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*

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.

BACKGROUND:Gingival thickness is an important indicator to determine gingival phenotype.The correct evaluation of gingival phenotype is helpful for the smooth going of periodontal surgery,implant implantation and orthodontic treatment.The search for a comfortable,accurate and convenient method of measuring gingival thickness has always been a research hotspot in this field. OBJECTIVE:To analyze the gingival thickness in different dental positions and to study the consistency of cone-beam computed tomography(CBCT)image and digital intraoral scanners and cone-beam computed tomography(DIS-CBCT)superimposition image for measuring gingival thickness and determining whether the gingiva is thick or thin. METHODS:Twenty volunteers(10 males and 10 females)with complete maxillary dentition were recruited.The thickness of the gingiva 2 mm below the buccal gingival margin of 160 teeth was measured by CBCT image and DIS-CBCT digital superimposition image.Gingival thickness was used to determine whether the gingiva was thick or thin.Paired t-test was used to analyze the differences in gingival thickness measured by the two methods.Pearson correlation analysis was used to evaluate the correlation between the gingival thickness results of the two methods.The intraclass correlation coefficient(ICC)and Bland-AItman chart were used to analyze the repeatability and consistency in measuring gingival thickness using the two methods.Kappa value was used to analyze the consistency in determining whether the gingiva was thick or thin using the two methods. RESULTS AND CONCLUSION:The gingival thickness measured by CBCT image and DIS-CBCT digital superimposition image was(1.47±0.39)and(1.42±0.36)mm,respectively(t=5.673,P＜0.05).Pearson correlation analysis showed that the gingival thickness measured by the two methods was positively correlated(r=0.968,P＜0.001).In the CBCT group,the values of intraobserver and interobserver ICC were 0.980-0.982 and 0.984,respectively;in the DIS-CBCT group,the values of intraobserver and interobserver ICC were 0.941-0.984 and 0.964,respectively(P＜0.001).The intergroup ICC value of gingival thickness measured by the two methods was 0.967(P＜0.001).Bland-AItman analysis showed that 4.37%(7/160)of the points measured by both methods for gingival thickness was outside the 95%limits of agreement.There were 71 cases of thick-gingiva and 89 cases of thin-gingiva measured by CBCT imaging,and 59 cases of thick-gingiva and 101 cases of thin-gingiva measured by DIS-CBCT digital superimposition image.The Kappa value of the two groups was 0.845(P＜0.001).These findings indicate that there is a significant difference in the thickness measurement of the gingiva 2 mm below the gingival margin between the CBCT group and the DIS-CBCT group,but the correlation is very strong.The repeatability and consistency of gingival thickness measurement are both high,and there is a good consistency between the two methods when used to determine whether the gingiva is thick or thin.

With the development of population aging, the incidence of lower limb artery ischemic diseases is gradually increasing. Although various treatments such as medication and endovascular surgery are currently available, patients with compromised microcirculation in the distal limbs and poor outflow pathways often do not achieve satisfactory results. Additionally, these treatments can be costly, and long-term patency rates are not ideal. The amendment in situ autologous great saphenous vein arterialization surgery utilizes the patient′s great saphenous vein to provide arterial blood in a retrograde manner and re-establishes blood supply to the tissues through the venous microcirculation system in the distal foot. This approach can achieve good limb salvage results and long-term patency. Therefore, this article aims to elaborate on the methods and value of amendment in situ autologous great saphenous vein arterialization surgery.

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 evaluate the clinical value of four dimensional ultrasound combined with pelvic floor surface electromyography in the assessment of bladder prolapse in primipara with different delivery modes.Methods:A total of 413 primipara 6-8 weeks after full-term delivery were selected from the obstetrics clinic of the Second Affiliated Hospital of Hainan Medical College from October 2021 to September 2023. They were divided into natural delivery group(349 cases) and cesarean section group(64 cases ). The characteristics of 4D pelvic floor ultrasound in the two groups were analyzed and summarized. Then 64 cases of primipara with pelvic floor surface electromyography were divided into bladder prolapse group (46 cases) and no bladder prolapse group(18 cases). The characteristics of four dimension ultrasound combined with pelvic floor surface electromyography in the two groups were analyzed, and the related risk factors of bladder prolapse were analyzed.Results:The bladder neck mobility and urethral rotation angle in the natural delivery group were higher than those in the cesarean section group (all P<0.05). Compared with the cesarean section group, the incidence of obvious prolapse and urethral infundibulation was higher in the natural delivery group, while the incidence of mild prolapse was lower than that in the cesarean section group (all P<0.05). Bladder neck mobility, urethral rotation angle and levator ani hiatal area in the prolapsed bladder group were higher than those in the non-prolapsed bladder group (all P<0.05). The maximum value of fast muscle stage and the mean value of slow muscle stage in the group with prolapse were lower than those in the group without prolapse (both P<0.05). Univariate Logistic regression analysis found that the risk factors for bladder prolapse were increased birth weight, natural delivery, increased bladder neck mobility, posterior bladder angle was opened, increased urethral rotation angle, increased levator ani hiatal area, decreased maximum value of fast muscle stage and decreased mean value of slow muscle stage. Multivariate Logistic regression analysis showed that increased ani hiatal area ( OR=2.216, P=0.015) and decreased maximum value of tater muscle stage ( OR=0.847, P=0.035) were risk factors for bladder prolapse. Conclusions:Pelvic floor ultrasound combine with pelvic floor surface electromyography can qualitatively and quantitatively evaluate the changes of pelvic floor muscle structure and function in postpartum women, and diagnose bladder prolapse and its degree. The increase of levator ani hiatal area and the decrease of maximum value of tater stage may be the risk factors for bladder prolapse at 6-8 weeks postpartum in primiparas.

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 prepare progesterone-2-chloro-4-nitroaniline cocrystal （CNA） so as to improve the solubility of progesterone and primarily evaluate the safety of the progesterone cocrystal in vivo. METHODS Using progesterone as the main body and CNA as the ligand， progesterone-CNA cocrystal was prepared with solvent evaporation method. The cocrystal was characterized by X-ray single crystal diffraction， X-ray powder diffraction （XRPD）， differential scanning calorimetry （DSC） and Fourier transform infrared spectroscopy （IR）. The dissolution rate of cocrystal was compared with those of progesterone and physical mixture. Forty-eight female KM mice were randomly divided into normal group （phosphate buffer containing 0.1% dimethyl sulfoxide）， progesterone group （16 mg/kg）， CNA group （9 mg/kg）， progesterone-CNA cocrystal low-dose， medium- dose and high-dose groups （6， 12.5， 25 mg/kg）， with 8 mice in each group. They were given relevant medicine/solvent intramuscularly， once a day， for consecutive 14 d. The safety of cocrystal was evaluated primarily by determining/observing the changes in body weight， organ index， tissue morphology， blood routine indicators， and liver and kidney function indicators. RESULTS The new crystal structure in the X-ray single crystal diffraction results， the new characteristic peak in the XRPD pattern， the change of melting point in the DSC results， and the change of the characteristic peak position in the range of 3 500- 2 750 cm－1 and 1 700-1 250 cm－1 in the infrared spectrum all Δ 基金项目国家重点研发计划项目（No.2022YFC3502100） indicated that progesterone-CNA cocrystal was successfully ＊第一作者 硕士研究生 。研究方向 ：药物制备技术与工艺 。 prepared， and the dissolution rate of cocrystal was more than E-mail：SWB_1221@163.com # 通信作者教授，硕士生导师，博士。研究方向：药物制备技术与 twice that of the progesterone raw material drug. The results of 工艺。E-mail：wuxx-415@126.com in vivo safety experiments showed that the mortality rate of all 中国药房 2023年第34卷第13期 China Pharmacy 2023 Vol. 34 No. 13 · 1567 · groups was zero. Compared with normal group， uterine indexes of mice in progesterone group and progesterone-CNA cocrystal groups were significantly increased （P＞0.05）， and endometrium was also thickened； there was no statistical difference in the changes of body mass， liver and kidney function， liver index， kidney index， the number of leukocyte， lymphocyte and neutrophil in routine blood test among those groups （P＞0.05）， and the morphology of liver and kidney tissue has also no significant difference. However， the number of plasma red blood cells in the progesterone group decreased significantly （P＜0.05）， and there was no statistical significance in the number difference of red blood cells among progesterone-CNA cocrystal groups （P＞0.05）. CONCLUSIONS The progesterone-CNA cocrystal is successfully prepared with good safety in vivo， which significantly improve the solubility of progesterone.