BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

Objective: To understand the current status and associated factors of sleep problems among preschool children in Hainan Province, so as to provide scientific evidence for improving sleep health in this population. Methods: From January 2021 to June 2022, a total of 4 105 preschool children aged 3-6 years from 62 kindergartens in Hainan Province were selected using stratified cluster random sampling method. Demographic information and lifestyle habits were collected through the Hainan Province Child Growth and Development Survey Questionnaire. The Children s Sleep Habits Questionnaire (CSHQ) was employed to assess sleep status. Unconditional binary Logistic regression model was applied to investigate the associated factors of sleep problems among preschool children. Results: The overall CSHQ score for children was 58.03±18.84, with 80.95% of preschool children exhibiting sleep related issues. The top three most prevalent sleep problem domains were bedtime resistance (72.42%), sleep anxiety ( 54.88 %), and parasomnias (38.86%). Logistic regression analysis revealed that higher family annual income ( OR=0.60, 95%CI = 0.45-0.79), higher maternal education level ( OR=0.53, 95%CI =0.32-0.89), regular or daily vitamin D supplementation ( OR=0.77, 95%CI =0.60-0.99), and fully self initiated eating behavior ( OR=0.71, 95%CI =0.59-0.85) were negatively related with children s sleep problems; in addition, screen exposure ( OR=1.27, 95%CI =1.06-1.51) and picky eating ( OR= 1.47 , 95%CI =1.21-1.78) were positively related to children s sleep problems (all P <0.05). Conclusion The high detection rate of sleep problems among preschool children in Hainan Province is multifactorially associated with family environment, dietary habits, and lifestyle behaviors.

BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

Paradoxical psoriasis is a special adverse drug reaction characterized by the new onset, exacerbation, or phenotypic change of psoriatic lesions during treatment with biological agents. In recent years, with the increasing use of biologics, this condition has garnered growing attention from clinicians. The pathogenesis of paradoxical psoriasis is complex and its clinical manifestations are highly heterogeneous. Diagnosis currently relies primarily on clinical features and medication history due to the lack of unified diagnostic criteria. Furthermore, treatment strategies—such as whether to discontinue the original biologic agent or switch therapies—remain controversial, posing significant challenges in clinical management.This article presents a case of paradoxical psoriasis occurring in a patient with ankylosing spondylitis following treatment with the tumor necrosis factor-α inhibitor (TNFi) infliximab. By discussing the clinical characteristics of this case, we aim to enhance clinicians' understanding of this condition, reduce misdiagnosis and underdiagnosis, and provide valuable insights for its diagnosis and treatment.

OBJECTIVE: To investigate the efficacy and safety of autologous blood transfusion during weaning from venous-arterial extracorporeal membrane oxygenation (VA-ECMO) under controlled rotational speed. METHODS: A retrospective study was conducted, selecting patients who underwent extracorporeal membrane oxygenation (ECMO) and successfully weaned at the emergency and critical care medicine center of Henan Provincial Third People's Hospital from January 2023 to May 2024. General data including gender, age, body mass index (BMI), European system for cardiac operative risk evaluation (EuroScore), and disease types were collected. Vital signs at weaning [heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and peripheral oxygen saturation], parameters before and after weaning [B-type natriuretic peptide (BNP), hemoglobin (Hb), partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial lactate, central venous pressure (CVP), inferior vena cava collapsibility index, left ventricular ejection fraction (LVEF), and right heart load], post-weaning inflammatory markers at 1-day and 3-day [body temperature, white blood cell count (WBC), neutrophil percentage (NEU%), C-reactive protein (CRP), procalcitonin (PCT), interleukin-10 (IL-10)], as well as complications (infection, thrombosis, renal failure, gastrointestinal bleeding) and post-weaning blood return status were recorded. Patients were divided into an observation group (with post-weaning blood return) and a control group (without post-weaning blood return) based on the presence of blood return after weaning. The changes in the aforementioned parameters were compared between the two groups. RESULTS: A total of 62 patients were included, with 31 cases in each group. No statistically significant differences were observed between the two groups in baseline characteristics including gender, age, BMI, and EuroScore. At weaning, the observation group exhibited relatively stable vital signs, with no significant differences in heart rate, SBP, DBP, or peripheral oxygen saturation compared to the control group. After weaning, the observation group showed significantly lower levels of BNP, PaCO₂, arterial lactate, CVP, and right heart load compared to pre-weaning values [BNP (ng/L): 2 325.96±78.51 vs. 4 878.48±185.47, PaCO₂ (mmHg, 1 mmHg≈0.133 kPa): 35.23±3.25 vs. 40.75±4.41, arterial lactate (mmol/L): 2.43±0.61 vs. 6.19±1.31, CVP (cmH₂O, 1 cmH₂O≈0.098 kPa): 8.32±0.97 vs. 15.34±1.74, right heart load: 13.24±0.97 vs. 15.69±1.31, all P < 0.05], while Hb, PaO₂, inferior vena cava collapsibility index, and LVEF were significantly higher than pre-weaning values [Hb (g/L): 104.42±9.78 vs. 96.74±6.39, PaO₂ (mmHg): 94.12±7.78 vs. 75.51±4.39, inferior vena cava collapsibility (%): 28±7 vs. 17±3, LVEF (%): 62.41±6.49 vs. 45.30±4.51, all P < 0.05]. No statistically significant differences were found between the observation group and control group in these parameters. At 3 days post-weaning, the observation group demonstrated significantly lower levels of body temperature, WBC, NEU%, CRP, PCT, and IL-10 compared to 1 day post-weaning [body temperature (centigrade): 36.83±1.15 vs. 37.94±1.41, WBC (×10⁹/L): 7.82±0.96 vs. 14.34±2.15, NEU%: 0.71±0.05 vs. 0.80±0.07; CRP (mg/L): 4.34±0.78 vs. 8.94±1.21, PCT (μg/L): 0.11±0.02 vs. 0.26±0.05, IL-10 (ng/L): 8.93±1.52 vs. 13.51±2.17, all P < 0.05], with no significant differences compared to the control group. No statistically significant differences were observed between the two groups in the incidence of complications including infection, thrombosis, renal failure, and gastrointestinal bleeding. CONCLUSION Autologous blood reinfusion during VA-ECMO weaning under controlled rotational speed is safe and effective, without increasing risks of infection or thrombosis.
Humans ; Retrospective Studies ; Extracorporeal Membrane Oxygenation/methods* ; Blood Transfusion, Autologous ; Male ; Female ; Adult ; Middle Aged ; Natriuretic Peptide, Brain/blood*

BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

Objective To analyze the expression levels of matrix metalloproteinase-10(MMP-10)and Toll-like receptor 2(TLR2)in serum of patients underwent decompression surgery(DC)for severe traumatic brain injury(sTBI),and to explore their relationship with disease outcome.Methods From April 2021 to April 2024,sTBI patients(n=94)who received DC treatment in a single center were collected as the observation group.Another 90 healthy volunteers who underwent physical examinations at our hospital were selected as the control group.Six months after surgery,sTBI patients were assigned into the good group(n=53)and the adverse group(n=41)according to the Glasgow Outcome Scale(GOS).Data was collected from each group and their differences were compared.Enzyme linked immunosorbent assay(ELISA)was used to measure serum levels of MMP-10 and TLR2.Spearman method was used to analyze the correlation between MMP-10,TLR2 levels and disease outcomes.Logistic regression model used to analyze influencing factors of disease outcomes in sTBI patients after DC.The receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of serum MMP-10 and TLR2 levels for disease outcome in sTBI patients after DC.Results Compared with the control group,the expression levels of serum MMP-10 and TLR2 were prominently higher in the observation group(P＜0.05).Compared with the good group,the proportions of sTBI patients with cerebral herniation,multiple brain contusions and lacerations,and serum levels of MMP-10 and TLR2 were significantly higher in the adverse group,while Glasgow Coma Scale(GCS)score was significantly lower(P＜0.05).Serum levels of MMP-10 and TLR2 in sTBI patients were positively correlated with poor prognosis after DC(P＜0.05).Elevated levels of serum MMP-10 and TLR2,and the increased proportions of patients with cerebral herniation and multiple brain contusions were risk factors affecting the disease outcome after DC in sTBI patients,while elevated GCS score was a protective factor(P＜0.05).The area under the curve(AUC)for predicting disease outcome in sTBI patients after DC using serum MMP-10 and TLR2 alone and in combination was 0.839(95％CI:0.749-0.907),0.847(95％CI:0.758-0.913)and 0.925(95％CI:0.852-0.969),respectively.The combined detection was superior to the individual detections(Zcombination-MMP-10=2.199,Zcombination-TLR2=2.377,both P＜0.05).Conclusion The expression levels of serum MMP-10 and TLR2 in sTBI patients are significantly elevated,and both are prominently correlated with disease outcome after DC.

As a non-invasive treatment method,transcutaneous acupoint electrical stimulation(TAES)can regulate neurological function,endocrine function and immune function through electrical stimulation for specific acupoints,which shows wide application potential in postoperative pain management,promotion of bone healing and rehabilitation in orthopedic surgery.TAES treatment has a series characteristics include non-invasiveness,convenience and effectiveness,which provides a new adjuvant treatment method for orthopedic diseases.This review elaborated the research advances of the application of TAES in orthopedics field,which provided references for further exploring its mechanism and clinical application in the future research.

AIM:To investigate the expression profile and biological significance of long noncoding RNA(lncRNA)zinc finger antisense 1(ZFAS1)in the brains of mice with diabetic encephalopathy(DE).METHODS:Ten db/m mice served as the normal control group,while twenty 22-week-old db/db mice were used to establish the DE model and randomly divided into two subgroups:ten as the db/db model control and the remaining ten receiving ZFAS1 gene knockdown(db/db+sh-ZFAS1)via lentiviral transfection.Weekly measurements of body weight and blood glucose levels were performed.Brain tissues were collected for Nissl staining to evaluate neuronal damage,TUNEL assay to detect apop-tosis,and immunofluorescence staining to examine neural biomarker expression.Serum levels of tumor necrosis factor-α(TNF-α)and oxidative stress markers,including reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px),were determined.Western blot was conducted to quantify the protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),p38 mitogen-activated protein kinase and phosphorylated p38(p-p38)in brain tissues.The expression levels of ZFAS1 and caspase-3 mRNA were determined by RT-qPCR.RESULTS:Knockdown of ZFAS1 in db/db mice significantly improved cognitive function,alleviated hippocampal neuronal damage,and reduced body weight and blood glucose levels(P<0.01).More-over,oxidative stress was mitigated,as evidenced by decreased MDA and ROS levels(P<0.01)and increased activity of antioxidant enzymes,GSH-Px,SOD and CAT(P<0.01 or P<0.05).Meanwhile,ZFAS1 silencing down-regulated Bax and p-p38/p38 protein expression(P<0.01 or P<0.05)while up-regulating Bcl-2(P<0.01).Consistently,RT-qPCR confirmed significant down-regulation of ZFAS1 and caspase-3 mRNA levels(P<0.01).CONCLUSION:lncRNA ZFAS1 is highly expressed in the hippocampus of DE mice.Down-regulation of ZFAS1 expression enhances cognitive func-tion,suppresses oxidative stress,and inhibits neuronal apoptosis,thereby attenuating neural damage in DE.

Objective:To analyze the relationship between the expression level of calumenin(CALU)and the prognosis of hepatocellular carcinoma(HCC)patients by bioinformatics tools and establish the prognostic prediction nomogram,and to clarify its possible mechanism.Methods:The data of 374 HCC tissue samples were downloaded from The Cancer Genome Atlas(TCGA)database and the data of 160 normal tissue samples were down loaded from Genotype-Tissue Expression(GTEx)database.Paired sample t-test was used to analyze the difference in CALU expression between the HCC tissue samples and the paired adjacent normal tissue samples.Human Protein Atlas(HPA)database was used to verify the results.DESeq2 package was used to screen the differentially expressed genes(DEGs)between CALU low expression group and CALU high expression group in the HCC tissue samples.R package pROC was used to analyze the receiver operating characteristic(ROC)curve.Univariate and multivariate Cox regression analyses were used to confirm the prognosis value of CALU in the HCC patients with different clinicopathological characteristics,and ggplot2 package was used to construct the forest plot.R packages rms and survival were used to construct the nomogram and its calibration curve,and the diagnostic value of CALU in distinguishing HCC tissue from normal tissue was analyzed.The data from Kaplan-Meier Plotter database were used to further verify the relationship between CALU and the prognosis of HCC patients.The gene transcriptional expression data of 216 HCC samples obtained from GSE14520 dataset were used to verify the prediction accuracy of the nomogram.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to determine the function and enrichment pathways of the DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the significantly enriched gene sets of the DEGs.Single-cell sequencing data of 10 HCC tissue samples and 8 adjacent normal tissue samples obtained from GSE149614 dataset were used to verify the relationship between CALU and the prognosis of HCC patients and its mechanism.Results:Compared with normal tissue,the expression level of CALU mRNA in HCC tissue was significantly increased(P＜0.001),and the expression level of CALU protein in HCC samples was also increased.A total of 928 DEGs were identified between CALU low expression group and CALU high expression group in the HCC samples,including 784 upregulated DEGs and 144 downregulated DEGs.The ROC analysis results indicated that CALU showed high diagnostic value in distinguishing cancer tissue from adjacent non-cancer tissue with an area under curve(AUC)of 0.839.Kaplan-Meier survival analysis showed that the survival rate of HCC patients in CALU high expression group was significantly lower than that in CALU group low expression(P＜0.001).Univariate and multivariate Cox regression analyses results demonstrated that high expression of CALU was an independent risk factor of the prognosis in HCC patients,and a prognosis prediction nomogram was constructed.The applicability of nomogram on the prognosis of HCC was verified by GSE14520 dataset.The GO enrichment analysis results showed that DEGs were mainly enriched in pathways related to the oxidative stress,ferroptosis and cuproptosis(P＜0.05).The KEGG enrichment analysis results showed that DEGs were mainly enriched in the pathways related to extracellular matrix(ECM)receptor interaction,linoleic acid metabolism and neuroactive ligand receptor interaction(P＜0.05).The GSEA results showed that high expression of CALU may promote the G1-S phase transition of the cell cycle,ubiquitination protein polymerization and HCC progression,while low expression of CALU may activate oxidative stress,ferroptosis and cuproptosis in HCC cells.Single-cell sequencing analysis results showed that the expression level of CALU mRNA was significantly increased in HCC cells with advanced tumor stages.HCC_CALU_High cell subset was mainly related to ubiquitination,p53 and cell cycle(P＜0.01),and HCC_CALU_Low cell subset was mainly related to oxidative stress,ferroptosis,and histone binding(P＜0.01).Conclusion:The high expression of CALU may be related to the poor prognosis of HCC patients.The constructed nomogram of HCC prognosis shows favourable effect in predicting the survival rate of the HCC patients.The up-regulation of CALU may promote HCC progression by regulating the G1-S phase of the cell cycle and ubiquitination of protein,while down-regulation of CALU may inhibit HCC progression by inducing oxidative stress,ferroptosis and cuproptosis in cells.