BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND:MXene nanoparticles,due to their unique hydrophilicity,biocompatibility,and antibacterial properties,are widely used in wound,tumor,nerve repair,and cardiovascular treatments.However,it is still unclear what effect MXene nanoparticles have on diabetic wound healing.OBJECTIVE:To investigate the in vitro antioxidant,anti-inflammatory and photothermal antibacterial properties of MXene nanoparticles Ti3C2Tx as well as their effect on wound repair in diabetic mice.METHODS:(1)In vitro experiments:The cytotoxicity of Ti3C2Tx nanoparticles on mouse fibroblasts(NIH-3T3)at various concentrations was evaluated using the methyl thiazolyl tetrazolium(MTT)assay.NIH-3T3 cells were exposed to H2O2,and the MTT assay was used to detect the protective effects of different mass concentrations of Ti3C2Tx on NIH-3T3 cells.NIH-3T3 cells were exposed to H2O2,and the effect of Ti3C2Tx(20 μg/mL)on the generation of reactive oxygen species in NIH-3T3 cells was analyzed under illumination(or no illumination)treatment.RAW264.7 macrophages were divided into three groups:control group,lipopolysaccharide group,and lipopolysaccharide+Ti3C2Tx group.Real-time quantitative PCR was used to detect the expression of specific genes(CD86,interleukin 6,CD206,arginase 1)in the cells.Escherichia coli(or Staphylococcus aureus)were divided into three groups:control group,Ti3C2Tx group,and Ti3C2Tx illumination group.The bacterial survival rate was calculated by plate colony counting method.(2)In vivo experiments:Streptozotocin was administered intraperitoneally to ICR mice to induce a diabetic condition.After successful modeling,a full-thickness skin defect wound was created on the back of the mice using a circular punch.The experiment was divided into three groups:control group(n=6),Ti3C2Tx group(n=6),and Ti3C2Tx illumination group(n=6).The wound healing was observed,and CD31 and CD206 immunohistochemical staining of wound tissue was performed on day 7 after intervention.Hematoxylin-eosin staining and Masson staining of wound tissue were performed on days 7 and 14 after intervention.Ti3C2Tx solution was injected subcutaneously into ICR mice.After illumination(or non-illumination)exposure,the toxic effects of Ti3C2Tx on mice were analyzed by blood biochemical detection.RESULTS AND CONCLUSION:(1)In vitro experiments:Ti3C2Tx showed no cytotoxicity on NIH-3T3 cells at mass concentrations ranging from 5-160 μg/mL.It increased the survival rate of NIH-3T3 cells at a mass concentration of 20 μg/mL.Ti3C2Tx at 10-80 μg/mL significantly improved the survival rate of NIH-3T3 cells under H2O2 intervention.Ti3C2Tx significantly inhibited the generation of reactive oxygen species in NIH-3T3 cells under the intervention of H2O2,and illumination treatment further enhanced the effect of Ti3C2Tx on inhibiting the generation of reactive oxygen species.Ti3C2Tx effectively inhibited macrophage inflammation induced by lipopolysaccharide and promoted the transformation of cells into M2 macrophages with anti-inflammatory properties.Both Ti3C2Tx and Ti3C2Tx illumination significantly inhibited the growth of Escherichia coli and Staphylococcus aureus,and the inhibitory effect of Ti3C2Tx illumination was more significant.(2)In vivo experiments:Gross and histological analyses of the wound surface showed that both Ti3C2Tx and Ti3C2Tx illumination promoted wound healing in diabetic mice,and the promotion effect of Ti3C2Tx irradiation was more significant.Immunohistochemical staining results showed that both Ti3C2Tx and Ti3C2Tx illumination inhibited the inflammatory response in diabetic wounds and promoted angiogenesis,and the effect of Ti3C2Tx illumination was more significant.Blood biochemical test results showed that Ti3C2Tx and illumination had no obvious toxic effects on mice.(3)These results indicate that Ti3C2Tx nanoparticles efficiently promote the healing of skin wounds in a diabetic mouse model through antioxidation,anti-inflammation,and antibacterial actions via photothermal effects.

Objective: To investigate the iodine nutrition status of children aged 8-10 in Guangming, Longhua and Yantian District of Shenzhen in 2023, and to explore the influencing factors of thyroid volume. To evaluate prevention strategies and to provide a scientific basis for the elimination of iodine deficiency disorders. Methods: Urine and household salt samples were randomly collected from 580 non-boarding students aged 8-10 years foriodine content detection. Thyroid volume was measured using a fully digital ultrasound imaging system, and goiter prevalence was calculated. Results: A total of 580 samples was tested. The median salt iodine concentration was 23.86 mg/kg, with 93.62% qualified iodized salt and 94.48% coverage rate. The median of urinary iodine was 265.00 μg/L, mainly distributed between 200 - < 300 μg/L and ≥300 μg/L. The proportion of children with ap⁃ propriate iodine was 20. 86% , and the proportion of children with insufficient or excessive urinary iodine levels was 10. 86% and 68. 28% of the total surveyed population , respectively. The median thyroid volume was 3. 27 mL , and the goiter rate was 1. 72% . Multiple linear regression analysis showed that age was the risk factor for thyroid volume (8=0 328, P<0.05). while urinary iodine was the protective factor for thyroid volume(B=-4.134x10-4,P<0.05). Conclusion The qualified iodized salt rate, median of urinary iodine,and goiter prevalence of 580 children aged 8 - 10 meet the elimination criteria for iodine deficiency disorders. Age and urinary iodine are closely related to thyroid volume change. The urinary iodine level of children is generally high and requires serious attention.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

BACKGROUND: Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. METHODS: The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI). RESULTS: The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356-128,645,155 cases), 693,444 cases (95% UI = 567,765-850,490 cases), and 17,672 cases (95% UI = 13,932-21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26-1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94-1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0-2235.14) in 1990 to 964.70 (801.26-1175.09) per 100,000 people in 2021. CONCLUSIONS Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.
Humans ; Urolithiasis/mortality* ; Male ; Female ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Adult ; Middle Aged ; Risk Factors ; Sex Factors