1.Research and application progress on recognition components of surface plasmon resonance sensors in the pharmaceutical field
Xiaofei WANG ; Ying ZHANG ; Jiayu GU ; Xiner HU ; Hai ZHANG ; Yan CAO
Journal of Pharmaceutical Practice and Service 2025;43(5):205-212
Surface plasmon resonance (SPR) sensor is an optical detection technique enables real-time and dynamic monitoring of biological samples. SPR-based biosensors have remarkable characteristics such as label-free detection and high sensitivity, making them important tools for studying molecular interactions. The recognition element, which plays a critical role in SPR sensors,which could specifically identify and capture of target analytes, closely influencing the selectivity performance of the sensor. The progress on SPR sensors in pharmaceutical research were reviewed, which focused on the application of recognition elements such as antibodies, aptamers, molecularly imprinted polymers, and metal nanoparticles.
2.Application of blood conservation measures with different red blood cell transfusion volumes in obstetrics and their impact on postpartum outcomes
Huimin DENG ; Fengcheng XU ; Meiting LI ; Lan HU ; Xiao WANG ; Shiyu WANG ; Xiaofei YUAN ; Jun ZHENG ; Zehua DONG ; Yuanshan LU ; Shaoheng CHEN
Chinese Journal of Blood Transfusion 2025;38(5):691-698
Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL(OR=1.699)(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma(FFP), cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.
3.A preclinical and first-in-human study of superstable homogeneous radiolipiodol for revolutionizing interventional diagnosis and treatment of hepatocellular carcinoma.
Hu CHEN ; Yongfu XIONG ; Minglei TENG ; Yesen LI ; Deliang ZHANG ; Yongjun REN ; Zheng LI ; Hui LIU ; Xiaofei WEN ; Zhenjie LI ; Yang ZHANG ; Syed Faheem ASKARI RIZVI ; Rongqiang ZHUANG ; Jinxiong HUANG ; Suping LI ; Jingsong MAO ; Hongwei CHENG ; Gang LIU
Acta Pharmaceutica Sinica B 2025;15(10):5022-5035
Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as 131I,177Lu, or 18F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, 18F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).
4.Identification and biomimetic synthesis of iphionanes and cyperanes from Artemisia hedinii and their anti-hepatic fibrosis activity.
Xiaofei LIU ; Xing WANG ; Chunping TANG ; Changqiang KE ; Bintao HU ; Sheng YAO ; Yang YE
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):871-880
Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry*
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Sesquiterpenes/chemical synthesis*
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Molecular Structure
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Humans
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Liver Cirrhosis/genetics*
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Biomimetics
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Plant Extracts/pharmacology*
5.Construction and validation of a novel prognostic risk scoring table for patients with acute-on-chronic liver failure
Zhanhu BI ; Haifeng HU ; Hong DU ; Linxu WANG ; Xiaofei YANG ; Yidi DING ; Jianqi LIAN
Journal of Clinical Hepatology 2025;41(10):2102-2109
ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure (ACLF), and to construct a risk scoring table that can accurately predict the prognosis of patients in the early stage. MethodsA retrospective analysis was performed for the clinical data of 502 patients with ACLF who were admitted to Tangdu Hospital, Air Force Medical University, from January 1, 2010 to December 31, 2020 (training set), and the influencing factors for 28-day mortality rate were identified. The 69 ACLF patients who were admitted to Tangdu Hospital, Air Force Medical University, from January 1 to December 31, 2021 were enrolled as the validation set. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A univariate Cox regression analysis was used to obtain the early warning indicators associated with the 28-day prognosis of ACLF patients, and variance inflation factors were used to assess multicollinearity among predictors; a multivariate Cox regression analysis was used to construct a risk model for ACLF prognosis (mortality). A risk scoring table for ACLF prognosis (mortality) was developed based on regression coefficients (β) from the model equation and weight assignments in the nomogram. Internal validation and comparison were performed for the risk model for ACLF prognosis (mortality), the scoring table for ACLF prognosis (mortality), and other scoring models (Child-Turcotte-Pugh [CTP] score, Model for End-Stage Liver Disease [MELD] score, MELD combined with serum sodium concentration [MELD-Na] score, and integrated MELD [iMELD] score) in the training set, while external validation and comprehensive evaluation of the scoring table and the other scoring models were performed in the validation set. The Nagelkerke’s R2 test and the Hosmer-Lemeshow test were used to assess the degree of fitting of the risk model for ACLF prognosis (mortality), the scoring table for ACLF prognosis (mortality), and other scoring models, and fitting curves were plotted. C-index was used to assess the discriminatory ability of the scoring table for ACLF prognosis (mortality) and the other scoring models, and the Z-test was used for comparison of C-index between different models. The decision curve analysis was used to compare the clinical benefits of the scoring table for ACLF prognosis (mortality) and the other scoring models. ResultsThe multivariate Cox regression analysis showed that age (hazard ratio [HR]=1.027, 95% confidence interval [CI]: 1.015 — 1.039, P<0.001), hepatic encephalopathy grade (grade 1: HR=2.928, 95%CI: 1.463 — 5.858, P=0.002; grade 2: HR=3.811, 95%CI: 2.078 — 6.988, P<0.001; grade 3: HR=3.916, 95%CI: 1.917 — 8.001, P<0.001; grade 4: HR=6.966, 95%CI: 4.559 — 10.644, P<0.001), an increase in total bilirubin (TBil) by ≥17.1 μmol/L per day (HR=1.771, 95%CI: 1.248 — 2.513, P=0.001), creatinine (HR=1.005, 95%CI: 1.004 — 1.006, P<0.001), neutrophil count (HR=1.092, 95%CI: 1.060 — 1.126, P<0.001), and international normalized ratio (HR=1.298, 95%CI: 1.187 — 1.418, P<0.001) were independent risk factors associated with the 28-day mortality rate of ACLF patients, and a risk scoring table was constructed for ACLF prognosis (mortality). The Nagelkerke’s R2 test showed that the risk scoring table for ACLF prognosis (mortality) had an R2 value of 0.599 in the training set and 0.722 in the validation set, which were higher than the R2 values of CTP, MELD, MELD-Na, and iMELD scores. The Hosmer-Lemeshow test showed that the risk scoring table for ACLF prognosis (mortality) had a P value of 0.280 in the training set and 0.788 in the validation set. The C-index analysis showed that the scoring table had a higher C-index than the other scoring models in the validation set (all P<0.001), as well as a higher C-index than CTP score in the training set (P<0.001). The decision curve analysis showed that the risk scoring table for ACLF prognosis (mortality) had higher clinical net benefits than the other scoring models. ConclusionCompared with other scoring models currently used in clinical practice, the novel risk scoring table for ACLF prognosis (mortality) constructed based on the six predictive factors of age, hepatic encephalopathy grade, an increase in TBil by ≥17.1 μmol/L per day, creatinine, neutrophil count, and international normalized ratio has a relatively high value in predicting the 28-day prognosis of ACLF patients.
6.Clinical features and early warning indicators of patients with acute-on-chronic liver failure and bacterial infection
Zhanhu BI ; Linxu WANG ; Haifeng HU ; Hong DU ; Yidi DING ; Xiaofei YANG ; Jiayi ZHAN ; Fei HU ; Denghui YU ; Hongkai XU ; Jianqi LIAN
Journal of Clinical Hepatology 2024;40(4):760-766
ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure (ACLF) and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1, 2010 to December 31, 2021, and according to the drug susceptibility results, the patients were divided into multidrug-resistant (MDR) bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic (ROC) curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection, sputum (27.7%) was the most common specimen for detection, followed by blood (24.6%), urine (18.5%), and ascites (17.7%). Bacterial infections were dominated by Gram-negative bacteria (58.5%). Of all bacteria, Escherichia coli (18.5%), Klebsiella pneumoniae (14.6%), and Enterococcus faecium (13.8%) were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin (72.2%), penicillin (57.4%), ampicillin (55.6%), and ciprofloxacin (53.7%), while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin (73.3%), cefazolin (50.0%), and cefepime (47.4%). The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection (61.5%). Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection, the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase (Z=2.089, P=0.037), aspartate aminotransferase (Z=2.063, P=0.039), white blood cell count (Z=2.207, P=0.027), and monocyte count (Z=4.413, P<0.001). The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection (odds ratio=7.120, 95% confidence interval [CI]: 2.478 — 20.456,P<0.001) and had an area under the ROC curve of 0.686 (95%CI: 0.597 — 0.776) in predicting ACLF with MDR bacterial infection(P<0.001), with the optimal cut-off value of 0.50×109/L, a sensitivity of 0.725, and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria, with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.
7.Population genetics analysis of Oncomelania hupensis in Jiaxing, Zhejiang Province, 2022
Weiling GU ; Hanqi PENG ; Hanxiang ZHANG ; Zelin XIANG ; Zhongwen CHEN ; Xiaofei FU ; Yunpeng QI ; Liang XIE ; Jie HU ; Dabing LYU
Shanghai Journal of Preventive Medicine 2024;36(6):559-562
ObjectiveTo genotype Oncomelania hupensis, based on microsatellites, in different snail-bearing environments in Jiaxing City, Zhejiang Province, for population genetics analysis in order to explore the reasons and influencing factors for the existence or proliferation of snails and to provide scientific basis for effective monitoring and control of snails. MethodsA total of 90 snail samples from three populations were collected in Yaobang Village (YB) and Sanxing Village (SX) in Pinghu City, and Yunhe Farm (YH) in Xiuzhou District, all were selected for snail checking in key snail habitats of Jiaxing City in 2022. DNA of the snails was genotyped and analyzed for population genetics using nine microsatellite loci. ResultsA total of 84 alleles were observed, and the mean number of alleles (Na) was 7.889, 5.667, and 3.778 for YB, SX, and YH respectively; the number of effective alleles (NeA) was 4.807, 3.329, and 2.294, respectively; and the coefficients of inbreeding (FIS) were 0.400, 0.377, and 0.493, respectively. Under the Infinite Allele Model (IAM), the SX and YH might have a recent bottleneck. The NEstimator and LDNe software calculated effective population sizes (Ne) were above 31.9. AMOVA analysis showed that the variation of snails in the three populations mainly existed among individuals, accounting for 41.4% of the total variation. The value of the index of genetic differentiation between populations (FST) was 0.286, indicating a high degree of genetic differentiation. The results of the principal component analysis and phylogenetic tree were consistent, and the three populations were divided into two lineages, YB and SX were one lineage, and YH belonged to another independent lineage. Population history and dynamics analysis showed that the gene flow of the three populations was insufficient, population divergence history indicated that YH might have diverged from SX first, and YB was produced by the contact fusion of SX and YH. ConclusionThe genetic diversity of snail populations in Jiaxing City is generally low, and the snail populations are unstable, with a great degree of genetic differentiation and insufficient gene flow among populations. This study can provide a basis for evaluating the effectiveness of the control of the snail as well as monitoring the trend of the spread of the snail.
8.Research progress on quantitative detection methods of lateral flow immunochromatography assay
Jiayu GU ; Xiner HU ; Xiaofei WANG ; Ying ZHANG ; Hai ZHANG ; Yan CAO
Journal of Pharmaceutical Practice and Service 2024;42(7):273-277,284
Lateral flow immunochromatography assay is a new instantaneous detection technology that employs a chromatographic membrane and labeling materials for detection.This detection technology is convenient,fast,and inexpensive,and is therefore widely used in a number of different fields,such as biomedicine,disease detection,food safety,environmental protection,and so on.Traditional lateral flow immunochromatography assay relied on visual observation and provided only qualitative or semi-quantitative results.By utilizing various types of markers and sensitive detection devices,lateral flow immunochromatography assay enables quantitative and multi-component detection of the analytes.The research progress on the lateral flow immunoassay detection system and its current applications in the context of recognition elements,labeling materials,and detection instruments were reviewed in this paper.
9.Efficacy analysis of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori in Ningxia
Chengcheng FENG ; Linke MA ; Jun LIU ; Xue LI ; Xiaoming SU ; Yuanyuan TANG ; Xiaofei LI ; Yanling LI ; Qiang WEI ; Zhanbin HOU ; Xilong ZHANG ; Shengjuan HU
Chinese Journal of Digestion 2024;44(5):302-307
Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.
10.Role of palmitoyltransferase modified NOD2 in brain injury after cardiopulmonary resuscitation in mice
Chengji ZHOU ; Yong TANG ; Peng JIANG ; Zhouquan HU ; Wei WEI ; Guoan WANG ; Xiaofei FU
Tianjin Medical Journal 2024;52(8):804-809
Objective To investigate the role of nucleotide-binding oligomerization domain 2(NOD2)modified by palmitoyltransferase(ZDHHC5)in brain injury after cardiopulmonary resuscitation(CPR)in mice.Methods Twenty-four male C57BL/6J mice were divided into the blank group,the control group,the ZDHHC5-si group and the NOD2-si group,with 6 mice in each group.Except for the blank group without any treatment,CPR modeling was performed in the other three groups.At 24 h before CPR,mice in the ZDHHC5-si group and the NOD2-si group were injected with ZDHHC5 siRNA and NOD2 siRNA via tail vein,respectively.The modified neurological deficit scale(mNSS)was used to evaluate the neurological function at 24 h,48 h and 72 h in each group.Blood samples and brain tissue were collected 72 h after modeling.Real-time fluorescent quantitative PCR(qPCR)was used to detect ZDHHC5 and NOD2 in brain tissue.The protein expression levels of IL-1β,TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay(ELISA).Colorimetric method and thiobarbituric acid(TBA)method were used to detect protein expression levels of MDA and MPO in brain tissue,respectively.Western blot assay was used to detect expression levels of Cleaved Caspase-3,ZDHHC5 and NOD2 in brain tissue.HE pathological sections of brain tissue were observed under light microscope.The pathological sections of brain tissue were observed by TUNEL under fluorescence microscope.Results Compared with the blank group,the mNSS score,the expression levels of IL-1β,TNF-α,IL-6,MDA and MPO,and the protein expression levels of Cleaved Caspase-3,ZDHHC5 and NOD2 were significantly increased(P<0.05),and brain tissue damage and cell apoptosis were aggravated in the other three groups.Compared with the control group,the above indicators were significantly decreased in the ZDHHC5-si group and the NOD2-si group(P<0.05),and brain tissue damage and cell apoptosis were significantly attenuated.Compared with the NOD2-si group,the above parameters were significantly decreased(P<0.05),and brain tissue damage and cell apoptosis were further attenuated in the ZDHHC5-si group.Conclusion In the mouse CPR model,NOD2 can produce palmitoylated NOD2 after regulated by ZDHHC5,which further promotes the release of inflammatory factors and causes neuronal apoptosis,ultimately damaging brain tissue and affecting neurological function.

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