OBJECTIVES: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU). METHODS: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives. RESULTS: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44. CONCLUSIONS This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans ; Macrophages/immunology* ; Diabetic Foot/pathology* ; Single-Cell Analysis ; Transcriptome ; Gene Expression Profiling ; Inflammation ; Skin ; Cell Communication ; Signal Transduction ; Cellular Reprogramming

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Combining the knowledge of traditional Chinese medicine and modern medicine on glucolipid metabolism disorders， it is believed that the formation process of glycolipid metabolism disorders can be presented as five states "depression， phlegm-dampness， heat， blood stasis， and deficiency"， and the turbid pathogens run through the whole process. Accordingly， the method of "regulating states and removing turbidity" is proposed， which is specifically the method of resolving depression and turbidity， dispelling phlegm-dampness and turbidity， clearing heat and turbidity， dispelling blood stasis and turbidity， and replenishing deficiency and removing turbidity. Combined with the biological basis of glycolipid metabolism disorder， through the analysis of the clinical application of each method and the related mechanism of action， it is clarified that the method of regulating states and resolving turbidity can play a role in improving glycolipid metabolism disorder by regulating lipid metabolism disorder， insulin resistance， bile acid metabolism abnormality， intestinal bacterial flora， and its metabolite abnormality and other mechanisms of action.

Objective To evaluate the molluscicidal effect and cost of spraying molluscicides with drones against Oncomelania hupensis snails in marshland and lake areas, so as to provide new insights into field snail control in China. Methods A marshland and lake setting measuring approximately 12 000 m² was selected in Wanzhi District, Wuhu City on June 2023 as the test field, and assigned to four groups, of 3 000 m² in each group. Environmental cleaning was not conducted in groups A or B, which were given 5% niclosamide ethanolamine salt granules sprayed with knapsack-type sprayers and drones at a dose of 40 g/m², and environmental cleaning was conducted in groups C and D, which were given 5% niclosamide ethanolamine salt granules sprayed with drones and knapsack-type sprayers at a dose of 40 g/m², respectively. O. hupensis snails were surveyed before chemical treatment and 1, 3, 5, 7, 14 days post-treatment. The uniformity of chemicals was determined on the day of treatment, and the snail mortality, corrected snail mortality and density of living snails were calculated and compared among groups. The cost of molluscicides, labor fees of environmental cleaning and chemical treatment and cost of equipment were calculated, and the cost for a 1% reduction in the mean density of living snails was calculated 14 days post-treatment. Results The mean densities of living snails and mortality rates of snails were 1.82 to 2.85 snails/0.1 m² and 1.41% to 2.94% in groups A, B, C and D before chemical treatment, and the mortality and corrected mortality of snails were 55.75%, 49.32%, 85.94% and 87.50%, and 55.00%, 48.47%, 85.70% and 87.29% in groups A, B, C and D 14 days post-treatment. There was a significant difference in the mortality of snails among the four groups 14 days post-treatment (χ² = 38.735, P < 0.005), and there was a higher snail mortality in Group D than in Group A (χ² = 16.876, P < 0.005), and higher in Group C than in Group B (χ² = 20.508, P < 0.005). The density of living snails reduced by 55.00%, 43.94%, 90.43% and 87.14% 14 days post-treatment relative to pre-treatment in groups A, B, C and D, respectively. The test for uniformity of chemicals showed that the mean dose of molluscicides were 57.34, 55.21, 40.19 g/m² and 32.37 g/m² in groups A, B, C and D, respectively, and the minimal standard deviation (7.07) and coefficient of variation (0.18) of mean doses were seen in Group C. The costs for chemical treatment were 0.33 Yuan in groups A and B and 1.53 Yuan in groups C and D, respectively. The costs for a 1% reduction in the mean density of living snails were 17.82, 22.47, 50.73 Yuan and 52.56 Yuan in groups A, B, C, and D 14 days post-treatment, respectively. Conclusions The molluscicidal effect and cost of spraying 5% niclosamide ethanolamine salt granules with drones are comparable to manual spraying, and chemical treatment with drones are high in uniformity of molluscicides, time- and labor-saving, and feasible for applications in complex environments, which deserves widespread applications in the field of snail control.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Due to the complexity of traditional Chinese medicine （TCM） interventions and the diversity of herbal components， single-omics technologies such as genomics， transcriptomics， proteomics， and metabolomics often cannot comprehensively elucidate the scientific connotations of TCM. Multi-omics technologies driven by system biology can analyze the theoretical connotations and application mechanisms of TCM from different levels such as genes， gene expression， proteins， and metabolites， in line with the holistic view of TCM， which helps to promote the modernization of TCM. By reviewing the literature on the application of omics technologies in the field of TCM， it is found that multi-omics technologies have been widely used in TCM for syndrome differentiation， evaluation of herbal quality， elucidation of pharmacological mechanisms， and drug toxicity assessment， providing comprehensive explanations of the mechanisms of action of TCM and overcoming the limitations of single-omics technologies， and having obtained significant achievements. However， multi-omics technologies also face challenges such as high cost， difficulties in data analysis due to large data volumes， and insufficient translation of research results. In the future， it is expected that through strengthening interdisciplinary cooperation， conducting long-term and dynamic clinical research， standardizing and normalizing data analysis processes， adopting appropriate and reasonable multi-omics integration patterns， establishing multi-omics databases for TCM， revealing the individualized characteristics， therapeutic mechanisms， and disease regulatory networks of TCM， the modernization of TCM will be promoted.

Ischemic stroke has a high rate of disability and mortality and is often accompanied by white matter injury(WMI).WMI patients often have cognitive disorders,emotional disorders,sensorimotor disorders,urinary incontinence and other symptoms,which seriously affect daily life.WMI can be detected early through imaging techniques,but there is a lack of appropriate intervention and specific treatment.Studying the pathological mechanism of WMI after ischemic stroke is helpful to prevent the occurrence of WMI,delay its progression,and contribute to the development of effective drugs or specific treatments.This article reviewed the research progress of WMI mechanism after ischemic stroke in order to provide scientific basis for clinical prevention and treatment.

Objective To investigate human papillomavirus(HPV)infection in Jiading District of Shang-hai,and to explore the relationship between different HPV subtypes and cervical lesions.Methods A retro-spective analysis was conducted for HPV subtype results and pathological results during the same period of time from 19 030 patients who visited Maternity and Children Health Care Hospital of Jiading District from March 13th,2023 to March 31,2024,and underwent the HPV subtype detection.The relationship between HPV infection and age and cervical lesions were analyzed.Results Out of 19 030 samples,3 506 were HPV positive,and the infection rate was 18.42%.There were 2 185 cases of single infection and 1 321 cases of mul-tiple infection.The HPV infection rate in each age group were as below:the infection rates were 30.34%in≤20-year-old group,18.46%in 20-30 year-old group,16.46%in>30-40 year-old group,14.83%in>40-50 year-old group,21.29%in>50-60 year-old group and 32.74%in>60 year-old group,and there was a statistically significant difference in HPV infection rates among different age groups(P<0.001).The top 5 subtypes were type 52(21.50%),53(10.84%),58(10.02%),33(8.33%)and 59(6.85%).The proportions of the who progressed to higher-level cervical lesions in individuals with HPV subtypes of the top 5 infection rates,as well as those with HPV16 and 18 positive,were significantly higher than that in HPV negative indi-viduals,among which the individuals with HPV16,18,58,and 33 were more likely to progress to severe cervi-cal lesions[atypical squamous cells:cannot exclude high-grade squamous intraepithelial lesion(ASC-H)+low-grade squamous intraepithelial lesion(LSIL)+high-grade squamous intraepithelial lesion(HSIL)+squamous cell carcinoma(SCC)](P<0.05).Compared to HPV 52 positive individuals with the highest infection rate,HPV 16,18,58,and 33 positive individuals were more likely to progress to higher-level cervical lesions(P<0.05).Conclusion HPV infection rates in≤20 year-old group and>60 year-old group are relatively high in Jiading District of Shanghai.The risk of progression to cervical lesions varies among different HPV subtypes.In addition to HPV 16 and 18,HPV 58 and HPV 33 are also closely related to higher levels of cervical lesions and should be given sufficient attention.