Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y14 Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y14 receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y14 receptor antagonists based on the scaffold hopping strategy. The optimized compound 39 (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC50: 0.40 nM). Moreover, compound 39 demonstrated notably improved solubility, liver microsomal stability, and oral bioavailability. Fluorescent ligand binding assay confirmed that 39 has the binding ability to the P2Y14 receptor, and molecular dynamics (MD) simulations revealed the formation of a unique intramolecular hydrogen bond (IMHB) in the binding conformation. In the experimental colitis mouse model, compound 39 showed a remarkable anti-IBD effect even at low doses. Compound 39, with a potent anti-IBD effect and favorable druggability, can be a promising candidate for further research. In addition, this work lays a strong foundation for the development of P2Y14 receptor antagonists and the therapeutic strategy for IBD.

Self-assembly of a ruthenium-based cGAS-STING photoactivator for carrier-free cancer immunotherapy.

The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway promotes antitumor immune responses by sensing cytosolic DNA fragments leaked from nucleus and mitochondria. Herein, we designed a highly charged ruthenium photosensitizer (Ru1) with a ß-carboline alkaloid derivative as the ligand for photo-activating of the cGAS-STING pathway. Due to the formation of multiple non-covalent intermolecular interactions, Ru1 can self-assemble into carrier-free nanoparticles (NPs). By incorporating the triphenylphosphine substituents, Ru1 can target and photo-damage mitochondrial DNA (mtDNA) to cause the cytoplasmic DNA leakage to activate the cGAS-STING pathway. Finally, Ru1 NPs show potent antitumor effects and elicit intense immune responses in vivo. In conclusion, we report the first self-assembling mtDNA-targeted photosensitizer, which can effectively activate the cGAS-STING pathway, thus providing innovations for the design of new photo-immunotherapeutic agents.

Synthesis of 1,2,4,5-tetra-substituted benzenes via copper-catalyzed dimerization of γ,δ-unsaturated ketones.

An efficient cyclization for the synthesis of 1,2,4,5-tetra-substituted benzenes via copper catalyzed dimerization of γ,δ-unsaturated ketones has been described. This one-pot procedure employs the γ,δ-unsaturated ketones as the sole substrate with multiple C-C bond formation. This protocol features broad substrate scope and provides a facile and robust method to construct polysubstituted benzene derivatives under mild conditions.

Advances in Research on the Effectiveness and Mechanism of Active Ingredients from Traditional Chinese Medicine in Regulating Hepatic Stellate Cells Autophagy Against Hepatic Fibrosis.

Hepatic fibrosis (HF) is a pathological process of structural and functional impairment of the liver and is a key component in the progression of chronic liver disease. There are no specific anti-hepatic fibrosis (anti-HF) drugs, and HF can only be improved or prevented by alleviating the cause. Autophagy of hepatic stellate cells (HSCs) is closely related to the development of HF. In recent years, traditional Chinese medicine (TCM) has achieved good therapeutic effects in the prevention and treatment of HF. Several active ingredients from TCM (AITCM) can regulate autophagy in HSCs to exert anti-HF effects through different pathways, but relevant reviews are lacking. This paper reviewed the research progress of AITCM regulating HSCs autophagy against HF, and also discussed the relationship between HSCs autophagy and HF, pointing out the problems and limitations of the current study, in order to provide references for the development of anti-HF drugs targeting HSCs autophagy in TCM. By reviewing the literature in PubMed, Web of Science, Embase, CNKI and other databases, we found that the relationship between autophagy of HSCs and HF is currently controversial. HSCs autophagy may promote HF by consuming lipid droplets (LDs) to provide energy for their activation. However, in contrast, inducing autophagy in HSCs can exert the anti-HF effect by stimulating their apoptosis or senescence, reducing type I collagen accumulation, inhibiting the extracellular vesicles release, degrading pro-fibrotic factors and other mechanisms. Some AITCM inhibit HSCs autophagy to resist HF, with the most promising direction being to target LDs. While, others induce HSCs autophagy to resist HF, with the most promising direction being to target HSCs apoptosis. Future research needs to focus on cell targeting research, autophagy targeting research and in vivo verification research, and to explore the reasons for the contradictory effects of HSCs autophagy on HF.

MRI radiomics enhances radiologists' ability for characterizing intestinal fibrosis in patients with Crohn's disease.

OBJECTIVES: We aimed to develop MRI-based radiomic models (RMs) to improve the diagnostic accuracy of radiologists in characterizing intestinal fibrosis in patients with Crohn's disease (CD). METHODS: This retrospective study included patients with refractory CD who underwent MR before surgery from November 2013 to September 2021. Resected bowel segments were histologically classified as none-mild or moderate-severe fibrosis. RMs based on different MR sequence combinations (RM1: T2WI and enhanced-T1WI; RM2: T2WI, enhanced-T1WI, diffusion-weighted imaging [DWI], and apparent diffusion coefficient [ADC]); RM3: T2WI, enhanced-T1WI, DWI, ADC, and magnetization transfer MRI [MTI]), were developed and validated in an independent test cohort. The RMs' diagnostic performance was compared to that of visual interpretation using identical sequences and a clinical model. RESULTS: The final population included 123 patients (81 men, 42 women; mean age: 30.26 ± 7.98 years; training cohort, n = 93; test cohort, n = 30). The area under the receiver operating characteristic curve (AUC) of RM1, RM2, and RM3 was 0.86 (p = 0.001), 0.88 (p = 0.001), and 0.93 (p = 0.02), respectively. The decision curve analysis confirmed a progressive improvement in the diagnostic performance of three RMs with the addition of more specific sequences. All RMs performance surpassed the visual interpretation based on the same MR sequences (visual model 1, AUC = 0.65, p = 0.56; visual model 2, AUC = 0.63, p = 0.04; visual model 3, AUC = 0.77, p = 0.002), as well as the clinical model composed of C-reactive protein and erythrocyte sedimentation rate (AUC = 0.60, p = 0.13). CONCLUSIONS: The RMs, utilizing various combinations of conventional, DWI and MTI sequences, significantly enhance radiologists' ability to accurately characterize intestinal fibrosis in patients with CD. CRITICAL RELEVANCE STATEMENT: The utilization of MRI-based RMs significantly enhances the diagnostic accuracy of radiologists in characterizing intestinal fibrosis. KEY POINTS: MRI-based RMs can characterize CD intestinal fibrosis using conventional, diffusion, and MTI sequences. The RMs achieved AUCs of 0.86-0.93 for assessing fibrosis grade. MRI-radiomics outperformed visual interpretation for grading CD intestinal fibrosis.

Chiral bisphosphine Ph-BPE ligand: a rising star in asymmetric synthesis.

Chiral 1,2-bis(2,5-diphenylphospholano)ethane (Ph-BPE) is a class of optimal organic bisphosphine ligands with C2-symmetry. Ph-BPE with its excellent catalytic performance in asymmetric synthesis has attracted much attention of chemists with increasing popularity and is growing into one of the most commonly used organophosphorus ligands, especially in asymmetric catalysis. Over two hundred examples have been reported since 2012. This review presents how Ph-BPE is utilized in asymmetric synthesis and how powerful it is as a chiral ligand or even a catalyst in a wide range of reactions including applications in the total synthesis of bioactive molecules.

Stabilizing and Activating Active Sites: 1T-MoS2 Supported Pd Single Atoms for Efficient Hydrogen Evolution Reaction.

Metallic 1T-MoS2 with high intrinsic electronic conductivity performs Pt-like catalytic activity for hydrogen evolution reaction (HER). However, obtaining pure 1T-MoS2 is challenging due to its high formation energy and metastable properties. Herein, an in situ SO4 2--anchoring strategy is reported to synthesize a thin layer of 1T-MoS2 loaded on commercial carbon. Single Pd atoms, constituting a substantial loading of 7.2 wt%, are then immobilized on the 1T-phase MoS2 via Pd─S bonds to modulate the electronic structure and ensure a stable active phase. The resulting Pd1/1T-MoS2/C catalyst exhibits superior HER performance, featuring a low overpotential of 53 mV at the current density of 10 mA cm-2, a small Tafel slope of 37 mV dec-1, and minimal charge transfer resistance in alkaline electrolyte. Moreover, the catalyst also demonstrates efficacy in acid and neutral electrolytes. Atomic structural characterization and theoretical calculations reveal that the high activity of Pd1/1T-MoS2/C is attributed to the near-zero hydrogen adsorption energy of the activated sulfur sites on the two adjacent shells of atomic Pd.

A new prediction model for acute kidney injury following liver transplantation using grafts from donors after cardiac death.

Acute kidney injury (AKI) is a major complication following liver transplantation (LT), which utilizes grafts from donors after cardiac death (DCD). We developed a machine-learning-based model to predict AKI, using data from 894 LT recipients (January 2015-March 2021), split into training and testing sets. Five machine learning algorithms were employed to construct the prediction models using 17 clinical variables. The performance of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. The best-performing model was further validated in an independent cohort of 195 LT recipients who received DCD grafts between April 2021 and December 2021. The Shapley additive explanations method was utilized to elucidate the predictions and identify the most crucial features. The gradient boosting machine (GBM) model demonstrated the highest AUC (0.76, 95% CI: 0.70-0.82), F1-score (0.73, 95% CI: 0.66-0.79) and sensitivity (0.74, 95% CI: 0.66-0.80) in the testing set and a comparable AUC (0.75, 95% CI: 0.67-0.81) in the validation set. The GBM model identified high preoperative indirect bilirubin, low intraoperative urine output, prolonged anesthesia duration, low preoperative platelet count and graft steatosis graded NASH Clinical Research Network 1 and above as the top five important features for predicting AKI following LT using DCD grafts. The GBM model is a reliable and interpretable tool for predicting AKI in recipients of LT using DCD grafts. This model can assist clinicians in identifying patients at high risk and providing timely interventions to prevent or mitigate AKI.

Effects of melatonin on sperm quality, enzyme activity, antioxidant gene expression and fertility of cryopreserved bovine semen.

Melatonin (MLT) has strong antioxidant capacity and can reduce the damage caused by oxidative stress in sperm, but there is still little content in the field we have studied. In this study, we are committed to scientific research on adding melatonin to Belgian blue bull semen diluent for cryopreservation. Different concentrations (0, 0.1, 0.3, 0.5 or 0.7 mg/mL) of MLT were added diluent. Sperm kinetic parameters, enzyme activity, antioxidant gene expression and fertility were analyzed after thawing. The results showed that MLT concentration of 0.3 mg/mL exerted positive effects on post-thaw kinetic parameters. Compared with other groups, 0.3 mg/mL MLT treated sperm acrosome and plasma membrane integrity, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels significantly increased. Meanwhile, the mRNA expression of antioxidant genes SOD2, CAT and GPx increased in the 0.3 mg/mL MLT treatment group, and the mRNA expression of apoptosis genes Caspase-3 and Bax were significantly reduced. In addition, in vitro fertilization (IVF) embryo cleavage, blastocyst rate and artificial insemination (AI) pregnancy rate were higher in 0.3 mg/mL MLT. Therefore, MLT showed cryoprotective capacity to the freezing diluent used for Belgian blue bull sperm during the process of freezing-thawing, and the optimal concentration of MLT for the frozen diluent was 0.3 mg/mL.

HHO optimized support vector machine classifier for traditional Chinese medicine syndrome differentiation of diabetic retinopathy.

AIM: To develop a classifier for traditional Chinese medicine (TCM) syndrome differentiation of diabetic retinopathy (DR), using optimized machine learning algorithms, which can provide the basis for TCM objective and intelligent syndrome differentiation. METHODS: Collated data on real-world DR cases were collected. A variety of machine learning methods were used to construct TCM syndrome classification model, and the best performance was selected as the basic model. Genetic Algorithm (GA) was used for feature selection to obtain the optimal feature combination. Harris Hawk Optimization (HHO) was used for parameter optimization, and a classification model based on feature selection and parameter optimization was constructed. The performance of the model was compared with other optimization algorithms. The models were evaluated with accuracy, precision, recall, and F1 score as indicators. RESULTS: Data on 970 cases that met screening requirements were collected. Support Vector Machine (SVM) was the best basic classification model. The accuracy rate of the model was 82.05%, the precision rate was 82.34%, the recall rate was 81.81%, and the F1 value was 81.76%. After GA screening, the optimal feature combination contained 37 feature values, which was consistent with TCM clinical practice. The model based on optimal combination and SVM (GA_SVM) had an accuracy improvement of 1.92% compared to the basic classifier. SVM model based on HHO and GA optimization (HHO_GA_SVM) had the best performance and convergence speed compared with other optimization algorithms. Compared with the basic classification model, the accuracy was improved by 3.51%. CONCLUSION: HHO and GA optimization can improve the model performance of SVM in TCM syndrome differentiation of DR. It provides a new method and research idea for TCM intelligent assisted syndrome differentiation.

Analysis of fluid force and flow fields during gliding in swimming using smoothed particle hydrodynamics method.

Gliding is a crucial phase in swimming, yet the understanding of fluid force and flow fields during gliding remains incomplete. This study analyzes gliding through Computational Fluid Dynamics simulations. Specifically, a numerical model based on the Smoothed Particle Hydrodynamics (SPH) method for flow-object interactions is established. Fluid motion is governed by continuity, Navier-Stokes, state, and displacement equations. Modified dynamic boundary particles are used to implement solid boundaries, and steady and uniform flows are generated with inflow and outflow conditions. The reliability of the SPH model is validated by replicating a documented laboratory experiment on a circular cylinder advancing steadily beneath a free surface. Reasonable agreement is observed between the numerical and experimental drag force and lift force. After the validation, the SPH model is employed to analyze the passive drag, vertical force, and pitching moment acting on a streamlined gliding 2D swimmer model as well as the surrounding velocity and vorticity fields, spanning gliding velocities from 1 m/s to 2.5 m/s, submergence depths from 0.2 m to 1 m, and attack angles from -10° to 10°. The results indicate that with the increasing gliding velocity, passive drag and pitching moment increase whereas vertical force decreases. The wake flow and free surface demonstrate signs of instability. Conversely, as the submergence depth increases, there is a decrease in passive drag and pitching moment, accompanied by an increase in vertical force. The undulation of the free surface and its interference in flow fields diminish. With the increase in the attack angle, passive drag and vertical force decrease whereas pitching moment increases, along with the alteration in wake direction and the increasing complexity of the free surface. These outcomes offer valuable insights into gliding dynamics, furnishing swimmers with a scientific basis for selecting appropriate submergence depth and attack angle.

A novel missense mutation of CCDC34 causes male infertility with oligoasthenoteratozoospermia in a consanguineous Pakistani family.

ABSTRACT: Male infertility is a worldwide health issue, affecting 8%-12% of the global population. Oligoasthenoteratozoospermia (OAT) represents a severe type of male infertility, characterized by reduced sperm count and motility and an increased frequency of sperm with aberrant morphology. Using whole-exome sequencing, this study identified a novel missense mutation (c.848C>A, p.A283E) in the coiled-coil domain-containing 34 gene (CCDC34) in a consanguineous Pakistani family. This rare mutation was predicted to be deleterious and to affect the protein stability. Hematoxylin and eosin staining of spermatozoa from the patient with OAT revealed multiple morphological abnormalities of the flagella and transmission electron microscopy indicated axonemal ultrastructural defects with a lack of outer dynein arms. These findings indicated that CCDC34 plays a role in maintaining the axonemal ultrastructure and the assembly or stability of the outer dynein arms, thus expanding the phenotypic spectrum of CCDC34 missense mutations.

Generation of a competing endogenous RNA network and validation of BNIP1 expression in the lung of irradiated mice.

BACKGROUND: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy, and it is mediated by long non-coding RNAs (lncRNAs). STUDY DESIGN AND METHODS: Mouse lung tissues were examined using RNA-Seq and RNA-Seq libraries 72 h after the administration of 6 Gy of X-ray irradiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and target miRNA-based mRNAs were predicted after irradiation to establish the lncRNA-miRNA-mRNA ceRNA axis. RESULTS: The analyses showed that relative to unirradiated controls, 323 mRNAs, 114 miRNAs, and 472 lncRNAs were significantly up-regulated following irradiation, whereas 1907 mRNAs, 77 miRNAs, and 1572 lncRNAs were significantly down-regulated following irradiation. Voltage-gated ion channels, trans-membrane receptor protein tyrosine kinases, and vascular endothelial growth factor have all been associated with dysregulated miRNA-mRNA relationships. KEGG pathway analysis of the dysregulated miRNA-mRNA targets revealed involvement in pathways associated with the hedgehog signaling pathway-fly, ErbB signaling, VEGF signaling, axon guidance, and focal adhesion. KEGG analysis of differentially expressed showed enrichment of mRNAs in primary immunodeficiency, the intestinal immune axis for IgA production, hematopoietic cell lineages, systemic lupus erythematosus, and Th1 and Th2 cell differentiation. Finally, the ceRNA network revealed that BNIP1 was a critical mRNA modulated by the most significant upregulation of lncRNA E230013L22Rik. CONCLUSION: In summary, the lncRNA-miRNA-mRNA ceRNA axis of RILI was constructed following irradiation in a mouse model. RNA dysregulation in the early stage of RILI may lead to severe complications at a later stage, with BNIP1 contributing to radiation-induced cellular apoptosis in RILI.

TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway.

OBJECTIVE: Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage. Notably, the knockout of transient receptor potential channel 6 (TRPC6) has shown promise in alleviating renal fibrosis. However, the regulatory impact of TRPC6 on renal fibrosis remains unclear. METHODS: In vivo, TRPC6 knockout (TRPC6-/-) mice and age-matched 129 SvEv (WT) mice underwent unilateral renal ischemia-reperfusion (uIR) injury surgery on the left renal pedicle or sham operation. Kidneys and serum were collected on days 7, 14, 21, and 28 after euthanasia. In vitro, primary tubular epithelial cells (PTECs) were isolated from TRPC6-/- and WT mice, followed by treatment with transforming growth factor ß1 (TGFß1) for 72 h. The anti-fibrotic effect of TRPC6-/- and the underlying mechanisms were assessed through hematoxylin-eosin staining, Masson staining, immunostaining, qRT-PCR, and Western blotting. RESULTS: Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFß1. TRPC6-/- alleviated renal fibrosis by reducing the expression of fibrotic markers (Col-1, α-SMA, and vimentin), as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro. Additionally, we found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3ß) signaling pathway, a pivotal player in renal fibrosis, was down-regulated following TRPC6 deletion. CONCLUSION: These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3ß pathway. Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

[Activated phosphoinositide 3-kinase delta syndrome: report of seven cases]. / PI3Kδ过度活化综合征7例报道.

OBJECTIVES: To summarize the clinical data of 7 children with activated phosphoinositide 3-kinase delta syndrome (APDS) and enhance understanding of the disease. METHODS: A retrospective analysis was conducted on clinical data of 7 APDS children admitted to Hunan Provincial People's Hospital from January 2019 to August 2023. RESULTS: Among the 7 children (4 males, 3 females), the median age of onset was 30 months, and the median age at diagnosis was 101 months. Recurrent respiratory tract infections, hepatosplenomegaly, and multiple lymphadenopathy were observed in all 7 cases. Sepsis was observed in 5 cases, otitis media and multiple caries were observed in 3 cases, and diarrhea and joint pain were observed in 2 cases. Lymphoma and systemic lupus erythematosus were observed in 1 case each. Fiberoptic bronchoscopy was performed in 4 cases, revealing scattered nodular protrusions in the bronchial lumen. The most common respiratory pathogen was Streptococcus pneumoniae (4 cases). Six patients had a p.E1021K missense mutation, and one had a p.434-475del splice site mutation. CONCLUSIONS: p.E1021K is the most common mutation site in APDS children. Children who present with one or more of the following symptoms: recurrent respiratory tract infections, hepatosplenomegaly, multiple lymphadenopathy, otitis media, and caries, and exhibit scattered nodular protrusions on fiberoptic bronchoscopy, should be vigilant for APDS. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(5): 499-505.

Three-Dimensional Bimetallic Ammonium K-Eu Nitrate with a Rare (6,6)-Connected Ion Topology Exhibiting Structural Phase Transition and Photoluminescence Properties.

A K-Eu bimetallic ammonium metal-nitrate three-dimensional (3D) framework incorporating R-N-methyl-3-hydroxyquinuclidine, (RM3HQ)2KEu(NO3)6 (RM3HQ = R-N-methyl-3-hydroxyquinuclidine, 1), was characterized and reported. Distinguishing from the former hybrid rare-earth double perovskites, 1 adopts a mixed corner- and face-sharing K+/Eu3+-centered polyhedral connectivity to form a 3D inorganic framework, showing a rare (6, 6)-connected ion topology with a 66 framework. Notably, 1 exhibits clear phase transition, and the switchable thermodynamic behavior is confirmed by variable-temperature dielectric measurements and second-harmonic generation response. Moreover, 1 also shows photoluminescence properties. The activator Eu3+ plays a crucial role in this process, leading to a significant narrow emission at 592 nm with a photoluminescence quantum yield (PLQY) of 20.76%. The fluorescence lifetime (FLT) of 1 is 4.32 ms. This finding enriches the bimetallic hybrid system for potential electronic and/or luminescence applications.

Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel Marker Spp1 in Gonadotropes.

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.