Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

ObjectiveTo investigate the attenuating effect of Dioscoreae Bulbiferae Rhizoma（DBR） processed with Phaseoli Radiati Semen（PRS） juice， and explore the attenuating mechanism based on ferroptosis of the main toxic target organ. MethodSixty male ICR mice were randomly divided into blank group， DBR group， water roasted DBR group（hereinafter referred to as water group）， PRS juice-roasted DBR group 1（DBR-PRS 10∶1， stuffy moistening for 40 min， stir-fried at 130 ℃ for 18 min， hereinafter referred to as group 1）， PRS juice-roasted DBR group 2（DBR-PRS 10∶1， stuffy moistening for 80 min， stir-fried at 100 ℃ for 14 min， hereinafter referred to as group 2）， PRS juice-roasted DBR group 3（DBR-PRS=20∶3， stuffy moistening for 40 min， stir-fried at 160 ℃ for 14 min， hereinafter referred to as group 3）. The raw and processed groups of DBR were gavaged with their corresponding 95% ethanol extract at a dose of 3 g·kg^-1·d^-1， while the blank group was gavaged with an equal volume of 0.5% sodium carboxymethyl cellulose， once a day for 14 consecutive days. Hematoxylin-eosin（HE） staining was used to observe the histopathological changes of mouse liver. Alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels in serum， as well as malondialdehyde（MDA）， ferrous ions（Fe²⁺）， reduced glutathione（GSH） and superoxide dismutase（SOD） levels in liver tissue were detected by the biochemical detection. Western blot was used to detect the expression of iron key proteins such as ferritin heavy chain 1（FTH1） and glutathione peroxidase 4（GPX4）. ResultHE staining results showed that the liver tissue structure of the blank group was clear， the morphology of hepatocytes was normal， the cytoplasms of hepatocytes in the DBR group and water group were loose and vacuolar， with obvious pathological damages， and the pathologic damages of mice in the group 1-3 were significantly improved. Compared with the blank group， the levels of ALT， AST， MDA and Fe²⁺ in mice from the DBR group were significantly increased（P<0.01）， while GSH and SOD levels were significantly reduced（P<0.01）， and the protein expression levels of FTH1 and GPX4 were significantly decreased（P<0.01）. Compared with the DBR group， the ALT， AST，MDA and Fe²⁺ levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the GSH and SOD levels and the protein expression levels of FTH1 and GPX4 were significantly increased（P<0.01）. Compared with the water group， the AST and MDA levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the SOD level significantly increased（P<0.05， P<0.01）， the FTH1 protein expression significantly increased（P<0.01）， and the serum ALT level of mice in the group 2-3 significantly reduce（P<0.01）， Fe²⁺ level significantly reduced（P<0.01）， GSH level significantly increased（P<0.05， P<0.01）， and GPX4 protein expression significantly increased（P<0.05， P<0.01）. Among the group 1-3， the group 3 had the best detoxification effect. ConclutionProcessing with PRS juice can reduce the liver injury induced by DBR， and the mechanism may be related to the inhibition of ferroptosis in the liver.

Pancreatic cancer is one of the most prevalent malignant tumors of the digestive system， and its incidence and mortality rates are increasing year by year. Most patients with pancreatic cancer are unable to receive surgery due to the advanced stage. Although chemotherapy regimens based on gemcitabine and fluorouracil have prolonged the survival time of patients to some extent， some patients cannot tolerate chemotherapy and hence lose the opportunity for treatment. With the advent of the era of precision medicine， molecular-targeted therapy has exhibited an excellent therapeutic efficacy and has thus become one of the most important treatment techniques for tumors； however， due to the high heterogeneity of pancreatic cancer and its complicated tumor microenvironment， molecular-targeted therapy for pancreatic cancer has not achieved notable results. Therefore， it is imperative to seek new therapeutic targets and medications to overcome this issue. This article reviews the latest advances in the research on molecular-targeted therapy for unresectable pancreatic cancer based on common molecular targets and tumor immunity-related therapeutic targets， in order to provide new treatment strategies for patients with pancreatic cancer.

Objective To investigate the therapeutic effect and mechanism of Chaihu Guizhi Ganjiang Decoction on non-alcoholic fatty liver disease(NAFLD)rats.Methods The experiment was conducted in five groups:normal group,model group,low-and high-dose groups of Chinese medicine(Chaihu Guizhi Ganjiang Decoction)and GSK872[receptor interacting protein kinase(RIP)3 inhibitor]group.Except for the normal group,the NAFLD rat model was constructed using high-fat chow feeding method in the remaining groups,respectively.At the end of treatment,hepatocyte apoptosis was observed by terminal transferase uridyl nick end labeling(TUNEL)method,and serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lipids[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and the levels of inflammatory factors tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)in liver tissues were measured by enzyme-linked immunosorbent assay(ELISA);and the levels of phosphorylation of RIP1,RIP3,and mixed lineage kinase structural domain-like protein(MLKL)were detected in liver tissues by Western Blot.Results Compared with the normal group,the apoptotic index of rat hepatocytes in the model group was elevated,ALT and AST in serum were significantly elevated,TC,TG and LDL-C levels were significantly elevated,and HDL-C level was significantly reduced,and the contents of TNF-α and IL-1β as well as the phosphorylated expression levels of RIP1,RIP3 and MLKL were significantly elevated in the liver tissues(P＜0.05);compared with the model group,the apoptotic index of hepatocytes in rats in the low-and high-dose groups of Chinese medicine and GSK872 group was reduced,the serum levels of ALT and AST were significantly reduced,the levels of TC,TG and LDL-C were significantly reduced,the level of HDL-C was significantly increased,and the contents of TNF-α and IL-1β and the phosphorylated expressions of RIP1,RIP3 and MLKL in the liver tissues were significantly reduced(P＜0.05);there was no significant difference in the above-mentioned indexes between the low-dose and high-dose groups of Chinese medicine and the GSK872 group(P＞0.05).Conclusion Chaihu Guizhi Ganjiang Decoction can effectively improve NAFLD in rats,and its mechanism may be related to the inhibition of RIP1/RIP3/MLKL signaling pathway activation,which in turn inhibits necrotic apoptosis.

Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.

Objective To investigate the status of thriving at work among junior nurses,and to analyze the influencing factors,so as to provide theoretical bases for promoting the job growth of junior nurses and improving the level of thriving at work.Methods From January to March 2023,431 junior nurses from 3 tertiary hospitals in Xinjiang Uygur Autonomous Region were selected as the research subjects.Questionnaire survey were conducted through the General Information Questionnaire,the Thriving at Work Scale,and the Job Crafting Scale.The univariate analysis and multiple linear regression were used to analyze the influencing factors of thriving at work among junior nurses.Results A total of 431 nurses with low seniority completed the survey.The total score of thriving at work is(35.46±6.74)score.Multiple linear regression analysis showed that age,education level and job remodeling score were the factors affecting the job prosperity of junior nurses(P＜0.05).Conclusion The thriving at work of junior nurses was at a moderate level.Nursing managers should strengthen the benign guidance of junior nurses,provide sufficient resource support,improve the level of job remodeling to promote the thriving at work of junior nurses and maintain the stability of organizational development.

ObjectiveTo investigate the mechanism of Ershiwuwei Guijiu pill in preventing and treating postmenopausal osteoporosis （PMOP） by activating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and inhibiting excessive autophagy. MethodFemale SD rats were ovariectomized and randomly divided into the sham operation group （Sham）， the operation group （OVX）， the Ershiwuwei Guijiu pill （GJ） group， and the raloxifene hydrochloride （RLX） group， with 10 rats in each group. Enzyme-linked immunosorbent assay （ELISA） and colorimetric methods were used to detect the levels of estrogen， bone metabolism markers in serum， and total superoxide dismutase （T-SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in tibial tissue. Flow cytometry was used to detect reactive oxygen species （ROS） levels in bone marrow mesenchymal stem cells. Masson staining was used to observe pathological changes in the proximal tibia， and micro-computed tomography （Micro-CT） was used to observe changes in tibial microstructural parameters. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of autophagy-related proteins Beclin1， microtubule-associated protein 1A/1B-light chain 3 （LC3）， autophagy-related 5 （Atg5）， as well as PI3K， Akt， and mTOR in tibial tissue. ResultCompared with the Sham group， the OVX group showed a significant decrease in serum levels of estradiol （E₂） and calcium ion （Ca²⁺）， and T-SOD， GSH-Px， PI3K， Akt， and mTOR mRNA levels in bone tissue （P<0.05， P<0.01）， significantly reduced bone mineral density （BMD）， bone surface/bone volume （BS/BV）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular connectivity （Con） in the tibia （P<0.05， P<0.01）， thinner epiphyseal growth plate， and the bone marrow cavity filled with fat vacuoles. Moreover， the levels of phosphorus （P）， MDA， ROS， and mRNA and protein expression of Beclin1， LC3， and Atg5， as well as trabecular separation （Tb.Sp） were significantly elevated （P<0.05， P<0.01）. Compared with the OVX group， the GJ and RLX groups showed significant increases in serum E₂ and Ca²⁺， and bone tissue levels of SOD， GSH-Px， and the mRNA levels of PI3K， Akt， and mTOR （P<0.05， P<0.01）， significantly increased BMD， BS/BV， Tb.Th， Tb.N， and Con in the tibia， thickened epiphyseal growth plate， and significantly reduced fat vacuoles in the bone marrow cavity （P<0.05， P<0.01）. Additionally， the levels of P， MDA， ROS， Beclin1， LC3， Atg5 mRNA and proteins， and Tb.Sp were significantly decreased （P<0.05， P<0.01）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR， which were significantly reduced in the OVX group （P<0.01）， were significantly increased in the GJ and RLX groups （P<0.01）. ConclusionThe Ershiwuwei Guijiu pill reduces oxidative stress and inhibits autophagy， thereby preventing and treating postmenopausal osteoporosis. Its mechanism may be related to the activation of the PI3K/Akt/mTOR signaling pathway， which inhibits autophagy.

Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.

Objective To study and verify the function of de novo interferon regulatory factor(IRF8)frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level.Methods The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells,or packed into lentivirus to infect two kinds of immune cell lines.Q-PCR,Western blot,immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation.Results The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully,and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well.Compared with wildtype,the molecular weight of IRF8 variant was slightly increased,while the expression level presents in opposition,even if on transcription level.Moreover,the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm,and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein.Conclusion The de novo frameshift mutation was presumed as gain-of-function(GOF)mutation.