Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Targeting cGAS-STING pathway is a promising strategy in tumor treatment. The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of the second messenger 2'3'-cGAMP, activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING. Notably, in tumor immune microenvironment, key components of cGAS-STING pathway are transferred among neighboring cells. The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity. The membrane-based system, including extracellular vesicles transport, phagocytosis and membrane fusion transmit dsDNA, cGAMP and activated STING, enhancing the immune surveillance and inflammatory. The membrane proteins, including specific protein channel and intercellular gap junctions, transfer cGAMP and dsDNA, which are crucial to regulate immune responses. And the ligand-receptor interactions for interferons transmission amplifies the anti-tumor response. This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment. We further explore how these mechanisms modulate immunological processes and discuss potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Objective:To analyze the efficacy of laparoscopic radical surgery, compared to open surgery, for incidental gallbladder cancer following cholecystectomy.Methods:Clinical data of 106 patients with incidental gallbladder cancer treated at the Second Affiliated Hospital Zhejiang University School of Medicine from April 2010 to February 2018 were retrospectively analyzed, including 66 males and 40 females, aged (64.7±7.9) years old. According to surgical approach, patients were divided into the laparoscopic group ( n=45) and open group ( n=61). Perioperative data, including intraoperative blood loss, postoperative hospital stay, and postoperative complications, were compared between the groups. Follow-ups were conducted via outpatient visits or telephone reviews. Survival analysis was performed using the Kaplan-Meier method, and the survival rates were compared using the log-rank test. Results:All 45 patients in the laparoscopic group successfully underwent the surgery without conversion to open surgery. Compared to the open group, the laparoscopic group had a reduced intraoperative blood loss [(100±25) ml vs. (200±46) ml] and a shortened postoperative hospital stay [3(2, 5) d vs. 5(4, 7) d] (both P<0.05). The postoperative complication rates were 6.7% (3/45) in the laparoscopic group and 13.1% (8/61) in the open group ( χ2=4.16, P=0.041). The cumulative survival rate after radical surgery for incidental gallbladder cancer was better in the laparoscopic group ( χ2=4.58, P=0.032). Conclusion:Compared to open surgery, laparoscopic radical surgery for incidental gallbladder cancer showed benefits in intraoperative blood loss, postoperative hospital stay, complication rates, and cumulative survival.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.

Targeting cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway is a promising strategy for tumor treatment.The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of a second messenger 2′3′-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP),activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING.Notably,in tumor immune microenvironment,key components of cGAS-STING pathway are transferred among neighboring cells.The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity.The membrane-based system,including extracellular vesicles transport,phagocytosis and membrane fusion transmit dsDNA,cGAMP and activated STING,enhances the immune surveillance and inflammatory responses.The membrane proteins,including a specific protein channel and intercellular gap junctions,transfer cGAMP and dsDNA,which are crucial to regulate immune responses.The ligand-receptor interactions for interferon transmission amplifies the anti-tumor response.This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment,explores how these mechanisms modulate immunological processes and discusses potential interventions and immunotherapeutic strategies targeting these signaling cascades.