BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

【Objective】 To summarize the clinicopathological features and prognosis of young patients (18-40 years old) with non-clear cell renal cell carcinoma (nccRCC) treated in a single center to provide reference for the diagnosis and treatment of similar patients. 【Methods】 Clinical data of 113 nccRCC patients treated during Jan. 2012 and Aug. 2022 were retrospectively analyzed, including 57 males (50.4%) and 56 females (49.6%). The average age of onset was (31.6±5.8) years. Among all patients, 57 had lesions (50.4%) on the left side, and 56 (49.6%) on the right side. Young patients undergoing renal cancer surgery accounted for approximately 12.4% of the total number of renal cancer patients undergoing surgery, and nccRCC accounted for 34.8% of the total number of cases. 【Results】 Minimally invasive surgery (laparoscopic or robot-assisted) was performed in 102 cases (90.3%), and open surgery in 11 cases (9.7%). Fifty-five cases (48.7%) underwent partial nephrectomy and 58 (51.3%) radical nephrectomy. Among them, 11 patients (9.7%) developed tumor thrombi. All surgeries were successful with no serious complications. The pathological types included 32 cases (28.3%) of chromophobe renal cell carcinoma, 25 cases (22.1%) of MiT family translocation renal cell carcinoma, and 20 cases (17.7%) of papillary renal cell carcinoma. The total proportion of the three pathological subtypes reached 68.1%. After 46 (2-115) months of follow-up, 8 cases (7.8%, 8/102) developed tumor metastasis and 2 died. 【Conclusion】 The nccRCC is rare in young patients. The major pathological type is chromophobe, and the major treatment method is minimally invasive surgery. Most pathological types have good long-term prognosis, while patients with tumor thrombi have a high risk of metastasis and poor prognosis.

Objective:To investigate the association of serum fibroblast growth factor 23(FGF23) level with insulin resistance(IR) and sex hormone levels in patients with polycystic ovary syndrome(PCOS).Methods:A retrospective study was performed in eighty-seven patients with PCOS, fifty-seven patients with simple IR, and sixty-one healthy women who were admitted to Affiliated Hospital of Zunyi Medical University during October 2021 and November 2022. According to the homeostasis model assessment-IR index, all subjects were divided into normal control group( n=61), IR group( n=57), PCOS without IR group(PCOS group, n=15), and PCOS+ IR group( n=72). The levels of serum FGF23, adiponectin, and sex hormones in all groups were compared, and their correlations with glucose and lipid metabolism indicators were analyzed. Results:The FGF23 level was significantly elevated in the IR group, while markedly reduced in the PCOS group and PCOS+ IR group, with the PCOS group showing a significantly lower concentration. The adiponectin levels were significantly decreased in the IR group, PCOS group, and PCOS+ IR group(all P<0.05). The correlation analysis showed that FGF23 level was positively correlated with adiponectin and sex hormone binding globulin, and negatively correlated with luteinizing hormone, luteinizing hormone/follicle stimulating hormone, and free testosterone index(all P<0.05). Logistic regression results indicated that both FGF23 and adiponectin could be used as good indicators for the diagnosis of PCOS and PCOS with IR(all P<0.05). Conclusion:FGF23 is closely related to IR and androgen as well, and under certain conditions, it can reflect the severity of IR and hyperandrogenemia in PCOS patients. The cutoff value of FGF23 obtained in this study can provide a good reference for the diagnosis of PCOS diseases.

【Objective】 To conduct the laboratory quality assessment between 12 blood stations in Hebei province, analyze the results and explore the accuracy and comparability of testing, so as to improve the level of testing ability and quality management. 【Methods】 With reference to the external quality assessment rules of National Center for Clinical Laboratories and combined with the instructions of quality assessment samples, daily testing process of the laboratories were assessed. The quality indicators include blood cell count (WBC, RBC, Hb, HCT, MCV, MCH, MCHC and PLT), biochemical items (TP) and coagulation parameters (FIB and FⅧ). 【Results】 There are still problems in laboratories in terms of personnel operation, instrument maintenance and the impact of different reagent batches, especially in biochemical items and coagulation parameters. The pass rate of biochemical items was the lowest, only 72.75%, and that of blood cell count was the highest, reaching 98.75%. 【Conclusion】 With the progress of the project, the quality monitoring level of daily blood sampling tests in the quality control laboratory of each blood station has been improved. However, it is still necessary for each laboratory to improve the testing ability and quality management to a higher level in Hebei.

Adult ; Humans ; Cardiovascular Diseases ; East Asian People ; Hypertension ; Prevalence ; Risk Factors ; Ethnicity

Objective: To investigate the relationship between violence exposure and depression in adolescents, and to explore possible moderating effects of emotional balance, so as to provide the evidence reference for understanding the status and characteristics of adolescents violence exposure. Methods: A total of 2 506 middle school students from three middle schools in Ganzhou selected by convenient cluster random sampling. Violence Exposure Scale(VES), Center for Epidemiological Studies Depression Scale(CES-D) and Emotional Balance Scale were used for questionnaire survey. Results: There were statistically significant differences in the scores of violence exposure among middle school students of different genders, grades, whether the only child or not, father educational level,mother s educational level and family types ( t/F =3.85, 21.14, 2.90, 7.62, 8.13 ,8.12, P < 0.01 ). There were statistically significant differences in the scores of depression among middle school students of different genders, grades and family types ( t/F =-7.05, 18.61,7.42, P <0.01 ). There were statistically significant differences in the scores of emotional balance among middle school students of different genders, grades, father s educational level and mother s educational level ( t/F =7.93, 9.22, 7.71 ,6.86, P <0.01 ) . Emotional balance was positively related to the depressive mood of middle school students ( r =0.34, P < 0.01 )，and emotional balance was negatively related to depression( r =-0.20, P <0.01). Emotional balance had the moderating effect on violence exposure and depression among middle school students ( t =-3.35, β =-0.02, P <0.01). Conclusion Violence exposure is related to depression of middle school students. Improving the emotional balance ability of adolescents can effectively reduce the negative effects of violent exposure on early adolescent depression, and reduce the incidence of adolescent depression.

Objective:To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban.Methods:From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment.Results:In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg·kg -1·min -1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg·kg -1·min -1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg·kg -1·min -1], but without significant difference ( P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg·kg -1·min -1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg·kg -1·min -1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. Conclusion:Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.

Objective:To assess the relationship between serum total bilirubin and fundus arteriosclerosis in different genders.Methods:The physical examination data of Huadong Sanatorium in 2018 were analyzed, and a total of 26 275 people were included in this retrospective cross-sectional study. The age of this study was 18-86 (47.7±11.1) years old. Among them, there were 15 244 males (58.02%) and 11 031 females (41.98%). Participants were divided into 4 groups according to total bilirubin quartile values: Q1<11.50 μmol/L, Q2∶11.50-13.93 μmol/L, Q3∶13.94-17.14 μmol/L and Q4>17.14 μmol/L. The relationship between total serum bilirubin and fundus arteriosclerosis is determined using univariate and multivariate logistic regression analysis methods. The restricted cubic spline method was used to detect the dose-response relationship between total bilirubin and fundus arteriosclerosis. Results:In males, univariate analysis showed that high level of total bilirubin was a protective factor for fundus arteriosclerosis ( OR=0.87, 95% CI 0.78-0.97, P=0.012). After adjusting for other confounding factors, multivariate analysis showed that high level of total bilirubin remained as an independent protective factor for fundus arteriosclerosis ( OR=0.86, 95% CI 0.74-0.99, P=0.047). There was a linear dose-response relationship between total bilirubin level and fundus arteriosclerosis ( P=0.012). In females, univariate analysis showed that there were no statistically significant association between high level of total bilirubin and fundus arteriosclerosis ( OR=0.96, 95% CI 0.80-1.17, P=0.709). After adjusting for other confounding factors, multivariate analysis showed no statistically significant association between high level of total bilirubin and fundus arteriosclerosis ( OR=0.98, 95% CI 0.76-1.27, P=0.888). No linear dose-response relationship between total bilirubin level and fundus arteriosclerosis was found in females ( P=0.253). Conclusion:There are gender differences in the relationship between total bilirubin and fundus arteriosclerosis in this cohort. Elevated levels of total bilirubin are associated with fundus arteriosclerosis in males but not in females.

Objective:Based on the perspective of status-seeking, to clarify the status quo of rural doctors′ subjective social status, and put forward countermeasures and suggestions to improve the subjective social status of rural doctors.Methods:By investigating 1 395 rural doctors in both 2015 and 2017 to clarify the status quo of rural doctors′ subjective social status through descriptive analysis, we compared the subjective social status of rural doctors with different characteristics by using differential analysis.Results:The overall subjective social status scoring of rural doctors was 3.17±0.48, including decision participation scoring(3.30±0.82), income scoring(2.19±0.80), social relationship scoring(4.05±0.61), career reputation scoring(3.09±0.84), career promotion scoring(2.38±0.67), and career value scoring(4.04±0.63). Rural doctors with middle or above academic titles, high-performance levels, as well as those comparable to doctors in township hospitals and self-employed clinics were found with higher subjective social status.Conclusions:Rural doctors held their subjective social status to be at an intermediate level, with higher ratings for interpersonal relationships and professional values and lower ratings for salary and training mechanisms. Positive feedback on the status-seeking behavior of rural doctors is recommended to improve village clinic services and reshape the image of rural doctors.