OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

Objective To explore the potential characteristics of self-management behavior in maintenance hemodialysis patients with hypertension and determine the influencing factors of different characteristics,so as to provide reference for improving self-management behavior.Methods A total of 192 maintenance hemodialysis patients with hypertension who received dialysis in The First Hospital Affiliated to Naval Medical University from May to September 2022 were enrolled by convenience sampling.A general information questionnaire,hypertension self-management behavior scale,Morisky medication adherence scale-8 items,and medication adherence self-efficacy scale-revision(MASES-R)were used to investigate the potential categories of self-management behavior in maintenance hemodialysis patients with hypertension,and the predictive indicators of each category were analyzed by latent profile analysis.Results Three latent categories of self-management behavior in maintenance hemodialysis patients with hypertension were identified:low self-management behavior,moderate self-management behavior,and high self-management behavior.Medication adherence and medication adherence self-efficacy were predictors of high self-management behavior.Monitoring blood pressure once daily was a predictor of moderate self-management behavior.Conclusion There is significant self-management characteristics among maintenance hemodialysis patients with hypertension.These characteristics and risk factors should be identified early to help patients improving their self-management.

Objective: To identify the risk factors for pulmonary arterial hypertension(PAH) in maintenance peritoneal dialysis(MPD) patients and to develop and validate a nomogram-based risk-prediction model. Methods: A total of 168 hospitalized MPD patients from the Department of Nephrology were enrolled.Body-fluid composition was measured by bioelectrical impedance analysis,and pulmonary-artery systolic pressure(PASP) was assessed by echocardiography.Patients were randomly allocated into a training set and a validation set at 1:1 ratio.Variables with P< 0. 05 in multivariable Logistic regression in the training set were incorporated to construct a nomogram .The validation set was used to test the model ’s predictive performance . ROC curves , calibration curves , and decision-curve analysis were applied to evaluate accuracy , consistency , and clinical usefulness of the model . Results: Dialysis vintage ( OR : 1 . 038 , 95% CI: 1 . 008 - 1 . 069 , P = 0. 012) , hemoglobin level ( OR : 0. 961 , 95% CI: 0. 929 - 0. 994 , P = 0. 021) , and extracellular water/intracellular water ratio (E/I) (OR : 1 . 069 , 95% CI: 1 . 024- 1 . 115 , P = 0. 002) were independent risk factors for PAH . ROC analysis yielded area under curve as 0. 867 (95% CI: 0. 782 - 0. 953) and 0. 808 (95% CI: 0. 714 - 0. 902) in the training and validation sets , respectively .Calibration plots showed that the predicted curves for both the training and validation sets closely overlapped with the ideal reference line , indicating that the nomogram risk-prediction model had good predictive performance . Decision-curve analysis demonstrated that , within threshold ranges of 0. 13 - 0. 76 ( training set ) and 0. 20 - 0. 76 (val- idation set ) , clinical net benefit was substantial when interventions were guided by the nomogram . Conclusion Dialysis vintage , hemoglobin level , and fluid-overload index (E/I) are independent risk factors for PAH in MPD patients . The nomogram based on these parameters reliably predicts PAH risk and may aid clinical decision-making.

Objective To investigate the value of non-contrast CT(NCCT)-based radiomics for identifying acute unilateral middle cerebral artery occlusion(MCAO)with negative hyperdense artery sign(HAS).Methods All 80 patients with acute unilateral MCAO confirmed by angiography(MR angiography[MRA]or CT angiography[CTA]or DSA)and presenting with negative NCCT presentation for HAS were enrolled from January 2015 to June 2023 in the Emergency Department of Stroke Center of Affiliated Hospital of Yangzhou university.On the NCCT images,the occluded segment of the middle cerebral artery on the affected side of each case and the corresponding segment of the vessel on the normal side were used as the regions of interest,and a total of 108 radiomic features were extracted.The least absolute shrinkage and selection operator(LASSO)was used to screen the key features,construct and calculate the radiomics score,and four imaging histology models,support vector machine(SVM),light gradient boosting machine(LightGBM),GradientBoosting and adaptive boosting(AdaBoost),were built respectively to predict MCAO.Predictive performance was evaluated by the area under the receiver operating characteristic curves,and comparisons between the modeled receiver operating characteristic curves were made using the Delong test.Finally,the value of the application of radiological modeling was assessed by clinical decision curve analysis(DCA).Results The NCCT images based on 160 vessels were finally screened for 6 key features,including skewness,energy,gray level size zone matrix(GLSZM)-gray uneven,GLSZM-low gray area emphasis,GLSZM-size area non-uniform standardization,GLSZM-area entropy.The area under the curve(AUC)of the SVM-test was 0.688(95％CI 0.497-0.878)with an accuracy of 0.688;the AUC of the LightGBM-test was 0.787(95％CI 0.620-0.955)with an accuracy of 0.781;the AUC of the GradientBoosting-test was 0.654(95％CI 0.457-0.852)with an accuracy of 0.688;the AUC of the AdaBoost-test was 0.707(95％CI 0.515-0.899)with an accuracy of 0.750.The Delong test showed a statistically significant difference between LightGBM-test and GradientBoosting-test(P=0.040),and no statistically significant difference in performance between the remaining models(all P＞0.05).DCA showed that the LightGBM-test performed better.Conclusion NCCT-based radiomics has good diagnostic efficacy for identifying acute unilateral MCAO with negative HAS,and this conclusion needs to be further verified by multi-center and large sample studies.

Objective To investigate the correlations between IgM deposition levels,glomerular ultra-structural and clinicopathological features in primary IgA nephropathy(IgAN).Methods Data from 155 IgAN patients were categorized into three cohorts by IgM deposition levels.We assessed differences in glomerular ultra-structure,clinical indices,MEST-C scores,and factors influencing IgM deposition levels.Results The marked IgM cohort showed higher urinary protein,IgG deposition,and T scores,with reduced serum albumin and lympho-cyte counts(P<0.05).Logistic regression identified FPE and T score as independent factors for IgM deposition.Conclusions IgM deposition correlates with FPE severity in IgAN,suggesting its utility in assessing renal dam-age and guiding treatment strategies.

AIM: To evaluation the effects of esketamine and butorphanol on postoperative pruritus induced by epidural morphine injection in cesarean delivery parturients. METHODS: A total of 162 parturients who underwent elective cesarean section under continuous epidural anesthesia in Taizhou Central Hospital (Taizhou University Hospital), were selected and randomly divided into esketamine group (group K), butorphanol group (group B) and blank control group (group C). 5min after umbilicus amputation, parturients in group K was injected with 3 mg morphine diluent through epidural catheter, and esketamine 0.2 mg/kg intravenously. Parturients in groups B and C were given the same dose of morphine,and butorphanol 10 μg/kg or the same volume of normal saline, respectively. The incidence of postoperative pruritus at different times, the degree of pruritus and incidence of other adverse reactions were compared among three groups. RESULTS: The highest incidence of pruritus occurred within 4 hours after operation. The incidence of postoperative pruritus at 4 hours in group K and B was significantly lower than that in group C (3.7% vs. 3.7% vs. 29.6%, P < 0.05), the total incidence of postoperative pruritus within 48 hours was also significantly lower than that in group C (13.0% vs. 11.1% vs. 40.7%, P < 0.05), and the incidence of moderate to severe pruritus was also significantly lower than that of group C (5.6% vs. 3.7% vs. 31.5%, P < 0.05). There was no significant difference between group K and group B (all P > 0.05). There were no significant differences in the incidence of postoperative nausea, vomiting, dizziness and postoperative pain scores among three groups (P > 0.05). CONCLUSION: Both esketamine and butorphanol can reduce the incidence and degree of pruritus caused by epidural morphine injection in parturients, without affecting the analgesic effect of morphine and without increasing the incidence of adverse reactions. Esketamine is as effective and safe as butorphanol in preventing pruritus after cesarean section.

Objective To investigate the effects of cholesterol-lowering agents on the proliferation, stemness characters, migration, invasion, and neutrophil extracellular traps formation (NETs) formation in liver cancer cells. Methods ASPP2 or HMGCR gene was knocked down in mouse liver cancer cell Hepa1-6 to establish cells with high or low cholesterol, respectively. Simvastatin and berberine were used to reduce cholesterol synthesis. CCK-8 and plate cloning assays were conducted to detect the proliferation ability of liver cancer cells. Sphere formation assay and qRT-PCR were used to analyze the stemness character and expression of related genes. Wound-healing assay and Transwell assay were used to analyze the ability of cell migration and invasion. Immunofluorescence staining was carried out to analyze the effect of lipid-lowering agent on NETs formation. Results Cholesterol-lowering agents significantly inhibited the proliferation and stemness-related gene expression of Hepa1-6 cells (P < 0.001), significantly inhibited the migration and invasion of Hepa1-6 cells (P < 0.001), and significantly inhibited the neutrophil-induced invasion and formation of NETs (P < 0.001). Conclusion Cholesterol-lowering agents suppress the proliferation and invasion via inhibiting the stemness characters and NETs formation in liver cancer cells. It is a potential strategy for the treatment of liver cancer metastasis.

Objective:To evalaute the efficacy of butorphanol mixed with different doses of hydromorphone in improving patient-controlled intravenous analgesia (PCIA) after secondary cesarean section.Methods:Two hundred American Society of Anesthesiologists physical status Ⅱsingleton pregnant parturients, aged 18-45 yr, at 37-42 week gestation, with body mass index≤30 kg/m 2, undergoing elective secondary cesarean section under combined spinal-epidural anesthesia, were allocated to one of 4 groups ( n=50 each) using a random number table method: butorphanol (group B) and butorphanol mixed with different doses of hydromorphone groups (group BH 1, group BH 2 and group BH 3). Flurbiprofen 50 mg, butorphanol 1 mg and granisetron 3 mg were intravenously injected after delivery during operation.The analgesic pump was connected and turned on at the end of operation.The PCIA solution contained butorphanol 0.24 mg/kg and granisetron 6 mg in group B, butorphanol 0.24 mg/kg and hydromorphone 0.06 mg/kg and granisetron 6 mg in group BH 1, butorphanol 0.24 mg/kg and hydromorphone 0.09 mg/kg and granisetron 6 mg in group BH 2, butorphanol 0.24 mg/kg and hydromorphone 0.12 mg/kg and granisetron 6 mg in group BH 3.The PCIA solution was diluted with normal saline to 150 ml, and the patient-controlled analgesia (PCA) pump was set up to deliver a 3.0 ml bolus dose with a 15-min lockout interval and background infusion at 2.5 ml/h in all the four groups.The degree of pain was evaluated using the VAS score.When the VAS score>5 points after pressuring analgesia pump at rest, flurbiprofen axetil 50 mg was intravenously injected for rescue analgesia.VAS scores during movement, at rest and during uterine contraction and observer′s assessment of alertness/sedation scale score were recorded at 3, 6, 24 and 48 h after operation.The requirement for rescue analgesia, effective pressing times of PCA, overall satisfaction score, OAA/S score<5, adverse reactions and time to the first flatus were recorded within 48 h after operation. Results:Compared with group B, VAS scores in different states were significantly decreased after operation, the effective pressing times of PCA were decreased within 48 h after surgery, and the overall satisfaction score was increased in BH 1, BH 2 and BH 3 groups ( P<0.05). Compared with group BH 1, no significant change was found in VAS score in different states after operation in group BH 2 ( P>0.05), and VAS score was significantly decreased at rest after operation in group BH 3 ( P<0.05). There was no significant difference in VAS scores between group BH 2 and group BH 3 ( P>0.05). There were no significant differences in the requirement for rescue analgesia, effective pressing times of PCA and overall satisfaction of the puerperae among BH 1, BH 2 and BH 3 groups ( P>0.05). There was no significant difference in the time to the first flatus after operation, requirement for rescue analgesia and incidence of observe′s assessment of alterness/sedation scale score<5 and adverse reactions among the four groups ( P>0.05). Conclusions:Compared with butorphanol alone, butorphanol mixed with hydromorphone is helpful in reducing maternal pain and improving the overall satisfaction, with fewer adverse reactions.Butorphanol 0.24 mg/kg mixed with hydromorphone 0.09 mg/kg is recommended.

Objective:To express virus-like particles of poliovirus type 2 (PV2-VLP) in insect cells using a recombinant baculovirus expressing P1 and 3CD and to preliminarily evaluate its immunogenicity.Methods:Based on the codon preference of High 5 cells, the sequences of P1 gene and 3CD gene of PV2 were optimized and inserted into pUC57-Amp to construct pUC57-PV2-P1 and pUC57-PV2-3CD. UC57-PV2-P1s mutant that carried P1 gene mutation affecting thermostability was then constructed. Recombinant baculovirus strains of rBac-PV2-P1s-3CD and rBac-PV2-P1-3CD (wild type) were constructed using homologous recombination. The expression of target proteins was detected by Western blot. PV2-VLP was purified by ion exchange chromatography. The structure of VLP was observed under transmission electron microscopy to evaluate the assembly efficiency. The immunogenicity of PV2-VLP was assessed in a rat model.Results:The recombinant baculovirus with stable expression of P1s and 3CD proteins was successfully constructed. Western blot results showed that the yield of VLP was higher after thermostability mutation than that of the wild type. A three-dimensional structure with a diameter of about 30 nm was observed under electron microscopy, indicating that the VLP was successfully assembled. Animal experiment showed that the recombinant PV2-VLP had immunogenicity and could effectively induce the production of neutralizing antibodies.Conclusions:Effective VLP vaccines could be successfully prepared using the insect cell-baculovirus expression system, which provided reference for the development of polio VLP vaccine.

Objective:To study the problems found in the implementation of key clinical specialty programs and come up with feasibility suggestions.Methods:November 2020 to January 2021, by means of quota sampling and snowball sampling, 22 depth interviews were made with principal-investigators, project team elites, leaders of functional departments, and experts of independent examination teams. The interview data were subject to theme analysis.Results:Six(27%) of the interviewees confused the concepts of " key specialty" and " key discipline" ; 9(41%) of them held that at specific stage of the program development, the connotation and implementation emphasis of specialty development and those of key disciplines were overlapped to some extent. Twenty(88%)of them held that functional management process and responsibility should be further refined, 19(86%) said that lack of professional financial knowledge hindered their program implementation, 16(73%) reported difficulties in information statistics, management and sharing, 19(86%)presented disputes in understanding the program examination criteria.Conclusions:In the implementation of key clinical specialty program, management at various levels should work in alignment with program teams, provide accurate definition and guidance to key steps and working mechanisms, refine the management process, provide accurate financial management, and build information platforms for big data collection and sharing.