Myasthenia gravis is an autoimmune disorder characterized by impaired neuromuscular transmission. Thymectomy is one of the therapeutic options for acetylcholine receptor antibody-positive myasthenia gravis patients. The quality of perioperative care is directly associated with surgical safety and patient outcomes. However, there is currently a lack of specialized nursing consensus or guidelines specifically addressing the care of these patients domestically or internationally. To promote the standardization and normalization of perioperative nursing care for myasthenia gravis patients undergoing thymectomy and to ensure treatment efficacy, a panel of 57 experts from relevant fields was convened. Based on evidence-based medicine and clinical practice experience, discussions were held on various aspects including condition assessment, nutritional support, medication management, and airway care, resulting in a consensus with 18 final recommendations by using the Delphi method through two rounds of expert consultation. This consensus aims to provide a scientific reference for the perioperative nursing care of myasthenia gravis patients undergoing thymectomy.

OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

Cyclic GMP-AMP synthase (cGAS), a pivotal molecule in innate immunity, has emerged as a keypoint in interdisciplinary research at the intersection of basic immunology and tumor biology. As a cytosolic nucleic acid sensor, cGAS is primarily characterized by its capacity to recognize double-stranded DNA (dsDNA) in the cytosol. Upon binding to dsDNA, cGAS undergoes a conformational change that promotes its dimerization and subsequent enzymatic activation. Once activated, it catalyzes the synthesis of the second messenger 2',3'-cGAMP from ATP and GTP. cGAMP then binds to the adaptor protein STING, which resides on the endoplasmic reticulum (ER) membrane. The binding process triggers STING to traffic from the ER to the Golgi apparatus, where it is phosphorylated by the kinase TBK1. Phosphorylated STING serves as a docking site for the transcription factor IRF3, facilitating its phosphorylation by TBK1. Once phosphorylated, IRF3 forms dimers and translocates to the nucleus, where it drives the expression of type I interferons and pro-inflammatory cytokines, initiating a potent antimicrobial state. The DNA-sensing mechanism of cGAS is inherently non-selective regarding the origin of its ligand. It readily detects exogenous DNA from invading pathogens, thereby playing an indispensable role in host defense against microbial infections. However, this same mechanism also enables cGAS to recognize self-DNA that leaks from the nucleus or mitochondria into the cytosol under various cellular stress conditions. While critical for immunity, the recognition of self-dsDNA by cGAS can disrupt cellular homeostasis and trigger aberrant inflammatory responses. The loss of self-tolerance can precipitate or exacerbate the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), highlighting the dual role of cGAS as both a sentinel for infection and a potential driver of autoimmune pathology. Notably, the subcellular localization of cGAS is not still. Increasing recent researches have revealed that cGAS is also abundant within the nucleus, challenging the traditional view of it solely as a cytosolic nucleic acid sensor. Within the nucleus, cGAS exhibits non-canonical functions that are distinct from its canonical immunological role. First, cGAS exists in a state of stringent immunological silence in the nucleus, with mechanisms involving its competitive binding to histones and its post-translational modifications which block the activation of cGAS enzymatic activity, thus, effectively preventing it from mounting an autoimmune attack on genomic DNA. Second, cGAS plays a critical role in maintaining genomic stability. Upon DNA damage, cGAS is rapidly recruited to the lesion site and participates in the DNA damage repair process. Moreover, under conditions of DNA replication stress, cGAS contributes to the stabilization of replication forks, preventing the cell from entering a state of uncontrolled hyper-replication. Consequently, in light of the dual role of cGAS in both immune regulation and tumor development, the development of small-molecule drugs targeting cGAS holds significant therapeutic promise. This review summarizes the structural characteristics of cGAS and its canonical function as a pattern recognition receptor in the cytosol, including the types of pathogens it recognizes and the autoimmune responses resulting from erroneous recognition of self-DNA. It then focuses on its emerging non-canonical functions within the nucleus, detailing its nucleocytoplasmic shuttling, the mechanisms underlying its nuclear immune quiescence, and its role in mediating DNA damage repair and replication fork stabilization. Finally, the review discusses the progress and application prospects of small-molecule drugs targeting cGAS for the treatment of autoimmune diseases and cancer.

Cyclic GMP-AMP synthase (cGAS), a pivotal molecule in innate immunity, has emerged as a keypoint in interdisciplinary research at the intersection of basic immunology and tumor biology. As a cytosolic nucleic acid sensor, cGAS is primarily characterized by its capacity to recognize double-stranded DNA (dsDNA) in the cytosol. Upon binding to dsDNA, cGAS undergoes a conformational change that promotes its dimerization and subsequent enzymatic activation. Once activated, it catalyzes the synthesis of the second messenger 2',3'-cGAMP from ATP and GTP. cGAMP then binds to the adaptor protein STING, which resides on the endoplasmic reticulum (ER) membrane. The binding process triggers STING to traffic from the ER to the Golgi apparatus, where it is phosphorylated by the kinase TBK1. Phosphorylated STING serves as a docking site for the transcription factor IRF3, facilitating its phosphorylation by TBK1. Once phosphorylated, IRF3 forms dimers and translocates to the nucleus, where it drives the expression of type I interferons and pro-inflammatory cytokines, initiating a potent antimicrobial state. The DNA-sensing mechanism of cGAS is inherently non-selective regarding the origin of its ligand. It readily detects exogenous DNA from invading pathogens, thereby playing an indispensable role in host defense against microbial infections. However, this same mechanism also enables cGAS to recognize self-DNA that leaks from the nucleus or mitochondria into the cytosol under various cellular stress conditions. While critical for immunity, the recognition of self-dsDNA by cGAS can disrupt cellular homeostasis and trigger aberrant inflammatory responses. The loss of self-tolerance can precipitate or exacerbate the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), highlighting the dual role of cGAS as both a sentinel for infection and a potential driver of autoimmune pathology. Notably, the subcellular localization of cGAS is not still. Increasing recent researches have revealed that cGAS is also abundant within the nucleus, challenging the traditional view of it solely as a cytosolic nucleic acid sensor. Within the nucleus, cGAS exhibits non-canonical functions that are distinct from its canonical immunological role. First, cGAS exists in a state of stringent immunological silence in the nucleus, with mechanisms involving its competitive binding to histones and its post-translational modifications which block the activation of cGAS enzymatic activity, thus, effectively preventing it from mounting an autoimmune attack on genomic DNA. Second, cGAS plays a critical role in maintaining genomic stability. Upon DNA damage, cGAS is rapidly recruited to the lesion site and participates in the DNA damage repair process. Moreover, under conditions of DNA replication stress, cGAS contributes to the stabilization of replication forks, preventing the cell from entering a state of uncontrolled hyper-replication. Consequently, in light of the dual role of cGAS in both immune regulation and tumor development, the development of small-molecule drugs targeting cGAS holds significant therapeutic promise. This review summarizes the structural characteristics of cGAS and its canonical function as a pattern recognition receptor in the cytosol, including the types of pathogens it recognizes and the autoimmune responses resulting from erroneous recognition of self-DNA. It then focuses on its emerging non-canonical functions within the nucleus, detailing its nucleocytoplasmic shuttling, the mechanisms underlying its nuclear immune quiescence, and its role in mediating DNA damage repair and replication fork stabilization. Finally, the review discusses the progress and application prospects of small-molecule drugs targeting cGAS for the treatment of autoimmune diseases and cancer.

Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

OBJECTIVE To systematically identify the dilemmas in value assessment of antitumor combination therapies， and to provide evidence for health insurance coverage， drug pricing， and clinical decision-making. METHODS The concept of “surplus value space” was introduced to cons truct a value assessment framework， under which the dilemmas in three assessment scenarios were analyzed. Optimization recommendations were proposed by drawing on international research addressing similar challenges. RESULTS & CONCLUSIONS The core dilemma of value assessment for antitumor combination therapies lies in insufficient surplus value space. When the cost of the backbone therapy exceeds its corresponding health value， the add-on drug encounters a “free but uneconomical”problem. Existing international value assessment methods have limitations such as flawed evaluation frameworks， difficulty in operationalizing the quality-adjusted life year allocation framework， and frequent occurrence of the “free but uneconomical”problem， rendering them inadequate for the complex scenarios of antitumor combination therapies. To address these dilemmas， strategies such as adjusting payment thresholds， exploring discounted pricing， conducting multi-product linkage negotiations， and delaying insurance access are recommended to improve the rationality and feasibility of value assessment for antitumor combination therapies.

Objective To investigate whether there exist differences in the improvement of left ventricular diastolic function between angiotensin receptor-neprilysin inhibitor(ARNI)and angiotensin-converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)in patients with hypertensive heart disease(HHD).Methods A retrospective cohort study was conducted on the HHD patients admitted in Department of Cardiovascular Diseases of our hospital from January 2021 to December 2024.The general information,echocardiographic parameters before and after treatment,and results of routine tests were collected.Finally,517 HHD patients were subjected,including 117 receiving ARNI treatment(ARNI group)and 400 getting ACEI/ARB treatment(ACEI/ARB group).A 1∶1 propensity score matching(PSM)was performed with a caliper value of 0.02,resulting in 89 matched cases for each group.Electrocardiography was performed to assess left ventricular diastolic dysfunction(LVDD),with various parameters,including left atrial volume index,early diastolic peak velocity at the interventricular septal portion of mitral annulus(septal e'),early diastolic peak velocity at the lateral wall portion of mitral annulus(lateral e'),tricuspid regurgitation velocity,and E/e'.These parameters were followed up and reassessed during the treatment period.Kaplan-Meier survival curve was plotted to compare the incidence of LVDD between the 2 groups.Multivariable logistic regression model was employed to identify the risk factors contributing to LVDD.Results The median follow-up time was 412(309,736)d in the whole cohort,and was 409(300,729)d for the patients after PSM.Kaplan-Meier survival analysis demonstrated that the incidence of LVDD was lower in the ARNI group than the ACEI/ARB group both before and after PSM(P<0.05).After treatment,the ARNI group obtained lower lateral e'[8.00(7.00,9.40)vs 9.00(7.10,10.30)cm/s,P<0.001],thinner left ventricular posterior wall thickness[12.20(10.80,12.80)vs 12.30(11.20,12.90)mm,P<0.048]when compared with the ACEI/ARB group.After adjusting for confounding factors,multivariable logistic regression analysis revealed that advanced age(OR=1.082,P<0.001),increased systolic blood pressure(OR=1.009,P=0.005),thicker left ventricular posterior wall thickness(OR=1.462,P<0.001),left atrial enlargement(OR=1.081,P<0.001),and use of calcium channel blocker(OR=1.548,P=0.006)were independent risk factors for LVDD,and positively correlated with the risk of LVDD.While,male(OR=0.709,P=0.043)and BMI(OR=0.933,P=0.006)were protective factors,which were negatively correlated with LVDD risk.Conclusion In HHD patients,ARNI is superior to ACEI/ARB in reducing the incidence of LVDD.

A portable molecularly imprinted(MIP)surface-enhanced Raman scattering(SERS)chip was fabricated via a green electrochemical approach for highly selective detection of bisphenol A(BPA).This MIP-AuNP/UIO-66/SPE sensor was fabricated through a single-step co-deposition process.The process involved electropolymerization onto a UIO-66 modified screen-printed electrode(SPE),by usingo-phenylenediamine(OPD)as functional monomer and BPA as template,and simultaneously electro-reduction generated gold nanoparticles(AuNPs),which served as the SERS-active substrate.Ultimately,this one-step method formed a three-dimensional porous architecture on the electrode surface.Under 785 nm laser excitation,the sensing chip exhibited a highly sensitive SERS response towards BPA.The intensity of its characteristic peak at 850 cm-1 showed a good linear relationship with logarithm of BPA concentration in the range of 1.0×10-10 to 1.0×10-6 mol/L,with a detection limit of 1.0×10-12 mol/L.More importantly,the fabricated chips maintained highly selective binding affinity for BPA in water samples even in the presence of structural analogs bisphenol F(BPF)and bisphenol S(BPS).When the chip was applied to detection of BPA in water samples from plastic bottle and paper cup,the recovery rates ranged from 94.0%to 103.0%with relative standard deviations(RSD)less than 4.7%.The developed chip offered a highly sensitive and selective solution for detection of trace BPA in complex water samples.

Objective To investigate the value of first platelet count(PLT)to respiratory rate(RR)ratio(PLT/RR)on admission in the diagnosis and prognosis of secondary sepsis in pneumonia patients.Methods A total of 100 patients with pneumonia admitted to the First Affiliated Hospital of Army Medical University from May 2023 to August 2024 were selected as subjects.According to the presence or absence of pneumonia sepsis,they were divided into sepsis group(63 cases)and non-sepsis group(37 cases).The secondary sepsis in pneumonia pa-tients were followed up continuously for 30 d.According to the survival situation,they were divided into sur-vival group(54 cases)and death group(9 cases).PLT in peripheral blood was measured,vital signs were col-lected on the first day of admission,and PLT/RR was calculated.The receiver operating characteristic curve was used to evaluate the predictive value of PLT,RR and PLT/RR for secondary sepsis in pneumonia pa-tients.The systemic inflammatory response syndrome(SIRS)score,modified early warning score(MEWS)and quick sequential organ failure assessment(qSOFA)score on admission were calculated,and the clinical predictive value of SIRS score,MEWS and qSOFA score was compared.Results PLT and PLT/RR in sepsis group were lower than those in non-sepsis group(P<0.000 1),RR was higher than that in non-sepsis group(P<0.01).The area under the curve(AUC,95%CI)of PLT,RR and PLT/RR were 0.858(0.785-0.931),0.693(0.589-0.796)and 0.902(0.843-0.962),respectively.The optimal cut-off values were 146.5×109/L,20.5 per minute and 8.075,respectively.The specificity were 8.1%,83.8%and 2.7%,respec-tively.The sensitivity was 33.3%,50.8%and 30.2%,respectively.Compared with the non-sepsis group,the sepsis group had a significantly higher SIRS score(P<0.001),a significantly lower MEWS(P<0.000 1),and no significant difference in qSOFA score between the two groups(P>0.05).The AUC(95%CI)of SIRS score,MEWS and qSOFA score in predicting secondary sepsis in pneumonia patients were 0.717(0.616-0.818),0.748(0.650-0.846)and 0.505(0.389-0.622),respectively.The optimal cut-off values were 4.5,2.5 and 1.5 points,respectively.The specificity were 91.9%,2.7%and 100.0%,respectively.The sensitivity was 42.9%,33.3%and 6.3%,respectively.PLT and PLT/RR in death group were lower than those in sur-vival group(P<0.05),RR was higher than that in survival group(P<0.05).Secondary sepsis in pneumonia patients were followed up for 30 d,Kaplan-Meier survival curve showed that patients with PLT≤138.5×109/L had a lower 30 d survival rate(P=0.007 8).Patients with RR>24.5 per minute had a lower 30 d sur-vival rate(P=0.016 1).Patients with PLT/RR≤6.375 had a lower 30 d survival rate(P=0.002 3).Conclu-sion PLT/RR can be used as a biological index to predict secondary sepsis in pneumonia patients,which is better than SIRS score,MEWS and qSOFA score,and the prognosis of secondary sepsis in pneumonia patients with low PLT/RR is worse.

Objective To explore the factors predicting the reliability of platelet-impedance(PLT-I)re-sults through a retrospective analysis of non-aggregated samples with abnormal platelet histograms.Methods A total of 322 samples with abnormal platelet histograms were collected from the Sysmex XN9000 automatic hematology analyzer,all of which showed no platelet aggregation as determined by the DI-60 auto-matic digital image analysis system.Using the platelet count fluorescent(PLT-F)results as a standard,the absolute and relative deviations of PLT-I results were calculated,and the parameters of samples with devia-tions within and outside the allowable range were analyzed.Logistic regression analysis was used to identify potential factors associated with deviations of PLT-I from PLT-F beyond the allowable range.The receiver op-erating characteristic(ROC)curve was used to evaluate the predictive value of these potential factors for devi-ations beyond the allowable range.Results The deviations of PLT-I from PLT-F were within the allowable range in 279 cases(86.65％)and outside the allowable range in 43 cases(13.35％).Comparisons between the two groups revealed statistically significant differences in mean red blood cell valume(MCV),red blood cell distribution width-cuefficient of variation(RDW-SD),DI-60 red cell fragments,platelet distribution width(PDW),and DI-60 large platelet ratio(P＜0.05).Logistic regression indicated that DI-60 red cell fragments and DI-60 large platelet ratio were independent potential factors for deviations of PLT-I from PLT-F beyond the allowable range(P＜0.05).The cut off values for predicting deviations beyond the allowable range were 1.75 for DI-60 red cell fragments and 66％for DI-60 large platelet ratio.The area under the curve(AUC)for the combined diagnosis of the two factors was 0.813,with a sensitivity of 88.4％and a specificity of 66.3％,indicating a higher predictive value than individual factors(P＜0.05).Conclusion When platelet histograms are abnormal,DI-60 large platelet ratio and DI-60 red cell fragments are independent potential factors predic-ting the reliability of PLT-I results,and their combination has a high predictive value.