Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation.

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.

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 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 qRT-PCR, RNase R assay, and DNA sequencing. Plasma levels of circRNAs were evaluated by qRT-PCR. The diagnostic value was appraised by 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 two-circRNAs 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.

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.

Metagenomic Analysis Reveals A Gut Microbiota Structure and Function Alteration between Healthy and Diarrheic Juvenile Yaks.

Diarrhea-induced mortality among juvenile yaks is highly prevalent in the pastoral areas of the Qinghai-Tibet plateau. Although numerous diseases have been linked to the gut microbial community, little is known about how diarrhea affects the gut microbiota in yaks. In this work, we investigated and compared changes in the gut microbiota of juvenile yaks with diarrhea. The results demonstrated a considerable drop in the alpha diversity of the gut microbiota in diarrheic yaks, accompanied by Eysipelatoclostridium, Parabacteroides, and Escherichia-Shigella, which significantly increased during diarrhea. Furthermore, a PICRust analysis verified the elevation of the gut-microbial metabolic pathways in diarrhea groups, including glycine, serine, and threonine metabolism, alanine, aspartate, oxidative phosphorylation, glutamate metabolism, antibiotic biosynthesis, and secondary metabolite biosynthesis. Taken together, our study showed that the harmful bacteria increased, and beneficial bacteria decreased significantly in the gut microbiota of yaks with diarrhea. Moreover, these results also indicated that the dysbiosis of the gut microbiota may be a significant driving factor of diarrhea in yaks.

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.

Massive Airway Bleeding Caused by Pulmonary Strongyloidiasis in a Patient with a Transplanted Kidney.

Introduction: We report a fatal case of massive airway bleeding caused by pulmonary strongyloidiasis in a patient with a transplanted kidney. Case Presentation: A 47-year-old male, regularly taking immunosuppressants post-kidney transplant, visited our hospital with symptoms of abdominal bloating, nausea, and emesis persisting for three days. After hospitalization, he developed a cough, hemoptysis, and respiratory failure. Sputum analysis confirmed an infestation with Strongyloides stercoralis. Despite receiving albendazole therapy and bronchoscopic management for bronchial hemorrhage, the patient ultimately died due to acute respiratory and circulatory collapse triggered by severe airway bleeding. Conclusion: Patients undergoing immunosuppressive therapy following kidney transplantation are at increased risk for disseminated strongyloidiasis. Consequently, infectious disease screening prior to transplantation, along with essential preventive pharmacotherapy, is of paramount importance.

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).

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.

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.

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.

Case Report: Comprehensive Management of Pneumocystis Jiroveci Pneumonia (PJP) and Secondary Infections of Multiple-Drug Resistant Enterobacter cloacae complex and Pseudomonas aeruginosa in a Kidney Transplant Recipient with Sulfonamide Allergies.

We report a case of pneumocystis jiroveci pneumonia (PJP) in a 46-year-old woman, who previously underwent kidney transplant for chronic renal failure. She did not receive PJP prophylaxis treatment for the history of sulfonamide allergies. Four months after renal transplantation, the patient had cough, chest tightness, and shortness of breath. Procalcitonin (PCT) (0.06 ng/mL) and C-reactive protein (CRP) (5.33 mg/L) were normal, but the level of 1, 3-ß-D-glucan test (G test, 193.89 pg/mL) were elevated. Metagenomics next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) rapidly and accurately identified P. jiroveci. Through sulfonamide desensitization and sulfamethoxazole-trimethoprim (TMP-SMX) combined with caspofungin (CAS) treatment, PJP was controlled. However, the patients' conditions were worsen for the hospital-acquired secondary pulmonary infection. A second BALF mNGS identified Enterobacter cloacae complex and Pseudomonas aeruginosa carrying carbapenem drug resistance genes, which were confirmed by subsequent culture and antimicrobial susceptibility test within 3 days. Finally, symptoms, such as chest tightness, cough, and shortness of breath, were improved and she was discharged after combined treatment with meropenem (MEM), polymyxin B (PMB), CAS, and TMP-SMX. In this case, mNGS, culture, and drug susceptibility testing were combined to monitor pathogenic microbial and adjust medication. At present, there are no case reports of mNGS use and sulfonamide desensitization in a kidney transplant recipient with sulfonamide allergies.

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.

Efficacy and Safety of Sevelamer Carbonate in Chinese Nondialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized, Double-Blind, Parallel-Group Study.

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

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.

Prophylactic Administration with Methylene Blue Improves Hemodynamic Stabilization During Obstructive Jaundice-Related Diseases' Operation: a Blinded Randomized Controlled Trial.

OBJECTIVES: Patients with obstruction jaundice are at a high risk of hypotension and need high volume of fluids and a high dose of catecholamine to maintain organ perfusion during operation procedure. All these likely contribute to high perioperative morbidity and mortality. The aim of the study is to evaluate the effects of methylene blue on the hemodynamics in patients undergoing surgeries associated with obstructive jaundice. DESIGN: A prospective, randomized, and controlled clinical study. SETTING: The enrolled patients randomly received 2 mg/kg of methylene blue in saline or saline (50 ml) before anesthesia induction. The primary outcome was the frequency and dose of noradrenaline administration to maintain mean arterial blood pressure over 65 mmHg or > 80% of baseline, and systemic vascular resistance (SVR) over 800 dyne/s/cm5 during operation. The secondary outcomes were liver and kidney functions, and ICU stay. PATIENTS: Seventy patients were enrolled in the study and randomly assigned to receive either methylene blue or control (n = 35/group). RESULTS: Fewer patients received noradrenaline in the methylene blue group when compared with the control group (13/35 vs 23/35, P = 0.017), and the noradrenaline dose administrated during operation was reduced in the methylene blue group when compared with the control group (0.32 ± 0.57 mg vs 1.787 ± 3.51 mg, P = 0.018). The blood level of creatinine, glutamic oxalacetic transaminase, and glutamic-pyruvic transaminase after the operation was reduced in the methylene blue group when compared with the control group. CONCLUSIONS: Prophylactic administration of methylene blue before operation associated with obstructive jaundice improves hemodynamic stability and short-term prognosis. QUESTION: Methylene blue use prevented refractory hypotension during cardiac surgery, sepsis, or anaphylactic shock. It is still unknown that methylene blue on the vascular hypo-tone associated with obstructive jaundice. FINDINGS: Prophylactic administration with methylene blue improved peri-operative hemodynamic stability, and hepatic and kidney function on the patients with obstructive jaundice. MEANINGS: Methylene blue is a promising and recommended drug for the patients undergoing the surgeries of relief obstructive jaundice during peri-operation management.

Clinical characteristics and prognosis of pulmonary renal syndrome in West China.

Pulmonary renal syndrome (PRS) is a rare and life-threatening syndrome. Interstitial lung disease (ILD) has been recently considered another phenotype of lung dysfunction in patients with PRS, but there are very limited data. The characteristics of fifty PRS patients were retrospectively reviewed after a 3-year follow-up, and the differences between PRS patients whose lung dysfunction presented as diffuse alveolar hemorrhage (DAH group) and those with interstitial lung disease (ILD group) were also analyzed. The median age at diagnosis of PRS patients was 50.78 ± 17.88 years, and the main symptoms at disease onset were proteinuria (94.00%), hemoptysis (68.00%), dyspnea (32.00%) and fever (12.00%). DAH patients were younger and had significantly lower hemoglobin levels, a higher incidence of hemoptysis, and higher serum creatinine levels at onset than ILD patients. Univariate analyses of PRS patients showed that respiratory failure and the initiation of mechanical ventilation predicted patient death and that the initiation of hemodialysis and higher serum creatinine levels at onset predicted ESRD. Multivariate analyses showed that respiratory failure and anti-GBM antibody positivity could independently predict patient death. Survival analyses showed that 1- and 3-year patient survival rates and ESRD-free survival rate were not significantly different between the two groups. ILD was another important phenotype of lung dysfunction in patients with PRS. Poor outcomes were observed in PRS patients with ILD and in PRS patients with DAH.

Effects of jet nebulization on ventilator performance with different invasive ventilation modes: A bench study.

Background: The effects of jet nebulization on ventilator performance in the volume control mode (VC) and pressure control mode (PC) of ventilation have not been determined. Objectives: The present study investigated the impact of jet nebulization on ventilator performance in different modes in vitro. Methods: Two types of jet nebulizer (ventilator-integrated jet nebulizers, external jet nebulizer) and six types of ventilator were connected with a simulated lung to simulate aerosol therapy during mechanical ventilation. The ventilation modes were set to VC and PC, and the driving flows of external jet nebulizer were set at 4 L/min and 8 L/min, respectively. Jet nebulizers were placed between patient airway and Y-piece or at 15 cm from the Y-piece in the inspiratory limb. The effects of jet nebulization were compared with the baseline of triggering performance, control performance, and tidal volume under different experimental conditions. Results: Ventilator-integrated jet nebulizers had no effect on ventilator performance in different modes (all P > 0.05). However, the effects of external jet nebulizers on ventilator performance varied widely: for triggering performance, all parameters were increased in different modes and nebulization positions (all P < 0.05), including the time from the beginning of the inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator (TPmin), the time to trigger (Ttrig), and the magnitude of airway pressure drop needed to trigger (Ptrig); for control performance, peak inspiratory pressure (Ppeak) and peak inspiratory flow(Pflow) were increased in the VC mode (P < 0.05), but not significantly changed in the PC mode (P > 0.05);the actual tidal volume (VT) and expiratory tidal volume monitored (VTe) were significantly increased (P < 0.05), however, the inspiratory tidal volume monitored (VTi) was not affected by jet nebulization in the VC mode. In the PC mode, there were no significant changes in VT, whereas VTi decreased and VTe increased (P < 0.05). The higher the driving flow of external jet nebulizers, the stronger the impact on ventilator performance (all P < 0.05). Conclusion: Triggering performance was decreased in both the VC and PC modes when using an external jet nebulizer, while the effects of nebulization on control performance and tidal volume varied significantly.

Position of different nebulizer types for aerosol delivery in an adult model of mechanical ventilation.

Background: The optimal positions of different types of nebulizer for aerosol delivery remain unclear. Methods: Three ICU ventilators employing three types of nebulizer were separately connected to a simulated lung to simulate nebulization during invasive ventilation. Assist/control-pressure control (A/C-PC) mode was utilized, with inspiratory pressure (Pi) set to 12 cmH2O and positive end expiratory pressure (PEEP) set to 5 cmH2O, and with a target Vt of 500 ml. The bias flow of all the ventilators was set to 2 L/min. The three nebulizers were the continuous jet nebulizer (c-JN), the inspiratory synchronized jet nebulizer (i-JN), and the vibrating mesh nebulizer (VMN). The five nebulizer positions were as follows: at the Y-piece (position 1) and 15 cm from the Y-piece (position 2) between the endotracheal tube and the Y-piece, at the Y-piece (position 3) and 15 cm from the Y-piece (position 4) in the inspiratory limb; and at the humidifier inlet (position 5). Aerosols were collected with a disposable filter placed at the simulated lung outlet (n = 3) and were measured by UV spectrophotometry (276 nm). The measurements were compared under different experimental conditions. Results: The aerosol delivery of c-JN, i-JN, and VMN was 5.33 ± 0.49~11.12 ± 0.36%, 7.73 ± 0.76~13.75 ± 0.46% and 11.13 ± 56-30.2 ± 1.63%, respectively. The higher aerosol delivery: for c-JN~Positions 2 (10.95 ± 0.15%), fori-JN~Positions 1 or 2 (12.91 ± 0.88% or 13.45 ± 0.42%), for VMN~Positions 4(29.03 ± 1.08%); the lower aerosol delivery: for c-JN~Positions 1, 3 or 5, fori-JN~Positions 4 or 5, for VMN~Positions 5.The highest aerosol delivery:For c-JN at Position 2 (10.95 ± .15%), for i-JN at Position 1 or 2 (12.91 ± .88% or 13.45 ± .42%), for VMN at Positions 4 (29. 03 ± 1.08%); the lower aerosol delivery: for c-JN at Positions 1, 3 or 5, for i-JN at Positions 4 or 5, for VMN at Positions 5. The highest aerosol deliveryof c-JN was lower than that of i-JN while the VMN was the highest (all P < .05). However, no differences were observed between the highest aerosol delivery with c-JN and the lowest aerosol delivery with i-JN. Similar results were found between the lowest aerosol delivery with VMN and the highest aerosol delivery with c-JN /i-JN in the Avea ventilator. There were no differences in the highest aerosol delivery of each nebulizer among the different ventilators (all p > 0.05). Conclusion: During adult mechanical ventilation, the type and position of nebulizer influences aerosol delivery efficiency, with no differences between ventilators.

Benzoic Acid Metabolism and Lipopolysaccharide Synthesis of Intestinal Microbiome Affects the Health of Ruminants under Free-Range and Captive Mode.

It is urgent to explore new ways to protect endangered wild animals and develop sustainable animal husbandry on the Qinghai-Tibet Plateau due to its fragile ecological environment. Ruminants, raised in captivity and free-range, have important niches in the Plateau and are the best models to analyze the effects of different feeding modes on their health. In this study, two ruminants, yaks and goats in free-range and captive modes, respectively, were selected to study the relationship between gut microbes and ruminant health. The results showed that the gut microbial diversity of free-range ruminants was higher than those of captive ruminants. Principal co-ordinates analysis (PCoA) showed that there were significant differences in the gut microbial communities in different breeding modes. Both the captive ruminants enriched the Succinivibrionaceae family, which had a strong potential to synthesize lipopolysaccharide, and the low exercise amount of the captive animals was significantly related to this function. Meanwhile, free-range ruminants enriched Oscillospiraceae, which had the potential to degrade benzoic acid, and this potential had a significant positive correlation with resistance to parasitic infections. We offer other possibilities, such as adding benzoic acid to feed or increasing the exercise time of captive ruminants to make them healthier.