SCAV-3 affects apoptotic cell degradation in Caenorhabditis elegans.

As the final step in apoptosis, apoptotic cells (ACs) are swiftly removed by specialized phagocytes, such as macrophages, or nonprofessional phagocytes, such as epidermal cells. Genetic studies of model organisms such as Caenorhabditis elegans have helped to elucidate the mechanisms of AC clearance and the underlying causes of disorders related to the dysregulation of these pathways. C. elegans possesses six class B scavenger receptor homologs, but whether they affect apoptosis is unknown. Here, we show that only the loss of function of scav-3, the C. elegans homolog of human lysosomal integral membrane protein-2, resulted in a considerable accumulation of cell corpses, which was caused by a failure in degradation rather than engulfment. SCAV-3 was found to be widely distributed and localized in lysosomes to maintain the integrity of the lysosomal membrane. Further study revealed that loss of scav-3 had no effect on phagosome maturation or the recruitment of lysosomes to phagosomes carrying cell corpses. Moreover, we discovered that the hydrolytic enzymes contained in the lysosomes were reduced in phagosomes in scav-3 mutants. Thus, hydrolases may leak from the damaged lysosome during phagolysosome formation due to the loss of scav-3 function, which reduces lysosome digestion activity and thus directly contributes to the elimination of ACs.

[Diagnostic value of early bedside ultrasound measurement of quadriceps femoris on in-hospital mortality of septic patients].

OBJECTIVE: To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality. METHODS: A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. RESULTS: A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95%CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. CONCLUSIONS: For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.

Study on the Predictive Value of Thromboelastography in Early Neurological Deterioration in Patients with Primary Acute Cerebral Infarction.

Objective: To investigate the predictive value of thromboelastography for the occurrence of early neurological deterioration (END) in patients with primary acute cerebral infarction (ACI). Methods: 150 patients who were hospitalized in the department of neurology of our hospital from September 2020 to September 2021 and were clearly diagnosed with primary ACI by head CT and head magnetic resonance imaging (MRI) were selected and divided into END and non-END groups according to the change in National Institute of Health Stroke Scale (NIHSS) score within 72 h of admission. The general baseline data and laboratory indexes of the first examination at admission were compared between the two groups, and the factors that may affect the occurrence of END were determined by univariate analysis and multivariate logistic regression analysis, and the predictive value of thromboelastography on the occurrence of END after ACI was analyzed by applying the receiver operating characteristic (ROC) curve. Results: Time to onset, baseline NIHSS score, percentage of diabetes, white blood cell (WBC) levels, C-reactive protein (CRP), and apolipoprotein B (Apo B) levels were higher in the END group than in the non-END group (P < 0.05); coagulation reaction time (RT) (3.97 ± 1.16 vs. 5.49 ± 1.03) and kinetic time (KT) (1.32 ± 0.67 vs. 1.82 ± 0.58) were lower in the END group than in the non-END group (P < 0.05). Inthe END group (P < 0.05) diabetes, baseline NHISS score, CRP level, Apo B level, and RT were independent risk factors for the development of END in patients with ACI (P < 0.05). The AUC of RT to predict the occurrence of END in patients with ACI was 0.855 (95% CI: 0784 to 0925, P = 0.001), with a sensitivity of 81.70% and specificity of 78.00% when the optimal cut-off value was 0.597. Conclusion: NIHSS score at admission, CRP, apolipoprotein B, RT shortening, and diabetes mellitus were independent risk factors for the development of END in ACI patients; RT shortening in TEG was predictive of END in ACI patients.

Risk factors for illness severity in patients with COVID-19 pneumonia: a prospective cohort study.

Background: Although COVID-19 pneumonia is spreading internationally, knowledge regarding the factors associated with the illness severity of patients remains limited. We aimed to identify the factors associated with the disease severity of patients with COVID-19 pneumonia induced by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We prospectively enrolled a single-center case series of adult patients with COVID-19 admitted to the Infectious Disease Hospital of Jining, Jining City, Shandong Province, China, from January 24 to March 1, 2020. Demographics, clinical characteristics, and laboratory findings were compared to investigate the risk factors related with the disease severity of COVID-19 pneumonia patients. Results: We included a total of 78 patients with COVID-19 pneumonia, of whom 6 had the severe type. As compared to a moderately ill cohort, our analysis showed that shortness of breath, fatigue, longer days from illness onset to diagnosis confirmed, neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, lymphocyte counts < 1.0 × 109/L, platelet < 100 × 109/L, C-reactive protein (CRP) > 10 mg/L, neutrophil to platelet ratio (NPR) > 2.3, neutrophil to lymphocyte ratio (NLR) > 3.9, aspartate aminotransferase (AST) > 40 U/L, albumin < 40 g/L, lactate dehydrogenase (LDH) > 245 U/L, and glucose > 6.1 mmol/L were predictors of disease severity in COVID-19 pneumonia. In the sex-, age-, and comorbid illness-matched case-control study, neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L remained associated with the early detection and identification of severe patients. Conclusion: We demonstrated that neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L might predict the severity of illness in patients with COVID-19 pneumonia.

Protective effects of ghrelin on brain mitochondria after cardiac arrest and resuscitation.

Mitochondrial dysfunction plays a critical role in brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Our recent study demonstrated that ghrelin protected against post-resuscitation brain injury with an elevated expression of mitochondrial uncoupling protein 2 (UCP2). However, the effects of ghrelin on mitochondrial dysfunction after CA are not clear. In the present study, the protective role of ghrelin was evaluated on mitochondrial dysfunction and the subsequent damage induced by CA in rats. In addition, mitochondrial unfolded protein response (UPRmt), an intrinsic cytoprotective pathway, was observed at the same time. Either vehicle (saline) or ghrelin (80 µg/kg) was injected blindly immediately after 6 min of CA and successful resuscitation. Neurological deficit was evaluated 6 h after CA and then cortex was collected for assessments. As a result, we found that ghrelin significantly improved the neurological deficit score in rats after CA. The functional analysis of isolated mitochondria revealed that ghrelin improved the mitochondrial ATP synthesis capacity and significantly reduced the reactive oxygen species (ROS) leakage after 6 h of CA. Concomitantly, we observed an increased ATP level and an attenuated oxidative stress in ghrelin treated animals. Moreover, ghrelin markedly improved the mitochondrial morphology compared with the vehicle animals. Further research revealed that ghrelin treatment significantly activated the UPRmt as demonstrated by the increased expression of heat shock protein 60 (HSP60), heat shock protein 10 (HSP10), caseinolytic protease 1 (CLPP1), and high-temperature requirement protein A2 (HTRA2). Our results suggest that ghrelin protected against cerebral mitochondria dysfunction after CA and the mechanism may involve a UPRmt pathway.

Apoptotic Cell Clearance in Drosophila melanogaster.

The swift clearance of apoptotic cells (ACs) (efferocytosis) by phagocytes is a critical event during development of all multicellular organisms. It is achieved through phagocytosis by professional or amateur phagocytes. Failure in this process can lead to the development of inflammatory autoimmune or neurodegenerative diseases. AC clearance has been conserved throughout evolution, although many details in its mechanisms remain to be explored. It has been studied in the context of mammalian macrophages, and in the nematode Caenorhabditis elegans, which lacks "professional" phagocytes such as macrophages, but in which other cell types can engulf apoptotic corpses. In Drosophila melanogaster, ACs are engulfed by macrophages, glial, and epithelial cells. Drosophila macrophages perform similar functions to those of mammalian macrophages. They are professional phagocytes that participate in phagocytosis of ACs and pathogens. Study of AC clearance in Drosophila has identified some key elements, like the receptors Croquemort and Draper, promoting Drosophila as a suitable model to genetically dissect this process. In this review, we survey recent works of AC clearance pathways in Drosophila, and discuss the physiological outcomes and consequences of this process.

Dendronpholides A-R, cembranoid diterpenes from the chinese soft coral Dendronephthya sp.

A systematic examination of the Chinese soft coral Dendronephthya sp. resulted in the isolation and characterization of 18 new cembranoid diterpenes, namely, dendronpholides A-R (2-19), along with 11-episinulariolide and an enantiomer of sandensolide. Their structures were determined through extensive spectroscopic (IR, MS, 2D NMR) data analyses and by comparison with those reported in literature. The cytotoxicity of several compounds against human tumor cell lines was also evaluated.

[Different levels of nitric oxide in seminal plasma of fertile and abnormospermic men].

OBJECTIVES: To understand the relation between nitric oxide (NO) level in seminal plasma and male fertility. METHODS: The levels of NO in seminal plasma of 174 fertile males and 217 abnormospermia patients were measured by using the reductase of nitric acid, Greiss reagent and spectrophotometry. RESULTS: 1. NO was found in all 174 samples (20-49 years) of fertile males which was (27.78 +/- 5.81) mumol/L. The NO level in seminal plasma in fertile males was became higher after age 40, and there was no significant difference between 20-29-year-old [(26.25 +/- 5.52) mumol/L] and 30-39-year-old[(28.11 +/- 5.87) mumol/L]. But the group of 40-49-year-old[(30.17 +/- 6.14) mumol/L] had a higher level of NO in seminal plasma than 20-29-year-old (P < 0.05). 2. The seminal plasma samples from nine types of abnormospermia were measured, which all had a higher level of NO than fertile males. In abnormospermia, the level of NO in seminal plasma of the patients with single abnormality increased slightly, two abnormality obviously increased, and the highest level of NO in seminal plasma appeared in three abnormality. CONCLUSIONS: This results confirmed that proper level of NO in seminal plasma may regulate the spermatogenesis.

Helicobacter pylori HspA Heat-shock Protein Gene Cloning, Expression and Immunogenicity.

Helicobacter pylori is the causative agent of gastritis and peptic ulcer in human. The heat-shock protein A (HspA)may stimulate the immunoresponse protecting human body against challenge of H.pylori. The gene encoding the structural A subunit of H.pylori heat-shock protein was amplified from H.pylori chromosomal DNA by PCR, and was inserted in the prokaryotic expression vector pET-22b(+), and then was transformed into the BL-21(DE3)E.coli strain to express the HspA recombinant protein. HspA gene was measured to be 354 base pairs, and the recombinant protein gene encoded polypeptides of 118 amino acid residues, corres-ponding to calculated molecular weight of 15 kD. Western blot analysis of HspA recombinant protein was confirmed that it could be specifically recognized by the serum of H.pylori-infected patients, and could also be re-cognized by the serum of immunized Balb/c mice with HspA itself. This result suggests that HspA may be an effective protein vaccine for prevention and treatment of the infection of H.pylori.