Septic cardiomyopathy(SIC)is an organ dysfunction frequently observed in sepsis and characterized by high mortality and poor prognosis.Understanding the complex pathogenesis of SIC and developing effective therapeutic tools are critical issues that require attention.Previous studies have demonstrated the significant role of mitochondrial dysfunction in the development of SIC.In the presence of SIC,and the mitochondrial dysfunction that result,the aberrant regulation of the mitochondrial quality control system(MQC)can exacerbate cardiomyocyte injury.Recent studies have demonstrated that the MQC maintains the dynamics of mitochondrial homeostasis through its regulation of mitochondrial biogenesis,fusion/fission,and autophagy.This article provides an overview of the role of MQC in SIC pathogenesis,reviews the latest studies in the field,and analyzes MQC's potential as a therapeutic target.

ObjectiveTo investigate the effects of acupuncture combined with Du-Moxibustion (ADM) on peripheral blood cell count and levels of immune factors in patients with occupational chronic benzene poisoning. Methods A total of 70 patients with occupational chronic benzene poisoning (leukopenia and neutropenia) were selected as the research subjects by judgement sampling method. They were randomly divided into a control group and an ADM group using a random number table method, with 35 cases in each group. Patients in the control group were treated with conventional Western medicine such as leukocyte boosting and symptomatic treatment. While patients in the ADM group were treated with ADM treatment in addition to treatments of the control group, once per week for five consecutive weeks. Peripheral blood samples of patients were collected before and after treatment from both groups, to detect cell counts and serum levels of immune factors. Results The white blood cell count, red blood cell count, absolute lymphocyte count, absolute neutrophil count, platelet count, and levels of hemoglobin, immunoglobulins (Ig) A, IgM, IgG, complement C3 and complement C4 of patients in both groups improved after treatment compared with those before treatment (all P<0.05). The white blood cell count, levels of IgA, IgM, IgG, complement C3 and complement C4 of patients in the ADM group were higher than those in the control group after treatment (all P<0.05). Conclusion ADM treatment can increase peripheral blood white blood cells and serum levels of immune factor in patients with occupational chronic benzene poisoning (leukopenia, neutropenia), which helps improve patient recovery and can be promoted clinically.

Objective : To investigate the outcomes of a novel direct pulp capping agent containing platelet-rich fibrin (PRF) and mineral trioxide aggregate (MTA). Methods : A total of 32 New Zealand rabbits were randomly divided into 4 groups, namely, the PRF+MTA group (P+M group), PRF group (P group), MTA group (M group) and blank control group (BC group), with 8 rabbits per group. Dental pulp exposure and direct pulp capping were performed, and complete crown square sealing was performed on 2 mandibular central incisor teeth of each rabbit. Four rabbits from each group were euthanized after each observation period (7 and 28 days). The experimental teeth were subjected to HE staining. Inflammatory cell infiltration, calcified bridge formation and pulp tissue disorganization were observed and graded. Results: Inflammatory cell infiltration: on the 7th day, group P+M and group M were lighter than group BC (P<0.05); on the 28th day, group P+M was lighter than group P and group BC (P<0.05); group P+M and group M did not significantly differ (P>0.05). Calcified bridge formation: on the 7th and 28th days, group P+M was lighter than group P, group M and group BC (P<0.05); on the 28th day, group M was higher than group BC (P<0.05). Under microscope, the calcified bridge contained cellular components and was surrounded by odontoblast-like cells, sharing a structure resembled osteodentin; dentin tubule-like structure could not be observed in calcified bridge, and the calcified bridge resembled certain points of osteodentin. Pulp tissue disorganization: on the 7th day, group P+M and group M were lighter than group BC (P<0.05); on the 28th day, group P+M was lighter than group P and group BC (P<0.05). group P+M and group M did not significantly differ (P>0.05). Conclusion The combination of PRF and MTA for direct pulp capping provided light inflammatory cell infiltration, stable pulp status and a strong ability of pulp tissue to form calcified bridge, and the calcified bridge resembled certain points of osteodentin.

Objective:To analyze the difference of clinical characteristics and outcomes of infants with moderate and severe pediatric acute respiratory distress syndrome(PARDS)diagnosed according to baseline oxygenation index(OI) in pediatric intensive care unit(PICU).Methods:Second analysis of the data collected from the "Efficacy of pulmonary surfactant (PS) in the treatment of children with moderate and severe ARDS" program.Retrospectively compare of the differences in clinical data such as general condition, underlying diseases, OI, mechanical ventilation, PS administration and outcomes among infants with moderate and severe PARDS divided by baseline OI who admitted to PICUs at 14 participating tertiary hospitals from 2016 to December 2021.Results:Among the 101 cases, 55 cases (54.5%) were moderate and 46 cases (45.5%) were severe PARDS.The proportion of male in the severe group (50.0% vs.72.7%, P=0.019) and the pediatric critical illness score(PCIS)[72 (68, 78) vs.76 (70, 80), P=0.019] were significantly lower than those in the moderate group, while there was no significant difference regarding age, body weight, etiology of PARDS and underlying diseases.The utilization rate of high-frequency ventilator in the severe group was significantly higher than that in the moderate group (34.8% vs.10.9%, P=0.004), but there was no significant difference in PS use, fluid load and pulmonary complications.The 24 h OI improvement (0.26±0.33 vs.0.04±0.34, P=0.001) and the 72 h OI improvement[0.34 (-0.04, 0.62) vs.0.15 (-0.14, 0.42), P=0.029)]in the severe group were significantly better than those in the moderate group, but there was no significant difference regarding mortality, length of hospital stay and intubation duration after diagnosis of PARDS between the two groups. Conclusion:In moderate and severe(divided by baseline OI) PARDS infants with invasive mechanical ventilation, children in severe group have better oxygenation improvement in the early stage after PARDS identified and are more likely to receive high frequency ventilation compared to those in moderate group.Baseline OI can not sensitively distinguish the outcomes and is not an ideal index for PARDS grading of this kind of patient.

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.
Humans ; Osteoclasts/physiology* ; Arthritis, Rheumatoid/pathology* ; Inflammation/pathology* ; Bone and Bones/pathology* ; Bone Resorption/pathology*

Objective:To investigate the role of Caveolin (Cav-3)/extracellular signal-regulated kinase (ERK) signaling pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by morphine preconditioning in rats with chronic heart failure.Methods:Clean-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, were used in this study.Chronic heart failure was induced by ligating the left anterior descending coronary artery for 6 weeks.Thirty-six Langendorff-perfused hearts with chronic heart failure were divided into 4 groups ( n=9 each) by a random number table method: myocardial I/R group (group IR), morphine preconditioning group (group MP), morphine preconditioning plus methyl-β-cyclodextrin group (group MP+ MβCD), and methyl-β-cyclodextrin group (group MβCD). Global myocardial I/R was induced by 30 min ischemia followed by 120 min reperfusion.In group MP, after 15 min of equilibration, hearts were subjected to 3 cycles of 5 min perfusion with K-H solution containing 1 μmol/L morphine for preconditioning followed by 5 min perfusion with K-H solution, 30 min in total, and after the end of treatment, hearts were subjected to 30 min ischemia followed by 120 min reperfusion.In group MP+ MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 10 min before preconditioning with morphine, and the other treatments were similar to those previously described in group MP.In group MβCD, hearts were perfused with K-H solution containing 200 μmol/L methyl-β-cyclodextrin at 40 min before ischemia, and the other treatments were similar to those previously described in group IR.At the end of 15 min of equilibration (T 0) and 5 and 10 min of reperfusion (T 1, 2), coronary outflow was collected for determination of actate dehydrogenase (LDH) activity by chemical colorimetry.Myocardial infarct size (IS) and area at risk (AAR) were measured, and IS/AAR was calculated at the end of 120 min reperfusion.Myocardial tissues of left ventricle were taken to detect the expression of Cav-3, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) by Western blot, and p-ERK1/2/ERK1/2 ratio was calculated. Results:Compared with group IR, IS, IS/AAR and LDH activity in coronary outflow were significantly decreased, the expression of Cav-3 was up-regulated, and p-ERK1/2/ERK1/2 ratio was increased in group MP ( P<0.05). Compared with group MP, IS, IS/AAR and LDH activity in coronary outflow were significantly increased, the expression of Cav-3 was down-regulated, and p-ERK1/2/ERK1/2 ratio was decreased in group MP+ MβCD ( P<0.05). Conclusions:The mechanism by which morphine preconditioning reduces I/R injury may be related to activation of Cav-3/ERK signaling pathway in rats with chronic heart failure.

Objective:To investigate the role of Bruton's tyrosine kinase (BTK) in pyroptosis of intestinal cells caused by endotoxin/lipopolysaccharide (LPS) in scalded mice.Methods:The experimental research method was applied. One hundred and twenty-eight male C57BL/6 mice aged 6-8 weeks were divided into sham injury group, scald alone group, scald+LPS group, scald+LPS+3 mg/kg LFM-A13 group, scald+LPS+10 mg/kg LFM-A13 group, and scald+LPS+30 mg/kg LFM-A13 group. There were 8 mice in sham injury group, and there were 24 mice in the other 5 groups, respectively. Mice in 5 scald groups were inflicted with 10% total body surface area full-thickness scald on the back, and mice in sham injury group were sham injured on the back. At post injury hour (PIH) 0 (immediately), mice in sham injury group and scald alone group were intraperitoneally injected with normal saline, mice in scald+LPS group were intraperitoneally injected with LPS, and mice in scald+LPS+3 mg/kg LFM-A13 group, scald+LPS+10 mg/kg LFM-A13 group, and scald+LPS+30 mg/kg LFM-A13 group were intraperitoneally injected with LPS and LFM-A13 in corresponding doses. Mice in sham injury group were sacrificed at PIH 0 to collect serum and intestinal tissue, and 8 mice in each group of 5 scald groups were sacrificed at PIH 0, 12, and 24 to collect intestinal tissue and serum at PIH 12. Immunohistochemistry was used to detect phosphorylation of BTK in intestinal tissue of mice. Western blotting was used to detect the protein expressions of phosphorylated BTK (p-BTK), cleaved cysteine aspartic acid specific protease 1 (caspase-1), and cleaved caspase-11 in intestinal tissue of mice. Enzyme-linked immunosorbent assay method was used to detect interleukin-1β (IL-1β) in serum and intestinal tissue of mice. Data were statistically analyzed with one-way analysis of variance and least significant difference test.Results:There was no obvious phosphorylation of BTK in intestinal tissue of mice in 6 groups at PIH 0 and scald alone group at PIH 12 and 24. Phosphorylation of BTK in intestinal tissue of mice in scald+LPS group at PIH 12 and 24 were obviously increased compared with those in scald alone group. Phosphorylation of BTK in intestinal tissue of mice in scald+LPS+3 mg/kg LFM-A13 group, scald+LPS+10 mg/kg LFM-A13 group, and scald+LPS+30 mg/kg LFM-A13 group were obviously decreased compared with those in scald+LPS group, and the degrees of decline gradually increased with increase of dose in LFM-A13. Compared with (0.130±0.010) of sham injury group and (0.120±0.040 and 0.110±0.040) of scald alone group, protein expressions of p-BTK in intestinal tissue of mice in scald+LPS group at PIH 12 and 24 were obviously increased (0.470±0.090 and 0.430±0.080, P<0.01). Compared with those in scald+LPS group, protein expressions of p-BTK in intestinal tissue of mice in scald+LPS+3 mg/kg LFM-A13 group at PIH 24, and scald+LPS+10 mg/kg LFM-A13 group and scald+LPS+30 mg/kg LFM-A13 group at PIH 12 and 24 were obviously decreased (0.280±0.060, 0.300±0.120, 0.150±0.050, 0.280±0.090, 0.140±0.040, P<0.05 or P<0.01). Compared with those in scald+LPS+3 mg/kg LFM-A13 group, protein expressions of p-BTK in intestinal tissue of mice in scald+LPS+10 mg/kg LFM-A13 group and scald+LPS+30 mg/kg LFM-A13 group at PIH 24 were obviously decreased ( P<0.01). Compared with those in sham injury group and scald alone group, protein expressions of cleaved caspase-1 and caspase-11 in intestinal tissue of mice in scald+LPS group were obviously increased at PIH 12 and 24 ( P<0.01). Compared with those in scald+LPS group, protein expressions of cleaved caspase-1 at PIH 12 and cleaved caspase-11 at PIH 12 and 24 in intestinal tissue of mice in scald+LPS+3 mg/kg LFM-A13 group and protein expressions of cleaved caspase-1 and caspase-11 in intestinal tissue of mice in scald+LPS+10 mg/kg LFM-A13 group and scald+LPS+30 mg/kg LFM-A13 group at PIH 12 and 24 were obviously decreased ( P<0.01). Compared with those in scald+LPS+3 mg/kg LFM-A13 group, protein expressions of cleaved caspase-1 and caspase-11 in intestinal tissue of mice in scald+LPS+10 mg/kg LFM-A13 group and scald+LPS+30 mg/kg LFM-A13 group at PIH 12 and 24 were obviously decreased ( P<0.05 or P<0.01). At PIH 12, content of IL-1β in intestinal tissue and serum of mice in scald+LPS group were obviously higher than those in sham injury group and scald alone group ( P<0.01), and content of IL-1β in intestinal tissue and serum of mice in scald+LPS+30 mg/kg LFM-A13 group were obviously lower than those in scald+LPS group ( P<0.01). Conclusions:Phosphorylation of BTK is related to increases of cleaved caspase-1 and caspase-11 in intestinal tissue, and IL-1β content in intestinal tissue and serum of scalded septic mice caused by LPS. Phosphorylation of BTK mediates intestinal cell pyroptosis of scalded mice caused by LPS. Inhibiting phosphorylation of BTK can alleviate intestinal cell pyroptosis of scalded mice, with protective effect on intestinal injury intestine.

Objective:To evaluate the safety, feasibility and operational performance of self-developed medical disposable portable endoscopy (YunSendo) for upper gastrointestinal endoscopy examination in Ba-Ma mini-pigs.Methods:A total of 10 Guangxi Ba-Ma mini-pigs were used in the experiment, and mucosal injury models were established in advance by biopsy forceps in esophagus, stomach, and duodenum. Each experimental animal underwent medical disposable portable endoscopy and Olympus endoscopy (GIF-Q260J) performed by two endoscopists separately. The time when the endoscope reached the duodenum, the number of detected mucosal injuries and endoscopic pictures of different parts with standard image acquisition were recorded. Endoscopic operational performance and endoscopic image quality were evaluated. Different endoscopists recorded experimental results with blind method. The procedures of the two endoscopic examinations were performed by coin-tossing method. The paired t test was used for statistical analysis. Results:There were no statistically significant differences in the insertion time and total operation time between medical disposable portable endoscopy and Olympus endoscopy ( (171.00±9.96) s vs. (164.00±17.84) s, (285.00±33.94) s vs. (273.40±23.46) s; t=1.289 and 1.281, P=0.230 and 0.232). There were no statistically significant differences in the percentage of time of clear visual field during endoscopy insertion and total operation between medical disposable portable endoscopy and Olympus endoscopy ((91.83±1.85)% vs. (91.52±1.51)%, (93.07±3.10)% vs. (92.06±2.57)%; t=0.401 and 0.689, P=0.698 and 0.508). Moreover, there were no statistically significant differences in the score of comprehensive operation performance, score of clear image number, score of image color recognition, score of image illumination, comprehensive score of image quality and number of detected mucosal injuries ((9.66±0.30) points vs. (9.86±0.15) points, (39.50±0.71) points vs. (39.30±1.06) points, (39.70±0.48) points vs. (39.40±0.70) points, (39.40±0.70) points vs. (39.50±0.71) points, (9.88±0.09) points vs. (9.85±0.20) points, 9.80±0.42 vs. 9.90±0.32; t=2.176, 1.000, 1.152, 0.317, 0.629 and 0.557, all P>0.05). There were no adverse events after operation in medical disposable portable endoscopy group and Olympus endoscopy group. Conclusions:The medical disposable portable endoscopy is safe and feasible for endoscopy examination in live animal models. Different parts of upper gastrointestinal tract and mucosal lesions can be clearly detected. The operational performance and the image quality are excellent, which is similar to Olympus endoscopy (GIF-Q260J).

Objective To investigate the clinical characteristics and associated risk factors for patients with mixed Candida/bacterial bloodstream infections (BSIs).Methods A retrospective study was conducted in the Second Affiliated hHospital of Zhejiang University School of Medicine from February 2012 to June 2015.The clinical data of cases was collected,and the clinical characteristics,the microbiology data and outcomes in patients with mixed Candida/bacterial BSIs confirmed by blood culture were compared with those with candidaemia.A Logistic regression analysis was performed to investigate the independent risk factors.Results A total of 136 candidaemia cases were analyzed including 40 cases (29.4％) of mixed Candida/boacterial BSIs and 96 cases of candidaemia.Among the 136 candidas strains,the proportion of non-albicans exceeded the albicans (50.7％ vs 49.3％),although the later was still the predominant one.There was no significant difference in the distribution of candidas strains between patients with mixed Candida/bacterial BSIs and patients with candidaemia.In patients with mixed Candida/bacterial BSIs,25 strains (61.0％) of gram-positive cocci and 16 strains (39.0％) of gram-negative bacilli were isolated.Compared with patients with candidaemia,patients with mixed Candida/bacterial BSIs needed longer period of antifungal therapy [12.0 (4.0-25.0)days vs 7.0 (3.0-13.5) days,P=0.027],but the crude 30-day and 90-day mortality did not differ between the two groups (40.0％ vs 32.3％;45.0％ vs 36.5％;both P＞0.05).Univariate analysis revealed that the prior hospital stay,ICU admission at the onset of candidaemia,blood transfusion,human albumin infusion,mechanical ventilation,linezolid use and high SOFA score were related with the occurrence of mixed Candida/bacterial BSIs (all P＜0.05).Multivariate analysis showed that only high SOFA score was the independent risk factor (P=0.003).Conclusions Gram-positive cocci were the predominant species in mixed Candida/bacterial BSIs.Compared with candidaemia,mixed Candida/bacterial BSIs needs a longer ICU stay,a longer hospital stay,and a prolonged antifungal therapy.High SOFA score is the independent risk factor for mixed Candida/ bacterial BSIs.

Objective: To evaluate the role of morphine preconditioning on necroptosis during myocardial ischemia-reperfusion (I/R) injury in the rats with heart failure. Methods: Clean-grade adult male Sprague-Dawley rats, weighing 200-230 g, were injected with 2 mg/kg doxorubicin via the tail vein once a week for 6 consecutive weeks to establish the chronic heart failure model.Thirty rats with chronic heart failure at the end of 8th week were divided into 3 groups (n=10 each) using a random number table method: sham operation group (group S), I/R group and morphine preconditioning group (group MPC). Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion in each group except group S. In group MPC, the rats were subjected to 3 cycles of 5-min infusion of 0.1 mg/kg morphine via the femoral vein at 5 min intervals before ischemia.The animals were sacrificed at the end of reperfusion, and the myocardial specimens were obtained for determination of the area at risk (AAR), infarct size (IS), expression of Fas mRNA (by quantitative real-time polymerase chain reaction) and expression of Fas, receptor-interacting protein 1 (RIP1) and RIP3 (by Western blot). The IS/AAR ratio was calculated. Results: Compared with group S, the IS and IS/AAR ratio were significantly increased at the end of reperfusion, and the expression of Fas protein and mRNA, RIP1 and RIP3 was up-regulated in group I/R (P<0.05). Compared with group I/R, the IS and IS/AAR ratio were significantly decreased at the end of reperfusion, and the expression of Fas protein and mRNA, RIP1 and RIP3 was down-regulated in group MPC (P<0.05). Conclusion The mechanism by which morphine preconditioning reduces myocardial I/R injury is related to inhibiting necroptosis in the rats with heart failure.