An inhibitor of leukotriene-A4 hydrolase from bat salivary glands facilitates virus infection.

SignificanceAn immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A4 hydrolase (LTA4H) to produce the lipid chemoattractant leukotriene B4 (LTB4), was identified and characterized from the submandibular salivary glands of the bat Myotis pilosus. To the best of our knowledge, this is a report of an endogenous LTA4H inhibitor in animals. MTX was highly concentrated in the bat salivary glands, suggesting a mechanism for the generation of immunological privilege and immune tolerance and providing evidence of viral shedding through oral secretions. Moreover, given that the immunosuppressant MTX selectively inhibited the proinflammatory activity of LTA4H, without affecting its antiinflammatory activity, MTX might be a potential candidate for the development of antiinflammatory drugs by targeting the LTA4-LTA4H-LTB4 inflammatory axis.

A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive. METHODS: The differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database. CircPDHK1 expression in ccRCC and adjacent noncancerous tissues (n = 148) were evaluated along with clinically relevant information. RT-qPCR, RNase R digestion, and actinomycin D (ActD) stability test were conducted to identify the characteristics of circPDHK1. The subcellular distribution of circPDHK1 was analyzed by subcellular fractionation assay and fluorescence in situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) and immunofluorescence (IF) were employed to evaluate the protein-coding ability of circPDHK1. ccRCC cells were transfected with siRNAs, plasmids or lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPDHK1 and its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays were further employed to identify the underlying mechanisms regulated by PDHK1-241aa. RESULTS: CircPDHK1 was upregulated in ccRCC tissues and closely related to WHO/ISUP stage, T stage, distant metastasis, VHL mutation and Ki-67 levels. CircPDHK1 had a functional internal ribosome entry site (IRES) and encoded a novel peptide PDHK1-241aa. Functionally, we confirmed that PDHK1-241aa and not the circPDHK1 promoted the proliferation, migration and invasion of ccRCC. Mechanistically, circPDHK1 was activated by HIF-2A at the transcriptional level. PDHK1-241aa was upregulated and interacted with PPP1CA, causing the relocation of PPP1CA to the nucleus. This thereby inhibited AKT dephosphorylation and activated the AKT-mTOR signaling pathway. CONCLUSIONS: Our data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.

Bioinformatics analysis and experimental validation reveal the anti-ferroptosis effect of FZD7 in acute kidney injury.

BACKGROUND: Ferroptosis plays an important role in acute kidney injury (AKI), but the specific regulatory mechanism of ferroptosis in AKI remains unclear. This study is expected to analyze ferroptosis-related genes (FRGs) in AKI and explore their underlying mechanisms. RESULTS: A total of 479 differentially expressed genes (DEGs), including 196 up-regulated genes and 283 down-regulated genes were identified in the AKI chip GSE30718. 341 FRGs were obtained from the Genecard, OMIM and NCBI database. Totally 11 ferroptosis-related DEGs in AKI were found, in which 7 genes (CD44, TIGAR, RB1, LCN2, JUN, ARNTL, ACSL4) were up-regulated and 4 genes (FZD7, EP300, FOXC1, DLST) were down-regulated. Three core genes (FZD7, JUN, EP300) were obtained by PPI and KEGG analysis, among which the function of FZD7 in AKI is unclear. The WGCNA analysis found that FZD7 belongs to a module that was negatively correlated with AKI. Further basic experiments confirmed that FZD7 is down-regulated in mouse model of ischemia-reperfusion-AKI and cellular model of hypoxia-reoxygenation(H/R). In addition, knockdown of FZD7 could further aggravate the down-regulation of cell viability induced by H/R and Erastin, while overexpression of FZD7 can rescue its down-regulation to some extent. Furthermore, we verified that knockdown of FZD7 decreased the expression of GPX4 and overexpression of FZD7 increased the expression of GPX4, suggesting that FZD7 may inhibit ferroptosis by regulating the expression of GPX4 and plays a vital role in the onset and development of AKI. CONCLUSIONS: This article revealed the anti-ferroptosis effect of FZD7 in acute kidney injury through bioinformatics analysis and experimental validation, suggesting that FZD7 is a promising target for AKI and provided more evidence about the vital role of ferroptosis in AKI.

Efficacy of Telitacicept in a systemic lupus erythematosus patient with suboptimal response to Belimumab: A case report.

As a therapeutic treatment for systemic lupus erythematosus (SLE), Belimumab reduces disease relapses and minimizes organ damage. Clinical practice, however, shows that the treatment is ineffective for a number of patients. Treatments for such cases are still lacking. As a biologic agent that targets both BLys and APRIL, Telitacicept inhibits both B cells and plasma cells. This case report describes a 35-year-old female with lupus nephritis (LN) who had previously undergone 10 cycles of Belimumab treatment but remained poorly controlled. Despite this, her condition improved significantly after switching to Telitacicept. This is the first report on the efficacy of Telitacicept in an SLE patient with suboptimal response to Belimumab. Telitacicept's role in this scenario needs more investigation and attention.

Identification of Plasma hsa_circ_0001230 and hsa_circ_0023879 as Potential Novel Biomarkers for Focal Segmental Glomerulosclerosis and circRNA-miRNA-mRNA Network Analysis.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is a common glomerulopathy with an unclear mechanism. The demand for FSGS clinical diagnostic biomarkers has not yet been met. Circular RNA (circRNA) is a novel non-coding RNA with multiple functions, but its diagnostic value for FSGS remains unexplored. This study aimed to identify circRNAs that could aid in early clinical diagnosis and to investigate their mechanisms in podocyte injury. METHODS: The signature of plasma circRNAs for FSGS was identified by circRNA microarray. The existence of circRNAs was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR), RNase R assay, and DNA sequencing. Plasma levels of circRNAs were evaluated by qRT-PCR. The diagnostic value was appraised by the receiver operating characteristic curve. The circRNA-miRNA-mRNA network was built with Cytoscape 7.3.2. Statistically significant differences were calculated by the Mann-Whitney U test. RESULTS: A total of 493 circRNAs (165 upregulated, 328 downregulated) were differentially expressed in the plasma of FSGS patients (n = 3) and normal controls (n = 3). Eight candidate circRNAs were demonstrated to be circular and stable transcripts. Among them, hsa_circ_0001230 and hsa_circ_0023879 were significantly upregulated in FSGS patients (n = 29) compared to normal controls (n = 51). The areas under the curve value of hsa_circ_0001230 and hsa_circ_0023879 were 0.668 and 0.753, respectively, while that of the two-circRNA panel was 0.763. The RNA pull-down analysis revealed that hsa_circ_0001230 and hsa_circ_0023879 could sponge hsa-miR-106a. Additionally, hsa_circ_0001230 and hsa_circ_0023879 positively regulated hsa-miR-106a target genes phosphatase and tensin homolog (PTEN) and Bcl-2-like protein 11 (BCL2L11) in podocytes. CONCLUSION: hsa_circ_0001230 and hsa_circ_0023879 are novel blood biomarkers for FSGS. They may regulate podocyte apoptosis by competitively binding to hsa-miR-106a.

Comparing the interactions of nitrendipine with lysozyme or human serum albumin and the effects of vitamin C and naringin on these interactions by spectroscopy and molecular docking methods.

The interactions between drugs and proteins play a pivotal role in determining the pharmacological effects and disposition of drugs within the human body. This study focuses on exploring the interaction between nitrendipine and lysozyme/human serum albumin. Spectroscopic analysis indicated a compound static quenching, indicative of the formation of stable complexes between the drug and proteins. The addition of vitamin C or naringin resulted in a decrease of the binding constant between nitrendipine and lysozyme/human serum albumin. The presence of these compounds may disrupt the interactions between the drug and proteins, potentially leading to an increased concentration of free nitrendipine in the bloodstream. Nitrendipine binds more easily to human serum albumin at 310 K, and human serum albumin has an average binding site ratio with nitrendipine approximately 0.1 higher than that with lysozyme. Vitamin C has a greater impact on the binding constant of nitrendipine to human serum albumin and lysozyme. Compared to the binary system of proteins with the drug, the ternary system with the addition of vitamin C at 310 K reduces the binding constants of lysozyme and human serum albumin by 85%. In conclusion, this study explores the significance of considering drug-protein interactions in understanding drug behavior and potential drug-food interactions.

Clinical features and prognosis of pregnancy-related renal damage and pregnancy after chronic kidney disease.

OBJECTIVE: To explore the clinical features of renal damage related to pregnancy and pregnancy after chronic kidney disease (CKD), providing clinical evidence for the relationship between renal damage and pregnancy. METHODS: A retrospective analysis was performed on patients admitted to our hospital between March 2013 and February 2021 who had both pregnancy and kidney damage. The study collected pathology results from renal biopsies, 24-hour urinary protein quantity, albumin (Alb), serum creatinine (Scr), blood lipids, coagulation function, blood routine, and other indicators during and after pregnancy. RESULTS: This study included 82 cases, with 48 cases in the pregnancy-related renal damage group. Thirty-four cases were in the post-CKD pregnancy group. Of the patients, 30 cases (88.24%) had CKD stage 1-2. Results showed better pregnancy and fetal outcomes in the post-CKD pregnancy group compared to the pregnancy-related renal damage group (Ρ was 0.029 and 0.036, respectively). Renal biopsy pathology revealed that 16 cases (33.33%) in the pregnancy-related renal damage group mainly had focal segmental glomerulosclerosis (FSGS), while the post-CKD pregnancy group was dominated by 14 cases (43.75%) of IgA nephropathy. The first blood test indicators revealed that the pregnancy-related renal damage group had lower estimated glomerular filtration (eGFR) and Alb levels compared to the post-CKD pregnancy group (Ρ was 0.003 and 0.000, respectively). Additionally, 24-hour urinary protein quantity, total cholesterol (Tch), triglyceride (TG), and platelet (PLT) counts were higher in the pregnancy-related renal damage group compared to the post-CKD pregnancy group (Ρ was 0.005, 0.001, 0.008, and 0.031, respectively). The abnormal rate of Scr during pregnancy was 41.67% (20/48) in the pregnancy-related renal damage group and 17.39% (4/23) in the post-CKD pregnancy group, with a statistically significant difference (Ρ was 0.043). CONCLUSION: The pregnancy-related renal damage group is mainly associated with FSGS, while the post-CKD pregnancy group is characterized by IgA nephropathy. Patients with CKD1-2 can have a successful pregnancy after achieving good control of eGFR, albumin, 24-hour urinary protein quantity and other indicators, resulting in better pregnancy and fetal outcomes. Abnormal Scr levels during pregnancy of pregnancy-related renal damage can be improved within 3 months after delivery.

Role of LL-37 in thrombotic complications in patients with COVID-19.

Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.

Bleeding due to successive duodenal and rectal ulcers in an 81-year-old patient with severe COVID-19: a case report.

BACKGROUND: In the early stages of the coronavirus disease 2019 (COVID-19) outbreak, the most widely recognised symptoms of the disease were fever, cough, shortness of breath, myalgia, and fatigue. However, in addition to these symptoms, COVID-19 can cause systemic symptoms outside the lungs. Older patients with severe COVID-19 often require admission to the intensive care unit (ICU). Acute rectal ulcer bleeding, characterised by painless, profuse haematochezia, caused by solitary or multiple rectal ulcers, is one of the main causes of severe haematochezia in patients with COVID-19 in the ICU. However, recurrent duodenal ulcer bleeding followed by rectal ulcer bleeding has not previously been reported in older patients during ICU treatment for severe COVID-19. CASES PRESENTATION: Herein, we report the case of an 81-year-old woman admitted to the emergency department due to severe COVID-19 and transferred to the ICU 2 days later for treatment. During treatment in the ICU, the patient developed recurrent duodenal ulcer bleeding and underwent endoscopic electrocoagulation haemostasis and gastroduodenal artery embolisation. However, the night after the final haemostatic operation, due to rectal ulcer bleeding, the patient discharged bloody stools intermittently, which was effectively controlled using endoscopic electrocoagulation, topical medication, blood transfusion, and haemostatic drugs. CONCLUSIONS: To the best of our knowledge, this is the first report of duodenal ulcer bleeding followed by rectal ulcer bleeding in an older patient with severe COVID-19 infection. This report creates awareness for clinicians about the multiple and complex gastrointestinal symptoms that may occur during COVID-19 treatment.

Electrochemical biomimetic enzyme cascade amplification combined with target-induced DNA walker for detection of thrombin.

Fe-N-doped carbon nanomaterials (Fe-N/CMs) were designed as a novel biomimetic enzyme with excellent peroxidase-like activity to achieve high-efficient enzyme cascade catalytic amplification with the aid of glucose oxidase (GOx), which was further combined with target-induced DNA walker amplification to develop a sensitive electrochemical biosensor for thrombin detection. Impressively, massive output DNA was transformed from small amounts of target thrombin by highly effective DNA walker amplification as protein-converting strategy, which could then induce the immobilization of functionalized nanozyme on the electrode surface to achieve the high-efficient electrochemical biomimetic enzyme cascade amplification. As a result, an amplified enzyme cascade catalytic signal was measured for thrombin detection ranging from 0.01 pM to 1 nM with a low detection limit of 3 fM. Importantly, the new biomimetic enzyme cascade reaction coupled the advantages of natural enzyme and nanozyme, which paved an avenue to construct varied artificial multienzymes amplification systems for biosensing, bioanalysis, and disease diagnosis applications.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

Discriminant models for the prediction of postponed viral shedding time and disease progression in COVID-19.

BACKGROUND: COVID-19 infection can cause life-threatening respiratory disease. This study aimed to fully characterize the clinical features associated with postponed viral shedding time and disease progression, then develop and validate two prognostic discriminant models. METHODS: This study included 125 hospitalized patients with COVID-19, for whom 44 parameters were recorded, including age, gender, underlying comorbidities, epidemiological features, laboratory indexes, imaging characteristics and therapeutic regimen, et al. Fisher's exact test and Mann-Whitney test were used for feature selection. All models were developed with fourfold cross-validation, and the final performances of each model were compared by the Area Under Receiving Operating Curve (AUROC). After optimizing the parameters via L2 regularization, prognostic discriminant models were built to predict postponed viral shedding time and disease progression of COVID-19 infection. The test set was then used to detect the predictive values via assessing models' sensitivity and specificity. RESULTS: Sixty-nine patients had a postponed viral shedding time (> 14 days), and 28 of 125 patients progressed into severe cases. Six and eleven demographic, clinical features and therapeutic regimen were significantly associated with postponed viral shedding time and disease progressing, respectively (p < 0.05). The optimal discriminant models are: y1 (postponed viral shedding time) = - 0.244 + 0.2829x1 (the interval from the onset of symptoms to antiviral treatment) + 0.2306x4 (age) + 0.234x28 (Urea) - 0.2847x34 (Dual-antiviral therapy) + 0.3084x38 (Treatment with antibiotics) + 0.3025x21 (Treatment with Methylprednisolone); y2 (disease progression) = - 0.348-0.099x2 (interval from Jan 1st,2020 to individualized onset of symptoms) + 0.0945x4 (age) + 0.1176x5 (imaging characteristics) + 0.0398x8 (short-term exposure to Wuhan) - 0.1646x19 (lymphocyte counts) + 0.0914x20 (Neutrophil counts) + 0.1254x21 (Neutrphil/lymphocyte ratio) + 0.1397x22 (C-Reactive Protein) + 0.0814x23 (Procalcitonin) + 0.1294x24 (Lactic dehydrogenase) + 0.1099x29 (Creatine kinase).The output ≥ 0 predicted postponed viral shedding time or disease progressing to severe/critical state. These two models yielded the maximum AUROC and faired best in terms of prognostic performance (sensitivity of78.6%, 75%, and specificity of 66.7%, 88.9% for prediction of postponed viral shedding time and disease severity, respectively). CONCLUSION: The two discriminant models could effectively predict the postponed viral shedding time and disease severity and could be used as early-warning tools for COVID-19.

Unexpected Complication of Central Venous Catheter Exchange: Catheter Fragment Migration.

Tunneled central venous catheter (TCVC) placement is often an easy and uncomplicated procedure. As such, some clinicians pay little attention to the procedure, and different complications occurred. Catheter fragment loss in major vessels is a rare but serious complication of in situ catheter exchange with few reported cases in the literature. Once catheter fragments slip into a deep vein, endovascular retrieval should be attempted, due to its high success rate and minimal associated morbidity. A 37-year-old male patient underwent replacement of his temporary catheter with TCVC through a trans-right-internal-jugular-vein approach for maintenance of dialysis. As a major unintended outcome of the operation, a catheter fragment slipped into the right internal jugular vein, then migrated and lodged in the inferior vena cava. We retrieved it with a gooseneck snare without complications. We report the case hoping to emphasize on and raise awareness of the fact that catheter fragment loss is a completely evitable complication, provided the operator follows the correct safety measures and protocols. However, if catheter fragment loss occurred, the fragment should be retrieved as soon as possible. A gooseneck snare is an ideal option for retrieving catheter fragments that have migrated into deep veins.

A novel urine cell-free DNA preservation solution and its application in kidney transplantation.

AIM: Urine cell-free DNA (cfDNA) is a new type of liquid biopsy biomarker used in tumours and allograft injury detection but is highly susceptible to degradation by the high nuclease activity of urine. This study presents a newly developed urine cfDNA preservation solution (AlloU), efficient for examining allograft injury in kidney transplant recipients (KTx). METHODS: We established urine-preserve solution called AlloU based on the response-surface methodology, with two commercial collection reagents (Streck and K2 EDTA preservation solution) included for analysis. A total of 120 urine samples from KTx patients, including morning, nocturnal and random urine from specific storage time were subjected to investigation. The urine total cfDNA concentration was quantified by fluorometry, fragment distribution was analysed by qPCR, and donor-derived cfDNA (ddcfDNA) was detected by next-generation sequencing. RESULTS: Urine total cfDNA concentration and fragment size of samples preserved with AlloU and Streck did not change significantly within 5 days whereas the ddcfDNA also did not change significantly within 7 days. However, compared with EDTA, the total cfDNA concentration increased significantly on the third day. When compare with different urine types, it was found that samples preserved with AlloU showed no significant differences in total cfDNA concentration, fragment size, and ddcfDNA concentration, however, the SD for morning urine was significantly smaller in total cfDNA and ddcfDNA concentration. CONCLUSION: To the best of our knowledge, this is the first report to verify the dynamics of urine cfDNA in KTx, especially in the analysis impact of different urine types on cfDNA detection.

Successful Treatment of Allopurinol-Induced Severe Skin Reactions with Double Filtration Plasmapheresis: A Case Report.

Severe cutaneous adverse reactions (SCAR) are uncommon and acute and frequently represent a drug reaction. For years, allopurinol use has remained the highest risk factor for SCARs worldwide. There are multiple risk factors for allopurinol-induced SCARs, including genetic and non-genetic factors. Renal failure has been found to be an important factor resulting in allopurinol-induced SCARs with greater severity and poorer prognosis. An 80-year-old female was admitted to our hospital after administration of allopurinol in December 2018. She developed erythaematous skin of the epidermis of the hips, which rapidly extended over the trunk and limbs, resulting in itching and flaking. The presumptive diagnosis was a drug-induced SCAR. Despite treatment with glucocorticoids and kidney support therapy, the skin lesions extended over the entire body. Fortunately, the progression of pruritic erythema was stopped by double-filtration plasmapheresis (DFPP). DFPP was discontinued after the signs of skin inflammation were no longer visible. Her skin, but not kidney function, recovered after 10 days of hospitalization. She tolerated DFPP well without development of any severe complications. We present here a case of allopurinol-induced SCAR, which was successfully treated with DFPP.

Antibiotic treatment regimens for bone infection after debridement: a study of 902 cases.

BACKGROUND: Our aim was to investigate the clinical efficacy and complications of antibiotic treatment regimens for patients with bone infection. METHODS: We retrospectively analysed patients with bone infection admitted to our hospital between March 2013 and October 2018. After surgical debridement was performed, the patients were divided into three groups: IV group (intravenous antibiotics for 2 weeks); oral group (intravenous antibiotics for 2 weeks followed by oral antibiotics for 4 weeks); and rifampicin group (intravenous antibiotics for 2 weeks followed by oral antibiotics plus rifampicin for 4 weeks). The infection control rate and complications were compared among the three groups. RESULTS: A total of 902 patients were enrolled. The infection sites included 509 tibias, 228 femurs, 32 humeri, 23 radii and ulnae, 40 calcanei, and 47 miscellaneous sites, as well as 23 multiple-site infections. After at least 6 months of follow-up, 148 (16.4%) patients had an infection recurrence. The recurrence rate of the IV group was 17.9%, which was not significantly higher than the recurrence rates of the oral group (10.1%) and rifampicin group (10.5%), P = 0.051. The incidence of abnormal alanine aminotransferase (ALT) levels in the IV group was 15.1%, which was lower than that in the oral group (18.0%) and rifampicin group (27.4%), P = 0.026. The rates of proteinuria in the three groups were 3.2, 4.5, and 9.3%, respectively, P = 0.020. CONCLUSIONS: After debridement of bone infection, short-term antibiotic treatment regimens might offer similar rates of infection eradication while avoiding the risk of renal and hepatic damage associated with prolonged antibiotic use. THE LEVEL OF CLINICAL RELEVANCE: Stage III.

Expression of SUMO1P3 Compared with SUMO1 is an Independent Predictor of Patient Outcome in Lung Adenocarcinoma.

BACKGROUND The small ubiquitin-like modifier 1 (SUMO1) and small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) are long noncoding RNAs (lncRNAs). The prognostic significance of SUMO1 and SUMO1P3 expression in non-small cell lung cancer (NSCLC) remains unclear. This study aimed to use clinical, genetic, and survival data from the Cancer Genome Atlas (TCGA), to analyze the prognostic significance of SUMO1 and SUMO1P3 expression in the two main subtypes of NSCLC, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MATERIAL AND METHODS Data were acquired from TCGA and in silico survival analysis was performed. SUMO1 and SUMO1P3 expression were compared between patients with LUAD and LUSC. Patient outcome was assessed as complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). Recurrence-free survival (RFS) was defined as the survival time from primary surgery to the time of locoregional or distant recurrence of lung cancer. RESULTS SUMO1P3 was significantly increased in LUSC and LUAD tissues compared with adjacent normal lung tissue and was significantly co-expressed with SUMO1. SUMO1P3 expression was significantly increased in patients with LUAD but not LUSC with reduced RFS after primary or follow-up treatment. Although patients with LUAD who had high SUMO1 or SUMO1P3 expression had reduced RFS compared with low expression groups, univariate and multivariate analysis showed that only SUMO1P3 expression was independently associated reduced RFS (HR, 1.418; 95% CI, 1.041-1.930; p=0.027). CONCLUSIONS SUMO1P3 expression was an independent indicator of reduced RFS in patients with LUAD.

Effect of Jet Nebulization on Noninvasive Positive-Pressure Ventilation Administered with Noninvasive or Intensive Care Unit Ventilators: A Bench Study.

BACKGROUND: Most of the patients on noninvasive positive pressure ventilation require aerosol inhalation therapy to moisturize the airways or deliver drugs in acute settings. However, the effect of jet nebulization on noninvasive positive pressure ventilation (NPPV) has not been determined. OBJECTIVES: This study was designed to investigate the impact of jet nebulization on NPPV applied in ventilators. METHODS: Aerosol therapy during NPPV was conducted in a simulated lung. The jet nebulizer was connected at both the distal and proximal end of the exhalation valve for the noninvasive ventilators, while it was placed both in front of the Y tube proximal to the patient and at 15 cm distance from the Y-tube inspiratory limb distal to the patient for the intensive care unit (ICU) ventilators. Driving flow was set at 4 and 8 L/min, respectively. RESULTS: TPmin (time from the beginning of the lung simulator's inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator), Ttrig (time to trigger), and Ptrig (the magnitude of airway pressure drop needed to trigger) were not significantly altered by jet nebulization in the noninvasive ventilators, while they were significantly increased in the ICU ventilators. The greater the driving flow, the stronger the impact on TPmin, Ttrig, and Ptrig. The actual tidal volume and control performance were not significantly affected by jet nebulization in either noninvasive or ICU ventilators. The tidal volume monitored was significantly increased at 8 L/min driving flow. The greater the driving flow, the stronger the impact on the tidal volume monitored. CONCLUSION: The effect of jet nebulization on NPPV was different when compared to invasive ventilation. Jet nebulization only affected the tidal volume monitored in the noninvasive ventilator. Jet nebulization also affected the triggering performance and tidal volume monitored in the ICU ventilator.

Anatomy Revisited: Hemodialysis Catheter Malposition into the Chest.

In most situations, central catheters are implanted in the right jugular vein as initial access for hemodialysis. However, after repeated punctures, the proximal vessels become stenosed and thrombosed and misplacement is likely to occur. Correct catheter position in the vein can be easily ascertained with X-ray or cross-sectional CT imaging. In this report, we describe the case of a 77-year-old patient on chronic hemodialysis via catheter due to arteriovenous fistula dysfunction. We placed a cuffed-tunneled hemodialysis catheter in the left internal jugular vein. Malpositioning of the catheter led to perforation of the great veins and migration of the catheter tip into the chest. It is important to be aware of the risk of potential incorrect positioning of dialysis catheters. Due to the stenosis and fragility of the vessel wall, perforation may occur. In cases of doubt, correct placement of large-bore catheters via the internal jugular vein should be verified by means of appropriate imaging before hemodialysis is performed.

Plasmapheresis Therapy in Kidney Transplant Rejection.

Kidney transplantation (KT) is considered an optimal treatment strategy for end-stage renal disease. But human leukocyte antigen-sensitized, ABO-incompatible and antibody-mediated rejection might be the alarming hurdles in KT. Therapeutic plasma exchange is the mainstay of the antibody reduction therapy for reducing autoantibody more effectively. Even in the treatment for highly sensitized patients, it has played an indispensable role. However, clinicians should tailor therapies to individual patient's needs and multimodal treatment will bring better outcomes. Early diagnosis and precise treatment would reduce morbidity, mortality, and economic costs.