Objective To compare the long-term survival outcomes of patients with T_1-2N₀M₀ duodenal neuroendocrine tumor (DNET) after endoscopic resection (ER) or surgical resection (SR). Methods Patients diagnosed with T_1-2N₀M₀ DNET between January 1, 2004, and December 31, 2015, were extracted from the SEER database. Kaplan-Meier survival curve and log-rank test were used to compare overall survival (OS) rate and cancer-specific survival (CSS) rate between patients undergoing ER or SR. Propensity score matching (PSM) was used to reduce grouping differences, and multivariate Cox regression was used to analyze factors affecting OS and CSS before and after PSM. Results A total of 656 patients were included, with 457 in ER group and 199 in SR group. Before PSM, there was no significant difference in the 5-year OS rate between the ER and SR groups (88.9% vs 89.6%), but there was a significant difference in the 5-year CSS rate (99.3% vs 96.9%, P＝0.017). Before PSM, multivariate Cox regression analysis showed advanced age was an independent risk factor for decreased OS (P＜0.001). After PSM, there was no significant difference between the ER group (n＝187) and SR group (n＝187) in 5-year OS rate (90.2% vs 88.9%) or CSS rate (98.9% vs 96.7%). After PSM, multivariate Cox regression also showed advanced age was an independent risk factor for decreased OS, while resection method was not an independent factor for OS or CSS. Conclusions There is no significant difference in OS or CSS after endoscopic treatment and surgical treatments for patients with T_1-2N₀M₀ DNET, and advanced age is an independent factor for OS.

To explore the application of humanistic care in children's fever clinics,the children's fever clinics of Guangzhou Women and Children's Medical Center conducted relevant research using narrative medicine as a guiding concept.This paper elaborated on the medical humanistic dilemmas and narrative care needs in children's fever clinics,and focused on exploring the practice paths of narrative medicine in pediatric with Chinese characteristics from five dimensions,including the cultivation of nursing staff's abilities of professional narrative and humanistic care,the establishment of health lectures featuring narrative patient education,the alleviation of medical anxiety for children and their families,related support of narrative nursing,and caring services.The aim was to improve the narrative care ability of nurses in children's fever clinics,develop methods for pediatric patients that can eliminate the fear of seeking medical treatment,and protect children's physical and mental health.A carrier of care,support,and emotional expression can be provided for parents.The foundation for nursing staff to achieve professional growth through narrative reflection can be laid.Thus,it can assist in establishing a life narrative community relationship between doctors and patients,and jointly explore the meaning of life.

Objective:To explore the effect of accurately localized mini anterolateral thigh perforator flap in repairing medium-sized skin and soft tissue defects in fingers.Methods:The study was a retrospective observational study. From December 2019 to September 2022, 15 patients with medium-sized skin and soft tissue defects who met the inclusion criteria in fingers were admitted to the Second Affiliated Hospital of Wenzhou Medical University, including 12 males and 3 females, aged 23 to 62 years. After debridement, the wounds were all accompanied by exposed tendons, bones, vessels and nerves, with an area from 4.0 cm×3.0 cm to 8.0 cm×3.5 cm. Computed tomography angiography and color Doppler ultrasonography examinations were performed on both lower limbs of the patient before surgery to accurately locate the anterolateral thigh perforators. When the flap with area from 6.0 cm×3.0 cm to 11.0 cm×4.0 cm was harvested, the flap was thinned. The artery and vein perforators of the flap were anastomosed respectively with the digital artery and dorsal metacarpal vein. If there was avulsion injury, infection, or burn in the recipient area, the main arterial and veinous vessels carried by the skin flap was anastomosed with the radial artery and accompanying vein. The lateral thigh cutaneous nerve carried by the flap was anastomosed with the stump of the digital nerve. The types of perforators of the lateral thigh artery were observed during operation and compared with the location of the vessels before operation. After operation, the survival and adverse complication of the flap were closely observed. During follow-up, the skin flap color, texture, and shape were observed; the wound healing in donor area was observed. At the last follow-up, the two-point discriminative distance of the affected finger pulp was measured, and the function of the affected finger was evaluated using the trial standard for the evaluation of functions of upper limbs of Hand Surgery Society of Chinese Medical Association, and the interphalangeal joint movement of the affected finger was observed; the patients' complaints about the adverse effects of flap resection on lower limbs were recorded.Results:During the operation, it was observed that the perforators of the flaps in 11 patients were the descending branch of the lateral circumflex thigh artery, in two patients, the perforators of skin flaps were the oblique branch of the lateral thigh artery, and the perforators in another two patients were the transverse branch of the lateral circumflex thigh artery, which were consistent with the preoperative vascular localization. After operation, all flaps survived without vascular crisis and infection. The patients were followed up for 6-12 months, the flaps had excellent color, texture, and appearance; only linear scars remained on the donor wound. At the last follow-up, the two-point discrimination distance in the finger pulp was 7-11 mm; the affected finger function was rated as excellent in 6 cases, good in 6 cases, and fair in 3 cases; the flexion and extension function of the finger was not affected; two patients complained of numbness in the lateral thigh after excision of the skin flap, and the other 13 patients had no complain of adverse complaints.Conclusions:The perforating branch in lateral thigh region can be accurately located by computed tomography angiography and color Doppler ultrasonography, accurate positioning of perforators before operation can reduce the damage to the donor area during the incision of the flap, the appearance and function of the affected finger can be restored to the maximum extent by thinning the transplanted flap and rebuilding the finger sensation. Therefore, it is an effective and reliable way to repair the medium-sized skin and soft tissue defects of fingers with the mini thigh anterolateral perforator flap.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

Objective To investigate the effect of E2 signaling in myofibers on muscular macrophage efferocytosis in mice with cardiotoxin-induced acute skeletal muscle injury.Methods Female wild-type C57BL/6 mice with and without ovariectomy and male C57BL/6 mice were given a CTX injection into the anterior tibial muscle to induce acute muscle injury,followed by intramuscular injection of β-estradiol(E2)or 4-hydroxytamoxifen(4-OHT).The changes in serum E2 of the mice were detected using ELISA,and the number,phenotypes,and efferocytosis of the macrophages in the inflammatory exudates and myofiber regeneration and repair were evaluated using immunofluorescence staining and flow cytometry.C2C12 cells were induced to differentiate into mature myotubes,which were treated with IFN-γ for 24 before treatment with β-Estradiol or 4-OHT.The treated myotubes were co-cultured with mouse peritoneal macrophages in a 1:2 ratio,followed by addition of PKH67-labeled apoptotic mouse mononuclear spleen cells induced by UV irradiation,and macrophage efferocytosis was observed using immunofluorescence staining and flow cytometry.Results Compared with the control mice,the female mice with ovariectomy showed significantly increased mononuclear macrophages in the inflammatory exudates,with increased M1 cell percentage,reduced M2 cell percentage and macrophage efferocytosis in the injured muscle,and obviously delayed myofiber regeneration and repair.In the cell co-culture systems,treatment of the myotubes with β-estradiol significantly increased the number and proportion of M2 macrophages and macrophage efferocytosis,while 4-OHT treatment resulted in the opposite changes.Conclusion In injured mouse skeletal muscles,myofiber E2 signaling promotes M1 to M2 transition to increase macrophage efferocytosis,thereby relieving inflammation and promoting muscle regeneration and repair.

Objective To rapidly evaluate the efficacy,safety,and economics of dexmedetomidine in patients on mechanical ventilation in intensive care unit(ICU),and to provide references for clinical and decision makers.Methods To search PubMed,Embase,Cochrane Library,CNKI,WanFang Data databases and official websites of domestic and foreign Health Technology assessment(HTA)institutions from the inception to June 14,2023.HTA reports,systematic reviews/Meta-analyses,and pharmacoeconomic studies of patients with mechanical ventilation in ICU compared with dexmedetomidine versus placebo or other traditional sedatives were included.Two reviewers independently identified studies,extracted data,assessed the quality of included studies,and descriptive analyzed and summarised the results.Results A total of 13 literatures were included,including 10 systematic reviews/Meta-analyses and 3 economic studies.The analysis results of effectiveness showed that compared with placebo or other traditional sedatives,the use of dexmedetomidine in the sedation of mechanically ventilated patients in the ICU was associated with a shorter duration of mechanical ventilation and a shorter length of stay in the ICU.The analysis results of safety displayed treatment with dexmedetomidine could reduce the incidence of delirium,but may increase the incidence of bradycardia.The results of the economic analysis showed that the dexmedetomidine group had a higher cost of medication,but a lower overall ICU cost.Conclusion Dexmedetomidine has good efficacy,safety and economics in the sedation of patients on mechanical ventilation in ICU,but the economic studies included in the search were mainly foreign studies,and domestic economy studies needs to be further demonstrated.

Aim To dynamically characterize neuronal damage in the cortex and hippocampus of mice follow-ing acute cerebral ischemia/reperfusion(I/R).Meth-ods Male C57BL/6J mice weighing 25-28 g under-went middle cerebral artery occlusion using the fila-ment method,followed by 1 hour of reperfusion to es-tablish the acute cerebral I/R injury mouse model.The experiment comprised a sham surgery group,I/R-6 h group,I/R-24 h group,and I/R-72 h group.Longa neurological function score was used to assess the neu-rological function.Triphenyltetrazolium chloride(TTC)staining was conducted to detect cerebral in-farct volume.Hematoxylin and eosin(HE)staining was utilized to observe brain tissue pathological dam-age.Nissl staining was performed to evaluate neuronal damage.Immunofluorescence histochemistry staining was employed to assess the activation of astrocytes and microglia,as well as neuronal loss.Transmission elec-tron microscopy was used to examine mitochondrial damage in hippocampal neurons.Western blot analysis was conducted to detect the expression levels of mito-chondrial fission-fusion-related proteins p-Drp1/Drp1,Mff,Fis1,and OPA1.Results With prolonged cere-bral I/R time,neurological functional impairment,cerebral infarct volume,neuronal damage in the cortex and hippocampus,glial cell activation,neuronal loss,and mitochondrial damage gradually worsened in mice.The expression of mitochondrial fission-related proteins increased gradually,while the expression of mitochon-drial fusion-related proteins decreased gradually.Con-clusions Neuronal pathological damage,such as glial cell activation,neuronal loss,and mitochondrial dam-age,is gradually aggravated with prolonged cerebral I/R time,which may be associated with mitochondrial dynamics imbalance.

Liver size is regulated by circadian clock and exhibits a diurnal rhythm. Pregnane X receptor (PXR) and peroxisome proliferator-activated receptor α (PPARα), members of nuclear receptor superfamily, are important regulators of liver size. We previously demonstrated that mPXR agonist pregnenolone 16α-carbonitrile (PCN) and mPPARα agonist pirinixic acid (WY-14643) promoted liver enlargement and liver regeneration after partial hepatectomy. However, whether PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations remains unclear. The aim of this study was to investigate the diurnal rhythm of PXR or PPARα activation-induced liver enlargement. Male C57BL/6 mice were intraperitoneally injected with corn oil, PCN or WY-14643 for three days, and liver samples were weighed and collected at various time points for analysis. The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2023-001613, SYSU-IACUC-2023-001783). The results showed that PXR or PPARα activation at various time points significantly induced liver enlargement, and liver size maintained normal diurnal oscillations during PXR or PPARα activation-induced hepatomegaly, without significant effects on the expression of core clock genes. This study reveals PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations, and provides novel data for nuclear receptor-induced liver enlargement and liver diurnal rhythm.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

Plant-derived exosome-like nanoparticles(PELNs) are a class of membranous vesicles with diameters approximately ranging from 30 to 300 nm, isolated from plant tissues. They contain components such as proteins, lipids, and nucleic acids. PELNs play an important role in the metabolism of plant substances and immune defense, and can also cross-regulate the physiological activities of fungi and animal cells, showing significant potential applications. In recent years, research on PELNs has significantly increased, highlighting three main issues:(1) the mixed sources of plant materials for PELNs;(2) the lack of a unified system for isolating and characterizing PELNs;(3) the urgent need to elucidate the molecular mechanisms underlying the cross-regulation of biological functions by PELNs. This article focused on these concerns. It began by summarizing the biological origin and composition of PELNs, discussing the techniques for isolating and characterizing PELNs, and analyzing their biomedical applications and potential future research directions., aiming to promote the establishment of standardized research protocols for PELNs and provide theoretical references for in-depth exploration of the mechanisms underlying PELNs' cross-regulatory effects.
Animals ; Exosomes/metabolism* ; Proteins/metabolism* ; Plants/metabolism* ; Nucleic Acids ; Nanoparticles