BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

OBJECTIVE To prepare nanoparticle-based targeting preparation loaded with triptolide （TP）， and evaluate its quality， targeting ability and cytotoxic effects. METHODS Polymer nanoparticles carrying TP-targeted folic acid （FA） receptor （TP@PLGA-PEG-FA） were fabricated using poly （lactic-co-glycolic acid）/polyethylene glycol/FA （PLGA-PEG-FA） as the carrier by emulsion and volatilization technique. The morphology and distribution were observed， and their particle size， Zeta potential， polydispersity index （PDI）， drug loading capacity and encapsulation efficiency were measured. Their stability， blood compatibility， in vitro drug release， uptake by RAW264.7 cells （localization with fluorescent dye Cy3.5）， and in vitro cytotoxicity were evaluated. RESULTS TP@PLGA-PEG-FA exhibited spherical shape and uniform distribution， with particle size of （122.60±0.02） nm， Zeta potential of （－17.6±0.6）mV， and PDI of 0.26±0.02； drug loading capacity and encapsulation efficiency of TP were measured to be （7.78±0.05）% and （68.62±0.03）%， respectively. The hemolysis rates of 100， 200， 300， 400 µg/mL TP@PLGA- PEG-FA were 0.77%， 0.92%， 1.34% and 1.63%， respectively. There were no significant changes in particle size， PDI and Zeta potential when TP@PLGA-PEG-FA were placed in 4 ℃ water for 14 days and in DMEM culture medium containing 10% fetal bovine serum at 37 ℃ for 12 h. The cumulative release rate of TP@PLGA-PEG-FA was （84.83±0.29）% in phosphate buffer at pH5.5 for 72 h， which was significantly higher than the cumulative release rates in phosphate buffer solutions at pH7.4 and 6.5 for 72 h （[ 42.37±0.35）% and （63.83±0.29）% ， respectively] （P＜0.05）. Activated RAW264.7 cells took up significantly more Cy3.5@PLGA-PEG-FA than they took up Cy3.5@PLGA-PEG-FA+free FA and Cy3.5@PLGA-PEG. When the mass concentration of TP was≥15.63 ng/mL， the survival rates of activated cells in the TP@PLGA-PEG-FA groups were significantly lower than those of the same mass concentration of free TP groups （P＜0.05）. CONCLUSIONS The prepared TP@PLGA-PEG-FA has high stability， good blood compatibility， active targeting and cytotoxicity to inflammatory cells.

Objective To investigate the value of ¹⁸F-FDG PET/CT metabolic parameters in the prognostic assessment of nasopharyngeal cancer patients. Methods The clinical data and PET/CT metabolic parameters of 185 nasopharyngeal cancer patients were retrospectively analyzed. The collected parameters were SUV_max, MTV, TLG, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG). The ROC curve was used to determine the optimal cut-off values of PET/CT metabolic parameters. Univariate and multivariate Cox regression models were used to screen the independent prognostic factors. Kaplan–Meier curves were used to analyze the survival differences. Results The results of univariate Cox regression analysis showed that age, pathologic type, WTLG, TMTV, MTV, and TLG were closely associated with OS and PFS; and SUV_max was associated with PFS (P<0.05). Multivariate Cox regression analysis results showed that age, TMTV, and WTLG were the independent prognostic factors for OS and PFS (P<0.05). The combination of WTLG with T/N staging (AUC=0.781 and 0.781) and TMTV with T/N staging (AUC=0.800 and 0.790) yielded greater predictive accuracy than that of WTLG and TMTV alone (AUC=0.724 and 0.719) or T/N staging (AUC=0.593 and 0.575). Conclusion TMTV and WTLG are important prognostic predictors of nasopharyngeal carcinoma. TLG and MTV of primary lesions are prognostic factors for patients’ PFS and OS. SUV_max has limited prognostic value. Systemic metabolic indexes (TMTV and WTLG), when combined with T/N staging, can optimize prognostic stratification.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective:To compare the outcomes of multiple scales, primarily the speech, spatial, and other qualities of hearing scale for parents（SSQ-P）, in children with ipsilateral vs. Contralateral cochleareimplantat ion（CRI）. Methods: A total of 69 children who received cochlear implantation surgery from April 1999 to June 2024 were included. Patients were divided into two groups based on whether the implantation was on the same side. General information such as gender, age, age at initial implantation and reimplantation was collected. The primary caregivers of the children were followed up by telephone using the categories of auditory performance（CAP）, speech intelligibility rating（SIR）, and SSQ-P questionnaires. Statistical methods including stepwise regression, linear regression, and permutation tests were employed to investigate if there were any statistically significant differences in the scores of CAP, SIR, SSQ-P total, SSQ-P speech perception, SSQ-P spatial hearing, and SSQ-P auditory quality dimensions between the ipsilateral and contralateral reimplantation groups. Results:Of the 69 children included, 62 were in the ipsilateral reimplantation group with a mean age of 11.1 years, and 7 were in the contralateral reimplantation group with a mean age of 11.7 years. Statistical analysis showed that patients in the contralateral reimplantation group had significantly lower SSQ-P total scores （P<0.05） and spatial hearing dimension scores （P<0.05） than those in the ipsilateral reimplantation group after controlling for the corresponding confounders. Conclusion:The effect of ipsilateral reimplantation of cochlear implants is superior to that of contralateral reimplantation in terms of overall auditory function and spatial hearing in daily life for children, but the mechanisms require further investigation.
Humans ; Cochlear Implantation ; Child ; Parents ; Speech Perception ; Male ; Cochlear Implants ; Female ; Hearing ; Surveys and Questionnaires ; Speech ; Child, Preschool

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

Objective To investigate the expressions of 12 cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-α,IFN-γ,TNF-α)and procalcitonin in patients with infective endocarditis(IE).Methods Ten IE patients admitted to our hospital from December 2021 to December 2022 were included into the IE group,10 patients with non-infectious and non-rheumatic valvular diseases who were admitted to our hospital at the same period were randomly selected as the control group,and blood sampling of all patients were conducted at admission.The expressions of 12 cytokines and blood routine indexes were detected by flow cytometry,and the level of procalcitonin was detected by ELISA.The correlations among the expression levels of cytokines in IE patients were analyzed by Pearson method and the correlations of IL-8 level and white blood cell count with procalcitonin in IE patients were analyzed by Spearman method.Results Compared with the control group,the levels of cytokines of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ and IL-12p70 in the IE group were significantly increased(P<0.05),the white blood cell count,neutrophil percentage and procalcitonin were significantly increased(P<0.05).There was no significant difference in the percentage of monocytes between the two groups(P>0.05).IFN-α of IE patients was positively correlated with IL-2,TNF-α,IL-1β and IL-12p70,IL-2 was positively correlated with TNF-α and IL-1β,IL-12p70 was positively correlated with IFN-γ,and procalcitonin was significantly positively correlated with IL-8 and white blood cell count,with statistically significant differences(P<0.05).Conclusion The levels of IL-1β,IL-2,IL-6,IL-10,TNF-α,IFN-α,IFN-γ,IL-12p70 and procalcitonin in IE patients are significantly higher than those in the normal population,and the detections of these indicators are of guiding significance for the early diagnosis of IE and the evaluation of the severity of the disease.

OBJECTIVE To mine adverse drug event （ADE） signals of lacosamide， and to provide references for clinically safe drug use. METHODS ADE data for lacosamide reported to the United States FDA adverse event reporting system from January 1， 2009， to December 31， 2022， were collected. Data mining was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method. Classification statistics were performed using the system organ class （SOC） and preferred terms （PT） from ADE terminology set of Medical Dictionary for Regulatory Activities （Version 25.0）. RESULTS A total of 21 360 lacosamide ADE reports were received， identifying 203 ADE signals across 24 SOCs， with 19 signals not included in the drug’s instruction. The top five PTs ranked by occurrence frequency were medication overdose， technical errors during device use， product use issues， intentional product misuse， and therapy discontinuation. The top five PTs ranked by signal strength were changes in seizure presentation type， congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， brain surgery， and vagus nerve stimulator implantation. ADEs not recorded in the drug instruction included congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， mitochondrial DNA mutation， dissociative identity disorder， and congenital auricular anomaly. CONCLUSIONS For lacosamide-induced ADEs that occur frequently and are already listed in the drug’s instructions， such as bradycardia and atrioventricular block， the clinical application should be careful and attentive， adjusting the dosage timely according to the patient’s condition to avoid severe ADEs. Newly discovered suspect ADEs， such as congenital hypoplasia of depressor anguli oris muscle， mitochondrial DNA mutation， overmature infant， dissociative identity disorder， pigmenturia， behavioral disorders， and dissociative disorders， should be vigilantly recognized to ensure the safety of drug use.

Objective To observe the clinical efficacy of withdrawal therapy based on regulating nutritive qi and defensive qi(shortened to Tiaohe Yingwei method)in treating sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.Methods Ninety patients with sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type were randomly divided into the treatment group and the control group,with 45 patients in each group.The control group was given oral use of Estazolam by 25%of weekly dose-reduction,while the treatment group was treated with Chinese medicinal decoction of Tiaohe Yingwei Zhumian Prescription based on Tiaohe Yingwei method together with Estazolam.The treatment course for the two groups lasted for 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)scores,total TCM syndrome scores,and Drug-withdrawal Syndrome Scale(DWSS)scores in the two groups were observed before and after treatment.After treatment,the efficacy for improving sleep efficiency value(IUSEV)and clinical safety in the two groups were evaluated.Results(1)During the trial,2 cases fell off in the treatment group,and 43 cases included in the statistics;3 cases fell off in the control group,and 42 cases included in the statistics.(2)After 4 weeks of treatment,the total effective rate for improving IUSEV of the treatment group was 88.37%(38/43),and that of the control group was 61.90%(26/42).The intergroup comparison by non-parametric rank-sum test showed that the efficacy for improving IUSEV in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,obvious reduction was shown in the overall PSQI scores and the scores of the items of sleep quality,time for falling asleep,sleep time,sleep efficiency,sleep disorder and daytime dysfunction in the two groups when compared with those before treatment(P＜0.05).The intergroup comparison showed that except for the items of sleep disorder and daytime dysfunction,the treatment group had stronger effect on decreasing the scores of the remaining items and the overall PSQI scores than the control group(P＜0.05).(4)After treatment,the total scores of TCM syndromes of both groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the total scores of TCM syndrome in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the total DWSS scores of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(6)During the course of treatment,no significant adverse reactions occurred in the two groups,or no abnormal changes were found in the safety indexes such as routine test of blood,urine and stool,liver and kidney function,and electrocardiogram of the patients.Conclusion Withdrawal therapy based on Tiaohe Yingwei method exerts certain effect for the treatment of sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.The therapy is effective on improving the quality of sleep and reducing the incidence of drug-withdrawal syndrome,and has a high safety.

To explore the effectiveness of "near peer learning" (NPL) in the electromyography(EMG)teaching module for neurology residents.