Conservative versus liberal oxygen therapy for intensive care unit patients: meta-analysis of randomized controlled trials.

BACKGROUND: It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients. METHODS: We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events. RESULTS: In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days. CONCLUSIONS: COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.

Clinical application of instant 3D printed cast versus polymer orthosis in the treatment of colles fracture: a randomized controlled trial.

BACKGROUND: The shortcomings of plaster in water resistance, air permeability, skin comfort, fixed stability and weight of wearing are still to be solved. 3D printed cast can overcome the above shortcomings. At present, there is a relative lack of data on the clinical application of 3D printed cast, probably due to its complexity, relatively long operating time, and high price. We aimed to compare and evaluate the short-term effectiveness, safety and advantages of 3D printed wrist cast versus polymer orthosis in the treatment of Colles fracture. METHODS: Forty patients with Colles fracture in our hospital from June to December 2022 were selected and divided into an observation group (20 patients, treated with instant 3D printed cast) and a control group (20 cases, treated with polymer orthosis). Both groups treated with manual reduction and external fixation. The visual analogue scale (VAS), immobilization effectiveness and satisfaction scores, Disability of the Arm, Shoulder and Hand (DASH) score, complications and imaging data were collected and compared before immobilization and at 2, 6 and 12 weeks after the fracture. RESULTS: VAS at 2 weeks after the fracture was significantly lower in the observation group than in the control group ( P < 0.05). The immobilization effectiveness and satisfaction scores at 6 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). The DASH scores at 2 and 6 weeks after the fracture were significantly lower in the observation group than in the control group (all P < 0.05). There wasn't rupture of the printed cast or orthosis in both groups. There were 2 cases of skin irritation in the control group, and no skin irritation occurred in the observation group. The palmar tilt angle and ulnar inclination angle at 2 weeks and 12 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). CONCLUSIONS: Both instant 3D printed cast and polymer orthosis are effective in the treatment of Colles fracture. But instant 3D printed cast is better than polymer orthosis in areas of good clinical and imaging performance, and high patient satisfaction and comfort.

Comparison between high-flow nasal cannula and conventional oxygen therapy in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT. OBJECTIVES: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations. DESIGN: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES AND METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation. RESULTS: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p = 0.0009, I2 = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO2/FiO2 < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p = 0.0007, I2 = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p = 0.005, I2 = 80%). HFNC was associated with an improvement of PaO2/FiO2 and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay. CONCLUSION: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO2/FiO2 < 200 mmHg and those in ICU settings. TRIAL REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. METHODS: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. RESULTS: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. CONCLUSIONS: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH).

BACKGROUND: Runt-related transcription factor-2 (Runx2) has been considered an inducer to improve bone repair ability of mesenchymal stem cells (MSCs). METHODS AND RESULTS: Twenty-four rabbits were used to establish Osteonecrosis of the femoral head (ONFH) and randomly devided into four groups: Adenovirus Runx2 (Ad-Runx2) group, Runx2-siRNA group, MSCs group and Model group. At 1 week after model establishment, the Ad-Runx2 group was treated with 5 × 107 MSCs transfected through Ad-Runx2, the Runx2-siRNA group was treated with 5 × 107 MSCs transfected through Runx2-siRNA, the MSCs group was injected with 5 × 107 untreated MSCs, and the Model group was treated with saline. The injection was administered at 1 week and 3 weeks after model establishment. The expression of bone morphogenetic protein 2 (BMP-2), Runx2 and Osterix from the femoral head was detected at 3 and 6 weeks after MSCs being injected, and Masson Trichrome Staining, Gross Morphology, X-ray and CT images observation were used to evaluate the repair effect of ONFH. The data revealed that the expression of BMP-2, Runx2 and Osterix in the Runx2-siRNA group was reduced at 3 weeks compared with the MSCs group, and then the expression further reduced at 6 weeks, but was still higher than the Model group besides Osterix; The expression of these three genes in the Ad-Runx2 group was higher than in the MSCs group. Masson Trichrome Staining, Gross Morphology and X-ray and CT images observation revealed that necrotic femoral head of the MSCs group was more regular and smooth than the Runx2-siRNA group, which has a collapsed and irregular femoral head. In the Ad-Runx2 group, necrotic femoral head was basically completely repaired and covered by rich cartilage and bone tissue. CONCLUSIONS: Overexpression of Runx2 can improve osteoblastic phenotype maintenance of MSCs and promote necrotic bone repair of ONFH.

Clinical efficacy and safety of ultrasound-assisted thrombolysis vs. standard catheter-directed thrombolysis in patients with acute pulmonary embolism: A study level meta-analysis of clinical trials.

Aim: To compare the clinical efficacy of ultrasound-assisted thrombolysis (USAT) vs. standard catheter-directed thrombolysis (SCDT) in patients with acute pulmonary embolism (aPE). Methods: This study analyzed the clinical outcomes of patients with non-low-risk aPE who received USAT or SCDT. The primary outcomes were all-cause death, total bleeding, and major bleeding. Secondary outcomes included pulmonary thrombotic load score (Miller), improvement in right ventricular-to-left ventricular ratio (RV/LV), dose and duration of the thrombolytic drug tissue plasminogen activator (tPA), length of stay (LOS) in the ICU, and total LOS in the hospital. Results: A total of seven articles and 451 patients were included in this study. 241 patients were in the USAT group and 210 patients were in the SCDT group. There were no significant differences in all-cause mortality, total bleeding, and major bleeding between the two groups. Miller scores for pulmonary thrombus also showed no difference between the two groups, but pulmonary artery systolic pressure (PASP) was lower in the SCDT group after-treatment. The reduction of RV/LV from baseline was more pronounced in the SCDT group than in the USAT group (OR: -0.14, 95%CI: -0.20 to 0.07, P < 0.0001, I 2 = 0%). Total dose of tPA and duration of infusion in the USAT group were lower than those in the SCDT group, but there was no significant statistical difference. LOS in the ICU was similar between the two groups, while LOS in the hospital was lower in the SCDT group. Conclusion: This study did not detect any differences in all-cause mortality, total bleeding, and major bleeding between non-low-risk aPE patients treated with USAT or SCDT. Improvement in right ventricular function was better in the SCDT group, and hospital LOS was lower in the SCDT group.

Immunogenomic Characteristics of Cell-Death-Associated Genes with Prognostic Implications in Bladder Cancer.

Bladder cancer is one of the most common genitourinary malignant cancers worldwide. Cell death processes, including apoptosis, ferroptosis, and necrosis, provide novel clinical and immunological insights promoting the management of precision medicine. Therefore, this study aimed to evaluate the transcriptomic profile of signatures in cell death pathways with significant prognostic implications in patients with bladder cancer from multiple independent cohorts (n = 1999). First, genes involved in apoptosis (n = 19), ferroptosis (n = 31), and necrosis (n = 6) were analyzed to evaluate the prognostic implications in bladder cancer. Significant genes were included to establish the cell-death index (CDI) of 36 genes that distinguished patients according to high and low risks. Survival analysis using the Kaplan-Meier curves clustered patients based on overall survival (18.8 vs. 96.7 months; hazard model [HR] = 3.12, P<00001). Cox proportional hazard model was significantly associated with a higher risk of mortality using 10 external independent cohorts in patients with CDIhigh (HR = 1.31, 95% CI: 1.04-1.62). To explore immune parameters associated with CDI, microenvironment cell-population-counter algorithms indicated increased intratumoral heterogeneity and macrophage/monocyte infiltration and CD8+ T cells in patients with CDIhigh group. Besides, the CDIhigh group showed an increased expression of the following immune checkpoints: CD276, PD-L1, CTLA-4, and T-cell exhaustion signatures. Cytokine expression analysis revealed the highest association of IL-9R, IL-17A, IL-17F, GDF7, and IFNW1 with the high-risk group. In addition, 42 patients with BCa receiving immunotherapies were enrolled from a real-world cohort, and expression patterns of three CDI hub genes (DRD5, SCL2A14, and IGF1) were detected using immunohistochemical staining. Patients with triple-negative staining of tumor tissues had significantly higher tumor-associated macrophage abundance, PD-L1 expression, predicted immunocompromised microenvironment, and prominently progressive progression (HR = 4.316, P = 0.0028). In conclusion, this study highlights the immunoevasive tumor microenvironment characterized by the higher tumor-associated macrophage infiltration with the presence of immune checkpoint and T-cell exhaustion genes in patients with BCa at CDIhigh risk who might suffer progression and be more suitable to benefit from immune checkpoint inhibitors or other immunotherapies.

Comparison between high-flow nasal cannula and noninvasive ventilation in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are important treatment approaches for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the differential impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. OBJECTIVES: We assessed the effects of HFNC versus NIV (interface or mode) on clinical outcomes of COVID-19. METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, MedRxiv, and BioRxiv for randomized controlled trials (RCTs) and observational studies (with a control group) of HFNC and NIV in patients with COVID-19-related AHRF published in English before February 2022. The primary outcome of interest was the mortality rate, and the secondary outcomes were intubation rate, PaO2/FiO2, intensive care unit (ICU) length of stay (LOS), hospital LOS, and days free from invasive mechanical ventilation [ventilator-free day (VFD)]. RESULTS: In all, 23 studies fulfilled the selection criteria, and 5354 patients were included. The mortality rate was higher in the NIV group than the HFNC group [odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.51-0.84, p = 0.0008, I2 = 60%]; however, in this subgroup, no significant difference in mortality was observed in the NIV-helmet group (OR = 1.21, 95% CI: 0.63-2.32, p = 0.57, I2 = 0%) or NIV-continuous positive airway pressure (CPAP) group (OR = 0.77, 95% CI: 0.51-1.17, p = 0.23, I2 = 65%) relative to the HFNC group. There were no differences in intubation rate, PaO2/FiO2, ICU LOS, hospital LOS, or days free from invasive mechanical ventilation (VFD) between the HFNC and NIV groups. CONCLUSION: Although mortality was lower with HFNC than NIV, there was no difference in mortality between HFNC and NIV on a subgroup of helmet or CPAP group. Future large sample RCTs are necessary to prove our findings. REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022321997).

Roles of stress response-related signaling and its contribution to the toxicity of zearalenone in mammals.

Zearalenone (ZEA) is a mycotoxin frequently found in cereal crops and cereal-derived foodstuffs worldwide. It affects plant productivity, and is also a serious hazard to humans and animals if being exposed to food/feed contaminated by ZEA. Studies over the last decade have shown that the toxicity of ZEA in animals is mainly mediated by the various stress responses, such as endoplasmic reticulum (ER) stress, oxidative stress, and others. Accumulating evidence shows that oxidative stress and ER stress signaling are actively implicated in and contributes to the pathophysiology of various diseases. Biochemically, the deleterious effects of ZEA are associated with apoptosis, DNA damage, and lipid peroxidation by regulating the expression of genes implicated in these biological processes. Despite these findings, the underlying mechanisms responsible for these alterations remain unclear. This review summarized the characteristics, metabolism, toxicity and the deleterious effects of ZEA exposure in various tissues of animals. Stress response signaling implicated in the toxicity as well as potential therapeutic options with the ability to reduce the deleterious effects of ZEA in animals were highlighted and discussed.

Effect of Mask Selection on the Leak Test in Ventilators Designed for Noninvasive Ventilation.

BACKGROUND: The mask leak test used for modern noninvasive ventilators can detect the leak characteristics of masks that are not recommended by the manufacturer, but it has not yet been determined whether this method is acceptable. METHODS: A noninvasive ventilator equipped with a single-limb circuit and an oronasal mask was connected to a lung simulator. The ventilator was set to S/T mode, and inspiratory positive airway pressure/expiratory positive airway pressure was set to 10/5, 15/5, and 20/5 cm H2O, respectively. Eight nonmanufacturer-recommended oronasal masks were connected to the ventilator. The lung simulator was used to simulate COPD, restrictive disease, and normal lung, respectively. When switching between masks, the mask leak test was set to "Cancel" or "Start Test" in the noninvasive ventilator. The parameters displayed on the lung simulator and ventilator were recorded before and after the mask leak test. RESULTS: There were no significant difference before versus after the mask leak test for any lung simulator parameter, including trigger performance (ie, time from the beginning of the simulated inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator, the magnitude of airway pressure drop needed to trigger, and time to trigger), inspiratory pressure delivery, PEEP, tidal volume, and displayed peak inspiratory pressure (all differences < 10%). At different noninvasive ventilation settings, tidal volumes displayed on the ventilator of the 3 masks were significantly different before and after mask leak test (all P < .05, and difference rate > 10%). CONCLUSIONS: The mask leak test had no effect on the ventilator performance when masks not recommended by the manufacturer were used, but tidal volume monitoring may be more accurate when some masks were used.

Adult with mass burnt lime aspiration: A case report and literature review.

BACKGROUND: Foreign body aspiration mainly occurs in children, which can cause a severe concurrent syndrome and even death without timely treatment. As a rare foreign body, aspiration of lime is seldom reported, and most cases involve a small amount of hydrated lime. Although the symptoms are usually severe, the prognosis is good after suitable treatment. Experience of treatment for lime aspiration is lacking, and this report provides novel evidence for treatment of mass burnt lime aspiration using bronchoscopy. CASE SUMMARY: We report an adult with a large amount of burnt lime aspiration. Because of delay in clearance of the inhaled lime in the trachea and bronchus at the local hospital, he suffered several severe complications, including complete occlusion of the right primary bronchus, aeropleura, aerodermectasia, pneumomediastinum, secondary infection and hypoxemia at 4 d after injury. After transferring to our department, bronchoscopy was immediately carried out to clear the lime in the major airway, using foreign body forceps, biopsy forceps, puncture needle, and hairbrush. The patient's condition recovered rapidly and at 3-months' follow-up, he demonstrated good recovery of the bronchus and lung parenchyma. CONCLUSION: After mass lime aspiration, flexible fiberoptic bronchoscopy is suggested as early as possible, using clamping, flushing or cryotherapy.

Ventricular tachycardia originating from the His bundle: A case report.

BACKGROUND: Ventricular tachycardia (VT) commonly occurs among patients with heart failure and can even cause sudden cardiac death. VT originating from the His bundle branch has been rarely reported. We present the case of a patient with VT from the His bundle branch. CASE SUMMARY: A 58-year-old female complained of paroxysmal palpitations and dizziness for approximately 6 mo. She had a history of fatty liver and cholecystitis, and carotid atherosclerosis could not be excluded from the ultrasound results. An evaluation of the electrocardiogram obtained after admission showed spontaneous conversion between two different morphologies. The possible electrophysiologic mechanism suggested that the dual-source VT originated from the same source, the His bundle branch. Finally, the His bundle branch was ablated, and a dual-chamber pacemaker was inserted into the patient's heart. No further VT occurred during the 3-year follow-up after hospital discharge. CONCLUSION: The diagnosis of VT originating from the His bundle is rare and difficult to establish. The results of this study showed VT originating from the His bundle based on a careful evaluation of the electrocardiogram, and the diagnosis was confirmed by an intracardiac electrophysiologic examination.

The Effect of Different Interfaces on the Aerosol Delivery with Vibrating Mesh Nebulizer During Noninvasive Positive Pressure Ventilation.

Background: The effect of different interfaces on the aerosol delivery with vibrating mesh nebulizer during noninvasive positive pressure ventilation (NIV) is not clear. Materials and Methods: Noninvasive ventilator and four interfaces were connected to IngMar ASL 5000 lung simulator. Meanwhile, the vibrating mesh nebulizer was connected to a ventilator circuit to simulate the nebulization during noninvasive ventilation. The nebulizer position was placed at proximal position (near the mask) and distal position (15 cm away from the mask); the inspiratory positive airway pressure (IPAP) and the expiratory positive airway pressure (EPAP) were set to 16/4, 16/8, 20/4, and 20/8 cmH2O, respectively. The aerosol was collected through a disposable filter placed between the simulated lung and the mask, after which the aerosol delivery was calculated. Meanwhile, we recorded the inspiratory tidal volume and the mean inspiratory flow. Results: The aerosol delivery varied between 1.7% ± 0.0% and 21.1% ± 1.1%. Only when EPAP was set to 4 cmH2O, the statistical difference in aerosol delivery was observed between the two types of interface, and between different leak port locations (p < 0.01; p = 0.04, respectively). When IPAP/EPAP was set to 16/4 and 20/4 cmH2O, respectively, at different nebulizer positions, there was a statistical difference between the interface with the same type but different leak port locations and between the interface with same leak port location but different inner volumes (all p < 0.01). Also, there was a correlation between the aerosol delivery and interface volume (p < 0.01, R2 = 0.55; p < 0.01, R2 = 0.51, respectively), and between aerosol delivery and the intentional leak of interfaces (p < 0.01, R2 = 0.59; p < 0.01, R2 = 0.48, respectively). When EPAP was set to 4 and 8 cmH2O, respectively, the aerosol delivery of nebulizer distal position was significantly higher than that of proximal position (12.2% ± 5.0% vs. 9.1% ± 4.1%, p < 0.05; 2.5% ± 0. 5% vs. 2.1% ± 0.3%, p < 0.01, respectively). Conclusion: Interfaces have a significant effect on aerosol delivery during NIV. The interfaces with different inner volumes, intentional leak, and leak port location may all have an effect on aerosol delivery. The addition of a 15 cm tube between the nebulizer and the mask significantly increases the aerosol delivery.

Percutaneous injection of platelet-rich plasma to treat atrophic nonunion after internal fixation of ulnar fracture: a case report.

Non-union is a serious postoperative complication of fracture. Early detection and intervention can avoid revision surgery. Platelet-rich plasma releases many active tissue factors and has potential to promote fracture healing. Percutaneous injection of platelet-rich plasma at the fracture site may avoid surgical treatment when non-union occurs. We present a case of atrophic non-union of an ulna fracture treated conservatively with percutaneous injection of platelet-rich plasma.

The Diagnostic Accuracy of PET(CT) in Patients With Neuroblastoma: A Meta-Analysis and Systematic Review.

OBJECTIVE: The objective of this study was to evaluate the overall diagnostic value of PET(CT) in patients with neuroblastoma (NB) based on qualified studies. METHODS: PubMed, Cochrane, and Embase database were searched by the index words to identify the qualified studies, and relevant literature sources were also searched. The latest research was performed in April 2019. Heterogeneity of the included studies was tested, which was used to select proper effect model to calculate pooled weighted sensitivity, specificity, and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) analyses were also performed. RESULTS: Eleven studies with 580 patients were involved in the meta-analysis to explore the diagnostic accuracy of PET(CT) for NB. PET(CT) has high diagnostic accuracy of NB: the global sensitivity was 91% (95% confidence interval [CI], 86%-94%), the global specificity was 78% (95% CI, 66%-86%), the global positive likelihood ratio was 4.07 (95% CI, 2.54-6.50), the global negative likelihood ratio was 0.12 (95% CI, 0.08-0.18), the global DOR was 27.43 (95% CI, 14.45-52.07), and the area under the SROC was high (area under the curve, 0.93; 95% CI, 0.90-0.95). Besides this, PET(CT) has high diagnostic accuracy of primary NB: the global sensitivity was 86% (95% CI, 73%-93%), the global specificity was 82% (95% CI, 57%-94%), the global positive likelihood ratio was 4.90 (95% CI, 1.63-14.72), the global negative likelihood ratio was 0.17 (95% CI, 0.07-0.40), the global DOR was 25.427 (95% CI, 3.988-162.098), and the area under the SROC was high (area under the curve, 0.91; 95% CI, 0.88-0.93). However, there has no significant accuracy of PET(CT) in NB with bone marrow. CONCLUSIONS: This study provides a systematic review and meta-analysis of diagnostic accuracy studies of PET(CT) for NB. The results indicated that PET(CT) is a highly accurate diagnostic tool for NB.

BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head.

Mesenchymal stem cells (MSCs) with multipotential differentiation capacity can differentiate into bone cells under specific conditions and can be used to treat osteonecrosis (ON) of the femoral head (ONFH) through cell transplantation. The current study aims to explore the role of bone marrow (BM) MSCs (BMSCs)-derived exosomes carrying microRNA-122-5p (miR-122-5p) in ONFH rabbit models.First, rabbit models with ONFH were established. ONFH-related miRNAs were screened using the Gene Expression Omnibus (GEO) database. A gain-of-function study was performed to investigate the effect of miR-122-5p on osteoblasts and BMSCs and effects of exosomes carrying miR-122-5p on ONFH. Co-culture experiments for osteoblasts and BMSCs were performed to examine the role of exosomal miR-122-5p in osteoblast proliferation and osteogenesis. The target relationship between miR-122-5p and Sprouty2 (SPRY2) was tested.MiR-122, significantly decreased in ONFH in the GSE89587 expression profile, was screened. MiR-122-5p negatively regulated SPRY2 and elevated the activity of receptor tyrosine kinase (RTK), thereby promoting the proliferation and differentiation of osteoblasts. In vivo experiments indicated that bone mineral density (BMD), trabecular bone volume (TBV), and mean trabecular plate thickness (MTPT) of femoral head were increased after over-expressing miR-122-5p in exosomes. Significant healing of necrotic femoral head was also observed.Exosomes carrying over-expressed miR-122-5p attenuated ONFH development by down-regulating SPRY2 via the RTK/Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Findings in the present study may provide miR-122-5p as a novel biomarker for ONFH treatment.

Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head.

Traumatic osteonecrosis of the femoral head (ONFH) is a condition leading to the collapse of the femoral head, and the primary treatment is a total hip replacement, which has a poor prognosis. The current study was conducted with the aim of investigating the role of exosomes from bone marrow-derived mesenchymal stem cells (BM-MSCs) carrying microRNA-224-3p (miR-224-3p) in traumatic ONFH. Initially, a microarray analysis was performed to screen the differentially expressed genes and miRs associated with traumatic ONFH. Patients with traumatic and nontraumatic ONFH were enrolled, and HUVECs were obtained. The BM-MSCs-derived exosomes were purified and characterized, after which HUVECs were cocultured with exosomes. The functional role of miR-224-3p in traumatic ONFH was determined using ectopic expression, depletion, and reporter assay experiments. Endothelial cell proliferation, migration, invasion abilities, and angiogenesis were evaluated. Based on microarray analysis, miR-224-3p was found to be down-regulated, whereas focal adhesion kinase family interacting protein of 200 kDa (FIP200) was up-regulated in ONFH. Traumatic ONFH exosomes resulted in the up-regulation of FIP200 and down-regulation of miR-224-3p. FIP200 was confirmed to be a target gene of miR-224-3p. Exosomes were internalized by vascular endothelial cells. The down-regulation of exosomal miR-224-3p was observed to promote endothelial cell proliferation, migration, invasion abilities, angiogenesis, and FIP200 expression. In addition, FIP200 overexpression promoted angiogenesis. In summary, the results highly indicated that lower miR-224-3p levels in exosomes derived from BM-MSCs promote angiogenesis of traumatic ONFH by up-regulating FIP200. The present study provides a potential strategy for the treatment of traumatic ONFH.-Xu, H.-J., Liao, W., Liu, X.-Z., Hu, J., Zou, W.-Z., Ning, Y., Yang, Y., Li, Z.-H. Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head.

Clinical observation of drug combined with physiotherapy in the treatment of dry eye caused by MGD / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the clinical curative effects of meibomian gland dysfunction(MGD)caused by evaporative dry eye by utilizing levofloxacin eye gel and Tobramycin and Dexamethasone Ophthalmic Ointment, respectively.<p>METHODS: The 180 cases(360 eyes)with dry eye(evaporative type)caused by confirmed meibomian gland dysfunction were randomly divided into two groups(<i>i.e.</i> A and B): In group A, 90 individuals with 180 eyes were treated with levofloxacin eye gel+ sodium hyaluronate eye solution; The other 90 cases in group B took Tobramycin and Dexamethasone Ophthalmic Ointment+ sodium hyaluronate eye drops for curing the MGD. In addition, the same comprehensive therapy were used to the MGD patients in groups A and B, after surface anesthesia on binoculus, secretion, obstructing meibomian gland secretions, were discharged by utilizing cotton stick to extrusion mass weekly and four times consecutive treatments were regard as a course of treatment. To remove residual the thin oil soften lipid in meibomian gland, heat can be applied to the eyelids with hot water(around 45℃)on towel for 15min and do that three times a day. After each hot compress, we use levofloxacin eye gel to the patients in group A by dropping into the conjunctival sac and apply to the root of the eyelid lashes. The group B of 90 patients were applied Tobramycin and Dexamethasone Ophthalmic Ointment to the root of the eyelid lashes. All patients were dripped odium eye drops eye into their eyes four times a day. <p>RESULTS: After treatment(<i>Z</i>= -0.64, <i>P</i>=0.524), there were no significant differences in clinical symptoms(<i>Z</i>= -1.37, <i>P</i>=0.171), secretion characteristics(<i>Z</i>= -1.06, <i>P</i>=0.288), tear film rupture time and tear secretion time between groups A and B(<i>P</i>>0.05). Corneal fluorescence staining score: group A(cured 83.3%, improved 11.1%, ineffective 5.6%)and group B(cured 55.6%, improved 27.8%, ineffective 16.7%). The therapeutic effect of group A was better than that of group B, with statistical significance(<i>Z</i>= -4.02, <i>P</i><0.001).<p>CONCLUSION: Physical therapy for meibomian gland dysfunction caused by evaporative dry eye is given priority, and medication is treated as adjunctive therapy. Generally, the patients can achieve totally anti-inflammatory, antibacterial, safe and stable, without side effects by using levofloxacin eye gel. However, the patients with worst condition and lingering illness should cured by Tobramycin and Dexamethasone Ophthalmic Ointment. In addition, statistical significant difference is not found between the two drugs on curative effects.

Recent advances in study of drugs against Gram-negative pathogens / 药学学报

The long-term use of antibiotics in clinical practice leads to bacterial variation and resistance. In addition, the excessive or improper use of antibiotics in medical and agricultural fields increases the occurrence of bacterial resistance. In 2017, the World Health Organization has for the first time released a list of 12 bacteria or bacterial families that pose the greatest threat to human health and for which new antibiotics are desperately needed, and three quarters of them are Gram-negative bacteria. Gram-negative bacteria has multi-layered cell wall that prevents many antibiotics from accessing their targets. Therefore, it is very difficult to develop drugs against Gram-negative bacteria, no new class of antibiotic has been approved for Gram-negative pathogens in over fifty years. Here, we summarized recent advances in the study of new antibacterial agents with different mechanisms of action against Gram-negative pathogens.

Clinical significance of intrapancreatic choledochal cyst excision in surgical management of type I choledochal cyst.

Objective To investigate the effectiveness of intrapancreatic choledochal cyst excision in treating type I choledochal cyst, and increase understanding of the need for thorough surgical management of the disease. Methods Primary and secondary (including multiple) surgical cases, treated between 2005 and 2015, were retrospectively analysed, and follow-up data of post-treatment effectiveness to date were reviewed. Differences in curative effects were compared between whole and partial excision of the choledochal cyst. Results Out of 350 cases, patients with whole excision of the choledochal cyst ( n = 272) experienced no associated symptoms in the long-term (3/272 [1.1%] experienced stomach ache or fever). Patients with partial resection of the choledochal cyst ( n = 78) developed associated symptoms, including new cyst, calculus of the bile duct (51/78 [65.4%]), and carcinogenesis (11/78 [14.1%]) in the residual intrapancreatic biliary duct. Post-treatment clinical manifestations were significantly different between patients with partial resection versus whole excision of the choledochal cyst ( P<0.05). Conclusion Surgical re-excision should be considered in patients with a residual intrapancreatic portion of the choledochal cyst due to prior incomplete surgery, regardless of clinical symptoms.