Cyclic GMP-AMP synthase (cGAS), a pivotal molecule in innate immunity, has emerged as a keypoint in interdisciplinary research at the intersection of basic immunology and tumor biology. As a cytosolic nucleic acid sensor, cGAS is primarily characterized by its capacity to recognize double-stranded DNA (dsDNA) in the cytosol. Upon binding to dsDNA, cGAS undergoes a conformational change that promotes its dimerization and subsequent enzymatic activation. Once activated, it catalyzes the synthesis of the second messenger 2',3'-cGAMP from ATP and GTP. cGAMP then binds to the adaptor protein STING, which resides on the endoplasmic reticulum (ER) membrane. The binding process triggers STING to traffic from the ER to the Golgi apparatus, where it is phosphorylated by the kinase TBK1. Phosphorylated STING serves as a docking site for the transcription factor IRF3, facilitating its phosphorylation by TBK1. Once phosphorylated, IRF3 forms dimers and translocates to the nucleus, where it drives the expression of type I interferons and pro-inflammatory cytokines, initiating a potent antimicrobial state. The DNA-sensing mechanism of cGAS is inherently non-selective regarding the origin of its ligand. It readily detects exogenous DNA from invading pathogens, thereby playing an indispensable role in host defense against microbial infections. However, this same mechanism also enables cGAS to recognize self-DNA that leaks from the nucleus or mitochondria into the cytosol under various cellular stress conditions. While critical for immunity, the recognition of self-dsDNA by cGAS can disrupt cellular homeostasis and trigger aberrant inflammatory responses. The loss of self-tolerance can precipitate or exacerbate the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), highlighting the dual role of cGAS as both a sentinel for infection and a potential driver of autoimmune pathology. Notably, the subcellular localization of cGAS is not still. Increasing recent researches have revealed that cGAS is also abundant within the nucleus, challenging the traditional view of it solely as a cytosolic nucleic acid sensor. Within the nucleus, cGAS exhibits non-canonical functions that are distinct from its canonical immunological role. First, cGAS exists in a state of stringent immunological silence in the nucleus, with mechanisms involving its competitive binding to histones and its post-translational modifications which block the activation of cGAS enzymatic activity, thus, effectively preventing it from mounting an autoimmune attack on genomic DNA. Second, cGAS plays a critical role in maintaining genomic stability. Upon DNA damage, cGAS is rapidly recruited to the lesion site and participates in the DNA damage repair process. Moreover, under conditions of DNA replication stress, cGAS contributes to the stabilization of replication forks, preventing the cell from entering a state of uncontrolled hyper-replication. Consequently, in light of the dual role of cGAS in both immune regulation and tumor development, the development of small-molecule drugs targeting cGAS holds significant therapeutic promise. This review summarizes the structural characteristics of cGAS and its canonical function as a pattern recognition receptor in the cytosol, including the types of pathogens it recognizes and the autoimmune responses resulting from erroneous recognition of self-DNA. It then focuses on its emerging non-canonical functions within the nucleus, detailing its nucleocytoplasmic shuttling, the mechanisms underlying its nuclear immune quiescence, and its role in mediating DNA damage repair and replication fork stabilization. Finally, the review discusses the progress and application prospects of small-molecule drugs targeting cGAS for the treatment of autoimmune diseases and cancer.

Cyclic GMP-AMP synthase (cGAS), a pivotal molecule in innate immunity, has emerged as a keypoint in interdisciplinary research at the intersection of basic immunology and tumor biology. As a cytosolic nucleic acid sensor, cGAS is primarily characterized by its capacity to recognize double-stranded DNA (dsDNA) in the cytosol. Upon binding to dsDNA, cGAS undergoes a conformational change that promotes its dimerization and subsequent enzymatic activation. Once activated, it catalyzes the synthesis of the second messenger 2',3'-cGAMP from ATP and GTP. cGAMP then binds to the adaptor protein STING, which resides on the endoplasmic reticulum (ER) membrane. The binding process triggers STING to traffic from the ER to the Golgi apparatus, where it is phosphorylated by the kinase TBK1. Phosphorylated STING serves as a docking site for the transcription factor IRF3, facilitating its phosphorylation by TBK1. Once phosphorylated, IRF3 forms dimers and translocates to the nucleus, where it drives the expression of type I interferons and pro-inflammatory cytokines, initiating a potent antimicrobial state. The DNA-sensing mechanism of cGAS is inherently non-selective regarding the origin of its ligand. It readily detects exogenous DNA from invading pathogens, thereby playing an indispensable role in host defense against microbial infections. However, this same mechanism also enables cGAS to recognize self-DNA that leaks from the nucleus or mitochondria into the cytosol under various cellular stress conditions. While critical for immunity, the recognition of self-dsDNA by cGAS can disrupt cellular homeostasis and trigger aberrant inflammatory responses. The loss of self-tolerance can precipitate or exacerbate the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), highlighting the dual role of cGAS as both a sentinel for infection and a potential driver of autoimmune pathology. Notably, the subcellular localization of cGAS is not still. Increasing recent researches have revealed that cGAS is also abundant within the nucleus, challenging the traditional view of it solely as a cytosolic nucleic acid sensor. Within the nucleus, cGAS exhibits non-canonical functions that are distinct from its canonical immunological role. First, cGAS exists in a state of stringent immunological silence in the nucleus, with mechanisms involving its competitive binding to histones and its post-translational modifications which block the activation of cGAS enzymatic activity, thus, effectively preventing it from mounting an autoimmune attack on genomic DNA. Second, cGAS plays a critical role in maintaining genomic stability. Upon DNA damage, cGAS is rapidly recruited to the lesion site and participates in the DNA damage repair process. Moreover, under conditions of DNA replication stress, cGAS contributes to the stabilization of replication forks, preventing the cell from entering a state of uncontrolled hyper-replication. Consequently, in light of the dual role of cGAS in both immune regulation and tumor development, the development of small-molecule drugs targeting cGAS holds significant therapeutic promise. This review summarizes the structural characteristics of cGAS and its canonical function as a pattern recognition receptor in the cytosol, including the types of pathogens it recognizes and the autoimmune responses resulting from erroneous recognition of self-DNA. It then focuses on its emerging non-canonical functions within the nucleus, detailing its nucleocytoplasmic shuttling, the mechanisms underlying its nuclear immune quiescence, and its role in mediating DNA damage repair and replication fork stabilization. Finally, the review discusses the progress and application prospects of small-molecule drugs targeting cGAS for the treatment of autoimmune diseases and cancer.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To assess the current status of microbial and parasitic quality control for laboratory animals in Jiangxi Province by analyzing microbiological and parasitic test results from production facilities between 2020 and 2024, and to provide a basis for enhancing quality control measures. MethodsIn accordance with the current national standards for laboratory animals at the time of testing, the Jiangxi Provincial Laboratory Animal Quality Inspection Station (affiliated to Institute of Occupational Medicine of Jiangxi) conducted microbial and parasitic testing on 451 laboratory animals of 4 species from 6 laboratory animal production units in Jiangxi Province between 2020 and 2024, and analyzed the quality status of laboratory animals in the province. ResultsPasteurella pneumotropica was detected in one mouse sample in 2020, with a detection rate of 5.00%. Pseudomonas aeruginosa was detected in one mouse sample and mouse hepatitis virus antibody was detected in another mouse sample in 2023, with a detection rate of 2.78%, respectively. No microorganisms or parasites that should be excluded from SPF grade mice as specified in the national standards were detected in 2021, 2022, or 2024, with a qualification rate of 100.00%. Pasteurella pneumotropica was detected in four rat samples in 2020, with a detection rate of 20.00%. Pseudomonas aeruginosa was detected in two rat samples in 2021, with a detection rate of 10.00%, and Tyzzer's disease agent antibody was detected in four rat samples in 2024, with a detection rate of 10.00%. No microorganisms or parasites that should be excluded from SPF grade rats as specified in the national standards were detected in 2022 or 2023, with a qualification rate of 100.00%. For rabbits and guinea pigs, no microorganisms or parasites required to be tested for conventional grade rabbits and guinea pigs as specified in the national standards were detected from 2020 to 2024, with the qualification rate of both species reaching 100.00%. ConclusionBased on the microbial and parasitic testing results, the quality of rabbits and guinea pigs in Jiangxi Province is satisfactory. However, some issues persist with rats and mice. It is recommended to enhance the quality of experimental animals in Jiangxi Province by increasing the frequency of random inspections by quality testing units or by improving the self-inspection capabilities of production and user facilities.

Objective Exploring the clinical efficacy of using autologous rib cartilage grafting to reconstruct finger hemiarticular defects.Methods From August 2022 to February 2024,for 6 patients with hemiarticular surface defects in the metacarpophalangeal joints and interphalangeal joints of 8 fingers,costal cartilage was used for joint remodeling and transplantation to reconstruct the hemiarticular surface defects of the fingers.All 8 joint transplants in 6 patients were two-stage surgeries.In the first stage,antibiotic bone cement was used to fill the space-occupying lesions,and in the second stage,costal cartilage joint remodeling was performed to reconstruct the finger joint defects.Postoperative follow-up and assessment of fracture healing according to Paley fracture healing scoring criteria.Outpatient and WeChat follow-up,upper limb function is evaluated according to the upper limb functional assessment standards of the Chinese Medical Association Hand Surgery Society.Record VAS pain score.Results In this group,there were a total of 6 patients with 8 cases of hemiarticular defects.Among them,2 patients had two joint surgical sites,while the remaining 4 patients had a single joint surgical site.There were 2 cases of metacarpophalangeal joint head defects,2 cases of proximal articular surface defects,3 cases of proximal articular head defects,and 1 case of thumb proximal articular head defect.After surgery,8 out of 6 patients'hand wounds healed successfully.All patients were followed up for 6-12 months postoperatively,with an average of 9 months.The VAS pain score(affected finger)for the last follow-up was 0-2 points,with an average of 0.6 points.According to Paley's scoring criteria,all 6 patients had excellent fracture healing.According to the evaluation criteria for upper limb functional assessment of the Chinese Medical Association Hand Surgery Society,3 cases were rated as excellent,3 cases were rated as good,and 2 cases were rated as fair.Conclusion For patients with half joint defects on one side of the finger,rib rib cartilage was used for joint reconstruction,which significantly improved the joint shape and function at the defect site,and reduced joint pain scores.

Objective Exploring the clinical efficacy of using autologous rib cartilage grafting to reconstruct finger hemiarticular defects.Methods From August 2022 to February 2024,for 6 patients with hemiarticular surface defects in the metacarpophalangeal joints and interphalangeal joints of 8 fingers,costal cartilage was used for joint remodeling and transplantation to reconstruct the hemiarticular surface defects of the fingers.All 8 joint transplants in 6 patients were two-stage surgeries.In the first stage,antibiotic bone cement was used to fill the space-occupying lesions,and in the second stage,costal cartilage joint remodeling was performed to reconstruct the finger joint defects.Postoperative follow-up and assessment of fracture healing according to Paley fracture healing scoring criteria.Outpatient and WeChat follow-up,upper limb function is evaluated according to the upper limb functional assessment standards of the Chinese Medical Association Hand Surgery Society.Record VAS pain score.Results In this group,there were a total of 6 patients with 8 cases of hemiarticular defects.Among them,2 patients had two joint surgical sites,while the remaining 4 patients had a single joint surgical site.There were 2 cases of metacarpophalangeal joint head defects,2 cases of proximal articular surface defects,3 cases of proximal articular head defects,and 1 case of thumb proximal articular head defect.After surgery,8 out of 6 patients'hand wounds healed successfully.All patients were followed up for 6-12 months postoperatively,with an average of 9 months.The VAS pain score(affected finger)for the last follow-up was 0-2 points,with an average of 0.6 points.According to Paley's scoring criteria,all 6 patients had excellent fracture healing.According to the evaluation criteria for upper limb functional assessment of the Chinese Medical Association Hand Surgery Society,3 cases were rated as excellent,3 cases were rated as good,and 2 cases were rated as fair.Conclusion For patients with half joint defects on one side of the finger,rib rib cartilage was used for joint reconstruction,which significantly improved the joint shape and function at the defect site,and reduced joint pain scores.

Aim To investigate the role of myotubula-rin related protein 7(MTMR7)in the pathogenesis of pulmonary hypertension manifested by pulmonary vas-cular intimal thickening,right ventricular hypertrophy,progressive right heart failure and dysfunction.Meth-ods A total of 40 healthy male C57BL/6J mice and Mtmr7-transgenic(Mtmr7-Tg)mice were divided into the control group,Mtmr7-Tg group,monocrotaline(MCT)group and MCT+Mtmr7-Tg group.Pulmonary artery acceleration time(PAT)and pulmonary artery ejection time(PET)of the pulmonary artery were measured by ultrasound.When the free wall of the right ventricle was separated,the right heart hypertro-phy index(RVHI)was calculated.Pulmonary artery remodeling was observed by immunostaining.Mouse pulmonary artery smooth muscle cells(PASMCs)were cultured in hypoxic environment to induce the prolifer-ation and migration.Results MTMR7 was expressed in pulmonary vessels.Compared to the wild-type mice,Mtmr7-Tg mice showed increased PAT/PET ratio(P＜0.05),reduced RVHI(P＜0.01)after MCT stimu-lus.PASMCs were transfected with adenovirus encond-ing Mtmr7 gene,which inhibited proliferation and mi-gration of PASMCs.After restoring the activity of ERK1/2 by chemerin-9,the proliferation and migra-tion ability of PASMCs was elevated.Conclusions MTMR7 can counteract the growth and mobility of mouse PASMCs induced by hypoxia,thereby comba-ting pulmonary arterial hypertension via reducing ERK1/2 phosphorylation.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective To explore clinical effect of accessory scaphoid bone fusion in treating type Ⅱ painful accessory scaphoid bone.Methods A retrospective analysis was performed on 26 patients with type Ⅱ painful accessory navicular bone treated by accessory navicular bone fusion from January 2012 to June 2022,including 1 male and 25 females,aged from 18 to 70 years old with an average of(44.61±16.32)years old;10 patients with type Ⅱ A and 16 patients with type Ⅱ B;20 patients with simple fusion and 6 patients with fusion plus calcaneal translocation osteotomy.Changes of Meary angle,Pitch angle,an-teroposterior talar-first metatarsal angle(T1MA),talonavicular coverage angle(TCA),lateral talocalcaneal angle(LTCA)be-fore operation and 6 months after operation were observed and compared,and American Orthopedic Foot and Ankle Society(AOFAS)foot and ankle score and visual analogue scale(VAS)were used to explore clinical effect.Results All 26 patients were followed up for 7 to 24 months with an average of(10.72±3.94)months.Meary angle,Pitch angle,T1MA,TCA and LTCA were improved from(9.20±2.57)°,(16.45±3.57)°,(33.34±5.02)°,(22.42±5.86)°,(48.89±4.43)° before opertaion to(3.33±1.06)°,(22.33±4.56)°,(23.89±3.48)°,(11.83±2.67)°,(36.50±3.50)° at 6 months after operation,the difference were statistically significant(P＜0.01).Postoperative AOFAS foot and ankle score were(86.24±4.33)and(93.18±6.02)for type Ⅱ A and type Ⅱ B at 6 months,which were significantly improved compared with those for type Ⅱ A and type Ⅱ B before op-eration(67.34±6.55)and(65.12±9.51),and the difference was statistically significant(P＜0.01);20 patients got excellent re-sult,5 good and 1 poor.Preoperative VAS of type ⅡA(5.67±1.58)and type Ⅱ B(5.77±1.49)were improved to(2.13±1.01)and(1.43±0.68)at 6 months after operation,with statistical significance(P＜0.01).Conclusion Fusion of accessory navicular bone in patients with type Ⅱ painful accessory navicular bone combined with internal calcaneal osteotomy in patients with par-tial calcaneal valvaration could effectively correct flat foot deformity and relieve pain,and could be used as a clinical treatment for painful accessory navicular bone.