The global distribution of medical resources is uneven and organ shortages are becoming increasingly serious. ASEAN countries have been working hard to explore and promote local organ transplantation in order to alleviate the serious imbalance between organ donation and organ transplantation needs. However, the development of cadaveric organ donation varies among ASEAN countries, and the cadaveric organ donation rate in most countries is generally low. Since 1991, China and ASEAN have evolved from dialogue to strategic cooperation, then to a community with a shared future, and further to a comprehensive strategic partnership, all demonstrating broad prospects for cooperation. This article analyzes the current situation and challenges of organ donation and transplantation in ASEAN countries, combining field visits and its own experience, and proposes strategies for strengthening international cooperation, optimizing policy environment, enhancing technical capabilities, and increasing public awareness in the field of organ donation and transplantation under the China-ASEAN development strategy framework. The aim is to build a more equitable, efficient, and sustainable organ donation and transplantation system, contributing to the realization of global public health security and a community of common health for mankind.

The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway is a cornerstone of host innate immunity, playing a central role in detecting cytosolic double-stranded DNA of both endogenous and exogenous origins. Upon activation, cGAS synthesizes the second messenger 2'3'-cyclic GMP-AMP (cGAMP), which binds and activates STING to trigger downstream immune responses, including the production of type I interferons and proinflammatory cytokines. Emerging studies highlight the cGAS-STING pathway as a promising therapeutic target for preventing and treating diverse pathologies, with particularly transformative potential in anticancer therapies. In this review, we dissect the key findings, functions, and associated components of the cGAS-STING pathway. In addition, we emphasize the factors that upregulate or downregulate the pathway, as well as the role of the cGAS-STING pathway in health and disease. By integrating mechanistic insights with clinical perspectives, this review aims to bridge fundamental discoveries with therapeutic applications of cGAS-STING biology.
Humans ; Nucleotidyltransferases/metabolism* ; Membrane Proteins/metabolism* ; Animals ; Immunity, Innate/physiology* ; Signal Transduction/physiology* ; Neoplasms/metabolism*

Biosensors have become powerful tools for real-time monitoring of specific small molecules and precise control of gene expression in biological systems. High-throughput sensors for 1, 4-butanediamine biosynthesis can greatly improve the screening efficiency of high-yielding 1, 4-butanediamine strains. However, the strategies for adapting the characteristics of biosensors are still rarely studied, which limits the applicability of 1, 4-butanediamine biosensors. In this paper, we propose the development of a 1, 4-butanediamine biosensor based on the transcriptional regulator PuuR, whose homologous operator puuO is installed in the constitutive promoter P_gapA of Escherichia coli to control the expression of the downstream superfolder green fluorescent protein (sfGFP) as the reporter protein. Finally, the biosensor showed a stable linear relationship between the GFP/OD₆₀₀ value and the concentration of 1, 4-butanediamine when the concentration of 1, 4-butanediamine was 0-50 mmol/L. The promoters with different strengths in the E. coli genome were used to modify the 1, 4-butanediamine biosensor, and the functional properties of the PuuR-based 1, 4-butanediamine biosensor were explored and improved, which laid the groundwork for high-throughput screening of engineered strains highly producing 1, 4-butanediamine.
Biosensing Techniques/methods* ; Escherichia coli/metabolism* ; Promoter Regions, Genetic/genetics* ; Green Fluorescent Proteins/metabolism* ; Transcription Factors/genetics* ; Escherichia coli Proteins/genetics* ; Diamines/metabolism* ; Gene Expression Regulation, Bacterial

Liver diseases are a group of complex clinical conditions caused by various factors and can lead to hepatocyte damage and liver dysfunction， posing a serious threat to human health. The cyclic GMP-AMP synthase （cGAS）-stimulator of interferon genes （STING） signaling pathway plays a key regulatory role in the course of liver diseases and is involved in the development， progression， and treatment of various diseases such as viral hepatitis， nonalcoholic fatty liver disease， liver fibrosis， and liver cancer. This article reviews the regulatory mechanisms of the cGAS-STING signaling pathway in processes such as inflammation， autophagy， antiviral response， and oxidative stress， analyzes its molecular function in liver diseases， and explores its application prospect as a potential target for the treatment of liver diseases， in order to provide a theoretical basis for developing novel therapeutic strategies for liver diseases.

Objective To investigate the application of Rotarex mechanical thrombectomy system in lower extremity arterial thrombosis and to evaluate its clinical efficacy.Methods The clinical data of 61 patients(71 limbs,35 cases in acute phase,21 cases in subacute phase and 5 cases in chronic phase)with lower extremity arterial thrombosis treated with Rotarex were analyzed retro-spectively.Distal protective device was used in patients with poor distal artery outflow.High pressure saline was used during the pro-cedure and stent was used in patients with flow-limiting dissection.Catheter aspiration was performed in patients with distal artery embo-lization.Anticoagulant therapy was used in patients with thromboembolism and dual antiplatelet therapy was used in patients with in-situ thrombosis.Postoperative follow-up was performed with color Doppler ultrasound or computed tomography angiography(CTA)at 1 month,3 months and 6 months.Results Fifty-nine cases were treated with 6F Rotarex catheters and 2 cases were treated with 8F Rotarex catheters.Distal protective device was used in 10 cases,balloon dilation was performed in 49 cases and stent was used in 5 cases.Catheter aspiration was performed in 10 cases.Vessel rupture occurred in 4 cases,among whom 3 cases were successfully treated with the method of balloon compression and 1 case was treated with covered stent.Severe adverse events occurred in 4 cases and perioperative toe amputation was performed in 7 cases.Follow-up time was 3 to 6 months(mean 4.9 months).Lower extremity ischemic event occurred in 1 case at 6th month follow-up and was treated with stent.No other lower extremity ischemic events occurred in the course of follow-up.Conclusion For the treatment of lower extremity arterial thrombosis,Rotarex mechanical thrombectomy sys-tem has the advantages of minimally invasion,rapid and high efficiency.Combined with the therapy of catheter aspiration and stent place-ment,vascular patency can be further maintained and the lower extremity ischemic symptoms can be quickly relieved.

Objective To investigate the effect of electroacupuncture preconditioning on microglia polarization in rats after cerebral ischemia reperfusion(IR)injury and explore the role of tyrosine kinase 2(J AK2)/signal transducer and activator of transcription 3(STAT3)pathway in the process.Methods Forty-five clean-grade healthy male Sprague-Dawley rats were randomly and equally divided into sham operation group,IR group and electroacupuncture preconditioning group.Rat model of IR injury was induced with thread occlusion of the internal carotid artery.Before modeling,electroacupuncture preconditioning was applied to Baihui acupoint for 5 consec-utive days in the preconditioning group,and exposure of the cervical blood vessels were inflicted in the sham-operation group.At 24 h after reperfusion,the severity of neurological deficit was observed by modified neurological deficit score(mNSS),and the cerebral infarct volume was observed by TTC staining.Western blotting was used to detect the protein levels of classical acti-vated type(M1)marker inducible nitric oxide synthase(iNOS),alternative activated type(M2)marker arginase 1(Arg-1),JAK2 and p-JAK2,and STAT3 and p-STAT3,and q-PCR was applied to detect the mRNA expression of iNOS and Arg-1.The expression of TNF-α and IL-10 was measured by ELISA.Results Compared with the sham operation group,the mNSS,infarct vol-ume,protein levels of p-JAK2/JAK2,p-STAT3/STAT3,protein and mRNA levels of iNOS and Arg-1,and expression of TNF-α and IL-10 were significantly increased in the IR and electroacu-puncture preconditioning groups(P＜0.01).The preconditioning group had obviously lower mNSS,smaller infarct volume,decreased protein levels of p-JAK2/JAK2,p-STAT3/STAT3,re-duced protein and mRNA levels of iNOS,and declined TNF-α expression,but elevated expression of Arg-1 at protein(2.0±0.2 vs 1.5±0.1)and mRNA(4.2±0.8 vs 3.1±0.3)levels and increased IL-10 expression(49.1±7.1 pg/mg vs 27.9±5.9 pg/mg)when compared with the IR group(P＜0.01).Conclusion Electroacupuncture preconditioning can promote the polarization of microglia to M2 and inhibit the polarization of microglia to M1 after cerebral IR injury,which may be relat-ed to the inhibition of JAK2/STAT3 pathway.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective:To discuss the method of modified balloon-occluded retrograde transvenous obliteration (M-BRTO) combined with antegrade transvenous obliteration (ATO) using tissue adhesive and (or) coils in the treatment of portal hypertension with spontaneous portosystemic shunt (SPSS), and to evaluate its clinical efficacy.Methods:From February 2018 to October 2022,clinical data of patients with portal hypertension with SPSS treatment in Henan Anyang District Hospital were retrospectively analyzed. A total of 21 patients were enrolled. Under the blood flow limit of SPSS outflow tract, ATO was firstly performed, then followed by M-BRTO. The ATO route could be performed from percutaneous transhepatic portal vein, percutaneous transumbilical vein or transjugular intrahepatic portal vein shunt (TIPS) approach and the M-BRTO route could be performed from femoral vein (FV), jugular vein (JV) or anterior cubical vein (ACV). The operation of M-BRTO+ATO was performed under local anesthesia and was suitable for patients with isolated gastric varicose bleeding, hepatic encephalopathy or cardiac insufficiency. TIPS combination with M-BRTO+ATO was performed under general anesthesia and was suitable for patients with gastrointestinal hemorrhage complicated with severe gastrorenal or splenorenal shunt, or with portal thrombosis. Abdominal plain CT scan was performed 1 week later to show the deposition of embolic agent. Abdominal color ultrasound was done 1 month later, contrast-enhanced CT scan was performed 3 months and 6 months later, and then color ultrasound or contrast-enhanced CT was performed every 6 months to show the portal vein blood flow or the patency of TIPS stent. Hepatic artery chemoembolization was performed 1 month later for patients with liver cancer.Results:A total of 23 times of operation were performed in 21 patients, including 1 case with 3 times of operation. The approach of percutaneous transhepatic route was used in 11 cases (7 cases combined with FV, 3 cases combined with JV and 1 case combined with ACV), the approach of TIPS route combination with FV was used in 9 cases, paraumbilical vein combination with FV was used in 2 cases and paraumbilical vein combination with ACV was used in 1 case. Ectopic embolization occurred in 3 cases (1 case to the spleen vein, 2 cases to the liver). Perioperative fever occurred in 5 cases, bleeding of hepatic puncture tract occurred in 1 case, and death happened in 2 cases (1 case of acute liver failure induced by bile duct stone, 1 case of acute heart failure combined with acute gastrointestinal massive hemorrhage). During the follow-up, 4 cases died (3 cases of liver cancer and 1 case of infection). The remaining 15 patients were followed up for 2 to 47 (22±13) months and there was no recurrence of hepatic encephalopathy and gastrointestinal hemorrhage during follow-up.Conclusions:The operation of M-BRTO+ATO using tissue adhesive or combining with coils as embolic agent can quickly obliterate outflow tract of SPSS and completely block the whole tract of SPSS, so it is a fast, safety and effective method for the treatment of PH with SPSS.

Objective    To systematically review the efficacy and safety of transfemoral transcatheter aortic valve replacement (TFTAVR) under local anesthesia (LA) and general anesthesia (GA). Methods    Electronic databases including PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang and CBM were searched to collect randomized controlled trial and cohort studies on clinical outcomes of TFTAVR under LA and GA from inception to September 2020. Two authors independently screened literature, extracted data and assessed the quality of studies, and a meta-analysis was performed by using Stata 16.0 software. Results    A total of 30 studies involving 52 087 patients were included in this study. There were 18 719 patients in the LA group and 33 368 patients in the GA group. The results of meta-analysis showed that the in-hospital all-cause mortality rate [RR=0.65, 95%CI (0.45, 0.94), P=0.021], 30-day all-cause mortality rate [RR=0.73, 95%CI (0.62, 0.86), P<0.001], 30-day stroke [RR=0.82, 95%CI (0.68, 0.98), P=0.025], cardiac arrest [RR=0.50, 95%CI (0.34, 0.73), P<0.001], ICU stay time [RR=−6.86, 95%CI (−12.31, −1.42), P=0.013], and total hospital stay  time [RR=−2.02, 95%CI (−2.59, −1.45), P<0.001] in the LA group were all better than those in the GA group. There was no significant difference in the in-hospital stroke [RR=0.83, 95%CI (0.69, 1.00), P=0.053], in-hospital myocardial infarction (MI) [RR=1.74, 95%CI (0.43, 7.00), P=0.434], or 30-day MI [RR=0.77, 95%CI (0.42, 1.42), P=0.404] between the two groups. Conclusion    LA provides a safe and effective way to induce sedation without intubation, and may be a good alternative to GA for TFTAVR.

Objective:To evaluate the role of glutathione S-transferase μ1 (GSTM1) expression in mild hypothermia-induced mitigation of cerebral ischemia-reperfusion (I/R) injury and the relationship with microglial polarization.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), mild hypothermia group (H group), and GSTM1 inhibitor + mild hypothermia group (IH group). The rat model of cerebral I/R injury was prepared using the filament occlusion method. The filament was removed to restore blood flow after the left middle cerebral artery was blocked for 2 h, and the rats′ brain and rectal temperature were maintained at 36-37 ℃ during the period. The vessels were only isolated and ligated without occlusion in S group. In H group, the entire body was wiped with 75% ethanol immediately after removing the filament, and the brain and rectal temperatures were maintained at 32-33 ℃ for 3 h, and the other procedures were the same as those previously described in I/R group. In IH group, GSTM1 inhibitor itaconic acid 8.6 mg/kg was intraperitoneally injected at 24 and 1 h before developing the model, and the other procedures were the same as those previously described in H group. Neurological deficits were evaluated using a modified neurological severity score (mNSS) at 24 h of reperfusion, and then the animals were sacrificed and the brains were removed for observation of cerebral infarction (by TTC staining) and for determination of the expression of GSTM1, M1-type microglial marker inducible nitric oxide synthase (iNOS), and M2-type microglial marker arginase-1 (Arg-1) (by Western blot), expression of GSTM1, iNOS and Arg-1 mRNA (quantitative real-time polymerase chain reaction) and contents of interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) (by enzyme-linked immunosorbent assay). Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, and the expression of iNOS and Arg-1 protein and mRNA was up-regulated, the expression of GSTM1 and mRNA was down-regulated, and the contents of IL-6, TNF-α, IL-10 and TGF-β were increased in the other three groups ( P<0.05). Compared with I/R group and IH group, the mNSS and percentage of cerebral infarct size were significantly decreased, and the expression of iNOS protein and mRNA was down-regulated, the expression of Arg-1 protein and mRNA and GSTM1 was up-regulated, the contents of TNF-α and IL-6 were decreased, and the contents of TGF-β and IL-10 were increased in H group ( P<0.05). Conclusions:Up-regulated expression of GSTM1 is involved in mild hypothermia-induced mitigation of cerebral I/R injury, which is associated with inhibition of microglial polarization toward the M1 phenotype and promotion of polarization toward the M2 phenotype.