Role and Mechanism of cGAS-STING Pathway in Cardiovascular System.

The cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway is a part of the innate immune system that plays a role in the cardiovascular system. It acts as a surveillance system, detecting and responding to cytosolic DNA, viral DNA, and other intracellular DNA species. Activation of the cGAS-STING pathway leads to the production of inflammatory cytokines and type I interferons, which are involved in the immune response. In the cardiovascular system, the cGAS-STING pathway has been implicated in various physiological and pathological processes. It contributes to vascular inflammation, atherosclerosis, endothelial dysfunction and cardiac remodeling and heart failure. In this review, we will elaborate on the research progress of the role of cGAS-STING in cardiovascular system.

Predictive value of serum cholinesterase in the mortality of acute pancreatitis: A retrospective cohort study.

BACKGROUND: Severe acute pancreatitis has a high mortality of 20%-40%, but there is a lack of optimal prognostic biomarker for the severity of acute pancreatitis (AP) or mortality. This study is designed to investigate the relationship between serum cholinesterase (ChE) level and poor outcomes of AP. METHODS: A total of 1904 AP patients were screened in the study, and we finally got 692 patients eligible for analysis. Patients were divided into 2 groups based on serum ChE. The primary outcome was mortality, and multivariable logistic regression analysis for mortality was completed. Additionally, we used receiver operating characteristic (ROC) curve analysis to clarify the predictive value of serum ChE for mortality and organ failure. RESULTS: Three hundred and seventy eight patients and 314 patients were included in the ChE-low and ChE-normal group, respectively. Patients in the ChE-low group were older (46.68 ± 12.70 vs. 43.56 ± 12.13 years old, p = .001) and had a lower percentage of man (62.4% vs. 71.0%, p = .017) when compared to the ChE-normal group. Mortality was significantly different in two groups (10.3% vs. 0.0%, p < .001). Moreover, organ failure also differed significantly in two groups (46.6% vs. 8.6%, p < .001). Decreased ChE level was independently associated with mortality in acute pancreatitis (odds ratio: 0.440; 95% confidence interval, 0.231, 0.838, p = .013). The area under the curve of serum ChE was 0.875 and 0.803 for mortality and organ failure, respectively. CONCLUSIONS: Lower level of serum ChE was independently associated with the severity and mortality of AP.

Nonthyroidal illness syndrome in acute pancreatitis patients: an 8-year cohort study.

BACKGROUND: Nonthyroidal illness syndrome (NTIS) is common in critical illness and is associated with poor prognosis. The aim of this study was to find the prevalence, charateristics, and prognosis of NTIS and its correlation with outcomes in AP patients. METHODS: A retrospective review of AP patients with a diagnosis of NTIS from Jan 2012 to September 2020 was performed. The serum thyroidal hormone (TH) disturbances, as well as the demographic characteristics and clinical outcomes of the study patients, were collected and analyzed. RESULTS: Over the eight years, 183 included AP patients were diagnosed as NTIS, constituting an incidence of 64.7%. Patients with NTIS were admitted with worse condition based on the higher APACHE II score, SOFA score, Balthazar's CT score, CRP and lower albumin than euthyroid patients. Also, these patients had a longer ICU duration (3, 2-10 vs 2, 0-3, days, P = 0.039) and tended to be more likely to develop infected pancreatic necrosis (IPN) (15.3% vs 6.3%, P = 0.087) and gastrointestinal fistula (6% vs 0%, P = 0.082) than euthyroid patients. Free triiodothyronine (FT3) was found the best performance in predicting death compared by other well-recognized biomarkers. CONCLUSION: NTIS is common in AP patients within 7 days after the onset of the disease. NTIS is associated with the worse characteristics at admission and poor outcome during the course. FT3 should be investigate as a potential biomarker in the prediction of death in AP patients.

Lacticaseibacillus rhamnosus TR08 alleviated intestinal injury and modulated microbiota dysbiosis in septic mice.

BACKGROUND: Probiotics are widely used in intestinal microbiota imbalance caused by sepsis, however, the protective mechanism is still unclear. This study aimed to explore protective effect of Lacticaseibacillus rhamnosus TR08 on intestinal injury in septic mice. RESULTS: The levels of serum inflammatory factors were reduced significantly in septic mice treated with L. rhamnosus TR08. The levels of sIgA in terminal ileum were significantly higher in probiotic treatment group than sepsis group. Intestinal pathological damage in septic mice improved and the expression of tight junction proteins increased after probiotic treatment. Sequencing of fecal microbiota showed that the abundance and diversity of probiotic treatment group were significantly better than those of sepsis group, and beneficial bacteria increased while some bacteria decreased in the phylum level. CONCLUSION: L. rhamnosus TR08 could improve the integrity of intestinal barrier, enhance the intestinal mucosal immunity in septic mice, and rebalance the intestinal microecosystem.

Clinical characteristics and management of gastric outlet obstruction in acute pancreatitis.

OBJECTIVE: The aim of this study was to describe the clinical characteristics and management of gastric outlet obstruction following acute pancreatitis(AP). BACKGROUND: Gastric outlet obstruction (GOO) is not uncommon in acute pancreatitis (AP) and can occur throughout the course. However, the clinical features and related treatment of GOO is rarely reported. METHODS: A retrospective review of AP patients with a diagnosis of GOO from March 2017 to June 2020 was performed. The diagnosis and management of GOO, as well as the demographic characteristics and clinical outcomes of the study patients, were collected and analyzed. RESULTS: Over the three years, there were 60 AP patients developed GOO, constituting an incidence of 5.7%. Thirty-three patients (55.0%, 33/60) developed GOO in the first 4 weeks and 27 patients (45.0%, 27/60) after 4 weeks from onset. Pancreatic necrosis compression (60.6%; 20/33), gastric outlet gastrointestinal edema (27.3%, 9/33) are the main causes of early-onset GOO (≤4 weeks), while wall-off necrosis (92.6%, 25/27) is the leading cause in the late phase (>4 weeks). The management of GOO incorporates both supportive and specific treatment like gastric decompression, gastric juice reinfusion, percutaneous catheter drainage, etc. The mortality of AP patients with GOO (≤4 weeks) was 21.2% and none patients who developed GOO (>4 weeks) died. CONCLUSIONS: GOO, as a gastrointestinal complication developed in AP patients, has two peak incidences in the duration of AP and needs to be paid more attention to.

Potential value of heparin in COVID-19 related cardiovascular disease.

There is increasing evidence that COVID-19 is a multi-organ infectious disease with respiratory system as its main clinical manifestation. In particular, its risk of cardiovascular infection calls for effective clinical intervention strategies. The multiple values of heparin in its cardiovascular system deserve to be considered.

Multidisciplinary approaches to combat emerging viruses: diagnostics, therapeutic gene and vaccine delivery, and nanotherapeutics.

Emerging viruses, such as filoviruses (Ebola, Marburg), SARS and MERS coronaviruses, and Zika, pose significant threats to global public health, particularly for individuals with co-morbidities. To address these challenges, this review article explores multidisciplinary strategies for combatting emerging viruses. We emphasize the importance of developing accurate diagnostics, innovative therapeutic gene and vaccine delivery systems, and long-acting nanotherapeutics. These approaches are designed to enhance the safety and efficacy of treatments against these deadly pathogens. We discuss the collaborative efforts of virologists, geneticists, formulation scientists, clinicians, immunologists, and medicinal chemists in advancing these therapeutic modalities.

Chemical reagents for the enrichment of modified peptides in MS-based identification.

Chemical reagents with special groups as enrichable handles have empowered the ability to label and enrich modified peptides. Here is an overview of different chemical reagents with affinity tags to isolate labeled peptides and the latest developments of enrichment strategies. Biotin is the most used affinity tag due to its high interaction with avidin. To decrease the unfavorable influence of biotin for its poor efficiency in ionization and fragmentation in downstream MS analysis, cleavable moieties were installed between the reactive groups and biotin to release labeled peptides from the biotin. To minimize the steric hindrance of biotin, a two-step method was developed, for which alkyne- or azide-tagged linkers were firstly used to label peptides and then biotin was installed through click chemistry. Recently, new linkers using a small phosphonic acid as the affinity tag for IMAC or TiO2 enrichment have been developed and successfully used to isolate chemically labeled peptides in XL-MS. A stable P-C instead of P-O bond was introduced to linkers to differentiate labeled and endogenous phosphopeptides. Furthermore, a membrane-permeable phosphonate-containing reagent was reported, which facilitated the study of living systems. Taking a cue from classic chemical reactions, stable metal-complex intermediates, including cobalt and palladium complexes, have been developed as peptide purification systems. Advanced enrichment strategies have also been proposed, such as the two-stage IMAC enrichment method and biotin-based two-step reaction strategy, allowing the reduction of unwanted peptides and improvements for the analysis of specific labeled peptides. Finally, future trends in the area are briefly discussed.

Clinical Effect of Electroacupuncture on Acute Pancreatitis: Efficacies and Mechanisms.

Acute pancreatitis (AP) is a common acute abdomen and the number one cause of acute digestive hospitalizations in the United States. Abdominal pain is the main clinical manifestation of abdominal symptoms, so reducing the abdominal symptoms caused by inflammation is very important to alleviate the pain of patients. Electroacupuncture (EA) as a traditional Chinese medicine (TCM) therapy has significant conditioning effects on various inflammatory diseases including AP. Continuous studies in recent years have shown that EA conditioning has significant effects on reducing inflammation and regulating gastrointestinal symptoms in AP. At the same time, there is sufficient evidence to further elucidate the mechanism of EA. In this review, we will summarize the effect of EA on AP and its mechanism, so as to better serve clinical practice in the treatment of AP in the future.

Potential value of neuroimmunotherapy for COVID-19: efficacies and mechanisms of vagus nerve stimulation, electroacupuncture, and cholinergic drugs.

COVID-19 is an inflammatory disease with multiple organs involved, mainly respiratory symptoms. Although the majority of patients with COVID-19 present with a mild to moderate self-limited course of illness, about 5-10% of patients with inflammatory disorders in severe COVID-19 have life-threatening progression. With the exception of a few drugs that have shown outstanding anti-COVID-19 effects, the efficacy of most drugs remains controversial. An increasing number of animal and clinical studies have shown that neuromodulation has a significant effect on reducing inflammatory markers of COVID-19, thus exerting an effective neuroimmunotherapeutic value. Currently, the main neuroimmunomodulatory measures effective against COVID-19 include vagus nerve stimulation, electroacupuncture, and cholinergic drugs. In this review, we will summarize the research progress of potential value of this neuroimmunotherapy measures for COVID-19 and elaborate its efficacies and mechanisms, in order to provide reliable evidence for clinical intervention.

Electroacupuncture in Regulating Gastrointestinal Symptoms of COVID-19: A Mini-review.

Nearly three years into the COVID-19 pandemic, there is still no effective treatment. In the meantime, more and more evidence indicate that gastrointestinal symptoms are important manifestations of COVID-19. Therefore, the involvement of multiple system symptoms brings a lot of burden and harm to patients. To our knowledge, traditional Chinese medicine (TCM) has a remarkable effect on improving gastrointestinal function. In particular, a considerable number of clinical practices during the pandemic have demonstrated the significant value of electroacupuncture (EA) in regulating the gastrointestinal function of COVID-19. In summary, EA can regulate the gastrointestinal function of COVID-19. As more is learned about EA, its potential value in COVID-19 deserves further consideration. In this review, we will elucidate the potential efficacy and mechanism of EA in the treatment of gastrointestinal symptoms of COVID-19.

Viral pancreatitis: research advances and mechanisms.

Acute pancreatitis is caused by trypsinogen activation in acinar cells caused by various injury forms (gallstone, high triglycerides, alcohol, etc.). Viral pancreatitis is a clinically rare disease type, which is easily neglected by clinicians and causes serious adverse consequences. Viral pancreatitis involves the entry of viruses into pancreatic cells, triggering inflammation, immune response activation, and enzymatic autodigestion, leading to tissue damage and potential complications. At present, there are few available reports on viral pancreatitis, most of which are case reports. This review brings attention to clinicians by describing the incidence of viral pancreatitis to enhance clinical understanding and patient care.

Association between circadian body temperature rhythm during the first 24 hours of ICU stay and 28-day mortality in elderly critically ill patients: A retrospective cohort study.

Disrupted circadian temperature rhythm is commonly observed in elderly patients in the intensive care unit (ICU), but the association between circadian temperature rhythm and mortality in elderly patients is unclear. Adult patients with a relatively complete record of body temperature (BT) during the first 24 hours of ICU stay in the Multi-parameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database were included in this retrospective cohort study. The circadian rhythm of body temperature was blunted as a ratio of the maximum BT between 12:00 and 24:00 divided by the minimum BT between 0:00 and 12:00, and we defined it as BT fluctuation ratio. The associations of BT fluctuation ratio with 28-day mortality were assessed separately using Cox proportional hazards model in elderly patients and non-elderly patients. The overall cohort comprised 12 767 patients. After adjusting for covariates, the analysis showed that the BT fluctuation ratio (%) was significantly associated with mortality at 28 days in total patients (hazard ratio: 1.044; 95% CI 1.001-1.088; P = 0.042), and still significantly in elderly patients (hazard ratio 1.055, 95% CI as 1.004-1.109, p = 0.035), but not significantly in non-elderly patients. The implementation of restricted cubic splines demonstrated a nonlinear correlation between the ratio of BT fluctuation and the hazard ratio of 28-day mortality, indicating that increased diurnal temperature fluctuations are linked to elevated risk of mortality. This study revealed that the augmented amplitude of the circadian rhythm of body temperature in the elderly patients constitutes a risk factor for the rise of 28-day mortality. Additionally, the circadian body temperature rhythm may facilitate the early detection of critically ill elderly patients.