BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

Penicillin G acylases (PGAs) are industrially important enzymes primarily used for the synthesis of first- and second-generation cephalosporins or penicillins. This study aims to establish a high-efficiency biosynthetic system for cefradine on the purpose of significantly enhancing its catalytic efficiency in cefradine synthesis and developing its potentials for industrial application. In this study, we identified and engineered penicillin G acylase and obtained a highly active mutant KsPGA M7(M168F/F313G) for the synthesis of cefradine. The mutant achieved a conversion rate over 95% in the scaled-up reaction. To validate its industrial applicability, we immobilized both the wild-type and mutant enzymes and applied them in continuous flow reactions, which achieved a space-time yield of 2 800 g/(L·d). This study lays a foundation for the future applications of penicillin G acylases in the industrial synthesis of cefradine.
Penicillin Amidase/biosynthesis* ; Protein Engineering/methods* ; Cephradine/metabolism* ; Escherichia coli/metabolism* ; Enzymes, Immobilized/metabolism* ; Recombinant Proteins/biosynthesis*

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective Based on the acupuncture literature data set,a named entity recognition method of acupuncture literature based on dictionary and deep learning model is proposed to improve the effect of acupuncture literature entity recognition.Methods In this paper,the entity recognition methods of acupuncture literature were explored,and the vector representation effects based on word2vec and ALBERTmodels and ALBERT+domain dictionary were compared.On this basis,a named entity extraction method combining domain dictionary and ALBERT-BiLSTM-CRF deep learning model was proposed.Results According to the extraction effect of three model entities,the P value of word2vec-BiLSTM-CRF is 81.82%,the R value is 70.76%,and the F1 value is 75.48%;ALBERT-BiLSTM-CRF has an P value of 83.10%,a R value of 81.14%and a F1 value of 81.98%."ALBERT-BiLSTM-CRF+dictionary"is 92.57%,91.42%and 91.85%.In terms of entity categories,the top three entities with the highest accuracy rate are acupuncture,needling and needling site,which are 98%,ninety-seven percent and ninety-seven percent respectively,while the three entities with the lowest accuracy rate are acupoint matching corresponding symptoms,disease names and sample size,which are 50.00%,50.68%and 52.43%respectively.Conclusion Compared with the original ALBERT-BiLSTM-CRF model,the precision rate,recall rate and F1 value increased after adding the dictionary,and the convergence speed of the model after adding the dictionary was twice that without adding the dictionary.It is effective to use"ALBERT-BiLSTM-CRF+dictionary"model to identify named entities in acupuncture literature.

Objective:To explore the influencing factors of clinical nurses in general hospitals to carry out hospice care under hospice shared care model, and further improve the quality of hospice care in general hospitals under this mode.Methods:Using the descriptive phenomenological research method, 13 clinical nurses from Sir Run Run Shaw Hospital Affiliated to Medical School of Zhejiang University were selected by purposive sampling from June to September 2023. Semi-structured interviews were conducted based on the capacity opportunity-motivation-behavior model, and Colaizzi′s 7-step analysis method was used to summarize and refine the theme.Results:There were 3 males and 10 females, aged 24-38 years old. Three themes and 11 sub-themes were extracted in this study: ability factors (theoretical knowledge cannot meet clinical needs, lack of clinical practice ability, insufficient self emotional regulation ability), motivation factors (willingness to carry out hospice shared care model, sense of professional benefit, professional identity, perception of care pressure, hospice care self-efficacy), opportunity factors (the influence of Confucian culture, systematic construction of hospice shared care model in hospitals, and multiple external support).Conclusions:Nurses' hospice care under hospice shared care model is affected by internal and external factors. Nurses can learn through multiple channels, find positive work experience, and use multi-dimensional support system to provide high-quality hospice care services for patients.

Objective We made a bidirectional two-sample Mendelian randomization(MR)analysis to investigate the causal connection between metabolites and atopic dermatitis(AD).Methods Single nucleotide polymorphic(SNP)sites associated with metabolites were extracted from the aggregated data of a genome-wide association study(GWAS)as instrumental variables.Causal association between six metabolites and AD was analyzed using the TwoSampleMR package in R software.The primary methods employed included inverse variance weighted(IVW),MR Egger,and weighted median.Heterogeneity testing was conducted using Cochran's Q statistics.MR Egger intercept was employed to test for level pleiotropy.Additionally,sensitivity analysis was carried out using the"leave-one-out"approach.Results The IVW analysis results indicated that ascorbic acid(OR=0.861,95％CI:0.751-0.987),arachidonic acid(OR=0.363,95％CI:0.193-0.683),and cortisone(OR=0.447,95％CI:0.221-0.906)were negatively correlated with the occurrence of AD,while uridine(OR=3.473,95％CI:1.043-11.562),serotonin(OR=1.896,95％CI:1.007-3.571),and 2-hydroxyglutaric acid(OR=2.158,95％CI:1.186-3.924)were positively correlated with the occurrence of AD,and the differences were statistically significant.Conclusion There is no significant evidence supporting a causal association between AD and metabolic disorder,but this study identified potential evidence for a causal effect of six metabolic factors on an increased risk of AD.

BACKGROUND:Although traditional therapies,including drugs and surgery,cannot repair the damaged myocardial tissue,the mortality rate of myocardial infarction remains high.Stem cells provide the possibility to solve this problem due to their self-renewal and multi-directional differentiation potential. OBJECTIVE:To analyze the research progress of stem cell therapy for myocardial infarction in recent ten years by bibliometric analysis. METHODS:The related articles on stem cells and myocardial infarction published in SCI-E and SSCI from January 1,2012 to December 1,2022 in the Web of Science database were searched.EXCEL,CiteSpace and VOSviewer software were used to make statistical and visualization analyses of the data such as the number of publications,authors,institutions,journals,countries and keywords. RESULTS AND CONCLUSION:A total of 3 210 core articles were published,and the total number increased year by year.hausenloy,derek j.is the author with the largest number of publications,China is the country with the largest number of publications,and the Fourth Military Medical University is the institution with the largest number of publications.The research hotspots in this field are changing from cell experiments and animal experiments to clinical trials.In the past ten years,research in this field has been highly popular and still has great development prospects.It is necessary to promote international and inter-agency exchange and learning,and further explore the role of stem cells in the treatment of myocardial infarction.

Objective:To explore the surgical intervention strategy for metastatic cervical lymph nodes surrounding the carotid artery in head and neck squamous cell carcinoma.Methods:A total of 62 patients with advanced head and neck tumors and carotid wrap by disease treated in Department of Otorhinolaryngology and Head and Neck Surgery, the Affiliated BenQ Hospital of Nanjing Medical University between June 2019 and December 2023 were reviewed, of whom 9 patients presented with metastatic squamous cell carcinoma in cervical lymph nodes of unknown primary or with no recurrence of primary lesion and all the 9 patients were males, aged from 48 to 79 years old, with≤level 2 of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS). Radiographically common carotid artery (CCA) and/or internal carotid artery (ICA) were surrounded by≥270° with tumor. All the 9 patients received implantation of covered stent in carotid artery and radical resection of metastatic cervical lymph nodes. The success rate, complications, surgery-related complications, local recurrence rate, quality of life (QOL) and overall survival (OS) were analyzed. The QOL of patients was compared by paired rank sum test, and P<0.05 indicated statistically significant difference. The OS was analyzed by Kaplan-Meier. Results:The success rate of stent implantation was 100%, with no implantation-related complications. R0 resection was performed in 8 cases and R1 resection in 1 case. The QOL of patients after surgery was improved, and the improvements in "pain", "mood" and "anxiety" were statistically significant( Z values were -2.236, -2.460 and -2.200, respectively, and all P values were<0.05). Follow-up was 1-18 months, with a median of 7 months, and 1 case was lost to follow-up. Local recurrence occurred in 3 patients with an incidence of 37.5% (3/8). OS was 59.9% at 12 months after surgery. Conclusion:Implantation of covered stent in carotid artery combined with radical resection is an effective method for the treatment of cervical lymph node metastasis.