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 feasibility and safety of fastest recovery after surgery(FRAS)in laparoscopic surgery of gastrointestinal tumors.Methods The clinical data of patients undergoing laparoscopic surgery for gastrointestinal tumors under FRAS and enhanced recovery after surgery(ERAS)from Jan.2023 to May 2024 were collected,and perioperative safety and medical cost were analyzed.Results A total of 87 patients were enrolled,including 43 in the FRAS group and 44 in the ERAS group.Compared with the ERAS group,the FRAS group had significantly shorter surgical time(3.0[2.5,3.5]h vs 3.0[2.5,4.0]h),first postoperative movement time([2.85±4.29]h vs[20.18±6.13]h),first postoperative oral feeding time(2.0[2.0,3.0]h vs 24.0[15.0,48.0]h),postoperative hospital stay(24.0[20.0,40.0]h vs 192.0[150.0,216.0]h),lower hospitalization costs(50 515.61[46 650.44,56 827.12]yuan vs 65 555.09[58 683.21,86 239.02]yuan),and lower medication costs(2 671.09[2 063.31,3 127.09]yuan vs 7 326.90[5 104.66,10 674.26]yuan)(all P＜0.05).Conclusion It is safe and feasible to use FRAS during the perioperative period of laparoscopic radical gastrectomy for gastrointestinal tumors,and FRAS can also reduce the costs of hospitalization and medications.

Objective:To screen the host interaction proteins of the severe fever with thrombocytopenia syndrome virus(SFTSV)nonstructural protein(NSs)by immunoprecipitation combined with mass spectrometry analysis,to discuss the functions,subcellular localization,and biological pathways of these interaction proteins,and to provide the basis for clarifying the replication and pathogenic mechanism of SFTSV.Methods:The eukaryotic expression vectors pSFTSV-NSs-Flag(experimental group)and Flag-CMV-3(negative group)were transfected into the human embryonic kidney 293T cells,and contorl group(no treatment)was set up.The lysates of the cells in various groups were collected,and the expression and localization of SFTSV NSs in the host cells were verified by indirect immunofluorescence and Western blotting methods.The protein lysates were treated with protein A/G and immunoprecipitation was used to enrich host proteins binding to NSs.The captured interaction proteins were initially analyzed by silver staining and Coomassie brilliant blue staining to observe the differential protein bands in various groups;liquid chromatography-tandem mass spectrometry was used to obtain the information of protein sequences;the reliable proteins were retained and searched by UniProt database;Gene Ontology(GO)functional enrichment analysis,IPR,eukaryotic orthologous groups(KOGs)functional annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis,subcellular localization,and transcription factor(TF)functional annotation were used to determine the subcellular structure,gene functions,and biological processes of the interaction proteins.Results:The immunofluorescence results showed that the SFTSV NSs expressed a single specific band at relative molecular mass 33 000 and was localized in the cytoplasm in a granular inclusion body-like manner.The silver staining and Coomassie brilliant blue staining results showed there were significant differential protein bands between experimental group and negative group.The mass spectrometry results identified 46 potential interaction proteins.The GO functional enrichment analysis,KOGs functional annotation,and KEGG signaling pathway enrichment analysis results showed that the biological pathways related to viral translation,cellular metabolism,and protein transport were enriched with a considerable number of proteins.Eight annotated proteins had intermediate filament domains.The highest percentage of subcellular localization was cytoplasmic proteins,consistent with the NSs localization site.The TF functional annotation analysis results showed one protein from the NF-Y family.Conclusion:The interaction proteins play roles in assisting the proper protein folding,participating in the cribosome translation,and forming the cytoskeleton,which may be involved in antiviral replication.These proteins can be used as candidate proteins for further study on the replication mechanism of SFTSV.

Objective:To investigate the feasibility of conducting active surveillance (AS) for low risk papillary thyroid microcarcinoma (PTMC) in China and to examine the factors in association with disease progression during AS.Methods:This study was a prospective observational research conducted from Jun. 2018 to Aug. 2022 at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Seventy-three patients with cytologically confirmed low-risk PTMC were enrolled in this study. They were followed up by ultrasonography, and the observed nodules were re-assessed whether or not to have disease progression. Disease progression was defined as having nodule enlarged more than 3 mm in any of diameters measured on ultrasound, or/and presence of suspicious lymph node metastasis.Results:The median follow-up time was 33 months. At the time of last follow-up, 16 cases (21.9%) exhibited disease progression, including 9 cases (12.3%) with suspicious lymph nodes detected by ultrasound, and 8 cases (11.0%) with lesion enlargement; one case (1.3%) exhibited both situations. The univariate chi-square analysis revealed that young patients (≤45 years old, P=0.041), presence of microcalcifications ( P=0.032), initial larger nodule (diameter greater than 7 mm, P=0.003), and elevated thyroid autoantibody levels ( P=0.008) were associated with disease progression. Multiple regression analysis showed elevated thyroid autoantibodies ( OR=4.311, P=0.030) and initial larger nodule ( OR=6.196, P=0.034) were independent risk factors for PTMC progression,respectively. Conclusions:AS for low-risk PTMC is a feasible and effective. During the observation, ultrasound can reveal suspicious lymph nodes and nodule enlargement, which are crucial indicators for assessing disease progression. Patients with initially larger nodule size and elevated thyroid autoantibody level are more likely to exhibit disease progression and should receive closer attention.

Objective To establish a three-dimensional visualization model of complex anal fistula based on high-resolution mag-netic resonance imaging(HR-MRI),and to explore its feasibility and clinical application value.Methods The clinical and imaging data of 26 patients with complex anal fistula were analyzed retrospectively,and a three-dimensional visualization model based on HR-MRI images was established.The Parks typing,internal orifice,external orifice,branch fistula and abscess were evaluated by radiolo-gists and anorectal surgeons in HR-MRI images and the three-dimensional visualization model,and the SPSS 22.0 software was used to analyze the assessment results against the clinical surgery one by one.Results A total of 26 patients had 17 trans sphincteric fis-tulas,7 inter sphincteric fistulas,and 2 suprasphincteric fistulas,and the accuracy of Parks typing based on HR-MRI images and three-dimensional visualization model was 100％;26 patients had a total of 33 internal orifices,and the evaluation of internal orifices based on HR-MRI images was better than that of three-dimensional visualization model(P=0.180 vs P=0.022);15 patients had a total of 32 external orifices,and the evaluation of external orifices based on three-dimensional visualization model was better than that of HR-MRI images(P=0.791 vs P=0.049);20 patients had perianal abscesses,and the evaluations based on HR-MRI images and three-dimensional visualization model were both highly accurate(P=0.549 vs P=0.625);18 patients with branch fistula,the evaluation of branch fistula based on three-dimensional visualization model was significantly better than that of HR-MRI images(P=1.000 vs P＜0.001).Conclusion Based on three-dimensional visualization model of HR-MRI,the evaluation of complex anal fistula Parks typing,external orifice,branch fistula and abscess is more accurate,which is worthy of further research and promotion.

Objective:To investigate the effectiveness of rotator cuff repair surgery in treating proximal humeral fractures and its association with patient age and Neer classification.Methods:A retrospective analysis was conducted on the clinical data of 90 patients with proximal humeral fractures who underwent rotator cuff repair surgery at the Marine Police Corps Hospital of the Chinese People's Armed Police Force between January 2020 and January 2023. The clinical data of these patients were retrieved from the hospital's medical record database. Based on the age distribution of the patients, they were divided into four groups: Group 1 (> 18 years old and < 30 years old, n = 10), Group 2 (≥ 30 years old and < 45 years old, n = 15), Group 3 (≥ 45 years old and < 60 years old, n = 40), and Group 4 (> 60 years old, n = 25). There were no statistically significant differences in baseline data among the four groups (all P > 0.05), indicating comparability. Additionally, these patients were divided into three groups based on Neer classification: Group I (Neer type II, n = 28), Group II (Neer type III, n = 30), and Group III (Neer type IV, n = 32). Differences in various outcome measures related to treatment efficacy, including operation time, intraoperative blood loss, fracture healing time, Visual Analogue Scale (VAS) score, Constant-Murley score, Neer shoulder function score, and the overall incidence of postoperative complications, were recorded and compared across different age groups. Overall efficacy was assessed according to the Neer criteria: > 90 points as excellent, 80-89 as good, 70-79 as fair, and < 70 as poor. Results:After 6 months of surgery, the overall clinical treatment effectiveness rate was 95.56% (86/90). At 2 weeks postoperatively, the VAS score was (3.45 ± 1.35) points, which was significantly decreased compared with the level measured preoperatively ( P < 0.05). At 6 months postoperatively, the Constant-Murley score and Neer shoulder function score were (90.34 ± 6.34) points and (86.34 ± 5.46) points, respectively (both P < 0.05), which were significantly increased compared with the levels measured preoperatively. There were significant differences in fracture healing time ( F = 4.89, P < 0.05), intraoperative blood loss ( F = 5.28, P < 0.05), VAS score ( F = 5.02, P < 0.05), and Neer shoulder function score ( F = 5.32, P < 0.05) and Constant-Murley scores ( F = 3.85, P < 0.05) compared with before treatment. There was no statistically significant difference in the overall incidence of postoperative complications or surgical time among Groups 1, 2, 3,and 4 [0 vs. 5.00% (2/40) vs. 6.67% (1/15) vs. 12.00% (3/25), χ2 = 0.98, P > 0.05]. Group III had longer surgical time and fracture healing time compared with Groups I and II ( F = 4.55, 4.23, both P < 0.05), with greater intraoperative blood loss ( F = 5.24, both P < 0.05). Additionally, Group III had a higher VAS score compared with Groups I and II ( F = 5.06, P < 0.05), while the Neer shoulder joint function score and Constant-Murley score in Group III were lower ( F = 3.83, 4.56, both P < 0.05). There was no statistically significant difference in the overall incidence of postoperative complications among the Groups I, II, and III [9.38% (3/32) vs. 3.57% (1/28) vs. 6.67% (2/30), χ2 = 1.00, all P > 0.05]. Pearson correlation analysis revealed a positive correlation between patient age, Neer classification, intraoperative blood loss, fracture healing time, and VAS score ( r = 0.565, all P < 0.05), and a negative correlation with the Neer shoulder joint function score ( r = -0.620, P < 0.05). However, there was no significant correlation between patient age, Neer classification, and the Constant-Murley score ( r = -0.008, P > 0.05). Conclusion:The rotator cuff repair is effective in treating proximal humeral fractures, but the effectiveness varies depending on patient age and Neer classification. Patient age and Neer classification are positively correlated with intraoperative blood loss, fracture healing time, and VAS score, while they are negatively correlated with the Neer shoulder joint function score.

Objective To investigate the safety and efficacy of sodium fluorescein-guided microsurgery in children with medulloblastoma,and to analyze the surgical efficacy and prognosis.Among them,12 cases underwent unilateral telovelar approach,2 cases underwent bilateral telovelar approach,and 6 cases underwent telovelar approach combined with transvermian approach.The intraoperative dose of sodium fluorescein was 2 mg/kg.Methods The clinical data of 20 patients with medulloblastoma treated with fluorescein sodium assisted microsurgery from January 2018 to August 2023 in Xinjiang Autonomous Region People's Hospital were retrospectively analyzed.Results Of the 20 patients,12 were male and 8 were female.The mean age of onset was(7.9±3.7)years.In all cases,there was clear tumor fluorescence,none of the cases had adverse reaction associated with the use of sodium fluorescein.There were 16 cases of gross-total resection,3 cases of near-total resection,1 case of partial resection,1 case of intracranial infection,2 case of subcutaneous effusion,2 cases of cerebellar mutism.The follow-up time was from 3 to 72 months.5 cases did not receive sufficient radiotherapy and chemotherapy,and 9 cases died due to tumor progression or recurrence.In all cases,the longest overall survival was 72 months,the mean survival time was 39.2 months,and the median survival time was 41.2 months.Conclusion Fluorescein sodium assisted microsurgery is safe and effective in pediatric medulloblastoma surgery.

Objective:To investigate the potential effect and mechanism of docosahexaenoic acid(DHA) on hippocampal neuronal apoptosis and c-Jun N-terminal kinase(JNK) protein in rats with subarachnoid hemorrhage(SAH).Methods:Forty eight SPF-grade male SD rats were randomly divided into control group, sham group, model group and DHA intervention group according to the random number table method, with 12 rats in each group.The rats in model group and DHA group were injected with autologous blood(0.3 mL) into the optic chiasma to establish the SAH model.Rats in model group were intraperitoneally injected with DHA(35 mg/kg) 3 hours after SAH model establishment, rats in sham operation group were injected with 0.3 mL 0.9% sodium chloride solution into the optic chiasma, and rats in control group were fed normally.Neurobehavioral function of all rats was evaluated after 24 hours.The apoptosis of neuron was observed by TUNEL staining, and the expression of phosphorylated JNK(p-JNK)and apoptosis-related proteins Bax and Bcl-2 was observed by Western blot.Statistical analysis was performed using GraphPad Prism 7.0 software.One-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparison.Results:(1)The differences in neurobehavioral function scores among the 4 groups of rats were statistically significant( F=103.60, P<0.05), the neurobehavioral function scores in model group(8.67±1.37) and DHA intervention group(13.67±1.51) were lower than that in control group(18.00±0.00) and sham group(17.67±0.52)( all P<0.05), while the neurobehavioral function score in DHA intervention group was higher than that in the model group( P<0.05).(2)The results of TUNEL staining showed that there were statistical differences in the number of hippocampal neuron apoptosis among the 4 groups( F=30.76, P<0.05), the number of hippocampal neuron apoptosis in model group(55.67±5.28) was higher than those in control group(25.83±7.06) and sham group(25.50±6.72) (both P<0.05), the number of hippocampal neuron apoptosis in DHA intervention group(35.17±5.78) was lower than that in model group.(3)The results of Western blot showed that there were no statistical differences in the Bax protein levels among the four groups( F=2.00, P>0.05).There were statistical differences in the expression levels of Bcl-2, p-JNK and Bax/Bcl-2 ratio among the 4 groups( F=8.48, 5.69, 5.39, all P<0.05).There was no statistical difference in Bcl-2, p-JNK protein levels and Bax/Bcl-2 ratio between the control group and sham group(all P>0.05).The p-JNK protein levels and Bax/Bcl-2 ratio in model group ((1.93±0.25), (2.05±0.86)) were higher than those in sham group ((1.42±0.33), (1.05±0.26)) (both P<0.05), the Bcl-2 protein level in model group (1.04±0.23) was lower than that in sham group (1.61±0.16) ( P<0.05).The p-JNK protein level and Bax/Bcl-2 ratio in DHA intervention group((1.43±0.33), (1.19±0.30)) were lower than those in model group(both P<0.05), the Bcl-2 protein level in DHA intervention group(1.42±0.28) was higher than that in model group( P<0.05). Conclusion:DHA can reduce neuronal apoptosis, inhibit the activation of p-JNK and improve neurological function of SAH model rats.

Objective:To investigate associations of serum vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) with carotid plaque stability in elderly patients with acute ischemic stroke (AIS).Methods:Elderly AIS patients with carotid plaque detected by carotid ultrasound in the First People's Hospital of Xianyang from April 2022 to April 2024 were selected, and they were further divided into stable plaque group and vulnerable plaque group. Multivariate logisitic regression analysis was used to determine the correlation between serum VEGF/VEGFR2 and carotid plaque stability. Receiver operating characteristic (ROC) curve was used to analyze the differential value of serum VEGF and VEGFR2 on plaque stability. Results:A total of 183 patients were enrolled, including 139 males (75.96%), aged 68.10±4.97 years. One hundred and one patients (55.19%) had vulnerable plaques, and 82 (44.81%) had stable plaques. There were significant differences in age, triglycerides, VEGF, VEGFR2, baseline National Institutes of Health Stroke Scale scores, and the proportion of patients with hypertension, diabetes, smoking, and statins between the vulnerable plaque group and the stable plaque group (all P<0.05). Multivariate logistic regression analysis showed that serum VEGF (odds ratio [ OR] 1.021, 95% confidence interval [ CI] 1.004-1.037; P=0.015] and VEGFR2 ( OR 1.009, 95% CI 1.005-1.012; P<0.001) were independently associated with vulnerable plaques. ROC curve analysis showed that serum VEGF and VEGFR2 alone were effective in distinguishing plaque stability, and the areas under the curve were 0.744 (95% CI 0.673-0.815) and 0.809 (95% CI 0.749-0.870), respectively. The area under the curve of the combination of the two was 0.874 (95% CI 0.825-0.924). Conclusion:Serum VEGF and VEGFR2 are independently associated with vulnerable carotid plaques in elderly patients with AIS, and both alone or in combination have good discriminatory value for the stability of carotid plaques.

Osteonecrosis of the femoral head (ONFH) is one of the common and difficult-to-treat orthopedic diseases caused by a variety of factors that lead to abnormal blood flow to the femoral head, which in turn leads to deformation and collapse of the femoral head and eventually results in severe hip joint dysfunction. The key to the treatment is early diagnosis and correct treatment according to the stage classification and active prevention of further aggravation of ONFH aiming to delay or avoid hip replacement surgery in young and middle-aged patients. At present, there are various non-surgical and surgical hip-preserving modalities for early ONFH, designed to slow down the progression of the disease, prevent the femoral head from collapsing and stop the mild collapse. In recent years, with the emergence and development of bone reconstruction biomaterials, artificial bone reconstruction after scraping of ONFH lesions has shown great potential in the treatment of early ONFH. The authors review the research progress in hip-preserving modalities for early ONFH in young and middle-aged patients from non-surgical and surgical perspectives, hoping to provide a reference for clinical treatment of early ONFH.