Since its emergence in the 1980s, the human immunodeficiency virus (HIV) has caused a global pandemic, posing a severe threat to human life and health as well as social development. Although pre-exposure prophylaxis (PrEP) effectively curbs HIV transmission and antiretroviral therapy (ART) significantly extends the lifespan of patients, vaccines remain a pivotal tool for blocking transmission and ending the pandemic. The high genetic variability of HIV-1, the glycan shield of its envelope glycoproteins, and the long-term persistence of latent reservoirs have repeatedly led to bottlenecks in traditional vaccine strategies. In recent years, mRNA technology has offered a novel approach to addressing these challenges, leveraging advantages such as sequence programmability, short production cycles, native conformational expression of antigens, and self-adjuvant effects. In recent years, mRNA vaccine technology has emerged as a transformative solution to longstanding vaccinology challenges, characterized by its sequence programmability, rapid production cycles, native conformational antigen expression, and intrinsic self-adjuvanting properties. Unlike traditional platforms reliant on pathogen culture or recombinant proteins, mRNA vaccines can be expeditiously designed and updated based solely on viral genomic sequences. Lipid nanoparticle (LNP)-encapsulated mRNA facilitates endogenous antigen expression and presentation, simultaneously eliciting potent humoral and cellular immune responses. Within this landscape, self-amplifying mRNA (saRNA) further extends in vivo antigen expression to enhance the persistence of immune responses. Moreover, the LNP delivery system not only protects mRNA from degradation and mediates endosomal escape but also synergizes with mRNA to optimize immune activation via self-adjuvant effects. Importantly, mRNA platforms circumvent the pre-existing immunity associated with viral vectors and the genomic integration risks of DNA vaccines, positioning them as a cornerstone for global pandemic preparedness. This review systematically delineates recent advances in mRNA technology for HIV-1 vaccine development, focusing on four pivotal research frontiers. First, mRNA innovations building upon the RV144 trial optimize antigens through codon modification and multivalent designs to induce more durable and broad-spectrum immunity. Second, particulate mRNA vaccine strategies, utilizing virus-like particles (VLPs) and ferritin nanoparticles, achieve in situ antigen self-assembly, significantly enhancing B cell activation and reducing infection risks in non-human primate models. Third, germline-targeting mRNA vaccines address the low-affinity barrier of broadly neutralizing antibody (bNAp) precursors, efficiently activating rare precursor B cells and promoting affinity maturation. Fourth, therapeutic mRNA vaccines offer unique advantages for an HIV functional cure; combining immunogens with mRNA-encoded adjuvants potentiates cellular immunity, while LNP-mediated “shock-and-kill” strategies specifically activate latent reservoirs to guide immune clearance. Comparative analyses with traditional platforms reveal that mRNA technology redefines antigen production and presentation, simulating chronic infection through sustained expression and enabling dual-pathway presentation via endogenous synthesis. Furthermore, we explore the mechanistic innovations of mRNA vaccines in inducing bNAps: sustained in vivo production prolongs the activation window for precursor B cells and maintains germinal center (GC) reactions; endogenously expressed antigens adopt native conformations to expose conserved epitopes; and self-adjuvanting effects modulate the functions of antigen-presenting cells (APCs) and follicular helper T cells (Tfh), driving somatic hypermutation and affinity maturation. We also address critical clinical translation challenges, including immune durability, adaptability to special populations, and large-scale LNP manufacturing, while proposing targeted optimization strategies. In conclusion, this review establishes a theoretical framework for utilizing mRNA technology to overcome HIV-1 immune escape, transitioning from a descriptive paradigm to a problem-solving-based synthesis of evidence. By integrating preclinical and early clinical data, we bridge the gap between basic design and translational verification. mRNA technology is poised to become a central pillar inHIV-1 prevention and therapy, providing a robust toolset to achieve the global goal of ending the AIDS pandemic and offering a blueprint for vaccine development against other recalcitrant infectious diseases.

OBJECTIVE: This study aimed to determine the expression levels and prognostic significance of MYCN in bone marrow of adult patients with newly diagnosed acute myeloid leukemia (AML). METHODS: A total of 62 newly diagnosed patients with non-M3 AML were enrolled as the study group, and 20 healthy donors as the control group. Real-time quantitative reverse transcription-polymerase chain reaction (PCR) was performed to detect the expression level of MYCN, and the relationship between MYCN expression and prognosis of AML patients was analyzed. RESULTS: MYCN was up-regulated in newly diagnosed AML patients compared with normal controls (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that MYCN could serve as a diagnostic biomarker for AML. Kaplan-Meier survival analysis showed that the patients with high MYCN expression had a shorter overall survival (OS) time than the patients with low MYCN expression (P =0.016). The expression level of MYCN was lower during the complete ressimion (CR) phase of AML compared to the initial diagnosis, but it returned to the initial diagnostic level or even higher during relapse phase. Multivariate Cox regression analysis showed that high expression of MYCN was an independent risk factor for OS of AML patients (P =0.021). CONCLUSION MYCN is highly expressed and associated with poor prognosis in de novo AML, which might be serve as a novel diagnostic and prognostic biomarker for adult AML.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Prognosis ; N-Myc Proto-Oncogene Protein ; Adult ; Female ; Male ; Middle Aged

Objective To investigate the effects of auricular point seed-pressing and earpoint scraping on sleep quality,sleep structure index and neurotransmitter in patients with sleep disorders in neurology department.Methods A total of 110 patients with sleep disorders treated in the Department of Neurology at Nanjing Hospital Affiliated to Nanjing Medical University from June 2022 to June 2024 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 55 cases in each group.The control group was treated with Estazolam Tablets,while the observation group received auricular point seed-pressing therapy combined with ear scraping therapy.The treatment course lasted for 4 weeks.After treatment,the clinical efficacy of the two groups was evaluated.Changes in the Pittsburgh Sleep Quality Index(PSQI)scores were observed before and after treatment,as well as sleep structure indicators,including total sleep time(TST),sleep latency(SL),arousal index(AI),non-rapid eye movement sleep time(NREM)[light sleep stage(S1),light to moderate sleep stage(S2),moderate sleep stage(S3),deep sleep stage(S4)],actual sleep time(AST),sleep efficiency(SE),and rapid eye movement sleep time(REM).The serum levels of norepinephrine(NE),5-hydroxytryptamine(5-HT),and gamma-aminobutyric acid(GABA)were compared before and after treatment,as well as changes in the Quality of Life Scale(SF-36)scores.The safety and incidence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate in the observation group was 96.61%(53/55),while it was 81.82%(45/55)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the PSQI scores of both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in PSQI scores compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the sleep structure indicators in the observation group,including TST,SL,AI,S1,S2,S3,S4,AST,SE,and REM,were significantly improved,and the differences were statistically significant compared to the control group(P＜0.05).(4)After treatment,the serum levels of NE,5-HT,and GABA in both groups were significantly improved,and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(5)After treatment,the SF-36 scores of both groups were significantly improved,and the observation group showed significantly better improvement in SF-36 scores compared to the control group,with a statistically significant difference(P＜0.05).(6)The total incidence of adverse reactions in the observation group was 0.00%(0/55),while it was 10.91%(6/55)in the control group.The incidence of adverse reactions in the observation group was significantly lower than that in the control group,with a statistically significant difference(P＜0.05).Conclusion Auricular point seed-pressing therapy combined with ear scraping therapy for the treatment of sleep disorders at the Department of Neurology can significantly improve patients'sleep quality,enhance sleep structure-related indicators,regulate neurotransmitter levels,thereby improving patients'quality of life with high safety and efficacy.

Progesterone receptor membrane component 1(PGRMC1)is closely related to hormone therapy which belongs to the membrane-associated progesterone receptor(MAPR)family.A large number of in vitro experiments,in vivo animal experiments,clinical samples of breast cancer patients and blood studies showed that all synthetic progesterone(excluding natural progesterone and dydrogesterone)can promote the rapid proliferation of breast cancer cells overexpressing PGRMC1.In patients with breast cancer,PGRMC1 is significantly negatively correlated with tumor grade and prognosis,and PGRMC1 level in blood is positively correlated with PGRMC1 expression in breast cancer tissues,and PGRMC1 is superior to traditional tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen(CA125),and CA153 in predicting early breast cancer.Therefore,PGRMC1 may serve as a predictive marker for identifying an elevated risk of breast cancer associated with menopausal hormone replacement therapy.

Objective:To explore the differences between the Phoenix sepsis scoring system including Phoenix sepsis score (PSS) and Phoenix-8 organ dysfunction score (hereinafter referred to as Phoenix-8) and the commonly used pediatric sepsis scores in evaluating clinical characteristics and prognostic analysis of pediatric patients with severe sepsis diagnosed under traditional standards, namely the diagnostic criteria from the 2005 International Pediatric Sepsis Consensus Conference.Methods:This study was a retrospective observational study. From December 2020 to March 2023, 202 pediatric patients with severe sepsis meeting the inclusion criteria were admitted to the Children's Hospital of Nanjing Medical University. Based on the sepsis diagnostic criteria outlined in the International Consensus Criteria for Pediatric Sepsis and Septic Shock (2024), the pediatric patients were categorized into a sepsis group and a non-sepsis group. Sepsis group was further subdivided into a death subgroup and a survival subgroup based on the outcomes. The age, hospitalization costs, disease outcome indicators (e.g., mortality rate and incidence of septic shock), major organ (e.g., heart, liver, lungs, and kidneys) damage and their correlations, as well as PSS, Phoenix-8 and commonly used pediatric sepsis scores (e.g., pediatric sequential organ failure assessment (pSOFA), pediatric risk of mortality score Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 score (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), and pediatric early warning score (PEWS)) were collected and compared. Receiver operating characteristic (ROC) curve and precision-recall curve were plotted to evaluate the predictive ability of PSS, Phoenix-8, and commonly used pediatric sepsis scores for mortality risk in pediatric patients with severe sepsis under traditional standards. Predictive performance was quantified using the area under the ROC curve (AUROC). Univariate logistic regression analysis was employed to quantify the odds ratios of PSS and Phoenix-8 for predicting mortality risk. Patients with severe sepsis under traditional standards were further stratified into subgroups based on complications and comorbidities, including central nervous system (CNS) diseases, multiple infections, cardiovascular system diseases, shock, and malignancies. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of PSS and Phoenix-8, and the DeLong test was used to compare whether there were statistically significant differences in the AUROC of PSS and Phoenix-8 for predicting mortality risk among different subgroups of pediatric patients. Results:Compared with those in non-sepsis group, pediatric patients in sepsis group were significantly older ( Z=-2.92, P<0.05) with higher incidences of septic shock and mortality, hospitalization costs, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, PSS, and Phoenix-8 (with χ2 values of 21.28 and 13.64, respectively, Z values of -1.99, -5.33, -5.10, -8.55, -6.91, -10.98, and -9.93, respectively, P<0.05), and lower PCIS ( Z=-3.34, P<0.05). Compared with those in survival subgroup, hospitalization costs, PSS, Phoenix-8, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, and P-MODS of pediatric patients in death subgroup was significantly higher (with Z values of -2.50, -3.50, -2.47, -5.11, -3.84, -2.94, -3.61, and -3.04, respectively, P<0.05). Compared with those in survival subgroup, the incidences of lung damage and liver damage of pediatric patients in death subgroup were also significantly higher (with χ2 values of 6.20 and 10.94, respectively, P<0.05), and 64.7% (97/150) of patients exhibited two or more concurrent organ damage. For predicting mortality risk in pediatric patients with severe sepsis under traditional standards, the AUROC values for PRISM Ⅲ, PCIS, PEWS, pSOFA, PELOD-2, P-MODS, PSS, and Phoenix-8 were approximately 0.70, with optimal cutoff values of 17.5, 91.0, 5.5, 4.5, 2.5, 4.5, 3.5, and 4.5, respectively; PELOD-2 demonstrated the highest sensitivity (0.83); while PRISM Ⅲ, PSS, and Phoenix-8 showed high specificity (>0.80). Univariate logistic regression analysis showed that for every 1-point increase in the PSS within 24 hours of pediatric intensive care unit admission, the relative risk of mortality increased by 63.7% (with odds ratio of 1.64, 95% confidence interval of 1.34-1.99, P<0.05). Similarly, for every 1-point increase in the Phoenix-8, the relative risk of mortality increased by 37.5% (with odds ratio of 1.38, 95% confidence interval of 1.18-1.60, P<0.05). The AUROC values (around 0.80) of PSS and Phoenix-8 for predicting mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases were relatively high. In contrast, the AUROC values (0.60-0.80) for predicting mortality risk in pediatric patients with severe sepsis combined with shock or malignant tumors were moderate. All models passed the Hosmer-Lemeshow goodness-of-fit test ( P>0.05). The DeLong test indicated no statistically significant differences in predictive ability between PSS and Phoenix-8 across subgroups of pediatric patients ( P>0.05). Conclusions:PSS and Phoenix-8 exhibited higher specificity than most of the commonly used pediatric sepsis scores in predicting mortality risk under traditional standards. Both scores performed much better in predicting the mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

⁶⁰Co-γ ray irradiation has the unique advantages of high efficiency， strong penetration， operation at room temperature and no residue， which has been widely used in the sterilization of Chinese medicinal materials， decoction pieces， Chinese patent medicine. However， the irradiation effect may cause changes in the content of chemical components in Chinese materia medica or the emergence of new radiolysis products， leading to reduced efficacy and uncontrollable safety risks. This paper reviewed the relevant literature at home and abroad， summarized the effect of irradiation sterilization on various types of chemical compositions of Chinese medicinal materials and their preparations， and analyzed and explored the rule of change. The results showed that the content changes of various chemical components in Chinese materia medica after ⁶⁰Co-γ ray irradiation sterilization varied. The contents of most flavonoids， terpenoids， phenylpropanoids and quinones decreased after irradiation， and the degree of decrease increased with the elevated irradiation dose. The contents of lignans， alkaloids， isoflavones and some terpenoids did not change significantly before and after irradiation， while the content changes of triterpenoid saponins， dihydroflavonols， chalcones， sugars and glycosides after irradiation were not yet uniform. Therefore， it is recommended to pay attention to the compositional changes of irradiated Chinese medicines， strengthen the research on the standards of irradiated Chinese medicines， and standardize the irradiation and sterilization of Chinese medicines in order to promote the healthy and rational application of irradiated Chinese medicines.

OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

Objective: To investigate the characteristics and trend of stroke incidence in Yixing City, Jiangsu Province from 2016 to 2023, so as to provide the reference for formulating prevention and control strategies of stroke. Methods: Data of stroke case in Yixing City from 2016 to 2023 were collected from the National Health Information Platform of Yixing City, including sex, age, time of onset, and diagnostic subtypes. Crude incidence was standardized using the data from the 2010 Chinese National Population Census to analyze the characteristics of stroke incidence. The incidence trend of stroke was analyzed by average annual percent change (AAPC). Results: A total of 54 157 stroke cases were reported in Yixing City from 2016 to 2023, with a crude incidence of 629.52/100 000 and a standardized incidence of 299.50/100 000, showing an upward trend (AAPC=9.744% and 5.955%, both P<0.05). The crude and standardized incidence of stroke in males were significantly higher than those in females (695.30/100 000 vs. 565.79/100 000, 328.73/100 000 vs. 270.71/100 000, both P<0.05). Stroke incidence exhibited an age-dependent increase (P<0.05), peaking in the ≥60 years age group (1 820.43/100 000). The crude and standardized incidence of ischemic stroke (555.46/100 000 and 262.26/100 000) were significantly higher than those of hemorrhagic stroke (52.80/100 000 and 28.03/100 000, both P<0.05). From 2016 to 2023, the standardized incidences of stroke in males, females, the 0-<40 years age group, the 40-<60 years age group, the ≥60 years age group, and ischemic stroke all showed an upward trend (AAPC=6.692%, 4.925%, 5.607%, 5.777%, 5.698%, and 8.481%, respectively, all P<0.05). No significant temporal trend was observed for hemorrhagic stroke incidence (P>0.05). Conclusions The incidence of stroke among residents in Yixing City showed an upward trend from 2016 to 2023, with males and elderly individuals being high-risk populations. Ischemic stroke emerged as the predominant subtype, while a concerning trend of increasing stroke incidence among younger adults was observed.