GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

Effects of lead exposure on development of heart and spine in zebrafish embryos / 环境与职业医学

Background Lead is widely distributed. Lead exposure interferes with early life development in zebrafish, but the mechanisms by which lead exposure affects skeletal development and cardiac development are not clear as yet. Objective To investigate the molecular mechanisms of bone development and cardiac development toxicity induced by lead acetate exposure. Methods Zebrafish embryos were exposed to different concentrations of lead acetate (0, 6, 12, 24, and 48 μmol·L−1) for 3 h post-fertilization (3 hpf) until 5 d post-fertilization (5 dpf). The malformation phenotypes of 5 dpf were counted, and the mRNA expressions of spinal development-related genes (bmp2b, bmp4, bmp9, runx2a, runx2b) and heart development-related genes (nkx2.5, myh6, myh7) were detected by quantitative PCR (qPCR). Expressions of genes of development-related regulatory pathways including Wnt/β-catenin pathway (wnt5a, wnt8a, wnt10a, β-catenin) and TGF-β pathway (tgf-β1, tgf-β2) as well as key molecule eph of Eph-Ephrin signaling were analyzed. Results At 5 dpf, the zebrafish in the lead acetate treated groups showed deformed phenotypes including spinal curvature and pericardial sac edema compared to the control group. In the lead acetate groups at 24 and 48 μmol·L−1, the spinal curvature deformity rates reached 26.47% and 71.52% (P<0.01) respectively. The qPCR results revealed that the expression levels of spinal development-related genes bmp2b, bmp4, bmp9, runx2a, and runx2b were downregulated in the 48 μmol·L−1 exposure group compared to the control group by 82.8%, 58.0%, 88.7%, 85.5%, and 69.2%, respectively (P<0.05 or P<0.01); the expression levels of heart development-related genes myh6, myh7, and nkx2.5 were down-regulated by 63.7%, 58.9%, and 55.2%, respectively (P<0.01); the expression levels of wnt8a and β-catenin in the Wnt/β-catenin pathway were down-regulated by 71.5% and 47.3% (P < 0.05 or P < 0.01), respectively; the expression level of tgf- β1 in the TGF-β pathway was down-regulated by 67.5% (P<0.01); the expression level of eph was down-regulated by 86.9% (P<0.01). Conclusion Lead acetate exerts developmental toxic effects on zebrafish heart and bone by down-regulating the expressions of genes related to spinal development and heart development, as well as inhibiting development-related Wnt/β-catenin and TGF-β pathways and Eph-Ephrin signaling, causing malformed phenotypes such as spinal curvature and pericardial sac edema.

Functional silver nanoparticles synthesis from sustainable point of view: 2000 to 2023 ‒ A review on game changing materials.

The green and facile synthesis of metallic silver nanoparticles (AgNPs) is getting tremendous attention for exploring superior applications because of their small dimensions and shape. AgNPs are already proven materials for superior coloration, biocidal, thermal, UV-protection, and mechanical performance. Originally, some conventional chemical-based reducing agents were used to synthesize AgNPs, but these posed potential risks, especially for enhanced toxicity. This became a driving force to innovate plant-based sustainable and green metallic nanoparticles (NPs). Moreover, the synthesized NPs using plant-based derivatives could be tuned and regulated to achieve the required shape and size of the AgNPs. AgNPs synthesized from naturally derived materials are safe, economical, eco-friendly, facile, and convenient, which is also motivating researchers to find greener routes and viable options, utilizing various parts of plants like flowers, stems, heartwood, leaves and carbohydrates like chitosan to meet the demands. This article intends to provide a comprehensive review of all aspects of AgNP materials, including green synthesis methodology and mechanism, incorporation of advanced technologies, morphological and elemental study, functional properties (coloration, UV-protection, biocidal, thermal, and mechanical properties), marketing value, future prospects and application, especially for the last 20 years or more. The article also includes a SWOT (Strengths, weaknesses, opportunities, and threats) analysis regarding the use of AgNPs. This report would facilitate the industries and consumers associated with AgNP synthesis and application through fulfilling the demand for sustainable, feasible, and low-cost product manufacturing protocols and their future prospects.

Value of the deep learning image reconstruction algorithm combined with low-kV technique in improving small vessel display level at routine abdominal contrast enhanced CT imaging / 中华放射学杂志

Objective:To evaluate the presentation of small arteries in abdominal contrast-enhanced CT late-arterial images using the deep learning image reconstruction (DLIR) combined with low tube voltage (kV) technique relative to the adaptive statistical iterative reconstruction V (ASiR-V) algorithm.Methods:Patients who were admitted to Peking University People′s Hospital from December 2021 to January 2022 and needed to be screened for abdominal diseases and receive abdominal and pelvic contrast-enhanced CT scan were prospectively collected. The patients were divided into low-voltage (LV) with 80 kV and high-voltage (HV) with 120 kV groups. According to two different reconstruction algorithms, each group was further divided into DLIR-H (D) subgroup and ASiR-V 50% (A) subgroup. The automatic tube current adjustment technique was used for CT enhanced scanning of patients, and the noise index value was uniformly set to 9. Subjective and objective evaluations were performed on the late-arterial images with a constructed slice thickness of 0.625 mm, and the radiation doses were recorded.Results:A total of 168 patients were included, including 76 males and 92 females, aged 18-85 (53±15) years old, body mass index (24±3) kg/m 2; 91 patients in the LV group and 77 in the HV group. The CT values of the aorta and common hepatic artery in the LV group were significantly higher than those in the HV group ( t=-14.20, P<0.001; t=-0.95, P<0.001). When the tube voltage was the same, the late-arterial image noise in subgroup D was significantly lower than that in subgroup A, and the signal to noise ratio (SNR) and contrast to noise ratio (CNR) of the liver, aorta and common hepatic artery were significantly higher than those in subgroup A (all P<0.001). The SNR and CNR of the aorta and common hepatic artery in the LV-D subgroup were significantly better than those in the LV-A, HV-D, and HV-A subgroups (all P<0.001). In the subjective evaluation of abdominal vascular display, the special resolution of the common hepatic artery, inferior mesenteric artery and the edge of the ascending branch of the left colic artery, and the contrast of the ascending branch of the left colic artery in the LV-D subgroup were significantly better than those of the LV-A, HV-D, and HV-A subgroups ( P<0.05). Moreover, the presentation rate of margin artery of splenic region (54.9%, 50/91) in the LV-D subgroup was significantly higher than those in the HV-D subgroup (24.7%, 19/77) and HV-A subgroup (32.5%, 25/77) (adjusted P<0.05). There was no significant difference in the radiation doses between LV and HV groups [(4.91±1.97) mSv vs (5.43±1.78) mSv, P>0.05]. Conclusion:The contrast-enhanced CT scan of abdomen with low tube voltage combined with DLIR algorithm can effectively improve the display level of the ascending vessel of left colonic artery from the inferior mesenteric artery and the margin artery, which brings more possibilities for the evaluation of similar small blood vessels.

Effects of different dialysis modalities on long-term prognosis after parathyroidectomy in patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To compare the survival rate of secondary hyperparathyroidism (SHPT) patients with different dialysis modalities after parathyroidectomy (PTX), and analyze the influencing factors of survival prognosis.Methods:Clinical data of dialysis patients diagnosed with SHPT and treated with PTX in the First People′s Hospital of Foshan from April 2014 to May 2019 were retrospectively collected and analyzed. The patients were divided into hemodialysis (HD) group and peritoneal dialysis (PD) group according to preoperative dialysis modalities, and the differences in baseline clinical data and cardiac ultrasound results were compared between the two groups. Kaplan-Meier survival analysis was used to compare the difference in cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the influencing factors of all-cause death. Receiver operating characteristic curve (ROC curve) was used to predict the risk of all-cause death.Results:A total of 99 patients were enrolled in this study, and 94 patients completed follow-up, including 23 patients who died. Compared with PD group ( n=45), HD group ( n=54) had higher dialysis age, blood pressure, intact parathyroid hormone, alkaline phosphatase, total heart valve calcification rate, mitral valve calcification proportion, interventricular septal thickness (IVST) and left ventricular mass index (all P<0.05). The median follow-up time was 46.00(32.75, 60.25) months. Kaplan-Meier survival analysis showed that there was no significant difference in cumulative survival rate between HD group and PD group (Log-rank test χ2=0.414, P=0.520). Multivariate Cox regression analysis showed that increasing age ( HR=1.066, 95% CI 1.017-1.118, P=0.008), systolic blood pressure>140 mmHg ( HR=2.601, 95% CI 1.002-6.752, P=0.049) and increasing IVST ( HR=1.269, 95% CI 1.036-1.554, P=0.021) were independent influencing factors for all-cause death in dialysis patients after PTX. ROC curve analysis results showed that the cut-off values of age, dialysis age and IVST for predicting all-cause death after PTX were 51.5 years old ( AUC=0.673, 95% CI 0.545-0.802, P=0.013) and 75.0 months ( AUC=0.654, 95% CI 0.528-0.780, P=0.027) and 13.5 mm ( AUC=0.680, 95% CI 0.557-0.803, P=0.010) respectively. The area under the ROC curve for age, dialysis age, IVST, left ventricular hypertrophy in combination with systolic blood pressure>140 mmHg in the prediction of all-cause death after PTX was 0.776(95% CI 0.677-0.875, P<0.001). Conclusions:There is no significant difference in cumulative survival rate between HD and PD patients with SHPT after PTX. Increasing age, systolic blood pressure>140 mmHg and increasing IVST are independent risk factors for all-cause death in dialysis patients with SHPT after PTX.

Effects of lycium barbarum polysaccharides on cis-dichlorodiamineplatinum (II)-induced apoptosis in mouse testis sertoli cells TM4 / 中国临床药理学与治疗学

AIM: To explore the effect of Lycium barbarum polysaccharides (LBP) on cis-dichlorodiamineplatinum (II) (CDDP)-induced apoptosis in mouse testis sertoli cells TM4 and its possible mechanism. METHODS: TM4 cells were cultured in vitro, the effect of LBP on the survival rate of TM4 cells induced by CDDP was detected by MTT assay, the effect of LBP on the expression of apoptosis related genes Bcl-2, Bax and Caspase-3 in TM4 cells induced by CDDP was detected by Western blot, and the change of cell apoptosis rate was detected by flow cytometry. RESULTS: Compared with control group, TM4 cell apoptosis was significantly increased in CDDP group, the expression of anti-apoptotic gene Bcl-2 and pro-caspase-3 in proenzyme state were significantly decreased, the expression of pro-apoptotic gene Bax and caspase-3 were significantly increased. Compared with CDDP group, the apoptosis of TM4 cells in CDDP+LBP group was significantly decreased, the expression levels of anti-apoptotic genes Bcl-2 and Pro-Caspase3 were significantly increased, the expression levels of pro-apoptotic gene Bax and Caspase-3 were significantly decreased. CONCLUSION: LBP, by acting on CDDP induced TM4 cells, can inhibit CDDP induced TM4 cell apoptosis by enhancing the expression of Bcl-2 and inhibiting the expression of Bax and Caspase-3, thus alleviating the damage caused by CDDP to TM4 cells.

Clinical characteristics and prenatal diagnosis of fetuses with sex chromosomal aneuploidies detected by non-invasive prenatal testing during early and midterm pregnancies / 中华医学遗传学杂志

OBJECTIVE@#To analyze the indication, karyotyping result, ultrasound finding, pregnancy decision and follow-up of fetuses with sex chromosome aneuploidies (SCA) detected by non-invasive prenatal testing (NIPT) during early and midterm pregnancies.@*METHODS@#The results of 225 singleton pregnancies with fetal SCA detected by NIPT were reviewed and analyzed.@*RESULTS@#The 225 cases included 45,X (n=37), 47,XXY (n=74), 47,XXX (n=50), 47,XYY (n=56) and mosaicisms (n=8), among which 121 (53.8%) have opted to terminate the pregnancy, including 45,X (n=31), 47,XXY (n=61), 47,XXX (n=14), 47,XYY (n=12) and 3 mosaicisms. The remainder 104 (46.2%) have elected to continue with the pregnancy, among which three have opted to terminate due to abnormalities detected by ultrasonography, and two had spontaneous abortions.@*CONCLUSION@#NIPT as a first-tier screening method can effectively detect fetal trisomies 21, 13 and 18 as well as SCA. The types of fetal SCA and presence of ultrasound abnormalities are critical factors for the termination of pregnancy.

Image Quality Assessment of Brain CT with Different Scanning Modes / 中国医学影像学杂志

Purpose To analyze the image quality of brain CT with 256-slice wide detector axial scanning mode,routine axial scanning mode and spiral scanning mode,and to provide a more effective brain CT examination method for patients.Materials and Methods The prospective study was conducted on 90 patients accepting routine brain CT examination,and they were randomly divided into three groups.CT examination with 160 mm axial scanning mode,40 mm axial scanning mode and 40 mm spiral scanning mode were respectively conducted using GE Revolution CT.The scanning condition was adjusted to remain constant radiation dose,and then the image quality was analyzed.CT attenuation of gray and white matter,contrast-to-noise ratio (CNR) of white-gray matter and image noise of the three scanning modes were compared.Subjective scoring on image quality of the three scanning modes was also performed.Results On body lateral cerebral ventricle level,there were no significant difference in CT attenuation of gray and white matter and CNR (P＞0.05).On centrum semiovale level,the CT attenuation of gray matter [(31.71 ± 1.82) HU],white matter [(22.97± 1.50) HU] and CNR 2.05±0.42 of 160 mm axial scanning mode was significantly different from the other two scanning modes (F=26.74,47.16 and 3.85,P＜0.05).On centmm semiovale level,image noise of 160 mm axial scanning mode was lower than the other two kinds of scanning methods (F=6.31,P＜0.05),in the basal ganglia and posterior fossa there were no statistically significant differences in the image noise between the three scanning modes (P＞0.05).The subjective score of the three scanning modes all met the diagnostic requirements,and there was no significant difference (P＞0.05).The effective dose and scanning time of 160 mm axial scanning mode was lower than those of the other two scanning modes,and the X-ray utilization was higher.Conclusion 160 mm wide detector axial scanning mode is more suitable for brain CT scan,and it can be used as the preferred scanning mode in the emergency and among non-cooperative patients.

Improvement of life quality of children with atopic dermatitis by therapeutic patient education / 临床儿科杂志

Objective To evaluate the effect of therapeutic patient education on improving life quality of children with atopic dermatitis (AD). Methods A total of 109 children with AD were enrolled, including 53 patients in the intervention group and 56 patients in the control group. The intervention group was given therapeutic patient education in addition to routine treatment, while the control group was given routine treatment without therapeutic patient education. After three months two groups were compared with the disease severity and quality of life in children and their families. Results Compared with control group, the intervention group had significant improvements in severity of AD (P?=?0.003) and also significant improvements in quality of life (IDQOL and CDLQI) (P?=?0.004). The family life quality (DFI) of the two groups were both improved, but the difference was not signiifcant (P?=?0.492). Conclusions Therapeutic patient education can improve symptoms of atopic dermatitis, and the quality of life of children as well.

Investigation of the relationship between aircraft noise and community annoyance in China.

A survey of community annoyance induced by aircraft noise exposure was carried out around Hangzhou Xiaoshan International Airport. To investigate the relationship curves between aircraft noise and the percentage of "highly annoyed" persons in China and also to get annoyance threshold of aircraft noise in China. Noise annoyance induced by aircraft noise exposure was assessed by 764 local residents around the airport using the International Commission on Biological Effect of Noise (ICBEN) scale. The status quo of aircraft noise pollution was measured by setting up 39 monitoring points. The interpolation was used to estimate the weighted effective continuous perceived noise levels (LWECPN) in different areas around the airport, and the graph of equal noise level contour was drawn. The membership function was used to calculate the annoyance threshold of aircraft noise. Data were analyzed using SPSS 16.0 and Origin 8.0. The results showed that if LWECPN was 64.3 dB (Ldn was 51.4 dB), then 15% respondents were highly annoyed. If LWECPN was 68.1 dB (Ldn was 55.0 dB), then 25% respondents were highly annoyed. The annoyance threshold of aircraft noise (LWECPN) was 73.7 dB, while the annoyance threshold of a single flight incident instantaneous noise level (LAmax) was 72.9 dB. People around the airport had felt annoyed before the aircraft noise LWECPN reached the standard limit.

A study of arteries of foot by flow sensitive dephasing prepared balanced steady-state free precession MR angiography in diabetes / 中华放射学杂志

Objective To investigate balanced steady-state free precession with flow-sensitive dephasing magnetization preparation (FSD-bSSFP) in the assessment of arteries of foot in diabetic patients.Methods The lower-extremity peripheral arteries of 43 diabetic patients were evaluated by FSD-bSSFP no contrast MRA and contrast-enhanced MRA (CE-MRA)in. Two experienced observers assessed the image quality, degree of venous contaminated and visibility of pedal artery branches by FSD-bSSFP and CE-MRA respectively in consensus. The signal intensity( SI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the source images of both groups were measured and Wilcoxon and t tests were performed. Results The image score of FSD-bSSFP group was 2.7 ± 1.1 and CE-MRA was 2.6 ± 0.8, there was no statistical difference ( Z = 0. 134, P ＞ 0. 05 ). The image score of demonstration of the pedal artery branches and degree of venous contamination on FSD-bSSFP were 3.2 ± 0. 9 and 1.8 ± 0. 4 respectively which were superior to that of CE-MRA (2.5 ± 0.9 and 2.1 ± 0.8 respectively). Significant statistical difference existed between the two groups in demonstration of pedal artery branches ( Z = 5.246, P ＜ 0.05 ) and degree of venous contamination (Z =2.541 ,P ＜0.05). SNR of FSD-bSSFP was 148.6 ±26.7, CNR was 88.3 ± 19.0. SNR of CE-MRA was 148.5 ± 45.6, CNR was 121.0 ± 41.0. No statistical difference existed between SNR between two methods (t = 0.013, P ＞ 0.05 ). But CNR of CE-MRA was superior to that of FSD-bSSFP and significant statistical difference existed between these two methods ( t = 5.113, P ＜ 0.01 ). Conclusion FSD-bSSFP without contrast could be used in the evaluation of foot arteries in patients of renal dysfunction and diabetes.

Two novel OXA-type extended-speetrum-β-lactamase genes in Pseudomonas aerugenosa in Hunan province:blaOXA-128 and blaOXA-129 / 中华检验医学杂志

spectrum beta-lactamase genes:blaOXA-128 and blaOXA-129.

The Thinking of Construction and Management of Laboratory of Medical Institute of Higher Learning / 中华医学教育探索杂志

Construction and management of laboratory of institute of higher learning directly affect the overall development and comprehensive strength of the school.This article makes analysis and discussion of the construction and management of the laboratories on the current status of the laboratories of medical institute of higher learning.

The protective effect of ulinastatin on the intestinal mucosal barrier in rats after intestinal ischemia-reperfusion / 西安交通大学学报(医学版)

Objective To investigate the protective effect of ulinastatin on the intestinal mucosal barrier in rats with ischemia-reperfusion.Methods Totally 24 SD rats were randomly divided into 3 groups after clamping superiormesenteric artery for 1 h and reperfusion for 1 h: blank control group,control group and treatment group.Rats in the treatment group were injected with ulinastatin(50 000 U/kg) through vena dorsalis penis after ischemia-reperfusion model was induced.The control group underwent laparotomy with only the manipulation of the intestine and the same dose of saline was used through the same way.Specimens were obtained after ischemia-reperfusion model was induced.Dynamic turbidimetry was used to evaluate the effect of ulinastatin on the intestinal endotoxin translocation in rats.Apoptosis of mucosal cells was detected by TUNEL method,and the expressions of Bax and Bcl-2 mRNA were determined by semi-quantitative RT-PCR.Results The serum endotoxin level and apoptotic index of mucosal cells were evidently lower in blank control group than in control group(P

The expression of E-cadherin and its relation with invasive ability of basal membrane in tumor cells / 西安交通大学学报(医学版)

Objective To study the effect of down-regulation of E-cadherin on the invasive ability of tumor cells. Methods Human pancreatic carcinoma cell lines JHP-1, PANC-1, and MIA PaCa-2 were selected. The immunocytochemistry, Western blot and invasive-MTT assay were used to observe the expression and the contents of E-cadherin in the tumor cells. Results Immunocytochemistry showed that E-cadherin expression was on cell membrane. The expressions of E-cadherin were preserved in JHP-1, reduced in PANC-1, and showed negative in MIA PaCa-2. Western blot analysis showed that the protein content was the highest in JHP-1 and lowest in MIA PaCa-2. According to invasive MTT assay, the invasive ability of MIA PaCa-2 was the strongest, followed by PANC-1 and JHP-1 (P