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.

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

Objective:To explore the value of ultrasonic velocity vector imaging(VVI)in assessing motion abnormality of myocardial segment of hyperthyroid heart disease.Methods:A total of 76 patients with hyperthyroid heart disease who admitted to hospital from August 2019 to August 2021 were selected.According to the damage degree of ascending aorta of patients,30 patients whose inner diameter of ascending aorta was greater than 30 mm were included in the"inner diameter>30mm"group,and 46 patients whose inner diameter of ascending aorta was less than 30 mm were included in the"inner diameter<30mm"group.Additionally,40 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group.All subjects underwent routine echocardiography examination,and the images were imported into the velocity vector imaging(VVI)workstation.And then,the clear and standard two-dimensional grayscale dynamic images were selected to conduct analysis.The left ventricle was tracked and analyzed,and the left ventricular long axis,the apical four chamber,and the velocity of reaching peak value,the time of 50%velocity and the time of 75%velocity of longitudinal myocardial movement of 18 segments of two chambers,as well as the mitral valve level of short axis,the velocity of reaching peak value of reaching peak value,the time of 50%velocity and the time of 75%velocity of radial myocardial movement of 12 segments of horizontal section of papillary muscle,of three cardiac cycles were stored and recorded.Results:There were significant differences in the time to peak of longitudinal contraction at the basal segment and middle segment of left ventricular lateral wall,and the basal segment of front wall,the basal segment,middle segment and apical segment of inferior wall,as well as the basal segment,middle segment and apical segment of posterior wall among three groups(F=45.02,23.19,8.70,19.82,16.17,18.07,36.85,48.65,36.64,P<0.05),respectively.There were significant differences in the velocity and time of reaching peak value of the radial contraction of the levels of papillary muscle and mitral valve of short axis of left ventricular inferior wall among the three groups(F=15.44,40.35,P<0.001),respectively.Conclusion:VVI technique can accurately detect the subtle changes of the synchronization of myocardial systolic motion of left ventricular short axis and long axis of patients with hyperthyroid heart disease,which has higher application value in assessing the abnormalities of myocardial segmental motion of patients with hyperthyroid heart disease.

Objective:To observe the value of superb microvascular imaging(SMI)combined with contrast-enhanced ultrasound(CEUS)in the differential diagnosis of benign and malignant superficial enlarged lymph nodes.Methods:A total of 82 patients with superficial enlarged lymph nodes who admitted to the Fourth Hospital of Qinhuangdao City from March 2020 to June 2022 were selected.All patients underwent SMI and CEUS examinations,and the ultrasound-guided needle biopsy was used as the"gold standard",and Kappa values was used to analyze the consistencies of single SMI and CEUS,and the combination of them with the"gold standard"in diagnosing benign and malignant superficial enlarged lymph nodes.Results:The results of ultrasound-guided needle biopsy showed that 34 superficial enlarged lymph nodes were benign lymph nodes and 63 superficial enlarged lymph nodes were malignant lymph nodes in 97 superficial enlarged lymph nodes of 82 patients.The results of SMI examination showed that 37 superficial enlarged lymph nodes were benign lymph nodes and 60 superficial enlarged lymph nodes were malignant lymph nodes in 97 superficial enlarged lymph nodes.The results of consistency analysis indicated that SMI has favorable value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,which has better consistency with needle biopsy(Kappa=0.712).The results of CEUS examination showed that 36 cases of the 97 superficially enlarged lymph nodes were benign lymph nodes and 61 cases were malignant lymph nodes.The results of consistency analysis indicated that CEUS has better value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,which has higher consistency with needle biopsy(Kappa=0.821).The results of SMI combined with CEUS examination showed that 35 cases of 97 superficial enlarged lymph nodes were benign lymph nodes and 62 cases were malignant lymph nodes.The result of consistency analysis indicated that SMI combined with CEUS has better value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,and has higher consistency with needle biopsy(Kappa=0.886).Conclusion:Both SMI and CEUS examinations have better value in differential diagnosis of benign and malignant superficial enlarged lymph nodes,and the combination of them can further improve the consistency with result of pathological examination,and enhance the diagnostic value,which has a certain guidance significance in clinical screening malignant lymph nodes.

【Objective】 To explore the expression of PCDH9 loss in regulating cell cycle and promoting tumor progression. 【Methods】 The clinical records of 127 cases of prostate cancer treated during 2018 and 2023 were collected, including 87 paraffin tissue samples from the G4-5 group and 40 from the G1-3 group. The expressions of PCDH9, p53, Rb and STAT3 were detected with immunohistochemical staining, and the relationship between their expressions and clinicopathological characteristics was analyzed. 【Results】 The expression deletion rate of PCDH9 in prostate cancer tissues in G4-5 group (44.8% vs.7.5%) was significantly higher than that in G1-3 group (P<0.001). The positive expression rates of p53 and STAT3 were 34.5% and 89.7%, respectively, and the expression loss rate of Rb was 27.6% in G4-5 group. The expression loss rates of PCDH9 and Rb were associated with neuroendocrine-like histological morphology, nerve invasion and vascular invasion (P<0.05). In G4-5 group of prostate cancer, PCDH9 expression was positively correlated with the expressions of p53 (r=0.345, P<0.05), Rb (r=0.503, P<0.05) and STAT3 (r=0.224, P<0.05). 【Conclusion】 PCDH9 is prone to loss of expression in high-group prostate cancer tissues, especially in cases with neuroendocrine-like histological morphology, which may regulate the cell cycle through the STAT3 signaling pathway, thereby promoting tumor progression.

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.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; 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.

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.