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.

Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo (TXL) capsule to treat atherosclerosis. However, clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable. In response, we developed this study to investigate the hypothesis that on the basis of statin therapy, treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome (ACS). The TXL-CAP study was an investigator-initiated, randomized, double-blind clinical trial conducted across 18 medical centers in China. Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness (FCT) < 100 μm and lipid arc > 90° as defined by optical coherence tomography (OCT) were recruited. A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL (n = 110) or placebo (n = 110) for a duration of 12 months. The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up. Secondary endpoints included: (1) changes of the maximum lipid arc and length of the target plaque, and the percentage of lipid, fibrous, and calcified plaques at the end of the 12-month period; (2) the incidence of composite cardiovascular events and coronary revascularization within the 12 months; (3) changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society (CCS) grading system and Seattle angina questionnaire (SAQ) score, respectively; and (4) changes in hs-CRP serum levels. The results of the TXL-CAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

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.

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.

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.