Background Nano-alumina (nano-Al₂O₃) is a widely utilized nanomaterial. Its impacts on the environment and biological systems have garnered significant attention. Zebrafish serves as a common model organism in scientific research due to its high homology with the human genome and is extensively used in toxicity studies. Objective To investigate the developmental toxicity and neurotoxicity of nano-Al₂O₃ exposure in zebrafish and the corresponding mechanisms of action. Method Zebrafish embryos at 6 h post-fertilization (hpf) were randomly assigned to a control group and five dose groups exposed to nano-Al₂O₃ at concentrations of 200, 400, 600, 800, and 1000 μg·mL⁻¹, respectively. Thirty embryos were included in each group, and the culture medium was replaced every 24 h until 144 hpf. The hatching rates at 48 and 72 hpf and the cumulative malformation rates up to 144 hpf were calculated. At 144 hpf, a zebrafish behavior analyzer was used to record the movement trajectories of the zebrafish, and the total distance traveled and average speed were analyzed for each group. At 144 hpf, the development of dopaminergic neurons in transgenic zebrafish expressing vmat2: GFP, brain vessels in those expressing vegf: GFP, and central nervous system neurons in those expressing elavl3: EGFP were observed under a fluorescence microscope, and statistical analysis was conducted using Image Pro Plus. Real-time quantitative PCR was employed to detect the expression levels of neuron development-related genes (syn2α, gap43, dat), Lewy body formation-related gene (α-syn), and autophagy-related genes (pink1, parkin) at 144 hpf. Results Compared to the control group, the nano-Al₂O₃ exposed groups exhibited reduced hatching rates at 48 hpf and increased cumulative malformation rates (P<0.05), with phenomena such as delayed development, absence of the swim bladder, and body curvature. The autonomous behavioral tests revealed that the nano-Al₂O₃ exposed zebrafish showed a decrease in the total distance swum (P<0.001) and a significant reduction in average speed compared to the control group. The fluorescence observations indicated that the length of dopaminergic neurons in vmat2: GFP transgenic zebrafish was reduced in the nano-Al₂O₃ exposed groups (P<0.001). Additionally, vegf: GFP transgenic zebrafish exhibited a significant absence of brain vessels, while elavl3: EGFP transgenic zebrafish showed a weakened fluorescence intensity of central nervous system neurons (P<0.001) and a decreased length of these neurons (P<0.01). The real-time quantitative PCR analysis revealed that compared to the control group, the gene expression levels of α-syn, syn2α, dat, and gap43 were upregulated in the zebrafish exposed to nano-Al₂O₃ (except for the 400 μg·mL⁻¹ exposure group) (P<0.01), while the expression levels of parkin were downregulated in the 600 and 800 μg·mL⁻¹ nano-Al₂O₃ exposed groups, and the expression levels of pink1 were downregulated in all exposure groups except for the 200 μg·mL⁻¹ group (P<0.05). Conclusion Exposure to nano-Al₂O₃ exhibits developmental toxicity in zebrafish larvae and induces Parkinsonism-like symptoms in zebrafish. The preliminary speculation of the mechanism suggests that it may be related to nano-Al₂O₃-induced mitochondrial autophagy impairment.

ObjectiveTo observe the therapeutic effects of Qishao Huoxue prescription on patients with lumbar disc herniation due to Qi stagnation and blood stasis and the effects of this prescription on hemorheological parameters and serum levels of inflammatory mediators. MethodA total of 86 patients with lumbar disc herniation due to Qi stagnation and blood stasis treated in the Wangjing Hospital of China Academy of Chinese Medical Sciences from January 2023 to February 2024 were selected and assigned according to the random number table into observation and control groups （n=43）. Patients in both groups received lumbar traction treatment. In addition， the observation group was orally treated with Qishao Huoxue prescription and the control group with celebrex for 3 weeks. The visual analogue scale （VAS） score， Oswestry disabilitiy index （ODI） score， 12-item Short-Form Survey （SF-12） score， traditional Chinese medicine （TCM） symptom score， hemorheological parameters ［whole blood high shear viscosity， middle shear viscosity， low shear viscosity， plasma viscosity （PV）， and fibrinogen （FIB）］， and the serum levels of inflammatory mediators ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and transforming growth factor-β₁ （TGF-β₁）］ were determined before and after treatment. In addition， the clinical efficacy and adverse reactions were observed and compared between the two groups. ResultAfter treatment， both groups showed declined VAS， ODI， and TCM symptom scores （P<0.05）， increased SF-12 physical component summary （PCS） and mental component summary （MCS） scores （P<0.05）. After treatment， the whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， and FIB decreased in the observation group （P<0.05）， while they did not show significant variations in the control group. After treatment， both groups of patients showed reductions in TNF-α， IL-6， and IL-1β levels and an elevation in the TGF-β₁ level （P<0.05）. Compared with the control group after treatment， the observation group showed decreases in VAS， ODI， TCM symptom scores and main symptom scores （P<0.05）， no significant differences in the secondary symptom scores， increased PCS and MCS scores （P<0.05）. The observation group outperformed the control group in terms of recovering whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， FIB， TNF-α， IL-6， IL-1β， and TGF-β₁ （P<0.05）. The total response rate in the observation group was 97.5% （40/41）， which was higher than that （88.1%， 37/42） in the control group （P<0.05）. No serious adverse reaction was observed in the two groups during the observation period. One case in the observation group showed subcutaneous bruising on the lower limbs， which gradually disappeared after withdrawal. ConclusionQishao Huoxue prescription demonstrated definite effect in treating lumbar disc herniation due to qi stagnation and blood stasis by recovering hemorheological parameters and inhibiting the expression of inflammatory mediators in the serum without inducing adverse reactions. It is worth applying in clinical practice.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To investigate the clinical characteristics and influence of co-mutated gene on acute myeloid leukemia patients(AML)with FMS-like tyrosine kinase-3(FLT3)mutations.Methods:A total of 273 FLT3+AML patients were enrolled,and the co-mutation gene data of the patients were collected to further analyze the prognosis of the patients.FLT3 and other common mutations were quantified by PCR amplification products direct sequencing and second-generation sequencing(NGS).Results:When patients were divided into FLT3 ITD+,FLT3 TKD+,FLT3 ITD++TKD+and FLT3 ITD-+TKD-group according to the type of FLT3 mutations,it was found that the frequencies of TET2,GATA2,NRAS and ASXL1 mutation were significantly different among the 4 groups(all P＜0.05).When patients were divided into allelic ratio(AR)≥0.5 and＜0.5 group,it was found that the frequencies of FLT3 ITD+,FLT3 ITD-+TKD-,NPM1,NRAS and C-kit were significantly different between the two groups(all P＜0.05).When patients were divided into normal and abnormal karyotype group,it was found that the frequencies of FLT3 ITD+,FLT3 TKD+,NPM1,GATA2 and C-kit were significantly different between the two groups(all P＜0.05).The median overall survival(OS)of AML patients with FLT3 TKD+(including FLT3 ITD++TKD+)was longer than that of patients with FLT3 ITD+alone(P＜0.05).The OS and relapse-free survival(RFS)of AML patients with FLT3++TET2+were both shorter than those of patients with FLT3++TET2-(both P＜0.05).Conclusion:The mutation frequencies of co-mutated genes are correlated with subtypes of FLT3,karyotype and AR.AML patients with FLT3 TKD+have longer OS than patients with FLT3 ITD+alone,and patients with co-mutation of TET2 have shorter median OS and RFS.

Objective:To determine the serum levels of CMTM6 mRNA and CCN1 in patients with acute leukemia (AL),and to analyze their relationship with the clinical efficacy and prognosis of the patients. Methods:103 AL patients admitted to our hospital from February 2015 to January 2019 were included as the study subjects. Additionally,100 healthy subjects who underwent physical examinations during the same period were included as the control group. qRT-PCR method was applied to detect the serum CMTM6 mRNA level of the study subjects,the serum CCN1 level was measured by ELISA. The levels of serum CMTM6 mRNA and CCN1 between the control group and AL patients,as well as between patients at initial diagnosis and after one course of chemotherapy were compared,the correlation of CMTM6 mRNA and CCN1 levels at initial diagnosis with clinicopathological features and short-term efficacy in AL patients was analyzed. The correlation of the CMTM6 mRNA and CCN1 expression levels with prognosis of the patients was analyzed by Kaplan-Meier curves. Results:Compared with the control group,the serum CMTM6 mRNA level in AL patients was significantly increased (P<0.05),while the serum CCN1 level was significantly decreased (P<0.05). There were no statistically significant differences in serum CMTM6 mRNA and CCN1 levels between patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) (P>0.05). Compared with those at the initial diagnosis,both the serum CMTM6 mRNA and CNN1 expression levels in AL patients were significantly altered after one course of chemotherapy,with CMTM6 mRNA significantly decreased (P<0.05) and CCN1 significantly increased (P<0.05). The 3-year recurrence-free survival (RFS) rate was lower in the CMTM6 high expression group and the CCN1 low expression group,compared with the CMTM6 low expression group and CCN1 high expression group,respectively (P<0.05). Conclusion:Serum CMTM6 is highly expressed and CCN1 is lowly expressed in AL patients. The expression levels of serum CMTM6 and CCN1 are associated with the 3-year prognosis of the patients.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To explore the patterns of failure after postoperative intensity-modulated radiotherapy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric cancer or gastroesophageal junction carcinoma with pathological stages T 3-4N 0 or T xN 1-3 admitted to Cancer Hospital of Chinese Academy of Medical Sciences from May 2009 to December 2018 were retrospectively analyzed. All patients received postoperative radiotherapy. During the follow-up, tumor recurrence was confirmed by imaging or endoscopic or pathological data, etc. According to the location of tumor recurrence, recurrence patterns were divided into local, regional and distant recurrence. Differences in recurrence patterns among different groups were compared using t-test and Chi-square test. Patient survival was assessed through Kaplan-Meier method. Results:A total of 76 patients were enrolled, with a median age of 49 years old (27-67 years old), 34 cases (45%) were classified as T 3 stage, 40 cases (53%) of T 4 stage, and 75 cases (99%) of N 1-3 stage, respectively. Seventy-three patients (92%) were classified as stage Ⅲ, and 38 patients (50%) underwent D2 dissection. The median follow-up time was 32.8 months (7.1-138.5 months). The median time of recurrence was 17.6 months (2.9-113.6 months). The median survival time after recurrence was 8.19 months (0.6-91.9 months). There were 13 cases (17%) of local recurrence, 6 cases (8%) of regional recurrence, and 72 cases (95%) of distant metastasis in patients. Peritoneal metastasis (33 cases, 43%) and distant lymph node metastasis (12 cases, 16%) were the main patterns of distant recurrence. Conclusions:By intensity-modulated radiotherapy technology, adjuvant radiotherapy yields favorable local and regional control for gastric cancer. Distant metastasis is still the main pattern of recurrence.

Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.