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 investigate the miRNA-mRNA regulatory network in a rat model of Tourette syndrome(TS)using transcriptomic technology and to screen key signaling pathways and potential traditional Chinese medicine(TCM)candidates for intervention.Methods:A TS rat model was established using iminodipropionitrile(IDPN).RNA sequencing was performed to identify differentially expressed miRNAs and mRNAs in the brain tissues of TS rats.Bioinformatics analysis was applied to construct interaction networks,and network pharmacology was further employed to screen potential TCM compounds.Results:After 7 days of IDPN modeling,the model group exhibited motor and stereotypical behavioral changes,with behavioral scores greater than 3 points.Hema toxylin-eosin(HE)staining revealed irregular neuronal nuclear morphology,uneven chromatin distribution,nuclear pyknosis,and increased glial cell density.KEGG enrichment analysis identified key pathways:calcium signaling pathway,neuroactive ligand-receptor interaction,p53 signaling pathway,ECM-receptor interaction,and TGF-β signaling pathway.miR-125a-3p,miR-106-3p,and miR-760-3p were identified as pivotal miRNAs.Potential TCM candidates included Ajuga decumbens,Acanthopanax bark,Codonopsis pilosula,Stephania japonica,Os Draconis,Notopterygium root,Siraitia grosvenorii,Zanthoxylum nitidum root,Morinda officinalis,and Corydalis yanhusuo.Conclusion:The miRNAs miR-106-3p,miR-125a-3p,and miR-760-3p may mediate TS pathogenesis by altering critical signaling networks,including the calcium signaling pathway,neuroactive ligand-receptor interaction,and ECM-receptor interaction pathways,leading to neuroimmune inflammation and dopaminergic system dysregulation.TCM compounds such as Corydalis yanhusuo and Ajuga decumbens may exert therapeutic effects through multi-component synergistic regulation of these miRNAs and downstream pathways.

Objective:To investigate postoperative analgesic effects of transversus abdominis plane block (TAPB) versus local infiltration analgesia (LIA) after laparotomy for cytoreductive surgery in patients with ovarian cancer. Methods:This study used a randomized controlled design. Ninety patients with ovarian cancer who underwent laparotomy for cytoreductive surgery at Jilin Cancer Hospital from June 2022 to June 2023 were prospectively included. The patients were randomly assigned to either the TAPB group or the LIA group ( n = 45 per group) using the random number table method. The TAPB group received TAPB postoperatively, while the LIA group received LIA. Postoperative pain in both groups was assessed, and the number of presses on the patient-controlled intravenous analgesia device, as well as the incidence of postoperative adverse reactions, were recorded. Results:At 6, 12, and 24 hours after surgery, the Visual Analog Scale (VAS) scores in the TAPB group were significantly lower than those in the LIA group [(2.91 ± 0.64) vs. (3.35 ± 0.82), t = -2.84, P = 0.006; (3.42 ± 0.96) vs. (4.27 ± 1.14), t = -3.83, P<0.001; (2.28 ± 0.51) vs. (2.86 ± 0.83), t = -3.99, P<0.001]. The number of presses on the patient-controlled intravenous analgesia device and the number of rescue treatments in the TAPB group were significantly lower than those in the LIA group [(10.24 ± 2.52) counts vs. (16.79 ± 4.38) counts, t = -8.70, P<0.001; (1.82 ± 0.46) counts vs. (2.68 ± 0.84) counts, t = -6.02, P<0.001]. There was no significant difference in incidence of postoperative adverse reactions including nausea, vomiting, and chills between the two groups [4.44% (2/45) vs. 6.67% (3/45), P>0.05]. Conclusions:In patients with ovarian cancer undergoing laparotomy for cytoreductive surgery, postoperative analgesia using TAPB demonstrates greater efficacy compared with LIA. TAPB more effectively alleviates postoperative pain and reduces the number of presses on the patient-controlled intravenous analgesia device, while also offering higher safety than LIA.

Objective:To explore the differences of metabolomic profiles in day 3 (D3) culture medium of embryos with varying developmental potentials, in order to provide a theoretical foundation for the establishment of embryo selection technology platform using metabolomics.Methods:Eight patients who received in vitro fertilization and embryo transfer (IVF-ET) treatment at Reproductive Medicine Center of Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital between November 13 and December 5, 2023 were selected as the study subjects. The D3 culture medium from patient embryos was collected and divided into high-quality blastocysts ( n=42), non-high-quality blastocysts ( n=33), and embryos that failed to form blastocysts (non-formation group, n=43) according to the formation of day 5 blastocysts. High-performance liquid chromatography-mass spectrometry was employed to perform non-targeted metabolomic analysis in the D3 culture medium from three distinct groups. Results:1) The metabolites in D3 culture medium of embryos with varying developmental potentials exhibit significant differences. Specifically, 79 differential metabolites were identified between the blastocyst formation group and the non-blastocyst formation group (all P<0.05); additionally, 73 differential metabolites were found between the high-quality blastocyst group and the non-high-quality blastocyst group (all P<0.05). 2) The area under the receiver operating characteristic curve of significantly differential metabolites for predicting potential of D3 embryo blastocyst formation and high-quality blastocyst formation were both greater than 0.9, demonstrating excellent predictive performance. 3) KEGG pathway enrichment analysis revealed that differential metabolites associated with blastocyst formation potential were primarily enriched in pathways including D-amino acid metabolism, glycine-serine-threonine metabolism, arginine biosynthesis, and histidine metabolism ( P<0.05). For high-quality blastocyst formation, the differential metabolites were predominantly enriched in pathways related to tryptophan metabolism, D-amino acid metabolism, serotonergic synapses, and protein digestion and absorption ( P<0.05). Conclusion:Embryos with different developmental potentials have significantly different metabolic profiles, and it is feasible to predict the developmental potential of D3 embryos by metabolomics analysis.

OBJECTIVE To explore the clinical efficacy of Suyin Jiedu Prescription in the treatment of Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type and its effect on serum Klotho and inflammation levels.METHODS A total of 102 patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type who met the inclu-sion criteria were randomly divided into a treatment group and a control group,51 cases in each group;a total of 84 cases were comple-ted,including 44 cases in the control group and 40 cases in the treatment group.The control group was given conventional Western medicine basic treatment,and the treatment group was given Suyin Jiedu Prescription on the basis of the control group treatment.The treatment course of both groups was 16 weeks.The levels of renal function indexes[hemoglobin(Hb),serum albumin(Alb),urea ni-trogen(BUN),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),24 h urine protein(UTP)]and TCM syndrome scores were observed in the two groups before and after treatment.The levels of serum Klotho,tumor necrosis factor α(TNF-α)and interleukin 18(IL-18)were detected by ELISA.The clinical efficacy between the two groups after treatment was compared.RE-SULTS After treatment,BUN and Scr levels of the two groups of patients were significantly decreased(P<0.05),eGFR was signifi-cantly increased(P<0.05,P<0.01),the treatment group was better than the control group(P<0.05);the TCM syndrome scores of the two groups were significantly decreased(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05,P<0.01);the serum Klotho level in the treatment group was significantly increased(P<0.05),the IL-18 level was significantly de-creased(P<0.01),and the serum Klotho,TNF-α,and IL-18 levels in the treatment group were better than those in the control group(P<0.05,P<0.01).The total clinical effective rate in the treatment group was higher than that in the control group(P<0.01).CONCLUSION Suyin Jiedu Prescription can effectively improve renal function and relieve clinical symptoms in patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type,which may be related to increasing Klotho level and reducing inflammation in the body.

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

OBJECTIVE To explore the clinical efficacy of Suyin Jiedu Prescription in the treatment of Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type and its effect on serum Klotho and inflammation levels.METHODS A total of 102 patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type who met the inclu-sion criteria were randomly divided into a treatment group and a control group,51 cases in each group;a total of 84 cases were comple-ted,including 44 cases in the control group and 40 cases in the treatment group.The control group was given conventional Western medicine basic treatment,and the treatment group was given Suyin Jiedu Prescription on the basis of the control group treatment.The treatment course of both groups was 16 weeks.The levels of renal function indexes[hemoglobin(Hb),serum albumin(Alb),urea ni-trogen(BUN),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),24 h urine protein(UTP)]and TCM syndrome scores were observed in the two groups before and after treatment.The levels of serum Klotho,tumor necrosis factor α(TNF-α)and interleukin 18(IL-18)were detected by ELISA.The clinical efficacy between the two groups after treatment was compared.RE-SULTS After treatment,BUN and Scr levels of the two groups of patients were significantly decreased(P<0.05),eGFR was signifi-cantly increased(P<0.05,P<0.01),the treatment group was better than the control group(P<0.05);the TCM syndrome scores of the two groups were significantly decreased(P<0.05,P<0.01),and the treatment group was better than the control group(P<0.05,P<0.01);the serum Klotho level in the treatment group was significantly increased(P<0.05),the IL-18 level was significantly de-creased(P<0.01),and the serum Klotho,TNF-α,and IL-18 levels in the treatment group were better than those in the control group(P<0.05,P<0.01).The total clinical effective rate in the treatment group was higher than that in the control group(P<0.01).CONCLUSION Suyin Jiedu Prescription can effectively improve renal function and relieve clinical symptoms in patients with Stage 3-5 non-dialysis chronic kidney disease of kidney deficiency and turbid toxin type,which may be related to increasing Klotho level and reducing inflammation in the body.