The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences between genders. Muscovy ducks of both sexes were selected for measurements of body weight, growth traits, hormone levels, and muscle gene expression. The results show that male ducks compared to females had greater weight and growth traits (p < 0.05). Compared to male ducks, the level of serum testosterone in female ducks was decreased, and the estradiol levels were increased (p < 0.05). The RNA-seq analysis identified 102 upregulated and 49 downregulated differentially expressed genes. KEGG analysis revealed that among the top 10 differentially enriched pathways, the AMPK signaling pathway is closely related to muscle growth and development. Additionally, the mRNA and protein levels of CD36, CPT1A, LPL, and SREBP1 were increased and the P-AMPK protein level decreased in the female ducks compared to the male ducks (p < 0.05). In conclusion, muscle development potential difference between male and female ducks is regulated by sex hormones. This process is likely mediated through the activation of the AMPK pathway.
Acute kidney injury (AKI) is one of the most common serious complications in critically ill patients, and it is an independent risk factor for death. In recent years, renal replacement therapy (RRT) has become one of the routine treatments for AKI patients, however there is no accepted consensus on the optimal timing of RRT over the world. This paper reviewed the clinical studies carried out by researchers in the field of critical care and nephrology, thereby summarized and analyzed the related parameters of the optimal time to carry out, with the exception of previously acknowledged classic RRT indications such as hyperkalemia, severe metabolic acidosis, volume overload and so on. The feasible parameters such as serum creatinine (SCr), blood urea nitrogen (BUN), urine volume, the time admitted in the intensive care unit (ICU) and several standards distinguished AKI stages are discussed in order to find out the cutoff points of those parameters which were best for the patients' outcome, and to provide guidance of decision making for the optimal timing of RRT for AKI patients.
Objective:To explore the incidence rate of anemia in patients with sepsis-induced multiple organ dysfunction syndrome(MODS). Methods:A total of 102 patients in intensive care unit (ICU) with sepsis-induced MODS were enrolled into the study. The hemoglobin and hematocrit were measured in the first,third and seventh day of admission. Results:The mean level of both hemoglobin and hematocrit were decreased significantly during the hospitalization,P for trend0.05. Conclusion:The hemoglobin will drop in the patients of infective MODS. The pathogenesis is complicated and influenced by lots of factors.
Certain high-risk factors related to the death of COVID-19 have been reported, however, there were few studies on a death prediction model. This study was conducted to delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) of different degree and establish a death prediction model. In this multi-centered, retrospective, observational study, we enrolled 523 COVID-19 cases discharged before February 20, 2020 in Henan Province, China, compared clinical data, screened for high-risk fatal factors, built a death prediction model and validated the model in 429 mild cases, 6 fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan. Out of the 523 cases, 429 were mild, 78 severe survivors, 16 non-survivors. The non-survivors with median age 71 were older and had more comorbidities than the mild and severe survivors. Non-survivors had a relatively delay in hospitalization, with higher white blood cell count, neutrophil percentage, D-dimer, LDH, BNP and PCT levels and lower proportion of eosinophils, lymphocytes and albumin. Discriminative models were constructed by using random forest with 16 non-survivors and 78 severe survivors. Age was the leading risk factors for poor prognosis, with AUC of 0·907 (95% CI 0·831-0·983). Mixed model constructed with combination of age, demographics, symptoms and laboratory findings at admission had better performance (p= 0.021) with a generalized AUC of 0·9852 (95% CI 0·961-1). We chose 0·441 as death prediction threshold (with 0·85 sensitivity and 0·987 specificity) and validated the model in 429 mild cases, 6 fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan successfully. Mixed model can accurately predict clinical outcomes of COVID-19 patients.
Abstract Background Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Tislelizumab, an anti-PD1 humanized IgG4 monoclonal antibody, has been demonstrated with clinical activity and is approved for treating recurrent/refractory classical Hodgkin lymphoma and locally advanced/metastatic urothelial carcinoma in China. However, the safety and efficacy of long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab followed by TME for LARC is still uncertain. Methods This NCRT-PD1-LARC trial will be a prospective, multicenter and phase II clinical trial designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. This trial will consecutively enroll 50 stage II/III LARC patients (cT3N0M0 and cT1-3N1-2M0) with the tumor distal location ≤ 7 cm from anal verge at 7 centers in China. The enrolled patients will receive long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6–8 weeks after the end of radiotherapy. The primary efficacy endpoint will be the pathological complete response (pCR) rate, which is defined as absence of viable tumor cells in the primary tumor and lymph nodes. Discussion To our knowledge, this trial is the first multicenter clinical trial in China to assess the safety and efficacy of NCRT plus anti-PD1 therapy followed by TME to treat patients with LARC. NCRT followed by TME was recognized as the most recommended treatment against LARC while could not be completely satisfied in clinic. This study expects to provide a solid basis and encouraging outcomes for this promising combination of radiotherapy, chemotherapy and immunotherapy in LARC. Trial registration Name of the registry: ClinicalTrials.gov. Trial registration number: NCT04911517. Date of registration: 23 May 2021. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT04911517?id=BFH-NCRTPD&draw=2&rank=1 .
Respiratory failure in acquired immunodeficiency syndrome (AIDS) patients was the leading cause of intensive care unit (ICU) admission in our center. We aimed to describe the pulmonary infections and outcomes for respiratory failure in AIDS patients.A retrospective study was conducted on AIDS adult patients with respiratory failure who were admitted to the ICU in Beijing Ditan hospital, China, from January 2012 to December 2021. We investigated pulmonary infections complicated by respiratory failure in AIDS patients. The primary outcome was ICU mortality, and a comparison between survivors and nonsurvivors was performed. Multiple logistic regression analysis was used to identify predictors of ICU mortality. The Kaplan-Meier curve and Log rank test were used for survival analysis.A total of 231 AIDS patients were admitted to ICU with respiratory failure over a 10-year period with a male predominance (95.7%). Pneumocystis jirovecii pneumonia was the main etiology of pulmonary infections (80.1%). The ICU mortality was 32.9%. In multivariate analysis, ICU mortality was independently associated with invasive mechanical ventilation (IMV) [odds ratio (OR), 27.910; 95% confidence interval (CI, 8.392-92.818; p = 0.000) and the time before ICU admission (OR, 0.959; 95% CI, 0.920-0.999; p = 0.046). In the survival analysis, patients with IMV and later admission to ICU had a higher probability of mortality.Pneumocystis jirovecii pneumonia was the primary etiology for respiratory failure in AIDS patients admitted to the ICU. Respiratory failure remains a severe illness with high mortality, and ICU mortality was negatively associated with IMV and later admission to ICU.
Background Antimicrobial resistance (AMR) poses a significant global health challenge, resulting in over 1.27 million deaths in 2019 and projected to cause up to 10 million deaths annually in the future. To address this issue, the healthcare sector requires rapid and accurate bacterial identification, which is currently not readily available for effective antimicrobial stewardship. In a UK national first, we implemented 16S ribosomal RNA (rRNA) sequencing using Oxford Nanopore Technology (ONT) in an NHS setting to enhance diagnostic capabilities, aiming to reduce antibiotic misuse and improve patient outcomes. Methods We implemented 16S rRNA sequencing via ONT, running samples from seven NHS hospitals across Cheshire and Merseyside. We focused on samples from sterile sites, such as “pus”, “fluid”, and “tissue”, typically collected from critical care units. The assay was validated against traditional methods including Sanger sequencing and MALDI-TOF, with a turnaround time of 24-72 hours. Clinical impact was measured by analysing changes in antibiotic regimens and patient outcomes based on 16S assay results over a period of several months post-launch. Findings ONT 16S rRNA sequencing significantly impacted antibiotic treatment in 34.2% of cases, reducing patient stays and outperforming traditional methods by detecting additional bacterial organisms and identifying bacteria missed by reference labs. It provided species-level identification and confirmed non-infectious conditions in 5.4% of cases, aiding alternative treatment decisions. Its speed, cost-effectiveness, and minimal training requirements contributed to its successful integration into clinical practice. Interpretation The integration of ONT 16S sequencing into routine NHS diagnostics has significantly improved antimicrobial stewardship by offering a faster, more sensitive, and accurate bacterial identification method. Earlier use of this assay in cases where routine cultures are likely to fail could enhance patient outcomes further by enabling timely, targeted antibiotic therapies, reducing hospital stays, and curbing unnecessary antibiotic use.
<b><i>Introduction:</i></b> Increased permeability of the renal capillaries is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall. Additionally, autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the endothelial adhesion junction. <b><i>Methods:</i></b> We observed the effect of ulinastatin in a septic rat model using contrast-enhanced ultrasonography (CEUS) to evaluate the perfusion of the renal cortex and medulla. Male adult Sprague Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50,000 U/kg) was injected into the tail vein immediately after the operation. The CEUS was performed to evaluate the renal microcirculation perfusion at 3, 6, 12, and 24 h after the operation. Histological staining was used to evaluate kidney injury scores. Western blot was used to quantify the expression of VE-cadherin, LC3II, and inflammatory factors (interleukin-1β, interleukin-6, and tumor necrosis factor-α) in kidney tissue, and enzyme-linked immunosorbent assay detected serum inflammatory factors and kidney function and early kidney injury biomarker levels. <b><i>Results:</i></b> Compared with the sham group, ulinastatin reduced the inflammatory response, inhibited autophagy, maintained the expression of VE-cadherin, and meliorated cortical and medullary perfusion. <b><i>Conclusion:</i></b> Ulinastatin effectively protects the adhesion junction and helps ameliorate the perfusion of kidney capillaries during sepsis by the inhibition of autophagy and the expression of inflammatory factors.
BACKGROUND. Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks.
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