1.Natural products modulate pyroptosis for treatment of spinal cord injury
Xuesan ZHANG ; Zheng ZHANG ; Le SHEN ; Qingqing GENG ; Shusen TAN ; Chunbiao LOU ; Kang HAN
Chinese Journal of Tissue Engineering Research 2025;29(30):6520-6528
BACKGROUND:Neuroinflammation is a major cause of exacerbation after spinal cord injury.In recent years,pyroptosis has received much attention due to its remarkable pro-inflammatory features.Some of these natural products can significantly inhibit the inflammatory response and improve the damaged nerve function by regulating the level of pyroptosis after spinal cord injury,which provides a new therapeutic idea for spinal cord injury.OBJECTIVE:To summarize the mechanism of action of natural products in regulating pyroptosis for the treatment of spinal cord injury,with a view to providing lessons and references for future research on the treatment of spinal cord injury.METHODS:The search terms"spinal cord injury,pyroptosis,inflammasome,natural products,natural compounds,traditional Chinese medicine"in Chinese and English were used to search for relevant literature since the establishment of the database up to September 2024 in the databases of PubMed,Web of Science,WanFang,and CNKI.According to the inclusion and exclusion criteria,75 relevant articles were finally obtained.RESULTS AND CONCLUSION:(1)Pyroptosis is an important pro-inflammatory pathway in spinal cord injury,and controlling pyroptosis is an effective way to improve damaged nerve function.(2)Some natural products can regulate pyroptosis via the NLRP3/Caspase-1 classical pyroptosis pathway,the NF-κB-related pathway,other upstream pathways such as Nrf2/HO-1,and autophagy,thereby affecting the level of tissue inflammation and accelerating neurological recovery after spinal cord injury.(3)The anti-pyroptosis effects of these natural products are mostly dependent on the NLRP3 classical pyroptosis pathway,and there is a lack of studies on other pyroptosis pathways.(4)There are still many problems in this field,such as the fact that these natural products are not currently supported by evidence from appropriate clinical studies.(5)The natural product has great potential in regulating pyroptosis and is expected to be a powerful weapon in the treatment of spinal cord injury.
2.High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression during ovarian hyperstimulation in mice.
Quanmin KANG ; Fang LE ; Xiayuan XU ; Lifang CHEN ; Shi ZHENG ; Lijun LOU ; Nan JIANG ; Ruimin ZHAO ; Yuanyuan ZHOU ; Juan SHEN ; Minhao HU ; Ning WANG ; Qiongxiao HUANG ; Fan JIN
Journal of Zhejiang University. Science. B 2025;26(3):269-285
Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female
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Mice
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Demethylation/drug effects*
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Embryonic Stem Cells
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Estrogens/administration & dosage*
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Gene Expression/drug effects*
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Histones/metabolism*
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Jumonji Domain-Containing Histone Demethylases/metabolism*
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Mice, Inbred C57BL
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Oocytes
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Ovary/drug effects*
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Reproductive Techniques, Assisted
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Animals
3.Consistency of cSNP genotyping between DNA and RNA using next-generation sequencing
Danni LOU ; Yixia ZHAO ; Lei MIAO ; Jie ZHAO ; Chi ZHANG ; Kelai KANG ; Sheng HU ; Jian YE ; Le WANG
Chinese Journal of Forensic Medicine 2025;40(3):295-301,307
Objective To evaluate the consistency of DNA coding region single nucleotide polymorphism(cSNP)genotyping at the DNA and RNA levels in common body fluid samples based on the next-generation sequencing platform.Methods After extensive literature retrieval,25 cSNP loci of 8 human tissue-specific mRNAs in peripheral blood,semen and vaginal secretion were selected.Two cSNP multiplex genotyping panels based on DNA and RNA,respectively,were developed for use on the MiSeq FGx sequencing platform.45 body fluid samples(including 14 peripheral blood samples,15 semen samples and 16 vaginal secretion samples)were sequenced and analyzed.The inconsistent typing results of DNA and RNA were rechecked by Sanger sequencing.Results The results of cSNP genotyping at the DNA and RNA levels in peripheral blood were completely consistent.Among the 15 semen samples,the genotypes of rs1995640 and rs 1995641 on the TGM4 gene were inconsistent in 3 cases.Among the 16 vaginal secretion samples,there were 2 cases,1 case and 2 case with inconsistent results of rs3869098,rs10947121 and rs12110470 in MUC22 gene,respectively.Conclusion In this study,MiSeq FGx sequencing and Sanger sequencing were used to test 25 cSNP loci with body fluid tissue specificity.The same typing results at the DNA and RNA levels were observed at 20 cSNPs.Inconsistent genotypes at the DNA and RNA levels were observed at 5 cSNPs on the TGM4 and MUC22 genes.This study provides experimental methods and data for forensic cSNP studies.
4.Natural products modulate pyroptosis for treatment of spinal cord injury
Xuesan ZHANG ; Zheng ZHANG ; Le SHEN ; Qingqing GENG ; Shusen TAN ; Chunbiao LOU ; Kang HAN
Chinese Journal of Tissue Engineering Research 2025;29(30):6520-6528
BACKGROUND:Neuroinflammation is a major cause of exacerbation after spinal cord injury.In recent years,pyroptosis has received much attention due to its remarkable pro-inflammatory features.Some of these natural products can significantly inhibit the inflammatory response and improve the damaged nerve function by regulating the level of pyroptosis after spinal cord injury,which provides a new therapeutic idea for spinal cord injury.OBJECTIVE:To summarize the mechanism of action of natural products in regulating pyroptosis for the treatment of spinal cord injury,with a view to providing lessons and references for future research on the treatment of spinal cord injury.METHODS:The search terms"spinal cord injury,pyroptosis,inflammasome,natural products,natural compounds,traditional Chinese medicine"in Chinese and English were used to search for relevant literature since the establishment of the database up to September 2024 in the databases of PubMed,Web of Science,WanFang,and CNKI.According to the inclusion and exclusion criteria,75 relevant articles were finally obtained.RESULTS AND CONCLUSION:(1)Pyroptosis is an important pro-inflammatory pathway in spinal cord injury,and controlling pyroptosis is an effective way to improve damaged nerve function.(2)Some natural products can regulate pyroptosis via the NLRP3/Caspase-1 classical pyroptosis pathway,the NF-κB-related pathway,other upstream pathways such as Nrf2/HO-1,and autophagy,thereby affecting the level of tissue inflammation and accelerating neurological recovery after spinal cord injury.(3)The anti-pyroptosis effects of these natural products are mostly dependent on the NLRP3 classical pyroptosis pathway,and there is a lack of studies on other pyroptosis pathways.(4)There are still many problems in this field,such as the fact that these natural products are not currently supported by evidence from appropriate clinical studies.(5)The natural product has great potential in regulating pyroptosis and is expected to be a powerful weapon in the treatment of spinal cord injury.
5.Consistency of cSNP genotyping between DNA and RNA using next-generation sequencing
Danni LOU ; Yixia ZHAO ; Lei MIAO ; Jie ZHAO ; Chi ZHANG ; Kelai KANG ; Sheng HU ; Jian YE ; Le WANG
Chinese Journal of Forensic Medicine 2025;40(3):295-301,307
Objective To evaluate the consistency of DNA coding region single nucleotide polymorphism(cSNP)genotyping at the DNA and RNA levels in common body fluid samples based on the next-generation sequencing platform.Methods After extensive literature retrieval,25 cSNP loci of 8 human tissue-specific mRNAs in peripheral blood,semen and vaginal secretion were selected.Two cSNP multiplex genotyping panels based on DNA and RNA,respectively,were developed for use on the MiSeq FGx sequencing platform.45 body fluid samples(including 14 peripheral blood samples,15 semen samples and 16 vaginal secretion samples)were sequenced and analyzed.The inconsistent typing results of DNA and RNA were rechecked by Sanger sequencing.Results The results of cSNP genotyping at the DNA and RNA levels in peripheral blood were completely consistent.Among the 15 semen samples,the genotypes of rs1995640 and rs 1995641 on the TGM4 gene were inconsistent in 3 cases.Among the 16 vaginal secretion samples,there were 2 cases,1 case and 2 case with inconsistent results of rs3869098,rs10947121 and rs12110470 in MUC22 gene,respectively.Conclusion In this study,MiSeq FGx sequencing and Sanger sequencing were used to test 25 cSNP loci with body fluid tissue specificity.The same typing results at the DNA and RNA levels were observed at 20 cSNPs.Inconsistent genotypes at the DNA and RNA levels were observed at 5 cSNPs on the TGM4 and MUC22 genes.This study provides experimental methods and data for forensic cSNP studies.
6.Virulence determinants and genetic diversity of foodborne Yersinia enterocolitica isolated from Wenzhou
Ai-Rong XIE ; Yi LI ; Hui-Huang LOU ; Zhong-Bi XIE ; Le-Yi ZHANG ; Yu-Qin HU ; Yue-Jin WU
Chinese Journal of Zoonoses 2024;40(1):40-45
The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4%(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6%,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8%.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6%,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.
7.Recent advances in chemical fluorescent probes sensitive to tumor microenvironments
Ke-liang LI ; Yang LIU ; Chun-yang LOU ; Tian-le HUANG ; Zhan-ying HONG ; Shan-chao WU ; Chun-quan SHENG
Acta Pharmaceutica Sinica 2023;58(8):2180-2192
Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.
8.Evaluation of knee cartilage based on MRI artificial intelligence reconstruction model of knee joint
Hong GAO ; Binge XUE ; Sha WU ; Yakui WANG ; Pengfei FU ; Le SHEN ; Jiawang LOU ; Qi MA ; Pu LIU ; Xu CAI
Chinese Journal of Orthopaedics 2023;43(5):316-321
Objective:To explore the feasibility of the AI intelligent reconstruction model based on knee joint magnetic resonance data developed by Nuctech Company Limited for evaluating knee cartilage injury.Methods:Thirty-three patients (a total of forty-one knees) who were hospitalized with severe knee osteoarthritis in Beijing Tsinghua Changgung Hospital from May 2021 to April 2022 were selected. All of them were planned to be performed total knee arthroplasty (TKA) for the treatment of knee osteoarthritis. Fifteen males with an average age of 71±5 years old and twenty six females with an average age of 71±9 years old were included in this study. There were 19 cases of left knee and 22 cases of right knee. Thin layer MRI examination on the patients' knee joints was performed before the surgery, and artificial intelligence model based on the thin layer MRI data of the knee joint was reconstructed. The cartilage part of the model was selected and corrected by Principal Component Analysis (PCA) in order to realize model straightening. The tibial plateau cartilage of knee joint which intercepted during operation was classified according to the International Cartilage Repair Society (ICRS). Finally the results were compared with the ICRS classification results of knee artificial intelligence reconstruction model and artificial recognition of knee joint MRI images.Results:Compared with the grade of cartilage injury intercepted during our operation which was according to the ICRS classification, the sensitivity of artificial intelligence reconstruction model for the diagnosis of cartilage injury with ICRS classification grade four was 93.1%. The specificity of artificial intelligence reconstruction model was 91.4%. The positive predictive value (PPV) of artificial intelligence reconstruction model was 92.2%. And the negative predictive value (NPV) of artificial intelligence reconstruction model was 80.3%. The area under ROC curve (AUC) was 0.92. The ICRS classification consistency between artificial intelligence model and physical inspection results was good with kappa value 0.81 ( P<0.001) . In the aspect of artificial recognition of cartilage injury grading in MRI images, the sensitivity of artificial recognition was 92.10% compared with the manual identification of cartilage injury classification in MRI images. The specificity of artificial recognition was 91.60%. The positive predictive value (PPV) of artificial recognition was 97.20% and the negative predictive value (NPV) of artificial recognition was 78.8%. The kappa value of the cartilage injury classification in MRI images consistency between artificial recognition and manual identification was 0.79 ( P<0.001). Conclusion:Based on the evaluation of cartilage injury by AI reconstruction model of knee joint, the sensitivity and specificity of the diagnosis of ICRS grade IV cartilage injury can be acceptable, but still needs to be improved.
9.Performance of memory task indicators for assessment of the risk of depressive disorders
Ge YU ; Le LOU ; Fangzhong XU
Journal of Preventive Medicine 2022;34(7):687-691
Objective:
To evaluate the risk of depressive disorders using memory task indicators, so as to provide insights into clinical assessment of depressive disorders.
Methods:
A total of 68 patients with depressive disorders undergoing treatments in the departments of psychiatrics and clinical psychology in a tertiary hospital during the period from January to September, 2021 were enrolled as the case group, while a total of 31 hospital employees, social volunteers and university students served as controls. The error rate and response time of classical memory task experiments were compared between the two groups, including implicit memory, short-term memory and working memory tasks. In addition, the predictive indicators of depressive disorders were identified using multivariable logistic regression analysis and receiver operative characteristics (ROC) curve.
Results:
The case group included 29 men and 39 women and had a mean age of (24.12±7.40) years, including 46 subjects with an educational level higher than diploma. The control group included 15 men and 16 women and had a mean age of (26.45±6.65) years, including 23 subjects with an educational level higher than diploma. Multivariable logistic regression analysis showed significant associations of age of >18 years (OR=3.431, 95%CI: 1.259-9.350), error rate of 2-back task (OR=1.056, 95%CI: 1.016-1.097) and error rate of short-term memory tasks (OR=1.078, 95%CI: 1.009-1.152) with the development of depressive disorders. ROC curve analysis showed that the error rate of 2-back tasks showed an area under the ROC curve (AUC) of 0.730 (95%CI: 0.630-0.831), cutoff of 22.5%, sensitivity of 42.6% and specificity of 93.5% for prediction of the risk of depressive disorders, and the error rate of short-term memory tasks showed an AUC of 0.717 (95%CI: 0.605-0.829), cutoff of 23.5%, sensitivity of 67.6% and specificity of 71.0% for prediction of the risk of depressive disorders. In addition, the combination of the error rate of 2-back tasks and the error rate of short-term memory tasks showed an AUC of 0.829 (95%CI: 0.734-0.923), sensitivity of 75.0% and specificity of 80.6% for prediction of the risk of depressive disorders.
Conclusion
Short-term and working memory task indicators are feasible for assessment of the risk of depressive disorders.
10.Development of Nasal Continuum Minimally Invasive Surgical Robot System.
Yuan ZHOU ; Wuzhou HONG ; Le XIE ; Fan FENG ; Haiting LIANG ; Dan LUO ; Keyong LI ; Binbin LOU
Chinese Journal of Medical Instrumentation 2022;46(4):399-403
In order to improve the operation difficulties in the narrow space of the nasal maxillary sinus, the nasal continuum minimally invasive surgical robot system is designed. The ball-and-socket joints and NiTiNol tubes are used as the main body of the continuum structure to improve the degree of freedom. The hardware systems and software systems are designed. The security control policies are planned. Finally, the robot confirmed prototype experiments are conducted and the feasibility of continuum robot confirmed through master-slave control experiment and animal experiment.
Animals
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Biomechanical Phenomena
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Equipment Design
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Minimally Invasive Surgical Procedures
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Robotic Surgical Procedures
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Robotics
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Software


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