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Abstract Objective Given the lack of global consensus on anesthesia selection for peritoneal dialysis catheter (PDC) placement via open surgery, this study investigates the safety and efficacy of combining local infiltration anesthesia (LIA) with monitored anesthesia care (MAC) in patients with end-stage renal disease (ESRD). Methods This retrospective analysis of ESRD patients who underwent open surgical placement of PDC in the Department of Nephrology, the First Affiliated Hospital of the Army Medical University from 1 August 2020 to 31 May 2022. Patients were categorized into two groups based on anesthesia method: LIA group and LIA + MA group. MA was defined as preoperative sedation (0.2–0.7 µg/kg/h) with dexmedetomidine injection (Huidrican trade name, DEX), and intraoperative analgesia with dexrazoxane injection (Garonin trade name, DEZ) as appropriate according to the patients’ pain scores. We compared the general clinical data of the two groups of patients, the changes in blood pressure and heart rate during the whole operation, the intraoperative and postoperative pain, the total duration of the operation and the immediate postoperative complications. Results The study included 123 patients (59 in the LIA + MAC group and 64 in the LIA group). The LIA + MA group exhibited lower pain scores measured by Visual Analogue Scale(VAS) during surgery (skin incision, subcutaneous adipose tissue dissection, anterior fascia, muscle traction, posterior fascia, peritoneum, and catheterization) compared to the LIA group(p

The transition period is a crucial stage in the reproductive cycle for dams and is linked closely with postpartum recovery, reproduction performance, and health. The confronting problem in the yak industry is that transition yaks under a conventional grazing feeding regime endure nutritional deficiency since this period is in late winter and early spring of the Qinghai-Tibet Plateau with the lack of grass on natural pasture. Therefore, this study aimed to investigate the effects of perinatal nutritional supplementation and early weaning on serum biochemistry, reproductive performance, and metabolomics in transition yaks. Eighteen healthy yaks in late pregnancy (233.9 ± 18.3 kg, 2–4 parity) were randomly assigned to three groups: conventional grazing feeding (GF, n = 6), additional nutrition supplementation (SF, n = 6), and additional nutrition supplementation with early weaning (SW, n = 6). Yaks in the GF, SF, and SW groups were free grazing on the same pasture in the daytime from −30 to 90 d relative to parturition. Yaks in SF and SW groups received total mixed ration supplementation in the barn during the night throughout the trial. Calves in the SW group were early weaned and separated from the dam at 60 d postpartum. Maternal body weight was measured at −30 and 90 d, and serum samples were collected to analyze serum biochemistry, hormones, and metabolomics at −15, 30, and 90 d relative to calving. In the SF and SW groups, yaks showed significantly higher body weight gain, serum glucose, globulin, and total protein concentrations. Lipid transportation molecules apolipoprotein B100 and very low-density lipoprotein of SF and SW yaks were significantly increased along with the decreased lipid mobilization products non-esterified fatty acid and β-hydroxybutyric acid when compared to GF yaks at −15 and 30 d. At 90 d, serum non-esterified fatty acid and β-hydroxybutyric acid levels were significantly lower in SW yaks than in SF ones, while apolipoprotein B100 and very low-density lipoprotein levels were significantly higher in SW yaks than in GF yaks. The serum levels of metabolic regulatory hormones, including insulin, leptin, and insulin-like growth factor I were significantly increased, and glucagon was significantly reduced in the SF and SW groups than in the GF group at −15 and 30 d. Among serum reproductive hormones, SF and SW yaks had significantly higher estradiol and progesterone concentrations than GF ones at −15 and 30 d. Follicle-stimulating and luteinizing hormone levels were increased in SW group than in SF and GF ones at 90 d. The calving rates in the following year were 0% (GF), 16.7% (SF), and 83.3% (SW), respectively. The serum metabolomics analysis revealed 848 metabolites in positive mode and 350 in negative mode. With the perinatal nutritional supplementation, the lipid and energy metabolism of transition yaks were improved, meanwhile, lipid mobilization and estrogen production-related pathways were down-regulated. These data suggest that perinatal nutrition supplementation reduces body weight loss, improves glucose and lipid metabolic adaptation to the transition period, and improves yaks’ reproductive performance. Additionally, the combination of early weaning and nutritional supplementation results in lower lipid mobilization and up-regulation of lipid transportation and reproductive hormone secretion, which may further contribute to postpartum recovery and acceleration of the reproductive cycle.

ABSTRACTThe 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.

BackgroundThe long interspersed nuclear element 1 (LINE1) retrotransposon has been identified as a specific substrate for fat mass and obesity-related gene (FTO), which facilitates the removal of N6-methyladenosine modifications from its targeted RNAs.MethodsThis study examined the dynamic interaction between FTO and LINE1 in yak tissues and muscle satellite cells, utilizing RT-qPCR, RNA immunoprecipitation (RIP), immunofluorescence staining, and techniques involving overexpression and interference of FTO and LINE1 to elucidate the relationship between FTO and LINE1 in yak tissues and muscle satellite cells.ResultsCloning and analysis of the FTO coding sequence in Jiulong yak revealed a conserved protein structure across various Bos breeds, with notable homology observed with domestic yak, domestic cattle, and Java bison. Comprehensive examination of FTO and LINE1 gene expression patterns in Jiulong yaks revealed consistent trends across tissues in both sexes. FTO mRNA levels were markedly elevated in the heart and kidney, while LINE1 RNA was predominantly expressed in the heart. Immunoprecipitation confirmed the direct interaction between the FTO protein and LINE1 RNA in yak tissues and muscle satellite cells. The FTO–LINE1 axis was confirmed by a significant decrease in LINE1 RNA enrichment following its expression interference in yak muscle satellite cells. Overexpression of FTO substantially reduced the expression of recombinant myogenic factor 5 (MYF5). However, FTO interference had no discernible effect on MYF5 and myoblast determination protein 1 (MYOD1) mRNA levels. Immunofluorescence analysis revealed no alterations in Ki-67 protein expression following FTO interference or overexpression. However, phalloidin staining demonstrated enhancement in the myotube fusion rate of yak muscle satellite cells upon LINE1 interference.ConclusionThis comprehensive mapping of the FTO and LINE1 mRNA expression patterns establishes a direct interaction between the FTO protein and LINE1 RNA in yak. The findings suggest that FTO overexpression promotes muscle satellite cells differentiation, whereas LINE1 negatively regulates myotube fusion. The study provides fundamental insights into the role of the FTO–LINE1 axis in determining the fate of muscle satellite cells in yak, laying a solid theoretical foundation for future investigations.

Abstract 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.

Abstract 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.

Abstract 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.

Abstract 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.

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.

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.

Abstract 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

Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-transportin 3 (TNPO3) was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues. The level of circ-TNPO3 expression correlated with differentiation of GC, and plasma circ-TNPO3 could serve as a potential diagnostic biomarker. Functionally, circ-TNPO3 inhibited proliferation and migration of GC in vitro and in vivo. We further verified that circ-TNPO3 competitively interacted with insulin-like growth factor 2 binding protein 3 (IGF2BP3) protein; thus, the role of IGF2BP3 in stabilizing MYC mRNA was weakened, which inhibited the expression of MYC and its target SNAIL. Taken together, circ-TNPO3 acts as a protein decoy for IGF2BP3 to regulate the MYC-SNAIL axis, thereby suppressing the proliferation and metastasis of GC. Therefore, circ-TNPO3 has the potential to serve as a therapeutic target for GC.

Heavy metals elements are not only related to the functions of ecosystems but also affect human health. To understand the characteristics of heavy metals in the topsoil of the Zoige alpine basin, a total of 252 grass and topsoil samples were collected in May and September 2014. The results showed that only Cd and Pb highly exceeded their background values (BV); in May and September, Cd was 2.02- and 1.55-fold higher than its BV, respectively, and Pb was 2.35- and 2.17-fold above its BV, respectively. The sources of Cd and Pb were homologous. In addition, the comprehensive potential ecological risk index was less than 150, indicating that heavy metal pollution in the study area is currently low. The spatial interpolation indicated that Cd and Pb pollution might be related to tourism and transportation, but the low biological absorption coefficient for all heavy metals showed that heavy metal absorption ability of forage was low and would not impact yak breeding. Finally, the soil was lightly contaminated by Cd and Pb due to the rapid development of the animal husbandry and tourism. The spatial variation of heavy metal in the basin is dominated by structural factors, and the random factors also have an effect on spatial distribution of As, Cd, Cu and Ni. The random factors such as overgrazing can exert an influence on physical structure and the circulation of nutrient substances of meadow soil through livestock grazing and trampling, ultimately affecting the content and distribution of soil heavy metals.

BackgroundThe effects of jet nebulization on ventilator performance in the volume control mode (VC) and pressure control mode (PC) of ventilation have not been determined.ObjectivesThe present study investigated the impact of jet nebulization on ventilator performance in different modes in vitro.MethodsTwo 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.ResultsVentilator-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).ConclusionTriggering 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.

BackgroundThe optimal positions of different types of nebulizer for aerosol delivery remain unclear.MethodsThree 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.ResultsThe 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).ConclusionDuring adult mechanical ventilation, the type and position of nebulizer influences aerosol delivery efficiency, with no differences between ventilators.

Abstract 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.

Objective: To investigate the differential expression of genes and microRNAs (miRNAs) in patients with lung adenocarcinoma and the relationship between such changes and patient prognosis. Methods: We analyzed the expression levels of genes and miRNAs in lung adenocarcinoma tissues and adjacent normal tissues using The Cancer Genome Atlas database (TCGA). We analyzed the function of the differentially expressed genes and miRNAs in a co-expression network. Finally, we performed survival analysis of differential genes and miRNAs in the co-expression network using clinical data from the TCGA database. Results: We successfully identified 6064 differentially expressed genes: 5324 upregulated genes and 740 downregulated genes. And we identified 161 differentially expressed miRNAs: 126 upregulated miRNAs and 35 downregulated miRNAs. We identified several genes that were related to each other in the co-expression network. Further analysis revealed that the high expression levels of G6PC, APOB, F2, PAQR9 , and PAQR9-AS1 genes were associated with poor prognosis. However, there was no significant correlation between the expression of hsa-mir-122 with regards to patient prognosis. Conclusions: Our data showed that hsa-mir-122 and a number of related genes may affect the prognosis of patients with lung adenocarcinoma by regulating the cytoskeleton, thus promoting tumor angiogenesis and the metastasis of tumor cells. The high expression levels of some differentially expressed genes was associated with the low survival rate in patients with lung adenocarcinoma. However, the levels of hsa-mir-122 were not correlated with patient prognosis.

Necroptosis, oxidative stress, and inflammation are major contributors to the pathogenesis of ischemic acute kidney injury. Necrostatin-1 (Nec-1), an inhibitor of the kinase domain of receptor-interacting protein kinase-1 (RIP1), has been reported to regulate renal ischemia and reperfusion (I/R) injury; however, its underlying mechanism of action remains unclear. HK-2 cells were used to create an in vitro I/R model, in which the cells were subjected to hypoxia, followed by 2, 6, and 12 h of reoxygenation. For the in vivo study, a rat model of renal I/R was established in which samples of rat blood serum and kidney tissue were harvested after reperfusion to assess renal function and detect histological changes. Cell viability and necroptosis were analyzed using the Cell Counting Kit (CCK)-8 assay and flow cytometry, respectively. The expression levels of molecules associated with necroptosis, oxidative stress, and inflammation were determined by real-time PCR, western blotting, immunofluorescence staining, and ELISA. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to confirm the relevant downstream signaling pathway. We found that pretreatment with Nec-1 significantly decreased hypoxia-inducible factor-1α (HIF-1α) and miR-26a expression, as well as the levels of factors associated with necroptosis (RIP1, RIP3, and Sirtuin-2), oxidative stress (malondialdehyde [MDA], NADP+/NADPH ratio), and inflammation (interleukin [IL]-1β, IL-10, and tumor necrosis factor alpha [TNF-α]) in I/R injury cells and the rat model. However, these effects could be reversed by miR-26a overexpression or TRPC6 knockdown. Mechanistic studies demonstrated that HIF-1α directly binds to the promoter region of miR-26a, and that TRPC6 is a potential target gene for miR-26a. Our findings indicate that Nec-1 can effectively protect against renal I/R injury by inhibiting necroptosis, oxidative stress, and inflammation, and may exert its effects through mediation of the HIF-1α/miR-26a/TRPC6/PARP1 signaling pathway. Keywords: ischemic/reperfusion injury, Nec-1, HIF-1α, miR-26a, TRPC6, necroptosis, oxidative stress, inflammation

Ensiling is a simple and effective method of alleviating a shortage of forage for ruminants. This study aimed to investigate the effects of lactic acid bacteria (LAB) inoculants and stage-increased temperature on the fermentation characteristics and chemical composition of oat silage on the Qinghai–Tibet Plateau. The silage was treated with local laboratory inoculant (I) and commercial inoculant (S) and stored at ambient temperature (p < 0.05) promoted the fermentation rate of silage by increasing the dominance of Lactiplantibacillus plantarum, with higher lactic, acetic and propionic acid contents and a lower ammonia-N ratio of the total N and final pH value. Compared with S, treatment with I increased the water-soluble carbohydrate and lactic acid contents and decreased the ammonia-N ratio of the total N and final pH value. This work demonstrated that increasing the storage temperature in stages using a warming infrastructure facilitates the preservation of oat silage in cold regions, and the inoculation of lactic acid bacteria could advance silage fermentation on the Qinghai–Tibet Plateau.

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.

Lung cancer is characterized by high morbidity and mortality rates, and it has become an important public health issue worldwide. The occurrence and development of tumors is a multi-gene and multi-stage complex process. As an oncogene, ribosomal oxygenase 2 (RIOX2) has been associated with a variety of cancers. In this article, we analyzed the correlation between RIOX2 expression and methylation in lung cancer based on the databases including the cancer genome atlas (TCGA) (https://portal.gdc.cancer.gov/) and the gene expression omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). It was found that RIOX2 is highly expressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues, whose expression is negatively correlated with its methylation level. In this regard, methylation at cg09716038, cg14773523, cg14941179, and cg22299097 had a significant negative correlation with RIOX2 expression in LUAD, whereas in LUSC, methylation at cg09716038, cg14773523, cg14941179, cg22299097, cg05451573, cg10779801, and cg23629183 is negatively correlated with RIOX2 expression. According to the analysis based on the databases, RIOX2 gene could not be considered as the independent prognostic biomarker in lung adenocarcinoma or squamous cell lung cancer. However, the molecular mechanism of RIOX2 gene in the development of lung cancer may be helpful in improving lung cancer therapy.

Sichuan, China, has abundant genetic resources of sheep (Ovis aries). However, their genetic diversity and population structure have been less studied, especially at the genome-wide level. In the present study, we employed the specific-locus amplified fragment sequencing for identifying genome-wide single nucleotide polymorphisms (SNPs) among five breeds of sheep distributed in Sichuan, including three local pure breeds, one composite breed, and one exotic breed of White Suffolk. From 494 million clean paired-end reads, we obtained a total of 327,845 high-quality SNPs that were evenly distributed among all 27 chromosomes, with a transition/transversion ratio of 2.56. Based on this SNP panel, we found that the overall nucleotide diversity was 0.2284 for all five breeds, with the highest and lowest diversity observed in Mage sheep (0.2125) and Butuo Black (0.1963) sheep, respectively. Both Wright's fixation index and Identity-by-State distance revealed that all individuals of Liangshan Semifine-wool, White Suffolk, and Butuo Black sheep were respectively clustered together, and the breeds could be separated from each other, whereas Jialuo and Mage sheep had the closest genetic relationship and could not be distinguished from each other. In conclusion, we provide a reference panel of genome-wide and high-quality SNPs in five sheep breeds in Sichuan, by which their genetic diversity and population structures were investigated.

Eupatorium fortunei Turcz. is a widely used Chinese herbal medicine in China. In this study, a gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) method was developed and validated to simultaneously determine the contents of p-cymene, thymol, neryl acetate, and β-caryophyllene in roots, stems, and leaves of Eupatorium fortunei Turcz. harvested at different growth periods. All four constituents could be detected in leaves, three could be detected in stems except β-caryophyllene, and only thymol could be detected in roots. The order of the total contents of four constituents in different parts was leaves > stems > roots. It indicated that the leaves could be the proper medicinal parts of Eupatorium fortunei Turcz. The content of four constituents in leaves varied a lot among different growth periods and showed an M-shaped change trend with the growth of Eupatorium fortunei Turcz. The four constituents accumulated to the highest values in early July followed by mid-September. Accordingly, the best harvest time of Eupatorium fortunei Turcz. is early July and mid-September.

Abstract Background Type IV lupus nephritis (LNIV) is a severe disease characterized by diffuse proliferative lesions, and its prognosis is worse with cellular crescent (LNIV-CC) involvement. Urinary exosomes have been shown to reflect the degree of kidney injury. This study was aimed to identify non-invasive diagnostic markers for LNIV-CC. We analysed the expression profile of microRNAs (miRNAs) isolated from urinary exosomes in patients with LNIV-CC and LNIV, and healthy individuals using high-throughput sequencing. Results A total of 66 differentially expressed miRNAs were identified, which were significantly enriched in 15 signalling pathways. Bioinformatic analysis revealed a co-expression network of miRNAs, predicted transcription factors and target mRNAs. Expression of three miRNAs including miR-3135b, miR-654-5p, and miR-146a-5p were further analysed and validated by reverse transcription-quantitative polymerase chain reaction. ROC analysis suggested these as candidate biomarkers for LNIV-CC. Conclusions LNIV-CC has a unique miRNA expression profile of urinary exosome and complex regulatory network. miR-3135b, miR-654-5p and miR-146a-5p in urinary exosomes could be used as novel non-invasive diagnostic markers for LNIV-CC.

Background/Aims: To reveal the potential pathogenesis of ischemia/reperfusion (I/R) injury. Methods: GSE9943 were downloaded from Genome Expression Omnibus database, including I/R and control samples for both Brown Norway (BN) and Sprague Dawley (SD) rats (3 rats/each group). Then differentially expressed genes (DEGs) were identified by limma package. miRNA-target gene network pairs were predicted using WebGestalt, and protein-protein interactions (PPI) were identified based on STRING database, followed by the networks construction using Cytoscape. Next, ClusterONE was used for modules screening. Furthermore, functional analyses were performed to common DEGs and genes. Results: Totally, 23 common DEGs of BR and SD rats were screened, enriched in functions, such as regulation of cellular protein metabolic process, response to wounding, proteinaceous extracellular matrix, and Enzyme inhibitor activity. MIR-29A, MIR-29B and MIR-29C were discovered both in up- and down-regulated miRNA-target gene networks. Genes in the PPI network were significantly disturbed in p53 signaling, complement and coagulation cascades pathway. Four modules were found significantly disturbed cytochrome P450, Serine/threonine protein kinase, calcium binding and Transient receptor potential channel protein domains. Conclusion: During I/R injury, many genes mutated, interrupting several biological functions, pathways and protein domains. MIR-29C and TRPC6 were suggested to be potential novel targets for this disease.

Increased expression of mineral dust-induced gene (mdig, also named as mina53, MINA, or NO52) has been observed in a number of human cancers. The mechanism of how mdig contribute to the pathogenesis of cancer remains to be fully elucidated. In this report, we demonstrated that overexpression of mdig decreased the nuclear staining signal by 4',6-diamidino-2-phenylindole (DAPI), along with a considerable enhancement in cell proliferation. Silencing mdig by shRNA resulted in a statistically significant decrease of cell proliferation. Intriguingly, mdig overexpression reduced the capacity of the cells in migration and invasion in vitro, whereas silencing mdig by shRNA/siRNA enhanced migration and invasion. Clinically, we found that increased expression of mdig in cancer tissues correlates with poorer overall survival of the lung cancer patients, esp., for those without lymph node metastasis. Taken together, our results suggest that mdig plays opposite roles on cell growth and motility, which possibly indicates the paradoxical effect of mdig at the different stages of carcinogenesis.