OBJECTIVES: To identify potential molecular targets of quercetin in the treatment of clear cell renal carcinoma (ccRCC). METHODS: The therapeutic targets of quercetin were screened from multiple databases by network pharmacology analysis, and the targets significantly correlated with ccRCC were screened from 4907 plasma proteins using a Mendelian randomization method. The drug-disease network model was constructed to screen the potential key targets. The functions of these targets were evaluated via bioinformatics analysis, and the screened targets were verified in cultured ccRCC cells. RESULTS: Network pharmacology analysis combined with Mendelian randomization identified TP53 (OR=3.325, 95% CI: 1.805-6.124, P=0.0001), ARF4 (OR=0.173, 95% CI: 0.065-0.456, P=0.0003), and DPP4 (OR=0.463, 95% CI: 0.302-0.711, P=0.0004) as the core targets in quercetin treatment of ccRCC. Bioinformatics analysis showed that TP53 was highly expressed in ccRCC, and patients with high TP53 expressions had worse survival outcomes. Molecular docking studies showed that the binding energy between quercetin and TP53 was -5.83 kcal/mol. In cultured 786-O cells, CCK-8 assay and wound healing assay showed that treatment with quercetin significantly inhibited cell proliferation and migration. Quercetin treatment also strongly suppressed the expression of TP53 at both the mRNA and protein levels in 786-O cells as shown by RT-qPCR and Western blotting. CONCLUSIONS TP53 may be the key target of quercetin in the treatment of ccRCC, which sheds light on potential molecular mechanism that mediate the therapeutic effect of quercetin.
Humans ; Quercetin/pharmacology* ; Carcinoma, Renal Cell/genetics* ; Cell Proliferation/drug effects* ; Kidney Neoplasms/genetics* ; Cell Movement/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Cell Line, Tumor ; Computational Biology

Objective:To explore the current situation of organizational silence among emergency nurses and analyze its influencing factors, so as to provide a basis for interventions.Methods:From April to July 2023, convenience sampling was used to select 150 nurses from the Emergency Department of the First Affiliated Hospital of Air Force Military Medical University as the research subject. These subjects were surveyed using the General Information Questionnaire, Nurse Organizational Silence Evaluation Questionnaire and the Emotional Intelligence Scale. Pearson correlation was used to analyze the correlation between organizational silence and emotional intelligence among emergency nurses, and multiple linear regression was used to analyze the influencing factors of nurse organizational silence.Results:A total of 150 questionnaires were distributed, and 132 valid questionnaires were collected, with an effective response rate of 88.00% (132/150). The score of the Nurse Organizational Silence Evaluation Questionnaire of 132 emergency nurses was (60.83±13.52). The results of Pearson correlation analysis showed that there was a negative correlation between emotional intelligence and organizational silence in emergency nurses ( r=-0.410, P<0.01). Multiple linear regression analysis showed that gender, education level, work years, perceived economic level, and emotional intelligence were the influencing factors of organizational silence among emergency nurses ( P<0.05), which could explain 33.9% of the variation. Conclusions:Nursing managers should focus on nurses who are female and with low education levels, short working years, and low perceived economic levels, and provide training to improve their emotional intelligence, thereby reducing the level of organizational silence among emergency nurses.

Objective:To investigate the risk factors for refracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted on the clinical data of 149 OVCF patients who were admitted to the First Affiliated Hospital of Soochow University from June 2019 to June 2022, including 21 males and 128 females, aged 56-97 years [(73.2±8.7)years]. Initial surgical segments included T 7 in 1 patient, T 8 in 10, T 9 in 6, T 10 in 6, T 11 in 19, T 12 in 28, L 1 in 38, L 2 in 18, L 3 in 11, L 4 in 7 and L 5 in 5. Patients were divided into refracture group ( n=32) and non-refracture group ( n=117) according to whether they had postoperative refracture after PKP. Refractured surgical segments included T 8 in 2 patients, T 9 in 2, T 11 in 4, T 12 in 5, L 1 in 7, L 2 in 4, L 3 in 6, and L 5 in 2. The age, gender, underlying diseases (hypertension, diabetes), body mass index (BMI), preoperative bone mineral density (BMD), smoking history, drinking history, follow-up time, preoperative visual analogue scale (VAS), and preoperative Oswestry dysfunction index (ODI) of the two groups were recorded. Preoperative paravertebral muscle-related parameters of the two groups were calculated including cross-sectional area of bilateral psoas, bilateral erector spinae, bilateral multifidus, and vertebral bodies, paravertebral muscle mass, and vertebral bone quality (VBQ) score. Univariate analysis was performed to evaluate the correlation between the fore-mentioned indicators and postoperative refracture after PKP in OVCF patients. Multivariate logistic regression analysis was employed to identify the independent risk factors for postoperative refracture after PKP in OVCF patients. Results:Univariate analysis revealed that there was certain correlation of BMI, preoperative BMD, cross-sectional area of bilateral psoas, bilateral erector spinae, bilateral multifidus, paravertebral muscle mass and VBQ score with postoperative refracture after PKP in OVCF patients ( P<0.01), while no correlation was found between age, gender, hypertension, diabetes, smoking history, drinking history, follow-up time, preoperative VAS, preoperative ODI, or cross-sectional area of vertebral bodies and postoperative refracture after PKP in OVCF patients ( P>0.05). Multivariate logistic regression analysis showed that preoperative BMD ≤-3.4 SD ( OR=0.27, 95% CI 0.09, 0.80, P<0.05), paravertebral muscle mass ≤281.2% ( OR=0.98, 95% CI 0.97, 0.99, P<0.01) and VBQ score ≥4.8 points ( OR=4.41, 95% CI 1.18, 16.44, P<0.05) were significantly correlated with postoperative refracture after PKP in OVCF patients. Conclusion:Preoperative BMD ≤-3.4 SD, paravertebral muscle mass ≤281.2%, and VBQ score ≥4.8 points are the independent risk factors for refracture after PKP in OVCF patients.

Objective:To analyze and evaluate the different methods in detecting anti-mitochondrial antibodies (AMA) for the diagnostic performance of primary biliary cholangitis (PBC).Methods:In this retrospective study, we collected serum samples of 37 PBC patients who were admitted to the Second Hospital of Jiaxing, from November 2022 to November 2023, 43 patients with other autoimmune diseases and 53 normal controls during the same time. The results of AMA were detected in parallel by indirect immunofluorescence assay (IIF), immunoblot tests (IB) and chemilluminescent microparticle immunoassay (CLIA). Fisher′s exact test was used to compare the count data between different groups, while a paired chi-square test was used to assess the results of the three test methods. We analyzed the performance of the three test methods; Venn diagram was used to show the consistency distribution of AMA results, the diagnostic performance of AMA for PBC were evaluated by area under receiver operating characteristic curve (ROC).Results:The positive rate of AMA in PBC group was significantly higher than that in the other two groups, and AMA was detected by CLIA which had higher positive rate (86.5%, 32/37) than the other two methods. As shown in the Venn diagram, the proportion of consistent AMA results among the three methods was 74.4%(99/133), and between IB and CLIA methods which used for detecting AMA-M2, the consistent proportion was 86.5%(115/133). Among comparison of the performance of three methods, the highest specificity (92.7%)was IIF method, and the highest sensitivity (86.5%) was CLIA method. The respective AUC of IIF, IB and CLIA methods were 0.801, 0.800 and 0.875. In the combined detection, the AUC of IIF+CLIA method was 0.942, which was better than the other two or triple combined method detection.Conclusion:For highly suspected PBC patients with negative IIF screening test, combined IB or CLIA could be used to detect AMA-M2. We recommended that clinicians should refer to the AMA results conducted by two or three methods, and preferentially recommended the IIF method combined with CLIA method for the detection of AMA.

Aging has become an increasingly important topic in the field of geriatrics, with the exploration of aging-related biomarkers providing a foundation for interventions aimed at delaying and reversing aging.Over the years, numerous biomarkers have been developed at both the cellular level(aging mechanisms, histology)and individual level(composite biomarkers, functional biomarkers).This article systematically discusses the characteristics and application scenarios of significant biomarkers at these two levels, and also outlines comparative studies conducted on aging biomarkers.Future research should consider synthesizing multidimensional aging biomarkers at all levels to achieve a more accurate and reliable assessment of aging.Furthermore, there is great potential for further exploration of aging biomarkers through the analysis of histologic data.

Objective:To summarize the distributional characteristics of postoperative occurrence of multi-drug resistant organism (MDRO) infections and their risk factors in simultaneous pancreas-kidney transplantation (SPK) recipients and examine the impact of MDRO infections on the survival of SPK recipients.Method:From January 2016 to December 2022, the relevant clinical data were retrospectively reviewed for 218 SPK recipients. The source of donor-recipient specimens and the composition percentage of MDRO pathogens were examined. According to whether or not MDRO infection occurred post-transplantation, they were assigned into two groups of MDRO (98 cases) and non-MDRO (120 cases). The clinical data of two groups of donors and recipients were analyzed. And the risk factors for an onset of MDRO infection were examined by binary Logistic regression. The survival rate of two recipient groups was compared by Kaplan-Meier method.Result:A total of 98/218 recipients (45%) developed MDRO infections. And 46 (46.9%) of sputum and 34 (34.7%) of urine were cultured positively and 49 (50%) pathogens expressed extended spectrum beta-lactamase. There were pneumonia (46 cases, 46.9%), urinary tract infections (34 cases, 34.7%), abdominal infections (16 cases, 16.3%) and bloodstream infections (2 cases, 2.0%). Univariate regression analysis revealed that length of renal failure ( P=0.037), length of hospitalization ( P<0.001), length of antibiotic use ( P<0.001), novel antibiotics ( P=0.014), albumin ( P<0.001) and leukocyte count ( P<0.001) were risk factors for an onset of MDRO infections. The results of multifactorial regression indicated that low albumin ( OR=0.855, 95% CI: 0.790~0.925, P<0.001) and leukopenia ( OR=0.656, 95% CI: 0.550~0.783, P<0.001) were independent risk factors for an onset of MDRO infections. The survival rates of recipients in MDRO group at Year 1/3 post-operation were 92.9% (91/98) and 89.8% (88/98). And the survival rate of recipients in non-MDRO group was 96.7% (116/120) at Year 1/3 post-operation. Inter-group difference was not statistically significant in 1-year survival rate of two recipient groups ( P=0.201); statistically significant inter-group difference in 3-year survival rate between two recipient groups ( P=0.041) . Conclusion:Low albumin and leukopenia are risk factors for MDRO infection. Infection with MDRO has some impact on the survival of recipients.

Objective To analyze the impact of mini plate and cannulated screw internal fixation on joint function recovery in patients with posterior malleolus fracture.Methods A total of 150 patients with posterior malleolus fractures,treated at our hospital from March 2021 to June 2023,were included in this study.They were divided into two groups using the odd-even number method.The control group consisted of 75 patients who underwent cannulated screw internal fixation,while the study group comprised 75 patients who received mini plate internal fixation.Clinical indicators,ankle range of motion,ankle function,and health status were compared and analyzed between the two groups.Additionally,levels of inflammatory factors,postoperative complications,and clinical efficacy were assessed.Results In terms of operation time and intraoperative blood loss,there was no statistically significant difference between the two groups(P＞0.05).However,the study group exhibited shorter ambulation days,fracture healing time,and hospitalization days compared to the control group(P＜0.05).Moreover,the study group demonstrated significantly improved ankle dorsiflexion,ankle plantar flexion,foot varus and foot valgus range of motion compared to the control group(P＜0.05).Additionally,higher AOFAS score and KPS score were observed in the study group as compared to the control group(P＜0.05).Furthermore,levels of IL-6,IL-8 and CRP were lower in the study group than in the control group(P＜0.05).The incidence of postoperative complica-tions was also lower in the study group than in the control group(P＜0.05).Conclusion Mini plate internal fixa-tion for posterior malleolus fracture yields ideal outcomes by promoting improvement in clinical indicators and ankle range of motion while effectively enhancing ankle function,reducing inflammatory reaction as well as minimizing postoperative complications.

Objective:The aim of this study is to develop a comprehensive index system for assessing the key first aid skills required for aeromedical evacuation of infected patients, with the goal of enhancing our army's medical support capabilities.Methods:This study combined literature review and two rounds of Delphi expert correspondence to construct the key first aid skills index system of aeromedical evacuation for infected patients. 19 experts from relevant disciplines were selected purposively to conduct Delphi expert consultation.Results:Both rounds of Delphi expert correspondence achieved a 100% response rate, indicating high effectiveness. The degree of authority among the experts was determined to be 0.87. In the first round, there was a Kendall coordination coefficient value of 0.184 for assessing the importance of primary indicators, while secondary indicators showed coefficients of 0.289 and 0.380 for importance and feasibility respectively. In the second round, these values increased slightly to 0.263, 0.304 (importance) and 0.398 (feasibility), respectively. The final evaluation index system of key first aid skills applied to the aeromedical evacuation of infected patients was constructed, including 3 primary indicators of life support technology, intensive care technology and isolation protection technology, and 40 secondary indicators.Conclusion:The evaluation index system of key first aid skills applied to the aeromedical evacuation of infected patients constructed through two rounds of Delphi expert correspondence is scientific and reasonable, which can provide reference for the training and assessment of key first aid skills applied to the aeromedical evacuation of infected patients, so as to promote the development of aeromedical evacuation for infectious patients in China.

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Objective:To explore the clinical efficacy of endoscopic sleeve gastrectomy (ESG) in the treatment of obesity.Method:A 26 year old female patient was admitted on October 20, 2022 due to a progressive increase in weight for 2 years. Her body mass index (BMI) was 30.04 kg/m 2, body fat percentage was 39.2%, and visceral fat grade was 15. ESG was performed using the OverStitch SX endoscopic suture system. Result:The surgery was successful, with approximately 5 ml of intraoperative bleeding.The patient discharged on the first day after surgery. Two weeks after surgery, small bowel follow-through showed a tubular shape of the stomach. At 6 months after surgery, the BMI was 25.2 kg/m 2, body fat percentage was 32%, visceral fat grade was 10. The total body weight loss rate (%TBWL) at 6 months after surgery was 16%, and the excess weight loss rate (%EWL) was 54.5%. Conclusion:ESG is effective for the treatment of obesity.