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.

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 analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the Integrative Epidemiology Unit (IEU) database in August 2023, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratio (OR), and sensitivity analyses were performed to ensure the accuracy of the results. Results Neuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.

ObjectiveTo explore the main mechanism of self-precipitation formed during the decoction of Sinitang（SNT）， and to provide a research basis for exploring the differences in the toxic and effective components of this compound. MethodsThe average precipitation yields of SNT， Glycyrrhizae Radix et Rhizoma（GRR）-Aconiti Lateralis Radix Praeparata（ALRP） decoction（GF）， ALRP-Zingiberis Rhizoma（ZR） decoction（FJ）， GRR-ZR decoction（GJD）， ALRP decoction（FZ）， ZR decoction（GJ） and GRR decoction（GC） were determined. The four main self-precipitation samples of SNT， GF， FZ and GC were physically characterized by particle size， scanning electron microscopy（SEM）， pH， total dissolved solids（TDS）， conductivity， and Fourier transform infrared spectroscopy（FT-IR） analysis. The chemical compositions of SNT decoction and its different phases was identified by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） for SNT， SNT self-precipitation and SNT supernatant， and the contents of its main toxic and effective components were determined by high performance liquid chromatography（HPLC）. ResultsPrecipitation yield results of the 7 samples of SNT decoction and single decoction showed that SNT had the highest self-precipitation yield. The formation of SNT self-precipitation was mainly related to the reaction between ALRP and GRR components to form complexes， and FT-IR showed that GRR had the greatest influence on the formation of self-precipitation. A total of 110 components were identified in the SNT decoction， including 100 components in the SNT self-precipitation and 106 components in the SNT supernatant. And quantitative results of the main toxic and effective components revealed that the reaction between ALRP and GRR components formed complexes， resulting in the following content hierarchy for free components：SNT decoctionsupernatantself-precipitation， these components included free liquiritin， benzoylmesaconine， benzoylaconitine， benzoylhypacoitine， liquiritigenin， aconitine， hypoaconitine， isoliquiritigenin and ammonium glycyrrhizinate. ConclusionSNT exhibits spontaneous precipitation during compound decoction， with GRR exerting the greatest influence on its formation. This suggests GRR plays a significant role in the detoxification of SNT. The differences in the self-precipitated toxic-effective components of SNT compound decoction primarily manifest as changes in component content， reflecting the characteristics of SNT "deposition in vitro and sustained release in vivo" and the importance of "administered at draught" in the clinical application of SNT.

AIM: To explore the efficacy of internal limiting membrane(ILM)flap technique and simple ILM peeling in the treatment of idiopathic macular hole(IMH)and related influencing factors.METHODS: A retrospective cohort study was conducted on totally 32 patients(35 eyes)with IMH who received surgery at our department from January 2023 to November 2024. All the patients simultaneously received phacoemulsification combined with intraocular lens implantation, and they were divided into study group(19 eyes)and control group(16 eyes), with ILM flap technique and simple ILM peeling received in the two groups, respectively. The closure situation of macular hole, best corrected vision acuity(BCVA), and macular structure were observed in the two groups of patients. Furthermore, the correlation of BCVA and healing type of macular hole at the last time of follow-up with each parameter was analyzed.RESULTS: There was no statistical difference between the two groups of patients in preoperative general characteristics(all P>0.05). At the last time of follow-up, the macular hole was heeled in both groups, with 7 eyes of U-shaped heeling, 6 eyes of V-shaped heeling, and 6 eyes of irregular heeling in the study group, and with 13 eyes of U-shaped of heeling, 1 eye of V-shaped heeling and 2 eyes of irregular heeling in the control group(χ2=7.167, P=0.028). The postoperative BCVA was better than preoperative level(all P<0.05), there were no statistical significant differences between the two groups of patients in macular choroidal thickness before and after surgery(P>0.05), but the macular retinal thickness of the study group was thinner than that of the control group(168.11±92.11 vs 235.56±92.18 μm, P=0.03). Pearson correlation analysis indicated that BCVA at the last time of follow-up was positively correlated with the preoperative minimum diameter(r=0.476, P<0.05)and the diameter hole index(r=0.361, P<0.05), and negatively correlated with traction hole index(r=-0.364, P=0.031); Keendall correlation analysis showed that the postoperative closure types positively correlated with the basal diameter(τ=0.296, P=0.029), minimum diameter(τ=0.366, P=0.007), and visual acuity at the last time of follow-up(τ=0.412, P=0.003), while negatively correlated with macular hole index(τ=-0.415, P=0.002)and traction hole index(τ=-0.511, P<0.01). During the follow-up period, neither group of patients experienced postoperative complications.CONCLUSION: Both ILM flap technique and simple ILM peeling are safe and effective in treating IMH. As the smaller the basal diameter and minimum diameter of the macular hole, the larger the macular hole index and traction hole index, the probability of U-shaped heeling after surgery is greater and the visual acuity is better.

Objective: To assess the awareness and associated factors of wild mushroom poisoning among students in Guizhou Province, so as to provide a scientific foundation for wild mushroom poisoning prevention and control among students. Methods: By a multi stage stratified cluster random sampling method, 1 162 students from Guizhou Province were selected in May 2024. The questionnaire survey was administered to evaluate knowledge regarding wild mushroom poisoning. Data were analyzed employing the χ 2 test and Logistic regression model. Results: Among the nine questions assessing awareness of wild mushroom poisoning, only three had the awareness rate exceeding 70%. Binary Logistic regression analysis revealed that students who "actively learn about the prevention of wild mushroom poisoning" ( OR=0.48, 95%CI =0.26-0.92) and "spread knowledge about wild mushroom poisoning to others" ( OR=0.47, 95%CI =0.33-0.69) scored higher on the wild mushroom poisoning knowledge questions ( P <0.05). Conversely, students with a habit of consuming wild mushrooms ( OR=1.52, 95%CI =1.15-2.02) scored lower ( P < 0.05 ). 42.3% of the students suggested that scientific dissemination and publicity about wild mushrooms should be intensified. Conclusions The awareness rate of wild mushroom poisoning knowledge among students in Guizhou Province requires further attention. Comprehensive knowledge should be disseminated systematically through various channels to further improve students awareness of the prevention and control of wild mushroom poisoning.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.