Objective: To enhance the ability of nanoparticles to target and bind tumor cells by constructing a neutrophil hitchhiking system based on hyaluronic acid (HA)-modified dual-drug loaded lipid nanoparticles. Methods: Lipid nanoparticles (LNPs) were prepared using microfluidic technology, and the nitrogen/phosphate (N/P) ratio, flow rate ratio, and drug-to-lipid ratio were optimized. HA-modified LNPs (HA-LNPs) were prepared and characterized. The interaction between the nanoparticles and tumor cells was evaluated through in vitro cell experiments. Results: The optimal preparation conditions for LNPs are N/P=8, flow rate ratio=5, and drug-to-lipid ratio=1∶30 (w∶w). HA-LNPs has a particle size of (177.28±2.41) nm, a polydispersity index (PDI) of 0.198±0.10, and an siRNA encapsulation efficiency of (91.37±0.47)%. The optimal binding rate with neutrophils was (98.64±2.34)%. Conclusion: An HA-modified dual-drug loaded lipid nanoparticle-neutrophil hitchhiking system was successfully constructed, enhancing the synergistic anti-tumor activity of the nanomedicine and the uptake of nanoparticles by tumor cells, providing a novel delivery strategy for targeted therapy of bone marrow tumors.

Objective To explore the characteristics of tumor immune microenvironment of pancreatic ductal adenocarcinoma(PDAC)based on the differentially expressed genes associated with macrophages in early and late tumor tissues of PDAC patients,so as to provide new targets for early diagnosis and treatment of PDAC.Methods Three early-stage and 4 late-stage tumor samples were collected from PDAC patients.Tissue transcriptome data were analyzed by single-cell sequencing technology.With The Cancer Genome Atlas(TCGA)database,macrophage related genes differentially expressed in early and late PDAC related to prognosis were obtained.The prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator(LASSO)-Cox method.The risk genes associated with PDAC prognosis were screened using the Gene Expression Profiling Interaction Analysis 2(GEPIA2)online survival analysis tool.Their immune infiltration was analyzed using the cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT)method,and their expression in different subpopulations of macrophages at different periods was resolved by t-distributed stochastic nearest-neighbour embedding(tSNE)clustering downscaling and the Monocle package.The protein-protein interactions and immunohistochemistry were further analyzed with the help of STRING database and The Human Protein Atlas(HPA)database.Results A total of 48 differentially expressed macrophage-related genes in early and late PDAC were found to be associated with prognosis.Eleven differentially expressed macrophage genes were screened as PDAC prognostic genes,and they were used to construct a prognostic risk scoring model for PDAC.Two prognostic genes with significant risk indicators were screened:2'-5'-oligoadenylate synthetase 2(OAS2)was mainly expressed in secreted phosphoprotein 1(SPP1)-positive macrophages,and assembly factor for spindle microtubules(ASPM)was mainly expressed in proliferation marker protein Ki-67(MKI67)-positive macrophages.There were significant differences in the expression of OAS2 in PDAC macrophages at different stages.Immune infiltration studies showed that OAS2 and ASPM were highly expressed in regulatory T cells and M2-type macrophages(both P＜0.05).Protein-protein interaction network showed the expression relationship between OAS2 and ASPM and other co-expressed proteins.Immunohistochemistry results showed that the expression of OAS2 was higher in tumor tissues than in normal tissues.Conclusion OAS2 and ASPM are both poor prognostic genes that are specifically expressed and exert negative immune effects in SPP1+macrophages and MKI67+macrophages,respectively,promoting the progression of PDAC and ultimately leading to a poor prognosis,and it is expected to provide new targets for the prevention and treatment of PDAC.

Objective To investigate the factors affecting the distribution of Pomacea and project the trends in the spread of suitable distribution areas of Pomacea in 2050 and 2070 in Dali Bai Autonomous Prefecture, so as to provide insights into Pomacea control in the prefecture. Methods The longitudes and latitudes of Pomacea sampling sites were captured based on Pomacea field survey data in 12 cities (counties) of Dali Bai Autonomous Prefecture from 2023 to 2024. A total of 19 climatic factors (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest month, mean temperature of the coldest month, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, mean temperature of the warmest quarter, and mean temperature of the coldest quarter) and representative concentration pathways (RCPs) were retrieved from the world climate database (www.worldclim.org). All climatic variables were employed to create a maximum entropy (MaxEnt) model. The predictive accuracy of the model was assessed with the area under the receiver operating characteristic (ROC) curve (AUC), and the contributions of these 19 climatic factors to the distribution of Pomacea were analyzed in Dali Bai Autonomous Prefecture using Jackknife test. In addition, the suitable distribution areas of Pomacea were predicted with the MaxEnt model in Dali Bai Autonomous Prefecture in 2024 and in 2050 and 2070 under RCP4.5. Results Data pertaining to 91 Pomacea sampling sites were captured. ROC analysis revealed the MaxEnt model had an AUC value of 0.885 ± 0.088 for predicting the suitable distribution areas of Pomacea in Dali Bai Autonomous Prefecture. Of the 19 climatic factors, the maximum temperature of the warmest month had the highest contribution to the distribution of Pomacea in Dali Bai Autonomous Prefecture, followed by mean temperature of the driest quarter, mean temperature of the wettest quarter and minimum temperature of the coldest month. The suitable distribution area of Pomacea was predicted to be 14 555.69 km² in Dali Bai Autonomous Prefecture in 2024, and would expand gradually to the southeastern part of the prefecture in the future due to climatic factors. The suitable distribution areas of Pomacea were projected to expand to 21 475.61 km² in 2050 and 25 782.52 km² in 2070 in Dali Bai Autonomous Prefecture, respectively. Conclusions Temperature is an important contributor to the distribution of Pomacea in Dali Bai Autonomous Prefecture, and the suitable distribution area of Pomacea will gradually expand to the southeastern part of the prefecture in 2050 and 2070.

Objective To identify the multi-dimensional needs of symptom management for oral cancer patients based on the journey map,and provide references for optimizing the symptom management of oral cancer patients.Methods From September 2023 to March 2024,the purposive sampling was used to select 15 perioperative oral cancer patients from a tertiary A general hospital in Zhengzhou for semi-structured interviews.The content analysis method was used to analyze the data and create a patient journey map.Results According to the time axis of diagnosis and treatment,the symptom management of patients with oral cancer was subdivided into 22 themes including identifying abnormal symptoms,clarifying diagnosis,anxiety,fear and uncertainty,guilt,high-risk behavioral inertia solidification,diagnostic trust crisis and so on from 3 dimensions of task,emotion,and pain point,and a journey map was formed.Conclusion The journey of symptom management for patients with oral cancer is long and complex,and the needs of patients'physiological and psychological symptom management are dynamically changing.In the future,the digital intelligence of big data technology can be combined to achieve whole-process,personalized and precise symptom management to improve the quality of life of oral cancer patients.

There is controversy over the specific and non-specific components in the efficacy evaluation of acupuncture therapy.The placebo effect,as a key non-specific factor,needs to be clarified in terms of its mechanism and clinical value.This article reviewed the research progress in the placebo effect of acupuncture from three aspects:cognitive process,influencing factors,and mechanism.It focused on the regulatory effects of patient expectations,doctor-patient interaction,and individual differences on the effect,summarized key mechanisms such as endogenous opioid system,dopamine reward pathway,and neural projection of rostral anterior cingulate cortex to pontine nucleus,and pointed out the methodological limitations of current comfort acupuncture designs,in order to provide theoretical basis for the optimization of acupuncture clinical research models and the deepening of the effect mechanism.

OBJECTIVES: This study aimed to analyze the influence of drug factors on the efficacy of bisphosphonate for chronic nonbacterial osteomyelitis to provide a reference for clinical treatment and promote clinical rational drug use by evaluation of effectiveness and safety of bisphosphonate treatment of chronic nonbacterial osteomyelitis. METHODS: Literature on the treatment of chronic nonbacterial osteomyelitis by using bisphosphonate was collected and analyzed from PubMed, Medline, Embase, Cochrane, ISI Web of Knowledge, CNKI, VIP, and Wanfang databases. RESULTS: A total of 489 cases were collected, with an average complete response rate of clinical presentation, laboratory tests and imaging findings of 80.37%, 80.56% and 79.22%, respectively. Except for opadronate, risedronate, ibandronate, pamidronate, alendronate, neidronate and zoledronate showed good efficacy, and the average complete response rates were 100%, 100%, 81.64%, 87.50%, 69.23% and 69.23%, respectively.The study found that in the pamidronate group, the average complete response rate of 0.5-1 mg/kg (maximum single dose≤60 mg) subgroup and the frequency of administration once every 3 months subgroup were better than other subgroups. CONCLUSIONS Bisphosphonate could be used to treat chronic nonbacterial osteomyelitis, which of efficacy were affected by different drug types, dose and frequency of administration. The optimal dose and frequency of administration of pamidronate were 0.5-1 mg/kg (maximum single dose≤60 mg) and once every 3 months, respectively.
Osteomyelitis/drug therapy* ; Humans ; Diphosphonates/administration & dosage* ; Chronic Disease ; Bone Density Conservation Agents/administration & dosage* ; Female ; Pamidronate ; Middle Aged ; Male

The gut microbiota is closely related to human health, and various gut microbiota health indices have been developed to assist in evaluating the health of the gut microbiota and even the overall health of the human body. Diets are one of the main factors that regulate the gut microbiota, while there is still no good method for evaluating the regulatory effects of dietary factors. To assess the regulatory effects of dietary factors on the gut microbiota of overweight individuals, we conducted an in vitro fermentation experiment based on 17 dietary factors, and developed an evaluation method for the regulatory effects of dietary factors based on the health index with principal component analysis (hiPCA). The results showed that most dietary factors had positive regulatory effects on the gut microbiota of overweight individuals. Galactooligosaccharides (GOS) and puerarin were the most significant dietary factors in regulating the gut microbiota of overweight individuals. The analysis of the contribution of species to the hiPCA indicated that GOS and puerarin might inhibit the activities of bacteria associated with overweight by regulating Eubacterium dolichum, Lactobacillus salivarius, Clostridium clostridioforme, Clostridium citroniae, and Lachnospiraceae bacterium 9_1_43BFAA. In addition, GOS may further enhance the inhibition of these activities by regulating Lachnospiraceae bacterium 6_1_63FAA, thereby reducing the gut health risks in overweight individuals. In summary, this study evaluated the health effects of dietary factors based on the hiPCA and specifically analyzed the role of different dietary factors in regulating the gut microbiota of overweight individuals. This provides new ideas and methods for improving gut microbiota health and has potential applications in the field of precision nutrition.
Humans ; Gastrointestinal Microbiome/physiology* ; Isoflavones/pharmacology* ; Overweight/microbiology* ; Diet ; Fermentation ; Oligosaccharides/pharmacology* ; Principal Component Analysis

BACKGROUND: Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths. METHODS: This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate. RESULTS: From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management. CONCLUSIONS The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.
Humans ; China/epidemiology* ; Stroke/mortality* ; Rural Population/statistics & numerical data* ; Male ; Female ; Urban Population/statistics & numerical data* ; Middle Aged ; Aged ; Aged, 80 and over ; Adult

OBJECTIVE: To investigate the effect of stretch on long non-coding RNA taurine upregulated gene 1 (TUG1)-mediated miR-545-3p/cannbinoida receptor 2 (CNR2) pathway regulating bone regeneration in the distraction area of rats during distraction osteogenesis. METHODS: Thirty-six 10-week-old male Sprague Dawley rats were randomly divided into 3 groups ( n=12 in each group): group A (femoral fracture+injection of interfering RNA), group B (distraction osteogenesis+injection of interfering RNA), and group C (distraction osteogenesis+injection of TUG1). Groups A and B were injected with 60 μg of interfering RNA at the beginning of incubation period (immediate after operation), the beginning of distraction phase (7 days after operation), and the end of distraction phase (21 days after operation), and group C was injected with 60 μg of synthetic TUG1 in vivo interfering sequence at the same time. The general situation of rats in each group was observed during the experiment. The mineralization of fracture space or distraction area was observed by X-ray films at 21, 35, and 49 days after operation. At 49 days after operation, the samples of the distraction area were taken for HE staining to observe the mineralization, and real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expressions of osteoblast-related genes such as TUG1, miR-545-3p, CNR2, alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Blood samples were collected from the abdominal aorta of the rats, and the expressions of ALP and C terminal telopeptide of type Ⅰ (CTX-Ⅰ) protein were detected by ELISA assay. RESULTS: The results of X-ray film and HE staining observations showed that osteogenesis in group C was superior to groups A and B at the same time point. The results of qRT-PCR showed that the relative mRNA expressions of TUG1, CNR2, ALP, OCN, and OPN in group C were significantly higher than those in group A and group B, and the relative mRNA expression of miR-545-3p in group C was significantly lower than that in group A and group B ( P<0.05). The relative mRNA expressions of TUG1 and ALP in group B were significantly higher than those in group A, and the relative mRNA expression of miR-545-3p in group B was significantly lower than that in group A ( P<0.05). There was no significant difference in the relative mRNA expressions of CNR2, OCN, and OPN between group A and group B ( P>0.05). The results of ELISA showed that the expressions of ALP and CTX-Ⅰ protein were significantly higher in group C than in group A and group B, and in group B than in group A ( P<0.05). CONCLUSION Under the action of stretch, the expression of TUG1 in the femoral distraction area of rats increases, which promotes the expression of CNR2 by inhibiting the expression of miR-545-3P, which is helpful to the mineralization of the extension area and osteogenesis.
Animals ; MicroRNAs/genetics* ; Rats, Sprague-Dawley ; Male ; Osteogenesis, Distraction/methods* ; Rats ; RNA, Long Noncoding/metabolism* ; Osteopontin/genetics* ; Osteogenesis ; Bone Regeneration ; RNA, Small Interfering/genetics* ; Osteocalcin/genetics* ; Alkaline Phosphatase/metabolism* ; Osteoblasts/cytology* ; Signal Transduction ; Femoral Fractures/surgery*