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.

Chimeric flap pedicled with superficial branch of superficial iliac circumflex artery in repair of soft tissue defects of dorsal hand and metacarpal bone / 中华显微外科杂志

Objective:To investigate the effect of chimeric flap pedicled with superficial branch of superficial iliac circumflex artery in repair of soft tissue defect of dorsal hand combined with metacarpal bone defect.Methods:From May 2015 to January 2022, 34 patients(28 males and 6 females) of soft tissue defects of dorsal hand with metacarpal bone defects were treated in the Department of Orthopedics of Yibin Third People's Hospital. The age of patients ranged from 22 to 51 years old, with an average age of 37 years old. The areas of soft tissue defects after debridement were 2.5 cm×5.0 cm-4.5 cm×9.0 cm, and the defects were all in dorsal hand and dorsal wrist. The lengths of metacarpal bone defect were 1.8-4.1 cm. All the patients had only single metacarpal bone defect, among which: 14 patients had defects in first metacarpal bone, 7 in second metacarpal bone, 4 in third metacarpal bone, 8 in fourth metacarpal bone and 1 in fifth metacarpal bone. All the patients were repaired by chimeric flap pedicled with superficial branch of superficial iliac circumflex artery. The size of flaps were 3.6 cm×5.4 cm-5.2 cm×9.5 cm. Anticoagulation, thermal preservation and plaster fixation were applied for 4-6 weeks after surgery. Postoperative follow-ups included regularly outpatient clinic visit, telephone or Wechat reviews. Follow-up items covered: the feeling and appearance of flaps in recipient sites, healing of the donor sites and recovery of hand functions.Results:All the 34 chimeric flaps survived. Regular follow-up lasted for 3 to 15(average, 10) months. All incisions in the donor sites of hip healed in stage I. TPD of the flaps was 5.1-7.3(mean, 6.4) mm. Appearance of flaps in the receiving area were satisfactory without swelling. Movement of wrists and metacarpophalangeal joints met the basic requirement of movement. The healing time of metacarpal defect was 2-3 months with an average of 2.8 months. Hand functions were evaluated at excellent in 6 patients and good in 28, according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Conclusion:The chimeric flap pedicled with superficial branch of superficial iliac circumflex artery is an ideal flap to repair the soft tissue defect in dorsal hand combined with metacarpal bone defect. It has advantages of less donor site damage, good blood supply of flap, simple surgical procedure, and one-stage repair of a combined soft tissue and metacarpal bone defects.

Efficacy and safety of Jiuhua hemorrhoid suppository plus diosmin for the treatment of hemorrhoid hemorrhage: a multicenter, randomized, and controlled trial / 数字中医药（英文）

Objective@# To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage.@*Methods@#The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration.@*Results@#The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug.@*Conclusion@#Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.

Inhibition of abnormal GRK2 transmembrane transfer to reduce maturation of dendritic cells in CIA mice by regulating JAK1-STAT1 signaling pathway / 中国药理学通报

Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of And-inflammatory and Immune Medicine, Ministry of Education .Anhui Collaborative Innovation Center of And-Inflammatory and Immune Medicine, Rheumatoid Arthritis Research Center of Anhui Medical University, Jlefei ,230032, China,Aim To reveal the role of the abnormal activation of G protein-coupled receptor kinase 2(GRK2)and abnormal signal transduction of JAK1-STAT1 in the abnormal immune response of rheumatoid arthritis(RA)by exploring the effects of GRK2 on the JAK1-STAT1 signaling pathway in dendritic cells(DCs)of collagen-induced arthritis(CIA)mice and the undelying mechanisms,so as to provide a basis for revealing the new mechanism of RA.Methods The CIA model was established,and the co-stimulatory molecular level of DCs was detected by flow cytometry,the cytokine levels of plasma in mice were detected by ELISA,and the expression of p-JAK1,p-STAT1 and GRK2 in spleen tissues was detected by immunohistochemistry.Bone marrow cells were induced into DCs in vitro and stimulated with IFN-α and PGE2 for 48 h.Flow cytometry was used to detect the level of co-stimulatory molecules and phagocytosis of DCs,and ELISA to detect the level of cytokines in cell supernatant.CO-IP was employed to detect the co-localization of GRK2 and JAK1 in DCs.Western blotting was used to detect the expression of JAK1-STAT1 and the cell membrane expression of GRK2.Imaging flow cytometry was applied to detect the nucleation rate of p-STAT1.Results In vivo the level of co-stimulatory molecules of dendritic cells of CIA mouse increased,and the expression of GRK2 and p-JAK1,p-STAT1 in spleen was positively correlated.The co-localization of GRK2 and JAK1 in spleen of the CIA group decreased significantly.In vitro GRK2 inhibitors reduced the level of costimulatory molecules,cytokines IL-6 and TNF-α,the expression of JAK1 and STAT1,the expression of GRK2 in the cell membrane,and the rate of p-STAT1 nuclear translocation,and increased the Ag uptake capacity of DCs and the co-localization rate of GRK2 and JAK1.Conclusions The abnormal GRK2 transfer to the cell membrane in DCs mediates the maturation of DCs and the activation of the JAK1-STAT1 signaling pathway.Inhibition of GRK2 transfer membrane can restore its control of the JAK1-STAT1 signal transduction of DCs,reduce the maturation of DCs,and play an important role in improving mouse CIA.

The expression of FOXO3 in pancreatic cancer and its effects on pancreatic cancer cells / 中华肝胆外科杂志

Objective:To investigate the expression of forkhead box protein O3(FOXO3) in pancreatic cancer and its effect on the motility and proliferation of pancreatic cancer cells.Methods:The FOXO3 expression in pancreatic cancer and adjacent tissues was retrieved from LinkedOmics database. Western blotting and real-time quantitative polymerase chain reaction were used to detect FOXO3 expression in pancreatic cancer cells and human pancreatic stellate cells. PANC-1 and MIAPaCa-2 pancreatic cancer cells with low FOXO3 expression were selected to transfect FOXO3 overexpression plasmid and negative control plasmid, respectively. The motility and proliferation ability of pancreatic cancer cells were detected by colony formation assay, cell scratch assay, Transwell assay and flow cytometry.Results:In the LinkedOmics database, the relative expression of FOXO3 protein in the cancer tissues of 64 patients with pancreatic cancer was significantly lower than that in the adjacent tissues ( t=8.36, P<0.001). The number of clones in PANC-1 cell line was (30.0±6.6) after overexpressed FOXO3, which was lower than that in negative control cells (92.7±6.7), and the difference was statistically significant ( t=11.54, P<0.001). After overexpressed FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the scratch repair rate was significantly decreased compared with the control group. In Transwell experiment, the number of cells in FOXO3 overexpressed group in PANC-1 cell lines was (21.0±6.6), which was lower than that of negative control groups (55.7±8.5), and the difference was statistically significant ( t=5.59, P=0.005). The results of MIAPaCa-2 cell line were consistent with that of PANC-1 cell line. After overexpressing of FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the proportion of cells in the G0/G1 phase decreased, while the proportion in the S phase increased. Conclusion:The expression of FOXO3 was decreased in pancreatic cancer. Overexpression of FOXO3 could significantly inhibit the proliferation, migration and invasion of pancreatic cancer cells and induce cell cycle arrest, which is a potential target for the treatment of pancreatic cancer.

Evaluation of early postoperative psychological pain in patients with esophageal cancer and analysis on its influential factors / 中国基层医药

Objective:To investigate early postoperative psychological pain in patients with esophageal cancer and analyze its influential factors, providing evidence for developing accurate psychological management plan during the perioperative period of esophageal cancer.Methods:A cross-sectional study was conducted on the demographic data, disease data, and psychological pain screening management tool (Distress Management Screening Measurement of patients with esophageal cancer who received treatment in Chifeng Municipal Hospital between January 2019 and January 2021 with a self-designed general data questionnaire.Results:The average score of the distress thermometer was 4.5 ± 0.8 points among the 106 patients with esophageal cancer in the early postoperative stage. DT score was < 4 points in 40 patients (37.7%) and it was ≥ 4 points in 66 patients (62.3%). Univariate analysis revealed that in the general data questionnaire, education level, hospital expense, smoking history, and operation methods were the influential factors of early postoperative esophageal cancer ( χ2 = 7.87, 9.56, 12.65, 7.03, all P < 0.05). In the list of psychological pain-related problems, fatigue, depression, pain, sleep, breathing, eating, and child care were the influential factors of early postoperative physiological pain in patients with esophageal cancer ( χ2 = 48.18, 64.19, 42.17, 27.14, 36.13, 35.01, 8.01, all P < 0.05). Multivariate regression analysis showed that in the general data questionnaire, education level, hospital expense, smoking history, and operation methods were the influential factors of early postoperative esophageal cancer ( χ2 = 14.71, 8.31, 13.56, 6.47, all P < 0.05). In the list of psychological pain-related problems, fatigue, depression, pain, breathing, and eating were the influential factors of early postoperative physiological pain in patients with esophageal cancer ( χ2 = 5.45, 3.91, 4.89, 3.96, 4.00, all P < 0.05). Conclusion:The incidence of early postoperative psychological pain is high in patients with esophageal cancer. The main influential factor of psychological factors are physical problems, while the influential factors emotional problems, education level, hospital expense, smoking history, and operation methods cannot be ignored.

Interference of P2X4 receptor expression in tumor-associated macrophages suppresses migration and invasion of glioma cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of interference of P2X4 receptor expression in tumor-associated macrophages (TAMs) on invasion and migration of glioma cells.@*METHODS@#C57BL/6 mouse models bearing gliomas in the caudate nucleus were examined for glioma pathology with HE staining and expressions of Iba-1 and P2X4 receptor with immunofluorescence assay. RAW264.7 cells were induced into TAMs using conditioned medium from GL261 cells, and the changes in mRNA expressions of macrophage polarization-related markers and the mRNA and protein expressions of P2X4 receptor were detected with RT-qPCR and Western blotting. The effect of siRNA-mediated P2X4 interference on IL-1β and IL-18 mRNA and protein expressions in the TAMs was detected with RT-qPCR and Western blotting. GL261 cells were cultured in the conditioned medium from the transfected TAMs, and the invasion and migration abilities of the cells were assessed with Transwell invasion and migration experiment.@*RESULTS@#The glioma tissues from the tumor-bearing mice showed a significantly greater number of Iba-1-positive cells, where an obviously increased P2X4 receptor expression was detected (P=0.001), than the brain tissues of the control mice (P < 0.001). The M2 macrophage markers (Arg-1 and IL-10) and M1 macrophage markers (iNOS and TNF-α) were both significantly up-regulated in the TAMs derived from RAW264.7 cells (all P < 0.01), but the up-regulation of the M2 macrophage markers was more prominent; the expression levels of P2X4 receptor protein and mRNA were both increased in the TAMs (P < 0.05). Interference of P2X4 receptor expression significantly lowered the mRNA(P < 0.01)and protein (P < 0.01, P < 0.05)expression levels of IL-1β and IL-18 in the TAMs and obviously inhibited the ability of the TAMs to promote invasion and migration of the glioma cells (P < 0.05).@*CONCLUSION@#Interference of P2X4 receptor in the TAMs suppresses the migration and invasion of glioma cells possibly by lowering the expressions of IL-1β and IL-18.

Short-term effects of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection / 中国胸心血管外科临床杂志

@#Objective    To evaluate the short-term therapeutic effect of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection (ATAAD). Methods    From November 2019 to July 2020, 28 patients with ATAAD were treated by extended adventitial inversion with graft eversion anastomosis technique in the Department of Cardiovascular Surgery, Dalian Municipal Central Hospital, including 19 males and 9 females, aged 60.11±11.11 years. The intima of the ascending aorta was trimed to 5 mm above the sinotubular junction. The adventitia of the ascending aorta was longitudinally cut to the reserved intima margin along the junction of the three aortic valves. The extended adventitial inversion was sutured continuously, no coronary sinus was sutured over the aortic annulus, and the left and right coronary sinus was sutured above the coronary ostium. The anastomotic graft was everted and inserted into the aortic lumen, and the everted graft was continuously sutured at the level of sinotubular junction which was 5 mm away from the edge of graft. Results    There was no intraoperative death, intractable root hemorrhage, residual root false lumen, root dilatation, anastomotic hematoma or other complications. There was no recurrence of the pain in the back of all patients, and the results of the CT angiography were not significantly changed. In 22 patients with no regurgitation, only 1 (4.55%) patient had a mild regurgitation. In 6 patients with mild aortic regurgitation, the disappearance rate of regurgitation was 50.0% (3/6). Conclusion    The treatment of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of aortic dissection eliminates the residual dissection at the root. The anastomotic hemorrhage is prevented, the root structure of aortic dissection is reconstructed and strengthened, the root function is restored, and the possible expansion of the root is prevented. The short-term results are satisfactory.

Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors / 中华肿瘤杂志

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

mRNA-LNP-based cancer immunotherapy / 中国肿瘤生物治疗杂志

@#[摘 要] 新兴的肿瘤免疫疗法是通过激活抗原特异性T细胞来实现强大的抗肿瘤反应，尽管其取得了令人瞩目的进展，但许多肿瘤患者对这些抗肿瘤疗法仅部分出现反应或根本没有反应。mRNA-脂质纳米颗粒（mRNA-LNP）技术可以应用于肿瘤免疫治疗，目前正在多个领域进行研究，包括治疗性肿瘤疫苗、双特异性抗体、细胞因子、共刺激配体和受体以及CAR-T细胞治疗等，而其中研究比较集中的领域则是治疗性肿瘤疫苗和肿瘤内免疫治疗。治疗性肿瘤疫苗使用编码含有在肿瘤中发现的突变肽，即创建一种由患者肿瘤特有的由新抗原组成的个性化肿瘤疫苗。肿瘤内免疫治疗是通过提供编码有效免疫刺激蛋白的mRNA将免疫细胞浸润很少的“冷”肿瘤转化为免疫细胞浸润增加的“热”肿瘤，以在有限的全身毒性的情况下促进有效的抗肿瘤免疫活性。mRNA-LNP技术在肿瘤免疫疗法的多个领域的应用为肿瘤免疫治疗注入了新的活力。

Genetic testing and clinical phenotypic analysis of familial vitreous amyloidosis in two Han Chinese families / 中华实验眼科杂志

Objective:To investigate the clinical characteristics of two Han families with familial vitreous amyloidosis (FVA) and the gene mutation.Methods:A pedigree investigation was performed.Two Han Chinese families with FVA treated in Xiangya Hospital of Central South University from January 2015 to December 2018 were collected.General examination and ophthalmic examination were performed among 112 members of the two families.Peripheral blood samples were collected from 32 family members (15 patients in MZ001 pedigree, 7 patients in MZ002 pedigree, and 5 persons with normal clinical phenotype from each pedigree) for DNA extraction, polymerase chain reaction (PCR) amplification, transthyretin ( TTR) gene screening and sequencing.Vitreous biopsy following three-channel 23-gauge pars plana vitrectomy was performed on the two probands in the two families.Vitreous specimens were sent for pathological examination.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Xiangya Hospital of Central South University (No.201412463), and written informed consent was obtained from all subjects before any medical examination. Results:In MZ001, there were 15 cases of the 63 members presented bilateral vitreous opacity at an average age of (43.6±5.8) years.No lesion was found in nervous system, cardiovascular system, kidney or liver in general inspection.The vitreous of the proband (Ⅲ13) was so sticky that could not be totally removed during vitrectomy.The vitreous specimen showed positive Congo red staining.Ⅲ13 had elevated intraocular pressure after vitrectomy and was diagnosed as open-angle glaucoma.Gene sequencing revealed Gly83Arg mutation in the exon 3 of TTR gene.In MZ002, 7 cases of 49 members had bilateral vitreous opacity at an average age of (50.4±5.5) years, among which, 3 cases appeared symptoms of limb numbness and decreased muscle strength.The vitreous body of the proband (Ⅱ11) in MZ002 pedigree was looser and easier to remove during vitrectomy than that of Ⅲ13 in MZ001 pedigree.Vitreous specimen of Ⅱ11 was positive with Congo red staining.Gene sequencing revealed an Ala36Pro variant in the exon 3 of TTR gene. Conclusions:Gly83Arg or Ala36Pro mutation of TTR gene can cause FVA.Different mutations can lead to different clinical phenotypes such as age of onset, clinical symptoms and complications of other systems.

Analysis on the current situation of pediatric nurses′ professional autonomy and its influencing factors / 中国实用护理杂志

Objective:To understand the degree of professional autonomy of nurses in Pediatric Nursing Alliance and the status of pediatric nursing practice environment, which providing guidance for the development of a series of specialized training in the alliance.Methods:Stratified random sampling method was used to conduct a questionnaire survey on nursing staff of different professional levels in Pediatric Nursing Alliance, which through the questionnaire star by using the questionnaire general information and training demand questionnaire, nurses practice professional autonomy scale, pediatric nursing staff structural empowerment questionnaire and nursing practice influencing factors questionnaire through the questionnaire star.Results:The total score for professional autonomy of nurses in the pediatric alliance was 192.66±18.63, the structural empowerment ( OR=1.137, 95% CI=1.084-1.194), lack of caring team ( OR=2.763, 95% CI=1.443-5.292) and performance evaluation ( OR=0.498, 95% CI= 0.274-0.908), specialized education and professional experience ( OR=0.548, 95% CI= 0.334-0.871) were affecting the clinical nursing practice. Conclusion:The degree of professional autonomy of nurses in the Pediatric Nursing Alliance is in the middle and high level. Key factors affecting nursing practice including insufficient structural empowerment, lack of opportunities to continue learning, lack of nursing teams, lack of effectiveness evaluation and the lack of specialized education and work experience, which guiding the pediatric nursing alliance to continuously deepen the connotation of pediatric nursing professional and innovative team collaboration new model, utilize the advantages of resources to actively cultivate specialized nursing research personnel, carry out multi-disciplinary and cross-disciplinary cooperation, improve the nursing quality evaluation index system, so as to enhance the professional nursing service capacity and value.

Application of graft eversion anastomosis technique in aortic surgery / 中华胸心血管外科杂志

Due to the emergence of various treatment methods for aortic diseases, the treatment methods of anastomosis have become diversified.The anastomosis of the graft distal eversion partly inserted into the aorta or graft inversion wholely inserted into the aorta increase the joint area between them, and it obviously reduces the impact of tidal blood flow and the lateral force on the anastomosis.Therefore, it has the outstanding advantages of reducing the risk of hemorrhage after anastomosis, simplifying the intraoperative suture operation and easy treatment of anastomotic hemorrhage.Similar techniques with different names are often used in the surgical treatment of aortic lesions and have achieved good anastomosis.In this paper, the concept is uniformly referred to as " Graft Eversion Anastomosis Technique" , and its application evolution in aortic surgery is systematically expounded, so as to further deepen the understanding of the technology.

Computational fluid dynamics study on the effects of morphology of prostatic urethra in mid-voiding after minimally invasive surgery with BPH / 中华泌尿外科杂志

It is important to investigate the mechanical effects of morphology of prostatic urethra (PU) for benign prostatic hyperplasia (BPH). PU and bladder neck transverse diameter ratio (RPU-1), which related to vortex, and their influence on urine flow were observed by CFD. The results showed that vortexes appeared and expanded with increasing RPU on both sides of PU when RPU-1>0.79, and velocity of external urethral orifice decreased gradually. CFD is an available method for urodynamics research. The quantitative simulation of the relationship between RPU-1 and vortex was proposed for the first time, providing a new idea for advancing theory of PU lumen repair in BPH.

Diagnostic accuracy of ultrasonography and radiography in children with acute chest trauma / 中华超声影像学杂志

Objective:To compare the diagnostic accuracy of lung ultrasonography and radiography in detection of acute traumatic intrathoracic injuries in children.Methods:A retrospective analysis was performed in 46 cases of children with chest trauma in Shenzhen Children′s Hospital from January 2017 to January 2021. The diagnostic efficiency of lung ultrasound and radiography in children with acute traumatic hemopneumothorax and lung contusion were compared. Computed tomography scan was used as gold standard.Results:The sensitivity and specificity of lung ultrasound were 0.79 and 0.98 for pneumothorax, 0.86 and 0.75 for hemothorax, 0.86 and 0.80 for pulmonary contusion, respectively. Area under the ROC curve of ultrasonography in detection of pneumothorax, hemothorax, and pulmonary contusion was 0.889 (95% CI=0.798-0.979, P<0.001), 0.804 (95% CI=0.707-0.901, P<0.001), and 0.831 (95% CI=0.623-1.000, P=0.013), respectively. Area under the ROC curve of radiography was 0.674 (95% CI=0.544-0.803, P=0.008) for detection of pneumothorax, 0.645 (95% CI=0.517-0.772, P=0.026) for hemothorax, and 0.547 (95% CI=0.289-0.805, P=0.724) for pulmonary contusion. Comparison of area under the ROC curve declared the significant superiority of ultrasonography in detection of pneumothorax, hemothorax and pulmonary contusion (all P<0.05). Conclusions:Lung ultrasound has higher sensitivity and accuracy than chest radiography in the initial evaluation of chest trauma. For children with acute chest trauma, lung ultrasound should be the first choice.

Clinical comparative study of double tract reconstruction of proximal gastric resection and Roux-en-Y of total gastrectomy in the treatment of adenocarcinoma of the esophagogastric junction / 中国医师杂志

Objective:To investigate the clinical efficacy of double tract reconstruction of proximal gastric resection and Roux-en-Y total gastrectomy in the treatment of adenocarcinoma of the esophagogastric junction, in order to provide reference for clinical selection.Methods:From June 2016 to June 2018, patients with adenocarcinoma of the esophagogastric junction in Chifeng City hospital were prospectively selected and randomly divided into proximal gastrectomy double channel anastomosis group (PG group) and total gastrectomy Roux-en-Y anastomosis group (TG group). The perioperative indexes, clinical pathology, early (≤ 30 days) and late (> 30 days) complications of the two groups were compared, and the nutritional status [body mass index (BMI), prealbumin, albumin, total protein], and anemia degree [hemoglobin (Hb), red blood cell count (RBC)] of the two groups at 3 months, 6 months and 12 months after operation were compared.Results:A total of 83 patients with adenocarcinoma of the esophagogastric junction were admitted, including 62 patients who were eligible for surgery, 31 cases in each group, 1 case in each group was lost to follow-up, and 30 cases in each group. There were no tumor recurrence or death in two groups. There were no statistically significant differences in age, gender, tumor size, tumor stage, preoperative complications, preoperative nutritional status and anemia between the two groups ( P>0.05). The time of first exhaust, time of starting fluid feeding and postoperative hospitalization in PG group was significantly earlier than that in TG group [(3.0±0.7)days vs (4.2±0.7)days, (7.9±0.9)days vs (9.0±0.9)days, (13.3±1.1)days vs (14.6±0.9)days, P<0.05], while the operation time was slightly longer [(252.0±36.9)min vs (225.8±31.1)min, P<0.05]. There was no significant difference in intraoperative blood loss and number of lymph node dissection between PG group and TG group [(241.7±81.0)ml vs (245.8±71.9)ml, (40.5±12.2)nodes vs (43.2±10.3)nodes, P>0.05]. There was no statistically significant difference in the occurrence of early and late postoperative complications ( P>0.05). The incidence of reflux esophagitis in PG group was less than that in TG group ( P<0.05). The nutritional status of PG group was significantly better than TG group in 3 months, 6 months and 12 months after the operation ( P<0.05). The Hb and RBC decreased in both groups at 3 and 6 months after operation, and the Hb and RBC in PG group were higher than those in TG group. There was no anemia in PG group and TG group 12 months after operation. Conclusions:Double tract reconstruction of proximal gastric resection is effective in the treatment of adenocarcinoma of the esophagogastric junction. It is worthy of further clinical promotion.

Research status and progress of sphincter preserveing surgery in anal fistulas / 国际外科学杂志

Anal fistula is a common disease, surgical treatment is the best option. There are many kinds of surgical treatments for anal fistula, traditional surgical methods, such as fistulotomy and fistulectomy are more thorough in treating internal opening, infection and fistula tract, but the injury to the sphincter is also greater. In recent years, surgery is becoming refined, many scholars pay more and more attention to the protection of anal sphincter, which has derived a series of minimally invasive surgeries, such as Endorectal advancement flap procedure, Ligation of intersphincteric fistula tract, Fistula laser closure procedure, Video-assisted anal fistula treatment, Over-the-scope clip, Endofistular polyurethane-sponge vacuum therapy and biological sphincter preservating procedures. This paper describes the application status and progress of sphincter preserving surgeries by reviewing relevant literature, in order to provide relevant reference for clinical workers, optimize the treatment plan and improve the cure rate.

Predictive value of myocardial perfusion in the prognosis after coronary artery bypass grafting / 中国胸心血管外科临床杂志

@#Objective    To evaluate the value of myocardial perfusion change before and after coronary artery bypass grafting (CABG) in predicting postoperative major adverse cardiovascular events (MACE). Methods    A total of 70 CABG patients who received CABG completed by the same operator from January to November 2017 were selected, including 45 males and 25 females with an average age of 64.83±9.09 years. The patients were divided into two groups according to whether the patients had MACE after 1 year of the surgery, including a non-MACE group (group A, n=60) and a MACE group (group B, n=10). The clinical data of patients were compared. Results    There were statistical difference in the myocardial contrast echocardiography (MCE) score in the group A before and after surgery (P<0.05), and there were statistically significant differences in the left ventricular size and left ventricular ejection fraction (LVEF) value before and 1 year after surgery (P<0.001), but no statistically significant difference in the size of left atrium (P=0.075). There was no significant difference in the preoperative and postoperative MCE score, and preoperative and postoperative 1-year cardiac ultrasound score in the group B (P>0.05). Conclusion    The change of myocardial perfusion after CABG surgery is associated with postoperative MACE. The evaluation of myocardial perfusion before and after CABG surgery is of great significance for the prognosis evaluation of patients.

Effect of fcl gene for butenyl-spinosyn biosynthesis and growth of Saccharopolyspora pogona / 生物工程学报

The fcl gene encodes GDP-fucose synthase, which catalyzes two-step differential isomerase and reductase reactions in the synthesis of GDP-L-fucose from GDP-D-mannose. It also participates in the biosynthesis of amino sugar and ribose sugar, and is one of the key enzymes to regulate the metabolism of sugar and nucleotides in organisms. The presence of fcl gene in Saccharopolyspora pogona was found through sequencing result of genome. The mutant S. pogona-fcl and S. pogona-Δfcl were constructed by gene engineering technology. The results showed that the gene had an effects on growth and development, protein expression and transcriptional level, insecticidal activity, and biosynthesis of butenyl-spinosyn of Saccharopolyspora pogona. The results of HPLC analysis showed that the yield of butenyl-spinosyn in S. pogona-Δfcl was 130% compared with that in S. pogona, which reduced by 25% in S. pogona-fcl. The results of determination of insecticidal activity showed that S. pogona-Δfcl had a stronger insecticidal activity against Helicoverpa armigera than that of S. pogona, while the S. pogona-fcl had a lower insecticidal activity against Helicoverpa armigera compared with S. pogona. Scanning electron microscopy (SEM) was used to observe the morphology of the mycelia. It was found that the surface of the S. pogona-Δfcl was wrinkled, and the mycelium showed a short rod shape. There was no significant difference in mycelial morphology between S. pogona-fcl and S. pogona. Aboved all showed that deletion of fcl gene in S. pogona hindered the growth and development of mycelia, but was beneficial to increase the biosynthesis of butenyl-spinosyn and improve insecticidal activity. Whereas the fcl gene over-expression was not conducive to the biosynthesis of butenyl-spinosyn and reduced their insecticidal activity. SDS-PAGE results showed that the difference of protein expression among the three strains was most obvious at 96 hours, which was identified by real-time fluorescence quantitative polymerase chain reaction, the results showed that there were significant differences of related genes in transcriptional levels among the three strains. Based on the results of the study, a network metabolic control map was constructed to analyze the effect of fcl gene on growth and the regulation pathway of butenyl-spinosyn biosynthesis, which provided an experimental basis for revealing the regulation mechanism of butenyl-spinosyn biosynthesis and related follow-up studies.

Immunological Evaluation of a Novel Mycobacterium tuberculosis Antigen Rv0674 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosis antigen Rv0674.@*METHODS@#To evaluate the diagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA.@*RESULTS@#The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/Poly I:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high- and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotype characterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines.@*CONCLUSION@#Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.