Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment.

BACKGROUND: Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management. RESULTS: Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time. CONCLUSIONS: Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.

Prognostic analysis and validation of lncRNAs in bladder cancer on the basis of neutrophil extracellular traps.

BACKGROUND: Complex interactions in the tumor microenvironment (TME) between bladder cancer (BLCA) and immune cells are critical for cancer progression. However, studies of neutrophil extracellular trap-associated long non-coding RNAs (NET-lncRNAs) in the TME of BLCA have not been reported. This study aims to screen for NET-lncRNAs in BLCA and to preliminarily explore their effects on BLCA development. METHODS: The correlation of NET-related gene sets, which were identified from the cancer genome atlas (TCGA) BLCA datasets, with lncRNAs was analyzed and the prognosis-related genes were identified through random forest analysis. The least absolute shrinkage and selection operator (LASSO) model was utilized to obtain prognostic risk scores for NET-lncRNAs (NET-Score). We collected clinical BLCA samples, as well as SV-HUC-1 and BLCA cells, to validate the expression of NET-lncRNAs. Survival and independent prognostic analysis were performed. In J82 and UM-UC-3 cells, after NKILA expression was inhibited, cell proliferation and apoptosis levels were detected. RESULTS: NET-related gene sets mainly included CREB5, MMP9, PADI4, CRISPLD2, CD93, DYSF, MAPK3, TECPR2, MAPK1 and PIK3CA. Then, four NET-lncRNAs, MAP 3 K4-AS1, MIR100HG, NKILA and THY1-AS1, were identified. NET-Score had the highest hazard ratio for BLCA. An elevated NET-Score was linked to a significant increase in immune cell infiltration and copy number variation, as well as a notable decrease in survival rate and drug sensitivity. NET-lncRNA-related genes were mainly enriched in the pathways of angiogenesis, immune response, cell cycle and T cell activation. MAP 3 K4-AS1, MIR100HG, NKILA and THY1-AS1 expressions were significantly increased in BLCA tissues. Compared with SV-HUC-1 cells, NKILA expression was elevated in J82 and UM-UC-3 cells. Inhibition of NKILA expression inhibited the proliferation and promoted apoptosis of J82 and UM-UC-3 cells. CONCLUSIONS: Several NET-lncRNAs, including MAP 3 K4-AS1, MIR100HG, NKILA and THY1-AS1, were successfully screened in the BLCA. The NET-Score was an independent prognostic factor for BLCA. In addition, inhibition of NKILA expression suppressed BLCA cell development. The above NET-lncRNAs could serve as potential prognostic markers and targets in BLCA.

Effects of body parameters on renal cortical stiffness measured by shear-wave elastography in patients with kidney transplantation. / 人体参数对剪切波弹性成像定量移植肾皮质硬度的影响.

OBJECTIVES: The results of elastic imaging in evaluating the function and histopathological changes of allogeneic renal transplantation are contradictory, one of the important reasons may be that there are differences in human parameters related to kidney transplantation among individuals. The purpose of this study is to explore the related human body parameters on shear-wave elastography (SWE) effects on quantitative stiffness of graft cortex. METHODS: From March 2021 to November 2021, a total of 63 patients with allogeneic kidney transplantation in the Department of Ultrasonography, Third Xiangya Hospital, Central South University, were selected to collect the parameters of two-dimensional, color Doppler and SWE. The subjects were divided into a <20% group and a 20%-30% group according to the variation of cortical hardness measurement. Mann Whitney U test was used to compare the differences in relevant human parameters, and Spearman rank correlation was used to analyze the correlation between relevant human parameters and cortical hardness of transplanted kidney. RESULTS: There was no significant difference between the 2 groups in age, sex, postoperative time, resistance index of interlobar artery, SCr, blood uric acid, ratio of fat layer to muscle layer, and BMI (all P>0.05). Compared with the <20% group, the patients in the 20%-30% group had smaller cortical hardness of the transplanted kidney, greater total distance between the transplanted kidney and the skin surface, and thicker fat layer or muscle layer in front of the transplanted kidney (all P<0.05). The age of patients, the total distance from the transplanted kidney to the skin surface, the thickness of fat layer and muscle layer, the ratio of fat layer to muscle layer, BMI, and the variation of cortical hardness were significantly negatively correlated with the cortical hardness of the transplanted kidney (all P<0.05). CONCLUSIONS: Human parameters relevant to kidney transplantation affect the accuracy of SWE in measuring the cortical hardness of the transplanted kidney. It is very important to obtain the highly stabile elastic measurement value and interpret the elastic measurement results according to different levels of human body related parameters in combination with individual conditions.

THEM6: A Novel Molecular Biomarker Predicts Tumor Microenvironment, Molecular Subtype, and Prognosis in Bladder Cancer.

Background: Thioesterase superfamily member 6 (THEM6) has been implicated in the development and progression of various cancers. However, prior research emphasized on its regulatory role merely, we aim to investigate the effect of THEM6 gene on the immunological role and its relationship with molecular subtype in bladder cancer (BLCA). Methods: Through pan-cancer analysis, we explored the THEM6 expression pattern and immunological role using The Cancer Genome Atlas (TCGA) database. In addition, we performed a correlation of THEM6 and its immunological functions, including immunomodulators, immune checkpoints, cancer immunity cycles, T cell inflamed score, and tumor-infiltrating immune cells in the BLCA tumor microenvironment (TME) based on TCGA and BLCA microarray cohort from Xiangya Hospital. We also assessed the accuracy of THEM6 in predicting the molecular subtype and its response to different interventions in BLCA. Finally, we computed and validated a prediction model established by THEM6-related different expressed immune-related genes that might help in BLCA prognosis. Results: THEM6 led to immunosuppression in BLCA TME. Furthermore, there was a downregulation in the immunological functions. Besides, THEM6 could effectively distinguish BLCA molecular subtypes, and THEM6 low expression implied basal subtype that was more effective to several interventions, such as immune checkpoint blockade (ICB) therapies, neoadjuvant chemotherapy, and radiotherapy. While THEM6 high expression indicated luminal subtype, hyperprogression and better response to targeted therapies, such as blocking THEM6 and several immune-inhibited oncogenic pathways. Conclusions: THEM6 may be with potential immune-modulating properties and may become a potential new immunotherapy target for BLCA. THEM6 could accurately predict the molecular subtype of BLCA, which was helpful for guiding the treatment. Simultaneously, the prediction model may exhibit an excellent predictive value in patients with BLCA.

Serology and gene sequence analysis of the B(A) subtype of patients in Hunan.

INTRODUCTION: B(A) is a relatively rare ABO subtype. The frequency of B(A) in European Caucasians is low, but is higher in China. B(A) is common in northern China, gradually decreasing from north to south. The frequency of B(A) has been researched in northern China, but not in southern China. This study aimed to investigate the serological characteristics and molecular mechanism of the B(A) subtype in Hunan. METHODS: The phenotypes of ABO blood group were analyzed by blood group serology for the patients in the Third Xiangya Hospital from 2016 to 2020; Exons 1-7 of the ABO gene were screened by PCR-SSP and sequencing. RESULTS: Nine cases were suspected as belonging to the B(A) subtype by serological tests. The activity of D-galactosyltransferase in these patients' serum was significantly higher than that of group B plasma; meanwhile, there was no activity of Nacetylgalactosyltransferase. The ABO genotype was ABO*B.01/O.01.01 or ABO*B.01/O.01.02, and the gene sequencing results confirmed the phenotype as B(A), whose gene frequence was 1/26,000. Allele ABO*BA.02 (1/38,000) had the highest frequency, followed by ABO*BA.04 (1/77,000). CONCLUSION: Among the patients in Hunan, the most common allele encoding the B(A) phenotype was ABO*BA.02. The identification of the B(A) blood group required serological methods combined with genotyping.

Annexin A8 regulated by lncRNA-TUG1/miR-140-3p axis promotes bladder cancer progression and metastasis.

Bladder cancer is the ninth most diagnosed cancer in the world. This study aims to investigate the role and mechanisms of the taurine-upregulated gene 1 (TUG1)/miR-140-3p/annexin A8 (ANXA8) axis in bladder cancer. Western blotting and qRT-PCR determined the expression levels of ANXA8, miR-140-3p, TUG1, and epithelial-mesenchymal transition (EMT) markers. RNA immunoprecipitation (RIP), luciferase assay, and RNA pull-down assay validated the association among ANXA8, miR-140-3p, and TUG1. The biological functions were determined by colony formation, Annexin V-fluorescein isothiocyanate (FITC)/propidium (PI) staining, and transwell assays. Xenograft tumorigenesis detected tumor growth and metastasis in vivo. Pathological analysis was examined by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) analyses. ANXA8 was elevated in bladder tumors and cells. Knockdown of ANXA8 suppressed cell growth, migration, invasion, and EMT in UMUC-3 and T24 cells. ANXA8 was determined as a miR-140-3p target gene. Overexpression of miR-140-3p suppressed cell proliferation, migration, invasion, and EMT via targeting ANXA8. TUG1 promoted ANXA8 expression via sponging miR-140-3p. Silencing of miR-140-3p or ANXA8 overexpression abrogated the tumor-suppressive effects of TUG1 silencing on bladder cancer cell growth and metastasis. The TUG1/miR-140-3p/ANXA8 axis was also implicated in tumor growth and lung metastasis in vivo. TUG1 promotes bladder cancer progression and metastasis through activating ANXA8 by sponging miR-140-3p, which sheds light on the mechanisms of bladder cancer pathogenesis.

A Comparison of CT Manifestations Between Coronavirus Disease 2019 (COVID-19) and Other Types of Viral Pneumonia.

BACKGROUND: Though imaging manifestations of COVID-19 and other types of viral pneumonia are similar, their clinical treatment methods differ. Accurate, non-invasive diagnostic methods using CT imaging can help develop an optimal therapeutic regimen for both conditions. OBJECTIVE: To compare the initial CT imaging features in COVID-19 with those in other types of viral pneumonia. METHODS: Clinical and imaging data of 51 patients with COVID-19 and 69 with other types of viral pneumonia were retrospectively studied. All significant imaging features (Youden index >0.3) were included for constituting the combined criteria for COVID-19 diagnosis, composed of two or more imaging features with a parallel model. McNemar's chi-square test or Fisher's exact test was used to compare the validity indices (sensitivity and specificity) among various criteria. RESULTS: Ground glass opacities (GGO) dominated density, peripheral distribution, unilateral lung, clear margin of lesion, rounded morphology, long axis parallel to the pleura, vascular thickening, and crazy-paving pattern were more common in COVID-19 (p <0.05). Consolidation-dominated density, both central and peripheral distributions, bilateral lung, indistinct margin of lesion, tree-inbud pattern, mediastinal or hilar lymphadenectasis, pleural effusion, and pleural thickening were more common in other types of viral pneumonia (p < 0.05). GGO-dominated density or long axis parallel to the pleura (with the highest sensitivity), and GGO-dominated density or long axis parallel to the pleura or vascular thickening (with the highest specificity) are well combined criteria of COVID-19. CONCLUSION: The initial CT imaging features are helpful for the differential diagnosis of COVID-19 and other types of viral pneumonia.

Inspiratory and Expiratory Chest High-resolution CT: Small-airway Disease Evaluation in Patients with COVID-19.

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) has occurred worldwide. However, the small-airway disease in patients with COVID-19 has not been explored. AIM: This study aimed to explore the small-airway disease in patients with COVID-19 using inspiratory and expiratory chest high-resolution computed tomography (CT). METHODS: This multicenter study included 108 patients with COVID-19. The patients were classified into five stages (0-IV) based on the CT images. The clinical and imaging data were compared among CT images in different stages. Patients were divided into three groups according to the time interval from the initial CT scan, and the clinical and air trapping data were compared among these groups. The correlation between clinical parameters and CT scores was evaluated. RESULTS: The clinical data, including age, frequency of breath shortness and dyspnea, neutrophil percentage, lymphocyte count, PaO2, PaCO2, SaO2, and time interval between the onset of illness and initial CT, showed significant differences among CT images in different stages. A significant difference in the CT score of air trapping was observed between stage I and stage III. A low negative correlation was found between the CT score of air trapping and the time interval between the onset of symptoms and initial CT. No significant difference was noted in the frequency and CT score of air trapping among different groups. CONCLUSION: Some patients with COVID-19 developed small-airway disease. Air trapping was more distinguished in the early stage of the disease and persisted during the 2-month follow-up. Longer-term follow-up studies are needed to confirm the findings.

Application value analysis of magnetic resonance imaging and computed tomography in the diagnosis of intracranial infection after craniocerebral surgery.

BACKGROUND: Intracranial infection is a common clinical disease. Computed tomography (CT) and magnetic resonance imaging (MRI) have certain sensitivity and have good diagnostic efficacy. AIM: To study the application value of MRI and CT in the diagnosis of intracranial infection after craniocerebral surgery. METHODS: We selected 82 patients who underwent craniocerebral surgery (including 40 patients with intracranial infection and 42 patients without infection) during the period from April 2016 to June 2019 in our hospital. All 82 patients received CT and MRI examinations, and their clinical data were reviewed. A retrospective analysis was performed, and the coincidence rate of positive diagnosis and the overall diagnosis coincidence rate of different pathogenic infection types were measured with the two examination methods. The diagnostic sensitivity and specificity as well as the positive and negative predictive values of the two examination methods were compared. RESULTS: For all types of pathogenic infections (Staphylococcus aureus, Staphylococcus hemolyticus, Staphylococcus epidermidis, and others), MRI scans had higher positive diagnostic coincidence rates than CT scans; the overall diagnostic coincidence rate, sensitivity, specificity, positive predictive value, and negative predictive values were significantly higher with MRI examinations than with CT examinations, and the differences were statistically significant (P < 0.05). CONCLUSION: MRI examination can accurately diagnose intracranial infection after clinical craniocerebral surgery. Compared with CT, MRI had higher diagnostic efficiency. The diagnostic sensitivity and specificity, the diagnostic coincidence rate, and the positive and negative predictive values were significantly higher with MRI than with conventional CT, which can be actively promoted.

Nomogram to identify severe coronavirus disease 2019 (COVID-19) based on initial clinical and CT characteristics: a multi-center study.

BACKGROUND: To develop and validate a nomogram for early identification of severe coronavirus disease 2019 (COVID-19) based on initial clinical and CT characteristics. METHODS: The initial clinical and CT imaging data of 217 patients with COVID-19 were analyzed retrospectively from January to March 2020. Two hundred seventeen patients with 146 mild cases and 71 severe cases were randomly divided into training and validation cohorts. Independent risk factors were selected to construct the nomogram for predicting severe COVID-19. Nomogram performance in terms of discrimination and calibration ability was evaluated using the area under the curve (AUC), calibration curve, decision curve, clinical impact curve and risk chart. RESULTS: In the training cohort, the severity score of lung in the severe group (7, interquartile range [IQR]:5-9) was significantly higher than that of the mild group (4, IQR,2-5) (P < 0.001). Age, density, mosaic perfusion sign and severity score of lung were independent risk factors for severe COVID-19. The nomogram had a AUC of 0.929 (95% CI, 0.889-0.969), sensitivity of 84.0% and specificity of 86.3%, in the training cohort, and a AUC of 0.936 (95% CI, 0.867-1.000), sensitivity of 90.5% and specificity of 88.6% in the validation cohort. The calibration curve, decision curve, clinical impact curve and risk chart showed that nomogram had high accuracy and superior net benefit in predicting severe COVID-19. CONCLUSION: The nomogram incorporating initial clinical and CT characteristics may help to identify the severe patients with COVID-19 in the early stage.

Improved Transcatheter aortic valve implantation for aortic regurgitation using a new-type stent: the first preclinical experience.

BACKGROUND: In this study, we sought to evaluate the feasibility of improved transcatheter aortic valve implantation (TAVI) in noncalcified aortic valve by using the novel concept of double-layer ChenValve prosthesis. TAVI was initially considered as an alternative treatment for high-risk patients with aortic stenosis. However, non noncalcified aortic valve disease was considered as a contraindication to TAVI. METHODS: ChenValve prosthesis, which consisted of a self-expanding Nitinol ring, a balloon-expandable cobalt-chromium alloy stent and a biological valve, was implanted at the desired position under fluoroscopic guidance in a transapical approach through a 20F sheath in 10 goats. Aortic angiography was performed to measure the diameter of the aotic annulus and assess the performance of the artificial valve. The ultrasound was used to evaluate the regurgitation or paravalvular leakage and trans-prosthetic vascular flow velocity postoperatively. The aortogram and transthoracic echocardiography were applied to observe whether the valve stent was implanted at the desired position. RESULTS: ChenValve prosthesis was successfully transppical implanted in all animals. The aortogram and transthoracic echocardiography performed immediately after implantation revealed that the valve stent was implanted at the desired position. There was no significant paravalvular leakage, obstruction of coronary artery ostia, stent malpositioning or dislodgement occurred. CONCLUSIONS: This preliminary trial with the novel double-layer ChenValve prosthesis demonstrated the feasibility of improved TAVI in noncalcified aortic valve. The mechanism of Nitinol ring-guided locating the aortic sinus enables us to anatomically correct position the artifact valve. This improved strategy seems to make the TAVI process more safe and repeatable in noncalcified aortic valve.

Correction to: Adipose mesenchymal stem cell exosomes promote wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis.

In the original publication of the article, the name of one of the corresponding authors was published incorrectly. The name should be 'Ke Tao' instead of 'Kao Tao'. The corrected author group is given in this Correction.

Adipose mesenchymal stem cell exosomes promote wound healing through accelerated keratinocyte migration and proliferation by activating the AKT/HIF-1α axis.

Accelerating wound healing is a key consideration for surgeons. The three stages of wound healing include the inflammatory response, cell proliferation and tissue repair, and much research has focused on the migration and proliferation of epidermal cells, since this is one of the most important steps in wound healing. Studies have shown that adipose mesenchymal stem cells (ADSCs) can promote wound healing by releasing exosomes, although the specific mechanism remains unclear. To clarify the role of adipose mesenchymal stem cell exosomes (ADSCs-exo), we constructed a HaCaT cells model and a mouse wound healing model to examine the effects of ADSCs-exo on wound healing. CCK8 assays and the scratch test showed that ADSCs-exo could promote the proliferation and migration of HaCaT cells. Western blotting and real-time PCR showed that ADSCs-exo upregulated the phosphorylation of AKT and the expression of HIF-1α in HaCaT cells. HIF-1α expression was reduced by inhibiting AKT phosphorylation,and the migration of HaCaT cells simultaneously slowed. These results were also confirmed in vivo. In conclusion, we confirmed that ADSCs-exo promote the proliferation and migration of HaCaT cells by regulating the activation of the AKT/HIF-1α signaling pathway, thus promoting wound healing.

Current status and factors influencing oral anticoagulant therapy among patients with non-valvular atrial fibrillation in Jiangsu province, China: a multi-center, cross-sectional study.

BACKGROUND: It has been reported that oral anticoagulation (OAC) is underused among Chinese patients with non-valvular atrial fibrillation (NVAF). Non-vitamin K antagonist oral anticoagulants (NOAC) have been recommended by recent guidelines and have been covered since 2017 by the Chinese medical insurance; thus, the overall situation of anticoagulant therapy may change. The aim of this study was to explore the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province. METHODS: This was a multi-center, cross-sectional study that was conducted in seven hospitals from January to September in 2017. The demographic characteristics and medical history of the patients were collected by questionnaire and from the medical records. Multivariate logistic regression was used to identify factors associated with anticoagulant therapy. RESULTS: A total of 593 patients were included in the analysis. A total of 35.6% of the participants received OAC (11.1% NOAC and 24.5% warfarin). Of those patients with a high risk of stroke, 11.1% were on NOAC, 24.8% on warfarin, 30.6% on aspirin, and 33.6% were not on medication. Self-paying, duration of AF ≥5 years were negatively associated with anticoagulant therapy in all patients (OR 1.724, 95% CI 1.086~2.794; OR 1.471, 95% CI 1.006~2.149, respectively), whereas, permanent AF was positively associated with anticoagulant therapy (OR 0.424, 95% CI 0.215~0.839). Among patients with high risk of stroke, self-paying and increasing age were negatively associated with anticoagulant therapy (OR 2.305, 95% CI 1.186~4.478; OR 1.087, 95% CI 1.041~1.135, respectively). CONCLUSIONS: Anticoagulant therapy is positively associated with permanent AF and negatively associated with self-paying, duration of AF > 5 years. Furthermore, the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province does not appear optimistic. Therefore, further studies should focus on how to improve the rate of OAC use among NVAF patients. In addition, policy makers should pay attention to the economic situation of the patients with NVAF using NOAC. TRIAL REGISTRATION: 2,017,029. Registered 20 March 2017 (retrospectively registered).

The timing of urinary catheter removal after gynecologic surgery: A meta-analysis of randomized controlled trials.

The present study aimed to assess the effect of removing an indwelling urinary catheter at different times on urinary retention and urinary infection in patients undergoing gynecologic surgery.Electronic databases including PubMed, EMbase, the Cochrane Central Register of Controlled Trials, and Ovid from inception to June 2018 were searched. Relevant randomized controlled trials (RCTs) of removal the indwelling urinary catheter in different time were included.Eight RCTs were included. Data were analyzed by RevMan 5.3 version. There was significant difference in urinary retention (relative risk [RR] 2.46, 95% confidence intervals [CIs] 1.10-5.53), P = .03) between the ≤6 hours and >6 hours indwelling urinary catheter removal groups, while no significant differences were found in the gynecologic surgery excluded the vaginal surgery group and vaginal surgery group. When compared with >6 hours indwelling urinary catheter removal group, the incidence of urinary infection was significantly reduced at the ≤6 hours removal group (RR = 0.66, 95% CI 0.48-0.89, P = .007). The urinary catheter removal time at ≤6 hours also significantly reduced the incidence of urinary retention (RR = 5.06, 95%CI 1.74-14.69, P = .003), and did not statistically increase the incidence of urinary infection (RR = 0.30, 95%CI 0.08 to 1.20, P = .09), compared with immediate urinary catheter removal after surgery.Removal time of the urinary catheter at ≤6 hours postoperatively seems to be more beneficial than immediate or >6 hours for patients undergoing gynecologic surgery which excluded the vaginal surgery.

High mobility group box 1 enables bacterial lipids to trigger receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis and apoptosis in mice.

Receptor-interacting protein kinase 3 (RIPK3) is a key regulator of programmed cell death and inflammation during viral infection or sterile tissue injury. Whether and how bacterial infection also activates RIPK3-dependent immune responses remains poorly understood. Here we show that bacterial lipids (lipid IVa or lipid A) form a complex with high mobility group box 1 (HMGB1), released by activated immune cells or damaged tissue during bacterial infection, and that this complex triggers RIPK3- and TIR domain-containing adapter-inducing IFN-ß (TRIF)-dependent immune responses. We found that these responses lead to macrophage death, interleukin (IL)-1α release, and IL-1ß maturation. In an air-pouch inflammatory infiltration model, genetic deletion of Ripk3, Trif, or IL-1 receptor (Il-1R), or monoclonal antibody-mediated HMGB1 neutralization uniformly attenuated inflammatory responses induced by Gram-negative bacteria that release lipid IVa and lipid A. These findings uncover a previously unrecognized mechanism by which host factors and bacterial components work in concert to orchestrate immune responses.

Toll-Like Receptor 4 Signaling Licenses the Cytosolic Transport of Lipopolysaccharide From Bacterial Outer Membrane Vesicles.

Outer membrane vesicles (OMVs), released by variety of bacteria, are membrane-enclosed entities enriched in microbial components, toxins, and virulent factors. OMVs could deliver lipopolysaccharide (LPS) into the cytosol of host cells and subsequently activate caspase-11, which critically orchestrates immune responses and mediates septic shock. Although it is known that caspase-11 is activated by intracellular LPS, how OMVs deliver LPS into the cytosol remains largely unknown. Here we show that the activation of toll-like receptor 4 (TLR4), a LPS receptor on the cytoplasmic membrane, licenses macrophages to transport LPS from OMVs into the cytosol through TIR domain-containing adaptor-inducing interferon-ß (TRIF). TRIF-mediated cytosolic delivery of LPS from OMVs depends on the production of type 1 interferon and the expression of guanylate-binding proteins (GBPs). Deletion of TRIF or GBPs prevents pyroptosis and lethality induced by OMVs or OMVs-releasing Escherichia coli. Together, these findings provide novel insight into how host coordinates extracellular and intracellular LPS sensing to orchestrate immune responses during gram-negative bacterial infection.

Mini-percutaneous nephrolithotomy for pediatric complex renal calculus disease: one-stage or two-stage?

OBJECTIVES: To compare two different treatment strategies, one-stage and two-stage multi-tract mini-percutaneous nephrolithotomy (mt-mPCNL), for pediatric complex renal calculus disease. METHODS: Between the period of July 2016 and July 2018, a total of 36 children aged 15 years and younger, with complex renal calculi disease, who underwent total ultrasound-guided mt-mPCNL by a single experienced urologist were enrolled in our study. All patients were assigned either to Group 1 (n = 18) who received one-stage mt-mPCNL or Group 2 (n = 18) who received planned two-stage mt-mPCNL. RESULTS: The demographic data were comparable between the two groups. There were no serious complications (Modified Clavien Grade ≥ III) observed in either group. The stone -free rate (SFR), operation time, postoperative creatinine increase, and perioperative complication rates were similar in both groups (P = 0.603, 0.818, 0.161, and 0.402, respectively). The postoperative hospital stay (5.8 days vs. 7.4 days) and cost (17373.3 CNY vs. 23717.1 CNY) were statistically less in Group 1. Group 2 had significantly less total estimated blood loss (70.6 ml vs. 130.0 ml, P < 0.001). The operation time of two cases in Group 1 with perioperative sepsis or systemic inflammatory response syndrome (SIRS) was more than two hours. CONCLUSIONS: Our preliminary results indicated that both one-stage and two-stage mt-mPCNL were safe and effective for pediatric complex renal calculi. Two-stage mt-mPCNL could significantly reduce blood loss; while one-stage mt-mPCNL could significantly decrease the length and costs of hospitalization. We also suggest that the planned two-stage mt-mPCNL should be applied in children with estimated operation time more than two hours.

Preliminary Research on Syndrome Types of Chinese Medicine in Children with Primary Nephrotic Syndrome.

OBJECTIVE: To provide an objective reference for the syndrome types of Chinese medicine (CM) associated with pediatric primary nephrotic syndrome (PNS). METHODS: A cross-sectional study was performed. Data on clinical symptoms, CM syndrome types, biochemical indices, and medications used were collected from 98 children with PNS. Then, the correlation between CM syndromes and biochemical indices, as well as medications used, was analyzed. RESULTS: The four most common symptoms in children with PNS were brown urine, red tongue, excessive sweating, and swelling of the face and limbs. The syndromes of qi deficiency of Fei (Lung) and Shen (Kidney) (FSQD) and yin deficiency of Gan (Liver) and Shen (GSYD) were the most common main CM syndrome types. FSQD syndrome score correlated significantly with the total cholesterol level, urine protein/creatinine ratio, and urine IgG and albumin levels (P<0.01 or P<0.05). The use of maintenance glucocorticoids combined with immunosuppressive agents correlated with FSQD syndrome, and the use of maintenance glucocorticoids alone correlated with GSYD syndrome (P<0.05). CONCLUSION: Two of the most common CM syndrome types were FSQD and GSYD syndromes. FSQD syndrome may be caused by some factors related to lipid levels, protein loss, and the use of immunosuppressive agents. The use of maintenance glucocorticoids may cause GSYD syndrome.