1.Chrysophanol affects macrophage polarization by promoting mitochondrial biosynthesis through AMPK/PGC-1α pathway
Lele Wang ; Caixia Tan ; Wei Zhang ; Ruihan Ge ; Chen Li ; Xinmin Wang ; Le Zhang
Acta Universitatis Medicinalis Anhui 2025;60(3):488-494
Objective :
To explore whether chrysophanol(CHR) affects macrophage polarization by promoting mitochondrial biosynthesis through AMPK/PGC-1α pathway.
Methods :
The molecular docking and binding ability of CHR with AMPK and PGC-1α were predicted by Autodock vina software. Human monocytes(THP-1) were induced to M0 macrophages by phorbol myristate acetate(PMA), and to M1 macrophages by lipopolysaccharide(LPS) combined with interferon-γ(IFN-γ), which were set as Control group. M1 macrophages treated with CHR were set as CHR group. M1 macrophages treated with CHR combined with AMPK inhibitor(Compound C) were set as CHR+Compound C group. The mRNA expression levels of M1 macrophage markers(iNOS, CD86) and mitochondrial biosynthesis related genes(PGC-1α, NFR-1, TFAM) were detected by Quantitative real time polymerase chain reaction(qRT-PCR). The expression level of M1 macrophage marker iNOS was detected by immunofluorescence. The protein expression levels of AMPK, p-AMPK and PGC-1α were detected by Western blot.
Results :
The docking results showed that the binding energies of CHR with AMPK and PGC-1α were-8.4 kcal/mol and-7.4 kcal/mol, respectively. qRT-PCR results showed that the in vitro model of M1 macrophages was successfully established. Compared with the Control group, CHR treatment significantly increased the mRNA expression of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.001). Compared with CHR treatment group, CHR combined with Compound C treatment significantly decreased the mRNA expression levels of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.05). Immunofluorescence results showed that CHR treatment inhibited the protein expression of iNOS compared with the Control group(P<0.001). Compared with CHR treatment group,CHR combined with Compound C treatment reversed the inhibitory effect of CHR on i NOS protein expression(P<0.05). Western blot results showed that compared with the Control group,the CHR treatment group had significant increase in the protein expression levels of p-AMPK and PGC-1α(P<0.001).Compared with CHR treatment group,CHR combined with Compound C treatment significantly decreased the protein expression levels of p-AMPK and PGC-1α(P<0.05).
Conclusion
Chrysophanol may inhibit macrophage polarization to M1 by activating AMPK/PGC-1α signaling pathway to promote mitochondrial biosynthesis.
2.A detection method of arsenic free fully automatic online digestion iodine analyzer for urinary iodine
Xiuxiu SUN ; Ji'an XIE ; Shudong XU ; Jian JIANG ; Ying WEI ; Ruihan ZONG ; Ningning CHEN ; Hui LIU
Chinese Journal of Endemiology 2025;44(11):920-924
Objective:To establish an arsenic free fully automatic online digestion iodine analyzer detection method for urinary iodine (hereinafter referred to as the method).Methods:Based on the principle of iodine catalyzed antimony cerium redox reaction, a fully automatic online digestion iodine analyzer was used to determine the iodine content in urine. The effectiveness of the method in terms of detection limit, precision, accuracy (determination of urinary iodine primary standard reference materials GBW09108z and GBW09110f and spiked recovery experiment), and interference experiments was validated. The method was compared with the arsenic cerium catalytic spectrophotometry method recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:The linear range of the method was 0 - 300 μg/L, with a correlation coefficient │ r│> 0.999 5. The qualitative and quantitative detection limits were 7.41 and 18.01 μg/L, respectively. The relative standard deviation ( RSD) of urine samples with different iodine concentrations ranged from 1.0% to 1.7%. The results of the determination of iodine concentrations in urine using standard substances GBW09108z and GBW09110f were within the given standard range, with RSD < 2.5%. The range of spiked recovery rates for urine samples with different iodine concentrations was 101.3% to 104.8%, with an overall average spiked recovery rate of 103.0%. The average concentration of the baseline iodine standard solution was determined to be 116.21 μg/L, and the relative error of the concentration determination with the addition of interfering substances was less than 5.0%. The comparison results showed that there was no statistically significant difference in the measurement results between the two methods ( t = - 0.06, P = 0.952). Conclusions:The method adopts automated detection, which is simple to operate, labor-saving, and does not require the use of arsenic trioxide. It has high precision and accuracy, and is suitable for detection of large quantities of samples.
3.Chondrodysplasia complicated with infantile early-onset epilepsy and medial temporal lobe dysgenesis caused by the FGFR3 gene mutation: a case report and literature review
Shanying WEI ; Xinling TENG ; Li WANG ; Guangfei SUN ; Ruihan LIU ; Qinliang ZHENG ; Yanchao TIAN ; Qiubo LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(7):537-541
The clinical data of an infant with chondrodysplasia accompanied by early-onset epilepsy and medial temporal lobe dysgenesis due to the FGFR3 gene mutation, who was treated in the Affiliated Hospital of Jining Medical University in March 2024 were retrospectively analyzed.The 9-day-old male infant presented with frequent apnea at 5 hours after birth and experienced first seizure at 24 hours after birth.Physical examination revealed short limbs.Magnetic resonance imaging (MRI) showed abnormal changes in bilateral temporal lobes, hippocampal structure and bilateral lateral ventricular temporal angles, so cerebral developmental abnormalities were considered in this child.Whole exome sequencing confirmed a heterozygous variation in the FGFR3 gene [c.1620C>A(p.Asn540Lys)].After receiving Phenobarbital monotherapy, the child still had frequent seizures, but the seizure was completely controlled after the additional use of Lvetiracetam.To August 2024, a total of 14 patients with achondroplasia, epilepsy, and medial temporal lobe dysplasia caused by FGFR3 gene mutations were identified.These patients typically experienced frequent seizures in early infancy, which could be accompanied by apnea and psychomotor retardation.MRI consistently showed abnormal development of bilateral temporal lobes and hippocampus.Seizures were hardly controlled by anti-seizure medications, and Phenobarbital was effective in some cases.Whole exome sequencing revealed gene variations of c.1620C>A or c. 1620C>G (p.Asn540Lys).Patients with achondroplasia caused by FGFR3 gene mutations may present with early-onset epilepsy and medial temporal lobe dysplasia.Early seizures are frequent and difficult to control, and Phenobarbital is effective in some cases.
4.A detection method of arsenic free fully automatic online digestion iodine analyzer for urinary iodine
Xiuxiu SUN ; Ji'an XIE ; Shudong XU ; Jian JIANG ; Ying WEI ; Ruihan ZONG ; Ningning CHEN ; Hui LIU
Chinese Journal of Endemiology 2025;44(11):920-924
Objective:To establish an arsenic free fully automatic online digestion iodine analyzer detection method for urinary iodine (hereinafter referred to as the method).Methods:Based on the principle of iodine catalyzed antimony cerium redox reaction, a fully automatic online digestion iodine analyzer was used to determine the iodine content in urine. The effectiveness of the method in terms of detection limit, precision, accuracy (determination of urinary iodine primary standard reference materials GBW09108z and GBW09110f and spiked recovery experiment), and interference experiments was validated. The method was compared with the arsenic cerium catalytic spectrophotometry method recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:The linear range of the method was 0 - 300 μg/L, with a correlation coefficient │ r│> 0.999 5. The qualitative and quantitative detection limits were 7.41 and 18.01 μg/L, respectively. The relative standard deviation ( RSD) of urine samples with different iodine concentrations ranged from 1.0% to 1.7%. The results of the determination of iodine concentrations in urine using standard substances GBW09108z and GBW09110f were within the given standard range, with RSD < 2.5%. The range of spiked recovery rates for urine samples with different iodine concentrations was 101.3% to 104.8%, with an overall average spiked recovery rate of 103.0%. The average concentration of the baseline iodine standard solution was determined to be 116.21 μg/L, and the relative error of the concentration determination with the addition of interfering substances was less than 5.0%. The comparison results showed that there was no statistically significant difference in the measurement results between the two methods ( t = - 0.06, P = 0.952). Conclusions:The method adopts automated detection, which is simple to operate, labor-saving, and does not require the use of arsenic trioxide. It has high precision and accuracy, and is suitable for detection of large quantities of samples.
5.Chondrodysplasia complicated with infantile early-onset epilepsy and medial temporal lobe dysgenesis caused by the FGFR3 gene mutation: a case report and literature review
Shanying WEI ; Xinling TENG ; Li WANG ; Guangfei SUN ; Ruihan LIU ; Qinliang ZHENG ; Yanchao TIAN ; Qiubo LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(7):537-541
The clinical data of an infant with chondrodysplasia accompanied by early-onset epilepsy and medial temporal lobe dysgenesis due to the FGFR3 gene mutation, who was treated in the Affiliated Hospital of Jining Medical University in March 2024 were retrospectively analyzed.The 9-day-old male infant presented with frequent apnea at 5 hours after birth and experienced first seizure at 24 hours after birth.Physical examination revealed short limbs.Magnetic resonance imaging (MRI) showed abnormal changes in bilateral temporal lobes, hippocampal structure and bilateral lateral ventricular temporal angles, so cerebral developmental abnormalities were considered in this child.Whole exome sequencing confirmed a heterozygous variation in the FGFR3 gene [c.1620C>A(p.Asn540Lys)].After receiving Phenobarbital monotherapy, the child still had frequent seizures, but the seizure was completely controlled after the additional use of Lvetiracetam.To August 2024, a total of 14 patients with achondroplasia, epilepsy, and medial temporal lobe dysplasia caused by FGFR3 gene mutations were identified.These patients typically experienced frequent seizures in early infancy, which could be accompanied by apnea and psychomotor retardation.MRI consistently showed abnormal development of bilateral temporal lobes and hippocampus.Seizures were hardly controlled by anti-seizure medications, and Phenobarbital was effective in some cases.Whole exome sequencing revealed gene variations of c.1620C>A or c. 1620C>G (p.Asn540Lys).Patients with achondroplasia caused by FGFR3 gene mutations may present with early-onset epilepsy and medial temporal lobe dysplasia.Early seizures are frequent and difficult to control, and Phenobarbital is effective in some cases.
6.CA Ⅸ-targeted Ag2S quantum dots bioprobe for NIR-Ⅱ imaging-guided hypoxia tumor chemo-photothermal therapy
Cui XINYUE ; Hu ZHUANG ; Li RUIHAN ; Jiang PENG ; Wei YONGCHANG ; Chen ZILIN
Journal of Pharmaceutical Analysis 2024;14(6):878-888
Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the tumors.Therefore,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned.As carbonic anhydrase Ⅸ(CA Ⅸ)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfo-namide(ABS)as a CA Ⅸ inhibitor has inherent inhibitory activity and good targeting effect.In this study,Ag2S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bio-probe(Ag2S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation reaction.Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor im-aging by the near infrared-Ⅱ(NIR-Ⅱ)fluorescence characteristics of Ag2S QDs.PEG modification of Ag2S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal sta-bility and high photothermal conversion efficiency(PCE)of 45.17%.Under laser irradiation,Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in vitro.It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility.Therefore,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.
7.Targeted therapies for lupus nephritis: Current perspectives and future directions
Xiuzhi JIA ; Yuewen LU ; Xunhua ZHENG ; Ruihan TANG ; Wei CHEN
Chinese Medical Journal 2024;137(1):34-43
Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.
8.Determination of arsenic in urine by hydride generation atomic fluorescence spectrometry with ammonium persulfate digestion
Siwei LIU ; Weidong LI ; Gang DING ; Shudong XU ; Ji'an XIE ; Ying WEI ; Tingting LIU ; Ruihan ZONG ; Kaiqian WANG
Chinese Journal of Endemiology 2022;41(7):585-590
Objective:To establish a hydride generation atomic fluorescence method using ammonium persulfate as the digestion reagent for determination of arsenic in urine (hereinafter referred to as this method).Methods:The collected urine samples with ammonium persulfate were heated and digested on the tubular electric heating automatic control constant temperature digester (60 holes), with 5% hydrochloric acid solution as reaction medium and current carrier and 1.5% potassium borohydride solution as reducing agent. Arsenic content was determined with a four-channel atomic fluorescence spectrometer. The arsenic standard solution of 0 - 10 μg/L was prepared to determine the standard curve of this method, and the method was evaluated from the detection limit, linear range, correlation coefficient, precision, standard addition recovery experiment, and urine arsenic quality control sample detection. The standard method "Determination of Arsenic in Urine by Hydride Generation Atomic Fluorescence Spectrometry" (WS/T 474-2015, referred to as the standard method) was used for comparison experiments.Results:When the sampling volume was 1 ml, the detection limit of this method (digest with 1 ml 1.5 mol/L ammonium persulfate) was 0.03 μg/L. In the range of arsenic content from 0 - 10 μg/L, the linear relationship between arsenic content and fluorescence intensity was good, and the correlation coefficients ( r) were all 0.999 9. The relative standard deviations( RSD) of the three replicates of urine samples with different concentrations were 1.00%, 0.89% and 0.49%, respectively. Urine arsenic quality control samples were tested, and the test results were all within the range of public values; the overall average recovery was 102.29%, and the recovery range was 92.10% - 108.15%. Compared with the standard method in the determination results of 20 urine samples, the difference was not statistically significant ( t = - 0.40, P > 0.05). Conclusions:The hydride generation atomic fluorescence spectrometry using ammonium persulfate as digestion reagent for the determination of arsenic in urine has the advantages of low detection limit, good precision, high accuracy, small amount of sampling and digestion reagent, simple operation, and less harmful gas generation in sample pretreatment. It is suitable for rapid determination of arsenic in urine in large quantities.
9.Effects of levetiracetam combined with topiramate on immune function and cognitive function in children with refractory epilepsy
Yujuan GAO ; Pengke PAN ; Ruihan WEI ; Xiaoyang WEI
Journal of Clinical Medicine in Practice 2017;21(9):73-77
Objective To investigate the effects of levetiracetam combined with topiramate on immune function and cognitive function in children with intractable epilepsy.Methods A total of 54 hospitalized children with intractable epilepsy were randomly divided into control group and combination group.All the children were treated with antiepileptic drugs,and the complications were prevented.The control group was treated with levetiracetam and the combination group was treated with topiramate.All the children were treated foR3 months.The levels of peripheral blood T lymphocyte subsets and immunoglobulin levels were detected by EEG analysis,and the cognitive function was evaluated.Results Compared with before treatment,levels of CD3+,CD4+ and CD4+/CD8+ increased significantly in both groups (P<0.05),CD8+ decreased significantly (P<0.05),and levels of serum IgA and IgG increased significantly (P<0.05).There were no significant changes in IgM and relative poweRof δ,α and β bands (P<0.05),and the relative poweRof the θ band decreased (P<0.05).Visual space and executive ability,attention and concentration,memory,calculation and orientation,and total scores increased significant (P<0.05),and scores of naming,language,abstract thinking did not change (P< 0.05).Compared with the control group,levels of CD3+,CD4+ and CD4+/CD8+ in the combined group were significantly higheR(P<0.05),CD8+ was significantly lower(P<0.05),levels of IgA,IgG were significantly higher(P<0.05),relative poweRreduction of the θ band were significantly lower(P<0.05),and visual space and executive ability,attention and concentration,memory,calculation and orientation and total score were significantly higheR(P<0.05),and the total effective rate was significantly higheR(P<0.05).Conclusion Levetiracetam combined with topiramate is effective in the treatment of intractable epilepsy in children,which can effectively improve the immune function and cognitive function.
10.Effects of levetiracetam combined with topiramate on immune function and cognitive function in children with refractory epilepsy
Yujuan GAO ; Pengke PAN ; Ruihan WEI ; Xiaoyang WEI
Journal of Clinical Medicine in Practice 2017;21(9):73-77
Objective To investigate the effects of levetiracetam combined with topiramate on immune function and cognitive function in children with intractable epilepsy.Methods A total of 54 hospitalized children with intractable epilepsy were randomly divided into control group and combination group.All the children were treated with antiepileptic drugs,and the complications were prevented.The control group was treated with levetiracetam and the combination group was treated with topiramate.All the children were treated foR3 months.The levels of peripheral blood T lymphocyte subsets and immunoglobulin levels were detected by EEG analysis,and the cognitive function was evaluated.Results Compared with before treatment,levels of CD3+,CD4+ and CD4+/CD8+ increased significantly in both groups (P<0.05),CD8+ decreased significantly (P<0.05),and levels of serum IgA and IgG increased significantly (P<0.05).There were no significant changes in IgM and relative poweRof δ,α and β bands (P<0.05),and the relative poweRof the θ band decreased (P<0.05).Visual space and executive ability,attention and concentration,memory,calculation and orientation,and total scores increased significant (P<0.05),and scores of naming,language,abstract thinking did not change (P< 0.05).Compared with the control group,levels of CD3+,CD4+ and CD4+/CD8+ in the combined group were significantly higheR(P<0.05),CD8+ was significantly lower(P<0.05),levels of IgA,IgG were significantly higher(P<0.05),relative poweRreduction of the θ band were significantly lower(P<0.05),and visual space and executive ability,attention and concentration,memory,calculation and orientation and total score were significantly higheR(P<0.05),and the total effective rate was significantly higheR(P<0.05).Conclusion Levetiracetam combined with topiramate is effective in the treatment of intractable epilepsy in children,which can effectively improve the immune function and cognitive function.


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