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 explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Guangzhou Women and Children's Medical Center (GWCMC) established a Rare Disease Medical Center in December 2023 and assumed responsibility for the construction of the Guangdong Provincial Rare Disease Quality Control Center. As a national children's regional medical center and a core institution for maternal and child health in the Guangdong-Hong Kong-Macao Greater Bay Area, GWCMC leverages its disciplinary strengths in maternal and pediatric specialties, centers on the diagnosis and treatment needs of rare diseases in women and children, and carries out a systematic layout in such aspects as clinical diagnosis, treatment and service system, technical system and platforms, scientific research innovation and academic influence, talent echelon and capacity building, as well as quality control and regional collaboration. This paper reviews the development trajectory of the GWCMC Rare Disease Center, summarizes its phased experience in high-quality development, and offers reflections on future directions.

In this study, there were three toxoplasmosis patients, two of whom developed symptoms in both eyes. One patient had a slight deviation of the lesion from the central fovea, which had a minor impact on vision. The diagnosis of this disease requires not only a close pet contact history and typical clinical manifestations, but also serology and the gold standard Goldmann-Witmer coefficient(GWC). However, the GWC of some patients cannot be detected at the initial stage, such as the first patient′s GWC, which did not meet the standard. All three patients underwent metagenomic testing to assist with diagnosis.

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.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.

[摘 要] 目的：以MG-63球形细胞作为骨肉瘤干细胞（OSC）富集模型，探讨靶向细胞膜表面HSP90β的单抗2G1对其生物学特征的影响及其与Wnt信号相关蛋白变化的关系。方法：采用无血清悬浮培养人骨肉瘤MG-63细胞获得MG-63球形细胞。通过免疫荧光共定位和免疫共沉淀实验鉴定单克隆抗体2G1识别的靶抗原；采用流式细胞术检测MG-63亲本细胞和MG-63球形细胞膜表面HSP90β的表达水平；通过甲基纤维素成球实验、Transwell迁移和侵袭实验评价单抗2G1对MG-63球形细胞成球、迁移和侵袭能力的影响；采用裸鼠皮下移植瘤模型观察单抗2G1对MG-63球形细胞体内成瘤能力的影响；进一步结合转录组测序、京都基因与基因组百科全书（KEGG）通路富集分析及WB检测，分析单抗2G1处理后相关分子通路及干细胞特性、上皮-间充质转化（EMT）、Wnt/β-catenin信号通路相关蛋白表达变化。结果：免疫荧光共定位和免疫共沉淀结果显示，单抗2G1识别的靶抗原为HSP90β。流式细胞术结果显示，MG-63球形细胞膜表面HSP90β阳性表达细胞比例为（20.77 ± 1.29）%，显著高于MG-63亲本细胞的（2.87 ± 0.33）%（P < 0.001）。与对照组相比，单抗2G1处理后MG-63球形细胞成球数由82.67 ± 4.70降至42.67 ± 4.00，迁移细胞数由117.00 ± 5.57降至78.33 ± 5.03，侵袭细胞数由130.70 ± 5.03降至89.33 ± 5.03（均P < 0.001）。裸鼠移植瘤实验显示，单抗2G1组移植瘤生长受到抑制，瘤质量抑制率和瘤体积抑制率分别为（31.83 ± 16.36）%和（22.00 ± 15.48）%。转录组测序共筛选出698个差异表达基因，其中329个基因上调，369个基因下调；KEGG富集分析显示差异表达基因涉及Wnt信号通路。WB法检测结果显示，与对照组相比，单抗2G1组SOX2、OCT4、N-cadherin、p-β-catenin和c-Myc表达下调，E-cadherin表达上调（均P < 0.001）。结论：细胞膜表面HSP90β在MG-63球形细胞中高表达，靶向HSP90β的单抗2G1可抑制MG-63球形细胞的成球、迁移、侵袭及体内成瘤能力，并影响其干细胞标志物、EMT相关标志物及Wnt/β-catenin信号通路蛋白的表达水平，提示HSP90β可能参与调控MG-63球形细胞的OSC样特征，可作为骨肉瘤靶向治疗的潜在研究靶点。

ObjectiveTo investigate the safety and efficacy of transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy （EHL）. MethodsA retrospective analysis was performed for the clinical data of 60 patients with large common bile duct stones who were admitted to Department of Gastroenterology， Jilin People’s Hospital， from May 1， 2023 to January 31， 2026， and according to the treatment method， the patients were divided into transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group and peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group， with 30 patients in each group. The two groups were compared in terms of the rate of successful single-session stone fragmentation and removal， procedural time， duration of electrohydraulic lithotripsy， clinical success rate， and complications. 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. ResultsCompared with the peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group， the transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group had a significantly higher technical success rate （83.33% vs 60.00%， χ²=4.022， P=0.045） and significantly shorter procedural time ［46.00 （42.25 — 49.00） min vs 54.50 （42.00 — 65.00） min， Z=2.012， P=0.044］ and duration of electrohydraulic lithotripsy ［8.00 （6.25 — 11.75） min vs 13.50 （9.25 — 17.75） min， Z=2.749， P=0.006］. Both groups achieved a clinical success rate of 100%， with no significant difference in the incidence rate of complications （P>0.05）. ConclusionTransparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy has a high rate of successful single-session stone fragmentation and removal and a short procedural time， with good safety and efficacy， and therefore， it holds promise for clinical application.

Objective:To analyze the clinical characteristics of patients with pregnancy-related chronic pain visiting the pain clinic.Methods:The number of pregnant patients who completed a pregnancy registration at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University from 2022 to 2024 was collected. The medical records were reviewed to identify the patients who visited the department of pain of our hospital due to chronic pain related to pregnancy. The clinical characteristics such as the visiting situation, gestational weeks, age and types of pain were analyzed.Results:From 2022 to 2024, the total number of registered pregnant patients was 64, 818, of which, 2, 224 cases visited the pain clinic, and the annual proportions of pregnancy-related chronic pain visits were 2.540%, 3.836% and 3.889% respectively. Among the patients who attended the clinic, 77.97% were pregnant (5.82% in early pregnancy, 41.93% in mid-pregnancy, and 52.25% in late pregnancy), and 21.03% were postpartum patients. A total of 83.72% were aged 20-34 yr. The types of pain were pelvic girdle pain (40.96%), limb joint pain (28.82%), low back pain (14.16%), cervical spondylosis (3.64%), peripheral nerve entrapment syndrome (3.42%), headache (2.97%), chest and back pain (2.79%), pelvic and perineal pain (1.66%), neuralgia (0.94%) and other pains (0.63%).Conclusions:From 2022 to 2024, the proportion of registered pregnant women at our hospital who visited to the pain clinic due to pregnancy-related chronic pain increases year by year. The common types of pain are pelvic girdle pain, limb joint pain and low back pain.

Objective:To examine the clinical features and genetic profiles of patients with thyroid peroxidase(TPO) gene mutations and provide diagnostic guidance for clinicians.Methods:A retrospective review of four patients with TPO mutations treated at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2014 to December 2023. Data on demographics, clinical manifestation, genotypes, treatment, and prognosis of these patients were analyzed.Results:Two males and two females, aged 13 to 27 years at diagnosis, presented with goiter as the initial symptom, with three cases menifesting during puberty. Laboratory findings showed mildly elevated or upper-limit-normal serum thyroid-stimulating hormone(TSH) levels, significantly increased free triiodothyronine/free thyroxine(FT 3/FT 4) ratios, and elevated thyroglobulin(TG) levels. Genetic testing revealed compound heterozygous pathogenic or likely pathogenic TPO mutations. Despite regular levothyroxine(L-T 4) therapy, goiter persisted. Three patients required thyroidectomy due to cosmetic or compressive symptoms, with pathology showing follicular hyperplasia. Conclusion:TPO mutations are characterized by adolescent-onset goiter, elevated FT 3/FT 4 ratios, and normal to high TSH. Genetic testing confirms the diagnosis. L-T 4 offers limited improvement, and surgery is often needed.