BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

To explore the clinical and genetic features of Aicardi-Goutières syndrome (AGS) caused by IFIH1 gene mutation.

Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds. This study explores the application of nanosilver (NAg) to reduce foreign body reactions during scaffold transplantation. An NAg hybrid collagen-chitosan scaffold (NAg-CCS) was prepared using the freeze-drying method. The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions. Skin tissue samples were collected for histological and immunological evaluation at variable intervals. Miniature pigs were used to assess the effects of NAg on skin wound healing. The wounds were photographed, and tissue samples were collected for molecular biological analysis at different time points post-transplantation. NAg-CCS has a porous structure and the results showed that it could release NAg constantly for two weeks. The NAg-CCS group rarely developed a foreign body reaction, while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment. Both matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were reduced significantly in the NAg-CCS group. The NAg-CCS group had higher interleukin (IL)-10 and lower IL-6 than the blank CCS group. In the wound healing study, M1 macrophage activation and inflammatory-related proteins (inducible nitric oxide synthase (iNOS), IL-6, and interferon-‍γ (IFN-‍γ)) were inhibited by NAg. In contrast, M2 macrophage activation and proinflammatory proteins (arginase-1, major histocompatibility complex-II (MHC-II), and found in inflammatory zone-1 (FIZZ-1)) were promoted, and this was responsible for suppressing the foreign body responses and accelerating wound healing. In conclusion, dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines, thereby promoting wound healing.
Animals ; Rats ; Swine ; Interleukin-6 ; Macrophage Activation ; Tissue Inhibitor of Metalloproteinase-1 ; Wound Healing ; Foreign-Body Reaction ; Foreign Bodies ; Chitosan

Objective: To explore the clinical application value of mixed reality technology in locating perforator vessels and assisting perforator vessel dissection to harvest anterolateral thigh flaps. Methods: Six patients who needed anterolateral thigh flap repair after resection of oral and maxillofacial tumors were recruited from the Department of Oral and Maxillofacial Surgery of Nanchong Central Hospital from January 2020 to January 2021. Before surgery, the CT angiography data of the lower limbs of the patients carrying the calibration points were imported into the data workstation to perform 3D reconstruction of the perforator vessels and surrounding tissues of the thigh, and the reconstruction results were imported into Microsoft HoloLens 2 glasses. During the operation, calibration was performed at the calibration point of the operative area so that the preoperative reconstruction results were superimposed on the operative area through Microsoft HoloLens 2 glasses. The clinical application value of mixed reality technology assisted perforator vessel location and anatomy of anterolateral femoral perforator flap was discussed from six aspects: whether the perforator vessel was reconstructed preoperatively, intraoperative calibration time, whether the actual position of the perforating vessels passing through the fascia lata fulcrum deviated from the preoperative reconstruction result within 1 cm, time required to harvest the flap, and whether the actual route of the perforator vessel was consistent with the reconstruction result, and whether the postoperative flap survived. Results : The position and course of perforating vessels were successfully reconstructed in 6 cases before the operation. The actual course of perforating vessels during the operation was consistent with the reconstruction results. The deviation between the actual position of the perforating points and the preoperative reconstruction results was within 1 cm, which met the requirements of the actual asisting of the anterolateral thigh flap. The average time of flap harvest was (70.50 ± 7.20) min. The average calibration time was (13.33 ± 5.50) min. All flaps survived. Conclusions Mixed reality technology projects the reconstruction results of anterolateral femoral perforator vessels directly into the operative area, which provides a new method for asisting localization and anatomy of anterolateral femoral flap perforator vessels and reduces the possibility of injury to perforator vessels.

Cucurbitaceae is an important family of flowering plants containing multiple species of important food plants, such as melons, cucumbers, squashes, and pumpkins. However, a highly efficient genetic transformation system has not been established for most of these species (Nanasato and Tabei, 2020). Watermelon (Citrullus lanatus), an economically important and globally cultivated fruit crop, is a model species for fruit quality research due to its rich diversity of fruit size, shape, flavor, aroma, texture, peel and flesh color, and nutritional composition (Guo et al., 2019). Through pan-genome sequencing, many candidate loci associated with fruit quality traits have been identified (Guo et al., 2019). However, few of these loci have been validated. The major barrier is the low transformation efficiency of the species, with only few successful cases of genetic transformation reported so far (Tian et al., 2017; Feng et al., 2021; Wang JF et al., 2021; Wang YP et al., 2021). For example, Tian et al. (2017) obtained only 16 transgenic lines from about 960 cotyledon fragments, yielding a transformation efficiency of 1.67%. Therefore, efficient genetic transformation could not only facilitate the functional genomic studies in watermelon as well as other horticultural species, but also speed up the transgenic and genome-editing breeding.
CRISPR-Cas Systems ; Citrullus/genetics* ; Cucurbitaceae/genetics* ; Gene Editing ; Plant Breeding ; Transformation, Genetic

Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency characterized by severe bacterial and fungal infections and tissue granuloma formation early in life. Diagnosis of CGD involves the granulocyte function assays and gene mutation analysis. X-linked CGD (XL-CGD) caused by gene defects of CYBB is the most prevalent type of CGD. The clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD were reported here. The patient is a 7-year-old boy manifested as recurrent lower respiratory tract infection and failed to thrive. The patient had a history of osteo- myelitis and perianal abscess, with Bacille Calmette-Guérin (BCG) vaccine complications. Respiratory burst of neutrophils was measured with DHR oxidation assay and the histogram showing no significant change in neutrophil fluorescence after stimulation of the patient and the mother's histogram had a pattern of 2 peaks after stimulation. A heterozygous mutation in the CYBB gene (c.866G > A, p.W289X) was identified through inheritance from the patient's mother. Genetic analysis from blood and cheek mucosal cells indicated the female was a mosaicism in CYBB with mutation was present in about 19.5% of her leukocytes. We reported the clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD for the first time in China to enrich the understanding of XL-CGD and provide new sights for the hereditary counseling.

The clinical data of a child with ABCB1 rs1045642 T/T genotype and skin photosensitivity induced by Voriconazole were analyzed retrospectively in Beijing Children′s Hospital, Capital Medical University in September 2020.Literature was reviewed to discuss the relationship between ABCB1 genetic polymorphism and Voriconazole pharmacokinetics.The patient was a 6.8-year-old boy, who was diagnosed with primary immunodeficiency disease.Long-term oral Voriconazole was administered for prevention and treatment of fungal infections.Skin photodistributed erythema and pigmentation occurred about 3-4 weeks after treatment.The skin lesions were significantly alleviated about 1 month after the withdrawal of Voriconazole.Gene test showed ABCB1 rs1045642 T/T in the patient.Some studies reported that ABCB1 rs1045642 T/T genotype reduced the clearance rate of Voriconazole.Monitoring such adverse reaction of Voriconazole in clinical practice is important. ABCB1 gene polymorphism is possible to correlate with the pharmacokinetics and adverse reactions of Voriconazole.However, further large-scale clinical studies are warranted to verify it.

Objective:To apply the best evidence of phaseⅠ cardiac rehabilitation after coronary artery bypass grafting (CABG) into clinical practice and evaluate its effects.Methods:Following the Australian Jonna Briggs Institute (JBI) clinical evidence program and evidence transformational practice application system, the evidence of phaseⅠ cardiac rehabilitation exercise after CABG was retrieved, screened and evaluated, and the review indicators were formulated. From September 2019 to February 2020, 41 nurses and 109 CABG patients from the Cardiovascular Surgery Ward of the Affiliated Hospital of Qingdao University were selected. The data of 56 patients were collected before the application of the best evidence, and those of 53 patients were collected after the application of the best evidence. The implementation rate of the review indicators, the degree of knowledge of the best evidence among nurses and patients, the Six Minute Walk Test (6MWT) distance and the left ventricular ejection fraction (LVEF) before and after the application of the best evidence were compared.Results:After the application of the evidence, the nurses' implementation rate of the 13 review indicators of phaseⅠ cardiac rehabilitation exercises was improved, and the difference was statistically significant ( P<0.05) ; the nurses' exercise knowledge score increased from (53.66±14.01) points to (71.59±14.93) points; the patients' exercise knowledge score increased from (26.22±17.46) points to (60.49±15.52) points, and the differences were statistically significant ( t=-5.61, -9.40; P<0.01) . After the application of the evidence, the patients' 6MWT distance increased from (241.82±72.05) m to (246.25±69.26) m, and the difference was statistically significant ( t=-2.238, P<0.05) ; however, there was no statistically significant difference in LVEF before and after the application of the evidence ( P>0.05) . Conclusions:The clinical application of the best evidence for phase I cardiac rehabilitation exercises in CABG patients can standardize nurses' behaviors, improve nurses and patients' knowledge of evidence, and increase the 6MWT distance of CABG patients.

Objective:To explore the role of continuous quality improvement measures based on the American hospital evaluation standard of the Joint Commission International (JCI) in prevention and control of nosocomial infection in Burn Department of the Second Affiliated Hospital of Zhejiang University School of Medicine (hereinafter referred to as the author′ s department).Methods:From 2013 to 2018, based on 11 JCI standards related to infection prevention and control and the current situation of the author′ s department, more than 50 doctors, nurses, and nursing assistants from the author′ s department participated in continuous improvement of the three-level management system of nosocomial infection in the author′ s department, focusing on implementing of management of patient with multidrug resistant bacteria infection, optimizing the infection control management of instrument and cloth, and implementing target management on 5 indicators such as hand hygiene implementation rate, and carrying out inspection, quality management, and improvement on 11 items of prevention and control of nosocomial infection. The implementation rate of hand hygiene from 2013 to 2018 and the accuracy rate of hand hygiene from 2016 to 2018 of medical staff in the author′ s department, and incidences of catheter-related bloodstream infection (CRBSI) of central venous, catheter-associated urinary tract infection (CAUTI), and ventilator associated pneumonia (VAP) of burn intensive care unit in the author′s department from 2013 to 2018 were monitored.The following 7 indicators were monitored from 2013 to 2018, including false negative rate of nosocomial infection, incidence of hyperglycemia during intensive insulin treatment for severely burned patients, the implementation rate of CRBSI preventive measures, the specification rate of surface fixation of indwelling catheter, the implementation rate of VAP preventive measures, the accuracy rate of bed temperature during the use of suspended bed, and the implementation rate of hand hygiene of standardized training medical staff in the author′ s department before and after improvement. Data were statistically analyzed with chi-square test.Results:The implementation rate of hand hygiene of medical staff in the author′ s department was 88.0%-89.5% from 2013 to 2018, the correct rate of hand hygiene of medical staff in the author′ s department was 95.10%-97.35%, and both reached the target values. The incidences of CRBSI in 2015, VAP in 2017, and CAUTI in 2013, 2014, and 2017 of burn intensive care unit failed to reach the respective target value and reached the respective target value after quality improvement, and the above-mentioned 3 indicators reached the respective target value in other years. From 2013 to 2018, the false negative rate of nosocomial infection and the incidence of hyperglycemia during intensive insulin treatment of severely burned patients in the author′ s department after improvement were significantly lower than those before improvement ( χ2=24.50, 4.74, P<0.05 or P<0.01), the implementation rate of CRBSI preventive measures, the specification rate of surface fixation of indwelling catheter, the implementation rate of VAP preventive measures, and the accuracy rate of bed temperature during the use of suspended bed after improvement in the author′ s department were significantly higher than those before improvement ( χ2=13.78, 6.50, 20.37, 13.92, P<0.05 or P<0.01), and the implementation rate of hand hygiene of standardized training medical staff in the author′ s department after improvement was similar to that before improvement ( χ2=1.71, P>0.05). Conclusions:The introduction of JCI standard can improve the implementation rate and accuracy rate of hand hygiene of medical staff in burn department, reduce the incidences of CRBSI, CAUTI, and VAP, and improve the effect of prevention and control of nosocomial infection in burn department.

Objective To examine the impact of vacuum sealing drainage on clinical outcomes of patients with post-sternotomy mediastinitis after cardiac surgery. Methods A systematic search were performed in Cochrane Library, Pubmed, Embase, China Biology Medicine(CBM), WanFang, VIP database. The quality of articles was critically appraised and data were extracted by 2 reviewers independently. Meta-analysis were conducted for the eligible researches. Results Fourteen cohort studies were inclued finally. Patients treated with VSD had significantly lower in-hospital mortalityand lower re-infection compared to those treated without VSD. While there had no significant defferences in length of ICU stay(days) and in-hospital stay (days) between VSD group and control group. Conclusions VSD therapy was associated with lower re-infection and in-hospital mortality than other conventional methods in patients with post-sternotomy mediastinitis after cardiac surgery and those results should be further tested in future research and practice.