDs were 1.5%-2.6%. Conclusion The method was easier to operate and more rapid, which was suitable for the determination of micro 2,4-dinitrtoluene in wastewater.
10.Inhibitory Kinetic Spectrophotometric Determination of Trace Catechol in Waste Water
Ningsheng CHEN ; Peigen CHEN ; Yingqiang FU
Journal of Environment and Health 1992;0(02):-
Objective To establish a kinetic spectrophotometric method for the determination of trace catechol in the waste water. Methods Trace catechol can sensitively inhibit the Arsenazo decolorization reaction with H2O2 catalyzed by Cu(Ⅱ)in dilute H2SO4 medium. Based on the changing of catalyzed reaction speed, a new inhibitory kinetic spectrophotometric method for the determination of trace catechol in the waste water was established. Results The optimum condition, kinetic parameters and reaction mechanism were investigated. It is shown that the linear range of determination was 0.2-1.8 mg/ L, the detection limit was 0.084 mg/L. The RSDs of ?A for 0.6 mg/L,1.12 mg/L and 1.6 mg/L catechol standard materials for 11 parallel determination were 2.4%, 1.2% and 1.6% respectively. The recovery rates were 98.0% and 96.0%. Conclusion This method can be used for determination of trace catechol in waste water with satisfactory results.

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