Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective:To prepare heparin (Hep)-modified gelatin methacryloyl (GelMA) microspheres and to investigate their application in liver-targeted delivery of adipose-derived mesenchymal stem cells (ADSCs).Methods:GelMA microspheres were modified with Hep to obtain GelMA-Hep microspheres. The surface morphology of the GelMA-Hep microspheres was observed by scanning electron microscopy. The changes of carbon atoms, nitrogen atoms and sulfur atoms on the surface of the GelMA-Hep microspheres were detected by X-ray photoelectron spectroscopy. The surface chemical group composition of the GelMA-Hep microspheres was analyzed by Fourier transform infrared spectrometer. The swelling properties of the GelMA-Hep microspheres were detected by water absorption swelling experiment. Human liver HL-7702 cells transfected with lentivirus were co-cultured with GelMA, GelMA-dopamine (GelMA-dop) and GelMA-Hep microspheres. The effects of microspheres on cell proliferation activity were evaluated by cell counting kit-8 method and live/dead cell staining experiment. The adhesion of microspheres to cells was observed by confocal microscopy. The GelMA-Hep microspheres loaded with ADSCs were injected into C57BL/6 mice through the tail vein, and its efficiency of liver-targeted delivery of ADSCs was observed by a small animal in vivo imaging system. The data were compared by independent sample t test or one-way analysis of variance. Results:The GelMA-Hep microspheres were prepared by modifying the GelMA microspheres with Hep. Compared with the GelMA microspheres, the size of the GelMA-Hep microspheres did not change significantly, and the surface did not collapse and showed some crystalline particles. The binding energy of sulfur atoms on the surface of the GelMA-Hep microspheres increased from 166 eV to 168 eV. On the surface of the GelMA-Hep microspheres, the characteristic peaks of sulfonic acid and sulfate groups of Hep were detected at 1 490 cm ?1 and from 1 135 cm ?1 to 1 050 cm ?1, respectively. The swelling rate of the GelMA-dop microspheres was uniform, while the swelling rate of the GelMA microspheres and the GelMA-Hep microsphere was quite different, but the final swelling mass of the three microspheres tended to be consistent at 5 min. After 12, 24, 36 and 48 h of culture, the relative proliferation of cells in the GelMA-Hep group (1.61±0.29, 1.78±0.05, 2.27±0.08, 2.26±0.33) were higher than those in the negative control group (1.00±0.00, 1.28±0.06, 1.39±0.02, 1.41±0.04) (all P<0.05). After 36 h of culture, the relative proliferation of cells in the GelMA-Hep group was higher than that in the GelMA-dop group (1.63±0.21), with significant difference ( P<0.05). Live/dead cell staining experiment showed that after 12 h of cell culture in the GelMA-Hep group, only a few microspheres had cell adhesion; at 24 h, the cells were densely distributed on the surface of the microspheres. After 36 h, the number of cells increased further. At 48 h, live cells were distributed throughout the microspheres. Confocal microscopy showed that after 24 h of culture, cells adhered to the surface of the microspheres in the GelMA-Hep group and showed a stretched morphology. The liver of the GelMA-Hep+ADSCs group showed strong fluorescence at 0.5 h, and the fluorescence brightness continued to 48.0 h. The number of ADSCs reaching the liver was more than that of ADSCs group and GelMA+ADSCs group. Conclusions:GelMA-Hep microspheres were successfully prepared, which can improve the efficiency of liver-targeted delivery of ADSCs.

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

Objective:To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV).Methods:A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA).Results:Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29(34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance.Conclusion:NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.

Objective:To analyze the categories, characteristics, and clinical symptoms of adverse reactions associated with thalidomide treatment for oral mucosal diseases, providing a reference for the safe use of this medication in patients.Methods:A cross-sectional study was conducted to retrospectively analyze the adverse reactions to thalidomide treatment in 44 patients with oral mucosal diseases who received treatment at the Third Affiliated Hospital of Air Force Medical University from January 2019 to December 2023. The correlation between the age and sex of patients experiencing adverse reactions, the timing of these reactions in relation to sex, the organs and their appendages affected by the adverse reactions, and the outcomes of these reactions were statistically analyzed.Results:The incidence of adverse reactions associated with thalidomide treatment at the hospital was 0.21% (44/21 329), with a higher prevalence among female patients. Multiple organs were affected in 50.00% (22/44) of the cases, though the reactions were relatively concentrated, primarily involving the skin and its appendages, the central and peripheral nervous systems, and the gastrointestinal system. The main manifestations included rash and dizziness.Conclusion:In the treatment of oral mucosal diseases with thalidomide, it is essential to monitor adverse drug reactions, particularly those affecting the nervous system. Special attention should be given to the potential teratogenicity of thalidomide in individuals of childbearing age. In addition, it is vital to consistently investigate strategies to ensure the safety of patients using medication at home.

Parkinson disease is a common neurodegenerative disease.At present,the main therapeutic drugs have problems such as adverse reactions,lack of targeting,and low bioavailability.The development of new drugs is an important direction for research related to Parkinson disease.TCM flavonoids have various pharmacological activities and are widely used in anti-tumor and cardiovascular disease treatment,but there is relatively little research on their intervention in neurological diseases.This article elaborated on the mechanism of intervention of TCM flavonoids in Parkinson disease and summarized treatment strategies from six categories:flavonoids,flavonols,isoflavones,flavonoid glycosides,dihydroflavonols,and others,with the purpose to provide reference for the research and clinical application of TCM flavonoids.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment

Abstract: Objective　To prepare a microparticle delivery system that regulates the release rate of extracellular vesicles (EVs), and to exert long-term enhancement of liver cell proliferation after only one intervention. Methods EVs was extracted by differential centrifugation. The structure of the EVs was observed by transmission electron microscopy and the membrane marker protein of EVs was detected by Western blotting. EVs-PLA microspheres with "core-shell" structure were prepared by emulsion-solvent evaporation method. Scanning and transmission electron microscopy were used to detect the morphology of EVs-PLA microspheres and EVs. The release test detected the release behavior of EVs in EVs-PLA microspheres. Scanning electron microscopy was used to detect the morphological changes of EVs-PLA microspheres at 8 weeks of release. EVs-PLA microspheres were co-cultured with hepatocytes, and Phalloidin/DAPI staining was used to observe the cell morphology and evaluate the cytotoxicity of the microspheres. CCK8-test was used to evaluate the cell proliferation activity. Western blot analysis was used to detect extracellular vesicles membrane marker protein expression. Results Comparing the ability of hepatocyte proliferation in the group treated with EVs-PLA microspheres and the control group, it was found that EVs-PLA microspheres did not cause cell apoptosis and mutation in cell structure, had biocompatibility and no cytotoxicity. The EVs-PLA microspheres with "core-shell" structure regulated the release behavior of EVs, which can continuously release EVs, exerting a continuous biological role in promoting hepatocyte proliferation after a single intervention. Conclusions The EVs-PLA microspheres can control-release EVs and promote hepatocyte proliferation continuously after a single intervention, providing a reference for further exploration of EVs-loaded delivery systems in promoting liver regeneration.

Objective:To explore the effects of an improved perioperative diet management based on the concept of enhanced recovery after surgery (ERAS) in patients undergoing total hip arthroplasty (THA) .Methods:From May 2020 to May 2022, convenience sampling was used to select 320 patients who underwent their first unilateral THA at the First Affiliated Hospital of Zhengzhou University. According to the random number table method, patients were divided into control group ( n=160) and observation group ( n=160). The control group adopted a routine perioperative diet management, while the observation group improved the perioperative diet management based on the ERAS concept, and nurses performed preoperative fasting and postoperative diet and drinking water nursing according to the plan. We compared the preoperative hunger and thirst between two groups of patients, and recorded the gastrointestinal function such as postoperative anal exhaust and defecation time, bowel sound recovery time, postoperative nausea and vomiting degree, and post eating nausea and vomiting degree between the two groups. Results:The number of preoperative hunger and thirst patients in the observation group was less than that in the control group, and the postoperative exhaust time, defecation time, and bowel sound recovery time were shorter than those in the control group ( P<0.05). The degree of nausea and vomiting after eating after surgery was lower than that in the control group. The differences were all statistically significant ( P<0.05) . Conclusions:The improved perioperative diet management based on ERAS has good clinical effects in THA patients, reducing perioperative discomfort and promoting postoperative gastrointestinal function recovery.