Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.

Pancreatic cancer is highly aggressive and often diagnosed at an advanced stage,leaving most patients ineligible for radical resection.This study retrospectively analyzed four patients with locally advanced or advanced pancreatic cancer to evaluate the clinical efficacy and safety of high-intensity focused ultrasound(HIFU)ablation combined with chemotherapy as a neoadjuvant and conversion therapy.All cases were reviewed and individualized treatment plans were formulated through a multidisciplinary team evaluation.All patients received HIFU plus gemcitabine and nab-paclitaxel chemotherapy,with assessments of tumor volume,vascular involvement,surgical conversion,symptom relief,and adverse events.Three patients achieved marked tumor shrinkage and reduction of vascular invasion,enabling successful R0 resection without recurrence during follow-up.The remaining patient achieved disease stability,significant pain relief,and maintained good quality of life under repeated HIFU therapy.All treatments were well tolerated,and no severe adverse reactions occurred.The combination of HIFU and chemotherapy demonstrated synergistic local and systemic effects,effectively achieving tumor downstaging,improving resectability,and alleviating symptoms.As a safe,noninvasive,and repeatable therapeutic approach,this strategy offers a promising option for patients with advanced pancreatic cancer.Further large-scale prospective studies are warranted to validate its long-term efficacy and elucidate underlying mechanisms.

Background and Aims:Acute pancreatitis(AP)is an acute inflammatory disease of the pancreas caused by abnormal activation of pancreatic enzymes.Although gallstones,hyperlipidemia,and alcohol use are the most common causes,a subset of patients develop AP secondary to rare etiologies that are often misdiagnosed or diagnosed late,leading to recurrence or inappropriate management.This study aims to summarize the clinical characteristics,diagnostic strategies,and treatment outcomes of four cases of AP caused by uncommon etiologies,supported by a literature review.Methods:Clinical data of 4 patients admitted to the Department of Hepatobiliary and Pancreatic Surgery,the Third Xiangya Hospital of Central South University,between November 2021 and September 2024,were retrospectively analyzed.Their etiological characteristics,diagnostic approaches,and treatment strategies were reviewed in combination with relevant literature.Results:The underlying causes of AP were intraductal papillary mucinous neoplasm,pancreatic neuroendocrine tumor,pancreatic ductal adenocarcinoma,and duodenojejunal intussusception.All cases initially presented as idiopathic AP.Three patients underwent definitive surgical treatment and recovered well,while one patient with pancreatic cancer received only palliative care due to delayed diagnosis and died three months later.Conclusion:AP secondary to rare etiologies often mimics common forms in clinical presentation but poses diagnostic challenges.For patients with recurrent or idiopathic AP,clinicians should emphasize etiological tracing and utilize advanced imaging and endoscopic modalities for early identification.Timely etiological intervention,particularly surgical management when appropriate,is essential for preventing recurrence and improving prognosis.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To explore potential categories of post-stroke depression in acute-phase stroke patients and its correlation with the degree of neurological deficits,and to provide references for healthcare professionals in developing targeted interventions.Methods Using convenience sampling,patients with acute stroke who were hospitalized in neurological ward of 2 tertiary general hospitals in Henan Province from January to April 2024 were selected as the survey participants.The investigation was conducted using the General Information Questionnaire,the National Institute of Health Stroke Scale,and the Patient Health Questionnaire-9.The correlation between potential categories of post-stroke depression and the degree of neurological deficit was analysed using unordered multiclassified logistic regression.Results Post-stroke depression score was 10.22±3.61 in 193 acute-phase stroke patients,and post-stroke depression could be categorized into 3 potential categories,namely"low depressive symptoms"(44.6％),"melancholic depression"(15.0％),and"atypical depression"(40.4％).There was a significant difference in the degree of neurological deficits(H=38.074,P＜0.001).Compared with severe neurological deficits,patients with mild deficits were more likely to be categorized as"melancholic depression"(OR=0.016,P=0.001)and"atypical depression"(OR=0.040,P＜0.001),and patients with moderate deficits were more likely to be classified as"atypical depression"(OR=0.085,P=0.001).Conclusion Post-stroke depression in acute-phase stroke patients has obvious categorization characteristics,and it is recommended that healthcare professionals should pay more attention to patients with different degrees of neurological deficits and adopt targeted interventions according to the different categories of post-stroke depression in order to alleviate their depressive symptoms.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective:To investigate the effects of Japan tallow(JT)on liver injury and gut microbiota regulation in type 2 diabetes mellitus(T2DM)mice,thereby providing a theoretical basis for developing therapeutic edible oils for diabetes treatment.Methods:T2DM animal model was established through a combined approach of nutritional intervention and chemical induction.Experimental animals were first fed a high-fat diet(HFD)for 6 weeks,followed by intraperitoneal injection of freshly prepared streptozotocin(STZ).After successful model establishment,the mice were divided into five groups(n=6 per group):control group without any intervention;T2DM group;HFD reversion to standard chow group;metformin group;and JT intervention group,which received respective treatments for 4 weeks.At the endpoint,fresh fecal samples were collected from all groups,and the gut microbiota composition was analyzed using 16s rDNA high-throughput sequencing.Liver histopathological changes were examined using histological methods.Results:Compared with the normal control(ND),T2DM mice showed significantly increased fasting blood glucose(FBG)levels,with evident hepatocyte lipid accumulation,steatosis,inflammatory cell infiltration,and widespread vacuolar and fatty degeneration.After Japan tallow(JT)intervention,FBG levels decreased significantly,liver color approximated normal appearance,and pathological morphology improved noticeably.16s rDNA sequencing analysis demonstrated that JT treatment could effectively regulate the intestinal microbiota structure in T2DM mice.Increased microbial α-diversity indices(Chao1,observed_species,Faith_pd,Simpson);At the phylum level,increased Verrucomicrobia abundance while decreased Proteobacteria were detected;At the family level,elevated Bifidobacteriaceae and reduced Porphyromonadaceae were seen;At the genus level,Bifidobacterium was promoted and Akkermansia proliferat while Escherichia and Klebsiella were downregulated.Conclusions:Japan tallow exhibits significant effects in alleviating liver tissue damage and regulating intestinal microbiota disorders in T2DM mice,our study indicated new theoretical basis for the research and development of potential strategy for diabetes.

OBJECTIVE To observe the effect of Shixiang plaster on promoting the wound healing of diabetic foot ulcer.METHODS Totally 50 male SPF grade SD rats were prepared to establish the diabetic models by feeding with high glucose and high fat forage and intraperitoneal injection of streptozotocin,the rats models that were es-tablished successfully were randomly divided into the model group,the Shixiang plaster group and the Kangfuxin solution group.The models of diabetic ulcers were established.The Shixiang plaster group was treated with exter-nal Shixiang plaster,the Kangfuxin solution group was given external Kangfuxin solution,and the model group was treated with coverage with sterile gauze.The wound healing status of the rats was observed,the wound tis-sues were collected for bacterial culture and hematoxylin-eosin(HE)staining after drug administration for 14 and 28 days,respectively.The expression levels of nuclear factor-red cell-2-related factor 2(Nrf-2),heme oxygenase-1(HO-1),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and vascular endothelial growth factor(VEGF)were detected by immunohistochemistry(IHC),the expression levels of Nrf-2 and HO-1 were detected with the use of Western Blot,and the levels of serum malondialdehyde(MDA),superoxide dismutase(SOD)and reactive oxygen species(ROS)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS After the drug administration for 14 and 28 days,the wound healing rates of the Shixiang plaster group were(62.15±3.82)％and(81.68±3.83)％,respectively,higher than(47.14±2.80)％and(69.96±6.49)％of the Kangfuxin solu-tion group and(29.14±9.52)％and(57.91±6.63)％of the model group,and there were significant differences(F=21.716,12.626,P=0.002,0.007).The bacterial colony counts of the Shixiang plaster group were less than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days(P＜0.05).The result of HE staining showed that the Shixiang plaster group had a better wound healing.The result of IHC indicated that the expression levels of Nrf-2,HO-1 and VEGF of the Kangfuxin solution group and the Shix-iang plaster group were up-regulated after the drug administration for 28 days,while the expression levels of TNF-α and IL-6 were down-regulated.The expression levels of Nrf-2 and HO-1 proteins of the Shixiang plaster group were higher than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days,the levels of serum MDA and ROS of the Shixiang plaster group were lower than those of the Kangfuxin solution group and the model group,and the serum SOD level of the Shixiang plaster group was higher than that of the model group(P＜0.05).CONCLUSIONS Shixiang plaster can effectively promote the wound heal-ing of the rats with diabetic foot ulcers and reduce the bacterial colony counts of wound surfaces.The mechanism may be associated with the alleviation of oxidative stress injury by mediating the Nrf-2/HO-1 signaling pathways,promotion of angiogenesis and inhibition of excessive inflammatory reactions.

Objective:To identify the latent profiles of transition shock among newly employed nurses and explore its influencing factors.Methods:This study was a cross-sectional study. Using the convenience sampling method, 215 newly employed nurses were selected as the research subjects. The General Information Questionnaire for Newly Employed Nurses, the New Nurse Transition Shock Evaluation Scale, and the Adversity Quotient Scale were used for the survey. The method of latent profile analysis was adopted to identify the types of nurses' transition shock.Results:There were three categories of transition shock among newly employed nurses. Among them, there were 134 nurses (62.32%) with moderate transition shock, 37 nurses (17.21%) with low-level transition shock and positive psychology, and 44 nurses (20.47%) with high-level transition shock and lack of knowledge and skills. Gender, whether being an only child, reasons for choosing a career, and adversity quotient were the influencing factors of the latent profiles of nurses' transition shock ( P<0.05) . Conclusions:The transition shock of newly employed nurses is at a moderate level, with three latent types: moderate transition shock type, low-level transition shock-positive psychology type, and high-level transition shock-lack of knowledge and skills type. Managers should formulate detailed intervention strategies according to the influencing factors of different categories to reduce the level of transition shock among newly employed nurses.