Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO₂), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO₂ maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.

Lymphoma has become one of the fastest growing haematological tumour, and effective self-management is an important means for patients to reduce symptom burden and improve quality of life. This article reviews the concept and development of self-management in lymphoma patients, the current status of self-management, influencing factors and intervention models, and proposes recommendations for self-management interventions, with the aim of providing a reference for conducting related research.

Lymphoma has become one of the fastest growing haematological tumour, and effective self-management is an important means for patients to reduce symptom burden and improve quality of life. This article reviews the concept and development of self-management in lymphoma patients, the current status of self-management, influencing factors and intervention models, and proposes recommendations for self-management interventions, with the aim of providing a reference for conducting related research.

Objective To analyze the effect of Meleis transition theory in the intervention of family caregivers of advanced lung cancer patients.Methods From January 2022 to June 2023,94 patients with advanced lung cancer and their family caregivers treated in 4 hospitals of a tertiary A hospital in Zhejiang Province were selected by convenience sampling method,and they were divided into a control group(n=47)and an experimental group(n=47)according to random number table method.The family caregivers of the experimental group received a four-week intervention based on the Meleis transition theory on the basis of routine nursing education,including role recognition,disease knowledge,life care,psychological support,and social resource connection.Family caregivers in the control group received routine nursing education,caregiving education and guidance.The differences in the readiness,caring ability,psychological burden and patients'quality of life were compared between the 2 groups.Results There was no lost follow-up cases in the control group and experimental group.After intervention,the preparation,ability,and quality of life of family caregivers in the experimental group were better than those in the control group,and the psychological burden of caregivers was significantly lower than that in the control group(P＜0.05).Conclusion The intervention of caregiving ability of family caregivers based on Meleis transition theory can effectively improve the caregiving ability of caregivers,reduce the psychological burden of caregivers,improve the quality of care,and improve the quality of life of patients.

Epstein-Barr virus (EBV), a double-stranded DNA virus with an envelope, is a ubiquitous pathogen that is prevalent in humans, although most people who contract it do not develop symptoms (Kerr, 2019). While the primary cells EBV attacks are epithelial cells and B lymphocytes, its target range expands to a variety of cell types in immunodeficient hosts. Serological change occurs in 90% of infected patients. Therefore, immunoglobulin M (IgM) and IgG, serologically reactive to viral capsid antigens, are reliable biomarkers for the detection of acute and chronic EBV infections (Cohen, 2000). Symptoms of EBV infection vary according to age and immune status. Young patients with primary infection may present with infectious mononucleosis; there is a typical triad of symptoms including fever, angina, and lymphadenectasis (Houen and Trier, 2021). In immunocompromised patients, response after EBV infection may be atypical, with unexplained fever. The nucleic acid of EBV can be detected to confirm whether high-risk patients are infected (Smets et al., 2000). EBV is also associated with the occurrence of certain tumors (such as lymphoma and nasopharyngeal carcinoma) because it transforms host cells (Shannon-Lowe et al., 2017; Tsao et al., 2017).
Humans ; Trachea ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Virus Diseases ; Fever ; Granuloma

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1^Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Objective:To analyze the registration characteristics and reporting quality of Taijiquan-related clinical trials.Methods:A database search of the China Clinical Trials Registry (ChiCTR) and ClinicalTrials.gov was performed by computer to collect basic information, study content, interventions, and other registration information of Taijiquan-related clinical trials from inception to June 30, 2022. The WHO TRDS was used to evaluate the registration quality of clinical trials.Results:Totally 381 Taijiquan-related clinical trials were incorporated, of which 241 (63.25%) were prospective registration and 140 (36.75%) were retrospective registration. The quantity of Taijiquan-related clinical trial registrations generally showed an increasing trend, reaching a peak in 2020 (14.70%). The number of clinical trials registered in Shanghai accounted for the most (9.97%). The largest contributor to the registered trials was Fujian University of Traditional Chinese Medicine (4.46%). 55.12% of registered studies were funded by hospitals and universities. The registered studies were most focused on cognitive impairment. 74.54% of the studies adopted randomized parallel controls, and the sample size was mainly between 20 and 200 (80.31%), and the age of the subjects was concentrated above 39 years (53.28%). The average report completion rate of WHO TRDS items was 86.90%.Conclusions:Presently, the development trend of clinical trials related to Taijiquan is relatively promising. However, imbalances exist in some aspects, for instance distribution of registration areas and institutions, funding allocation, and population of subjects. The description of some registration items is missing or not comprehensive, so corresponding measures are required to improve the quality of clinical trial design and to optimize registration details.

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious challenge to emergency departments that usually encounter emergencies and severe diseases.[1⇓⇓⇓-5] Angiotensin-converting enzyme 2 (ACE2), a protein that interacts with the viral spike protein(s), allows SARS-CoV-2 to penetrate epithelial cells.[6] There is mounting evidence that suggests that the digestive system may also be affected.[7] An observational study described potential patterns of pancreatic injury (elevated amylase and lipase) in patients with coronavirus disease 2019 (COVID-19).[8] Additionally, sporadic case reports have described secondary pancreatitis in patients with SARS-CoV-2 infection and presented imaging evidence.[9] Moreover, a previous study showed that COVID-19 patients not only have a higher risk of developing acute pancreatitis (AP), but also have a significantly higher mortality than those without COVID-19.[10] Using bioinformatics analysis, it may be possible to reveal how COVID-19 and AP are related. In this study, two RNA-seq datasets of SARS-CoV-2 and AP were selected for analysis.

Objective:To observe the incidence of syncope in patients with acute and critical cardiovascular diseases and to explore the risk factors of death.Methods:925 cases of acute heart failure, acute myocardial infarction, pulmonary embolism, arrhythmia and aortic dissection rupture who participated in Prospective, Multi-CenterRegistered Research Project for Chinese Syncope Patients from March 2018 to March 2020, admitted to the department of emergency of Nanyang Second General Hospital were selected as the research objects. The incidence and mortality of syncope were recorded, and the patients were divided into syncope group and non-syncope group according to whether they were accompanied by syncope or not. The incidence of syncope in male and female patients with different cardiovascular critical diseases, the age and mortality of cardiovascular critical patients with syncope or not were analyzed and compared. Multivariate Logistic regression analysis was used to analyze the risk factors of death, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on the prognosis of patients.Results:The incidence of syncope in 5 kinds of cardiovascular critical patients from high to low was: acute myocardial infarction 3.03% (28/925), arrhythmia 2.70% (25/925), pulmonary embolism 1.51% (14/925), aortic dissection rupture 1.41% (13/925), acute heart failure 0.65% (6/925), with statistically significant differences ( χ2 = 10.765, P = 0.010). There was no significant difference in the incidence of syncope between male and female patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia and acute heart failure. The age of patients with aortic dissection rupture, acute myocardial infarction and arrhythmia in syncope group were significantly higher than those in non-syncope group [aortic dissection rupture (years old): 66.29±15.64 vs. 57.63±14.23, acute myocardial infarction (years old): 69.55±15.13 vs. 62.10±15.75, arrhythmia (years old): 70.48±14.93 vs. 60.29±16.31, all P < 0.05]. The mortality of patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia, acute heart failure in syncope group were significantly higher than those in non-syncope group [pulmonary embolism: 5.81% (5/86) vs. 0.95% (8/839), aortic dissection rupture: 4.65% (4/86) vs. 0.60% (5/839), acute myocardial infarction: 4.65% (4/86) vs. 1.19% (10/839), arrhythmia: 2.33% (2/86) vs. 0.95% (8/839), acute heart failure: 2.33% (2/86) vs. 0.60% (5/839), all P < 0.05]. Multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 2.158, 95% confidence interval (95% CI) was 0.921-4.785, P = 0.000], pulmonary embolism ( OR = 15.391, 95% CI was 8.904-27.314, P = 0.001), aortic dissection rupture ( OR = 13.079, 95% CI was 6.237-25.509, P = 0.000), acute myocardial infarction ( OR = 18.826, 95% CI was 10.420-32.921, P = 0.000), syncope ( OR = 4.940, 95% CI was 1.764-9.287, P = 0.000) were risk factors for the prognosis of patients with acute and critical cardiovascular diseases. ROC curve analysis showed that syncope had a certain predictive value for 28-day prognosis of patients [the area under the ROC curve (AUC) = 0.760, P = 0.000], when the cut-off value was 4.12, the sensitivity was 88.51%, the specificity was 78.05%, the positive predictive value was 81.31%, and the negative predictive value was 84.27%. Conclusions:Syncope is an independent risk factor of death in patients with acute and critical cardiovascular diseases. For patients with syncope as the chief complaint, we should quickly identify the types of acute and critical diseases and assess the risk of sudden death.