Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

Objective To characterize the properties of Hepa1-6-derived microparticles (Hepa1-6-MPs), investigate their stimulatory effects on dendritic cells (DCs) and their cellular uptake pathways, and explore the specific cytotoxic effects of CD8⁺ T cells induced by Hepa1-6-MP-loaded DCs on hepatoma cell lines, with the aim of developing a novel immunotherapeutic model for hepatocellular carcinoma (HCC). Methods The isolated Hepa1-6-MPs were identified using Western blotting, transmission electron microscopy (TEM) and dynamic light scattering (DLS). Flow cytometry was used to assess the uptake pathways of Hepa1-6-MPs by DCs. Subsequently, enzyme-linked immunosorbent assay (ELISA) was used to measure the effects of Hepa1-6-MP-loaded DCs on the release levels of tumor necrosis factor α(TNF-α) and interferon γ(IFN-γ) into the supernatant of CD8⁺ T cells. Lactate dehydrogenase (LDH) tests were conducted to evaluate the cytotoxic effects of CD8⁺ T cells stimulated by Hepa1-6-MP-loaded DCs on hepatoma cells. Results The morphology, size and protein markers of Hepa1-6-MPs met the established criteria. Hepa1-6-MPs enhanced the expression of DC maturation markers CD80 and CD86, and were internalized by DCs via clathrin-mediated endocytosis and phagocytosis pathways. Subsequently, Hepa1-6-MP-loaded DCs stimulated CD8⁺ T cells to release high levels of TNF-α and IFN-γ, which induced their specific cytotoxicity against HCC cells. Conclusion These findings suggest that Hepa1-6-MP-loaded DCs may be a promising HCC immunotherapeutic tool.
Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Dendritic Cells/immunology* ; Humans ; Cancer Vaccines/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Interferon-gamma/immunology* ; Cell-Derived Microparticles/immunology* ; Animals

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

[Objective] To investigate the clinical manifestations and explore the experience of diagnosis and treatment of spontaneous perirenal urine extravasation after urinary tract obstruction so as to improve the understanding of the disease. [Methods] The clinical data of 23 patients with spontaneous perirenal urine extravasation after obstruction treated at our hospital during 2018 and 2020 were retrospectively analyzed, including the primary diseases, clinical manifestations, imaging examination, treatment and prognosis. The key points of diagnosis and treatment were summarized. [Results] Of the 23 patients, there were 15 males and 8 females, with an average age of 43.4 years. These cases were diagnosed by imaging tests such as ultrasound, computed tomography urography (CTU) and CT. Ureteroscopic lithotripsy was performed in 3 patients with ureteral calculi, retrograde ureteral catheterization in 4 patients and percutaneous nephrostomy in 13 patients. Afterwards, a second phase surgery was performed based on the patients' condition. Of the 3 patients with tumor metastasis who underwent retrograde ureteral catheterization, 2 operation were successful, and 1 operation failed and then converted to nephrostomy and drainage under B-ultrasound localization. [Conclusion] CTU should be performed as soon as possible to make a definite diagnosis. Treatment can be achieved with ureteral retrograde catheterization or percutaneous nephrostomy to achieve local decompression, followed by secondary surgery to treat the primary cause of obstruction.

In order to understand nurses’ willingness to participate in humanistic nursing training and its influencing factors, and provide reference for managers to understand the current situation and improve nurses’ enthusiasm for humanistic nursing training. The convenience sampling method was used to investigate 23 707 nurses in 28 provinces (autonomous regions and municipalities directly under the central government) through a self-designed questionnaire distributed on the Internet. The results showed that 98.1% of nurses thought that participating in humanistic nursing related training was helpful to clinical work, but only 88.6% of the respondents were willing to participate in humanistic nursing training. Thirty factors were analyzed from four aspects of basic characteristics of individuals, cognitive relevant experience and organizational atmosphere. Fifteen factors had significant significance in binary Logistic regression analysis (P<0.05). Among them, the factors that had a positive impact on training willingness were: marriage, education, professional title, post establishment, agree with humanistic care is the basic duty of a nurse praised, experience of being praised at work, family support, rapport with patients, passion of colleagues to participate in training, sustained high-quality care demonstration activities, join the humanistic care related organization, hospital reimbursement of training expenses (OR value of 6.559~1.113, P<0.001). The OR value of humanistic nursing as a nurse’s responsibility was 6.559 and the 95%CI was 5.585~7.702. The factors that hindered nurses from participating in training were: work occupied most of time and energy, think humanistic nursing is abstract and difficult to understand, think the mastered humanistic knowledge and skills meet the needs of work (OR value of 0.657~0.722, P<0.001). Through the analysis, it is considered that nurses have a extremely consistent high recognition of the significance of humanistic nursing training, but their willingness to receive training is affected by many factors such as individual experience, cognitive attitude and organizational atmosphere. In order to realize nurses’ high recognition of humanistic nursing training to high enthusiasm of behavior, the aspects of individual cognition and organizational atmosphere must be discussed.

Objective To understand the epidemiological characteristics and current situation of pertussis in Hubei Province from 2016 to 2021. Methods Data on the incidence of pertussis and immunization history of cases in Hubei Province from 2016 to 2021 were collected and descriptive epidemiological analysis was conducted. Results From 2016 to 2021, a total of 1 236 pertussis cases were reported in Hubei Province, with an average annual reported incidence rate of 0.35/100 000. The average annual reported incidence of pertussis in the age group ≤ 5 years old was 6.22/100 000, and the age group <1 year old reported the highest annual incidence rate (21.51/100 000). The proportion of pertussis among preschool children and students had increased significantly since 2020. Among the 1 111 cases with a known immunization history, 17.55% were under the age of vaccination , 41.85% were not vaccinated, and 17.46% had completed the whole course of vaccination. Conclusion Since 2016, the incidence of pertussis in Hubei Province has been on the rise. The risk of pertussis is higher in infants and young children who have not reached the age of vaccination and who have not been vaccinated in time according to the immunization program after reaching the age of vaccination. The timeliness and vaccination rate of DTP vaccine should be improved to reduce the risk of pertussis in infants and young children. In addition, more attention should be paid to the prevalence of pertussis among preschool children and students.

Objective To understand the current status of emergency vaccination of hemorrhagic fever with renal syndrome (HFRS) vaccine in Jingzhou, serological monitoring and the incidence of vaccinated population, and to evaluate the protective effect of emergency vaccination of HFRS vaccine on the control of HFRS epidemic in the city. Methods From 2018 to 2020, HFRS vaccination was carried out in Jianli City, Honghu City, Jiangling County, Gongan County and some townships in Shashi City, Jingzhou City, focusing on people aged 30-59 years old. The incidence of HFRS, vaccination history of cases and HFRS vaccination data of Jingzhou City were collected and analyzed by descriptive epidemiological methods. The sera of those who had not been vaccinated with HFRS vaccine (non-vaccinated group) and those who had been vaccinated with HFRS vaccine (vaccinated group) were collected for IgG antibody detection, and the serum IgG was detected by ELISA method. The correlation between the change in the number of cases in townships where people were vaccinated (comparison between 2017-2018 and 2020) and the vaccination rate before 2019 was analyzed. Results A total of 446 900 doses of HFRS vaccine were vaccinated from 2018 to 2020, covering 22 townships in 5 counties and cities, accounting for 17.19% (22/128) of the total number of townships in the city. A total of 120 953 people completed 3 doses of vaccination, accounting for 11.30% of the total population and 23.77% of the population aged 30-59 in the vaccinated township. The positive rate of IgG in the unvaccinated group in Jingzhou was 9.91% (85/858). The positive rate of IgG in the vaccination group was 40.96% (34/83). The positive rates of IgG in the 1-dose group, 2- dose group, and 3-dose group were 0 (0/2), 18.18% (6/33), and 58.33% (28/48), respectively. From 2017 to 2020, a total of 16 cases had been vaccinated with HFRS before the onset of the disease, and 81.25% (13/16) received 2 doses or less of HFRS vaccine. The changes in the number of cases was negatively correlated with the vaccination rate of the whole population in townships where people were vaccinated (r_s=-0.58, P=0.011). The changes in the number of cases was negatively correlated with the vaccination rate of people aged 30-59 years in townships where people were vaccinated (r_s=-0.46, P=0.055). Conclusion The HFRS vaccination before 2019 has played a certain protective effect on the vaccinated population. However, the inoculation rate of HFRS vaccine in Jingzhou City is still low, and the protective effect on the whole population has not yet appeared.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Objective: The aim of the study was to investigate the association of outdoor physical activity and insomnia symptoms with depressive symptoms in college students, so as to provide a theoretical basis for preventing and improving depression of the college students. Methods: A sample survey of 9 349 college students from 4 colleges and universities in 3 provinces in Hubei, Jiangxi and Chongqing were conducted from November to December 2021. The Patient Health Questionnaire, Insomnia Severity Index and outdoor physical activity questionnaire were used to evaluate the depressive symptoms, insomnia symptoms and outdoor activities of college students, respectively. The χ 2 test was used to compare the difference of the positive rate of depressive symptoms in college students. Logistic regression analysis was used to analyze the association between outdoor physical activity, insomnia symptoms and depressive symptoms. Generalized linear model was used to analyze the association of interaction effect of outdoor activity and insomnia symptoms with depressive symptoms. Results: The detection rate of depressive symptoms in college students was 37.4%. Significant differences in the detection rate of depressive symptoms were observed among college students with different majors, nationalities,educational backgrounds, family residence, family type, family economic conditions, study burden, number of friends, father s education level,mother s education level( P <0.05). Logistic regression analysis showed that outdoor physical activity ( OR=0.51-0.69, P <0.01) and insomnia symptoms ( OR=6.15-21.30, P <0.01) were associated with depressive symptoms( P <0.01). Generalized linear model showed that insomnia symptoms( B =0.57), outdoor physical activity ( B =-0.15) and their interaction terms ( B =-0.02) were associated with college students depression( P <0.05). Conclusion This study suggests that insufficient time for outdoor physical activity and insomnia symptoms may increase the risk of depressive symptoms in college students. College students with insufficient time for outdoor physical activity and insomnia have a higher risk of developing depressive symptoms.