Nutrition therapy in critically ill patients with severe acute pancreatitis.

A significant proportion of patients (10%-20%) with acute pancreatitis develop severe acute pancreatitis characterized by pancreatic necrosis, systemic inflammation, and organ failure, commonly requiring intensive care unit (ICU) admission. In this specific population, nutrition therapy is more challenging than that in the general ICU population, primarily because of inevitable gastrointestinal involvement by pancreatic inflammation. In this review, we discussed several key aspects of nutrition therapy in this population, including key pathophysiology that may impede nutrition therapy, the timing and implementation of enteral nutrition and parenteral nutrition, the importance of specific nutrient supplements, and the long-term outcomes that may be addressed by nutrition therapy.

Interactions of CDKAL1 rs7747752 polymorphism and serum levels of L-carnitine and choline are related to increased risk of gestational diabetes mellitus.

BACKGROUND: Interactions between genetic, metabolic, and environmental factors lead to gestational diabetes mellitus (GDM). We aimed to examine interactive effects of cyclin-dependent kinase 5 regulatory subunit-associated protein1-like 1(CDKAL1) rs7747752 polymorphism with low serum levels of L-carnitine, choline, and betaine for GDM. METHODS: A nested case-control study of 207 GDM women and their one-to-one, age-matched controls was organized from a prospective cohort of pregnant women in Tianjin, China. Conditional logistic regressions were used to test associations between CDKAL1 rs7747752 and serum levels of L-carnitine, choline, and betaine, and the risk of GDM. Additive interactions were performed to examine interactive effects of rs7747752 and low serum levels of L-carnitine, choline, and betaine on the risk of GDM. RESULTS: The CDKAL1 rs7747752 G > C was associated with GDM in additive, dominant, and recessive model (P <0.05). The rs7747752 CC genotype enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 6.14 (2.61-14.4) to 19.6 (5.65-68.1) and the OR of choline ≤ vs. > 110 nmol/mL from 2.37 (1.07-5.28) to 12.1 (3.22-45.6), with significant additive interactions. Similarly, CG genotype also enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 4.70 (2.01-11.0) to 11.4 (3.98-32.9), with a significant additive interaction. However, the additive interaction between rs7747752 and betaine ≤ 200 nmol/mL on the risk of GDM was not significant. CONCLUSIONS: The CC or CG genotype carriers in rs7747752 of CDKAL1 who have a low serum level of L-carnitine or choline are at a particular high risk of GDM. Randomized controlled trials are warranted to test the effect of supplement of L-carnitine or choline on the risk of GDM in the high-risk group.

Interleukin-37 protects against acinar cell pyroptosis in acute pancreatitis.

Acute pancreatitis (AP) is a local and/or systemic inflammatory disease that starts with acinar cell injury and necrosis; it has no effective medical treatment and thus remains a life-threatening condition. Interleukin-37 (IL-37), a natural immunomodulator, has demonstrated an antiinflammatory effect; however, the role of IL-37 in AP remains unknown. The serum IL-37 levels of 39 healthy controls and 94 patients with AP were measured. Cholecystokinin was applied to induce pancreatic acinar cell injury in vitro. Classical experimental AP models, such as caerulein, l-arginine, and taurolithocholic acid 3-sulfate disodium salt, were included in the in vivo study. A transgenic mouse model with the IL-37 gene and administration of recombinant IL-37 were used to further investigate the function of IL-37 in AP. Pancreas-specific gasdermin D-knockout (GSDMD-knockout) mice were used to explore the protective mechanism of IL-37. Our results showed that serum IL-37 levels in humans were negatively correlated with the severity of AP. Furthermore, IL-37-transgenic mice and supplementation with recombinant IL-37 could both protect against AP. Mechanistically, IL-37 was able to suppress pyroptosis of injured acinar cells, and specific depletion of GSDMD in the pancreas counteracted the protective effect of IL-37. Our study demonstrates that IL-37 protects against acinar cell pyroptosis in AP.

Correlation between T-Lymphocyte Subsets, Regulatory T Cells, and Hepatic Fibrosis in Patients with Nonalcoholic Fatty Liver.

Objective: The aim of this study is to assess the relationship between T-lymphocyte subsets, regulatory T cells (Treg), and hepatic fibrosis in patients with a nonalcoholic fatty liver disease (NAFLD). Methods: A retrospective analysis was conducted on 64 NAFLD patients (research group) and 73 healthy subjects (control group) in our hospital from January 2020 to December 2021. T-lymphocyte subsets (Th17) and Treg, liver function (alanine aminotransferase (ALT), aspartate aminotransferase (AST)), hepatic fibrosis indexes (type III procollagen (PCIII), type IV collagen (CIV), laminin (LN), hyaluronic acid (HA)), inflammatory factors (high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), interleukin-8 (IL-8)), and oxidative stress (OS) response ((superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA)) were tested. The relationship between Th17/Treg and the abovementioned indexes in NAFLD patients was analyzed. Results: In comparison to the control group, Th17 and Th17/Treg were higher in the research group (P < 0.05). In addition, liver function, liver fibrosis markers, inflammatory factors, and MDA were elevated, while SOD and GSH-PX decreased (P < 0.05). Subsequently, NAFLD patients were divided into groups A (Th17/Treg <1.15, n = 33) and B (Th17/Treg ≥1.15, n = 31) based on their median Th17/Treg levels. It was seen that liver injury, hepatic fibrosis, inflammation, and OS in group A were more severe (P < 0.05). The Pearson correlation coefficient revealed that Th17/Treg was positively correlated with AST, ALT, PCIII, MDA, and inflammatory factors but negatively correlated with SOD and GSH-PX (P < 0.05).

The Challenges and Effects of Ascorbic Acid Treatment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Preclinical and Clinical Studies.

Background: Oxidative stress has been implicated in the pathogenesis of acute pancreatitis (AP), and ascorbic acid (AA), as an important endogenous antioxidant substance, has been shown to reduce AP severity in preclinical studies. However, the effects of AA supplementation in clinical settings remain controversial. Methods: PubMed, EMBASE, MEDLINE, and SCOPUS databases were searched, and both preclinical and clinical studies were included. For clinical trials, the primary outcome was incidence of organ failure, and for preclinical studies, the primary outcome was histopathological scores of pancreatic injuries. Results: Meta-analysis of clinical trials showed that compared with controls, AA administration did not reduce the incidence of organ failure or mortality during hospitalization but was associated with significantly reduced length of hospital stay. Meta-analysis of preclinical studies showed that AA supplementation reduced pancreatic injury, demonstrated as decreased histological scores and serum amylase, lipase levels. Conclusion: AA administration has no effect on survival or organ failure in patients with AP but may reduce the length of hospital stay. However, the evidence to date remains sparse, scattered, and of suboptimal quality, making it difficult to draw any firm conclusion on the clinical benefits of AA in AP.

Electroacupuncture Ameliorates Acute Pancreatitis: A Role for the Vagus Nerve-Mediated Cholinergic Anti-Inflammatory Pathway.

Organ failure resulting from excessive inflammation is the leading cause of death in the early phase of acute pancreatitis (AP). The autonomic nervous system was reported to be involved in AP, and the vagus nerve could exert anti-inflammatory effects through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Acupuncture has been widely used in traditional Asian medicine, and recent studies suggested the inflammation modulating effect of electroacupuncture (EA) might be mediated by the autonomic nervous system. In this study, we aimed to investigate the effects of EA in AP animal models. Two independent AP mouse models were used, namely, caerulein hyperstimulation and pancreatic duct ligation. We found that EA at Zusanli acupoint increased vagus nerve activity, suppressed systemic inflammation, and alleviated the histopathological manifestations and leukocyte infiltrations of the pancreas. Induction of AP resulted in a remarkable decrease in the frequency of α7nAchR+ macrophages in the pancreas, while EA counteracted this phenomenon. The anti-inflammatory, pancreatic protective and upregulation of α7nAchR effects of EA were reduced in mice with vagotomy. Moreover, the therapeutic effects of EA were attenuated in mice treated with methyllycaconitine citrate, a selective α7nAChR antagonist. Taken together, EA could modulate inflammation, thereby exerting protective effects in AP. The mechanism may include activating the vagus nerve through the cholinergic anti-inflammatory pathway.

Tanshinone IIA Protects against Acute Pancreatitis in Mice by Inhibiting Oxidative Stress via the Nrf2/ROS Pathway.

BACKGROUND: Danshen (Salvia miltiorrhiza Bunge) and its main active component Tanshinone IIA (TSA) are clinically used in China. However, the effects of TSA on acute pancreatitis (AP) and its potential mechanism have not been investigated. In this study, our objective was to investigate the protective effects of TSA against AP via three classic mouse models. METHODS: Mouse models of AP were established by caerulein, sodium taurocholate, and L-arginine, separately. Pancreatic and pulmonary histopathological characteristics and serum amylase and lipase levels were evaluated, and changes in oxidative stress injury and the ultrastructure of acinar cells were observed. The reactive oxygen species (ROS) inhibitor N-Acetylcysteine (NAC) and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice were applied to clarify the protective mechanism of the drug. RESULTS: In the caerulein-induced AP model, TSA administration reduced serum amylase and lipase levels and ameliorated the histopathological manifestations of AP in pancreatic tissue. Additionally, TSA appreciably decreased ROS release, protected the structures of mitochondria and the endoplasmic reticulum, and increased the protein expression of Nrf2 and heme oxygenase 1 of pancreatic tissue. In addition, the protective effects of TSA against AP were counteracted by blocking the oxidative stress (NAC administration and Nrf2 knockout in mice). Furthermore, we found that TSA protects pancreatic tissue from damage and pancreatitis-associated lung injury in two additional mouse models induced by sodium taurocholate and by L-arginine. CONCLUSION: Our data confirmed the protective effects of TSA against AP in mice by inhibiting oxidative stress via the Nrf2/ROS pathway.

[Treatment of Simple Obesity Patients with Phlegm Dampness Stagnation Syndrome with Warming Needle Moxibustion].

OBJECTIVE: To observe the therapeutic effect of warming needle moxibustion stimulation of Hegu (LI 4), Tianshu (ST 25), Zhongwan (CV 12), Zusanli (ST 36), etc. for simple obesity patients with phlegm dampness stagnation syndrome (PDSS)．. METHODS: A total of 60 simple obesity patients with PDSS were equally randomized into control group (13 men and 17 women, 18－53 years in age) and treatment group (14 men and 16 women, 19－45 years in age). All the patients of both groups were treated by diet control (trying their best to reduce high fat, high glucose and high salt foods, supplementing proteins). Patients of the treatment group received additional treatment of warming needle moxibustion, i．e., the inserted acupuncture needles in bilateral Hegu (LI 4), Tianshu (ST 25), Zhongwan (CV 12), and Zusanli (ST 36), Fenglong (ST 40), etc., were manipulated for a while with reducing technique after "deqi"， followed by attachment of ignited moxa-cones at each of the needle handles for 30 min. The treatment was conducted once every other day for 8 weeks. The therapeutic effect was assessed according to the "Criteria for Diagnosis and Therapeutic Effect Evaluation of Simple Obesity" (1998). Before and after the treatment, body fat percentage (F%), body adiposity index (BAI), and body mass index (BMI) were calculated, serum triglyceride (TG), total cholesterol (CHO), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were detected using a biochemical analyzer. RESULTS: Following the treatment, of the two 30 cases of obesity patients in the control and treatment groups, 0 (0.0%) and 1 (3.3%) was under control, 11(36.7%) and 16 (53.3%) had a marked improvement, 8(26.7%) and 10 (33.3%) were effective, and 11 (36.7%) and 3 (10.0%) failed in the treatment, with the effective rates being 63.3% and 90.0%, respectively. The effective rate of the warming needle moxibustion plus diet control was significantly superior to that of the simple diet control (P<0.01). After the treatment, the BMI, F%, serum CHO and TG levels and BAI in the treatment group were significantly decreased in comparison with its own pre-treatment in treatment group (P<0.05, P<0.01), while serum HDL-C of the treatment group was obviously increased compared with its own pre-treatment (P<0.01). The decreased F%, CHO and TG levels were markedly lower in the treatment group than in the control group (P<0.05，P<0.01)．. CONCLUSION: Warming needle moxibustion has a positive effect for simple obesity patients with PDSS in controlling their symptoms.

Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting.

Growing evidence suggests acute skeletal muscle wasting is a key factor affecting nutritional support and prognosis in critical patients. Previously, plenty of studies of muscle wasting focused on the peripheral pathway, little was known about the central role. We tested the hypothesis whether central inflammatory pathway and neuropeptides were involved in the process. In lipopolysaccharide (LPS) treated rats, hypothalamic NF-κB pathway and inflammation were highly activated, which was accompanied with severe muscle wasting. Central inhibition of nuclear factor kappa-B (NF-κB) pathway activation by infusion of an inhibitor (PS1145) can efficiently reduce muscle wasting as well as attenuate hypothalamic neuropeptides alteration. Furthermore, knockdown the expression of anorexigenic neuropeptide proopiomelanocortin (POMC) expression with a lentiviral vector containing shRNA can significantly alleviate LPS-induced muscle wasting, whereas hypothalamic inflammation or NF-κB pathway was barely affected. Taken together, these results suggest activation of hypothalamic POMC is pivotal for acute muscle wasting caused by endotoxemia. Neuropeptide POMC expression may have mediated the contribution of hypothalamic inflammation to peripheral muscle wasting. Pharmaceuticals with the ability of inhibiting hypothalamic NF-κB pathway or POMC activation may have a therapeutic potential for acute muscle wasting and nutritional therapy in septic patients.

Codonopsis pilosula polysaccharide attenuates cecal ligation and puncture sepsis via circuiting regulatory T cells in mice.

BACKGROUND: Codonopsis pilosula polysaccharide (CPPS) isolated from one of the Chinese herbs is known to have a variety of immunomodulatory activities. However, it is not clear whether CPPS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of CPPS on the immune function of peripheral blood Tregs in sepsis induced by cecal ligation and puncture (CLP). METHODOLOGY AND PRINCIPAL FINDINGS: BALB/c mice were randomly divided into five groups: sham group, CLP group, CLP with CPPS (40, 100, and 250 mg/kg) treatment group, and they were killed on days 1, 2, 3, and 4 after CLP, respectively, with eight animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4 T cells. Phenotypes of Tregs, such as Toll-like receptor 4 (TLR4) and Foxp3, were analyzed by flow cytometry, and coculture medium cytokines levels were determined with enzyme-linked immunosorbent assay. The levels of TLR4 and the expression of Foxp3 in the Treg from CLP group were markedly increased in comparison to the sham group. Administration of CPPS could significantly decrease the TLR4 level and inhibited the expression of Foxp3 on Tregs in sepsis mice. At the same time, proliferative activity and expression of interleukin 2 and interleukin 2Rα on CD4 T cells were restored. In contrast, anti-TLR4 antibody could block the effect of CPPS on Treg immune function. CONCLUSIONS: Codonopsis pilosula polysaccharide might suppress excessive Tregs, at least in part, via TLR4 signaling on Tregs and trigger a shift of TH2 to TH1 with activation of CD4 T cells in sepsis induced by CLP.

Chemical composition and antibacterial activity of the essential oil from green huajiao (Zanthoxylum schinifolium) against selected foodborne pathogens.

Green huajiao, which is the ripe pericarp of the fruit of Zanthoxylum schinifolium Sieb. et Zucc, is widely consumed in Asia as a spice. In this work, the chemical composition of the essential oil from green huajiao was analyzed by gas chromatography (GC) and GC/mass spectrometry (MS), and the majority of components were identified. Linalool (28.2%), limonene (13.2%), and sabinene (12.1%) were found to be the major components. The antibacterial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of the essential oil were evaluated against selected bacteria, including food-borne pathogens. The results showed that the sensitivities to the essential oil were different for different bacteria tested, and the susceptibility of Gram-positive bacteria tested was observed to be greater than that of Gram-negative bacteria. The antibacterial activity of the essential oil was particularly strong against Staphylococcus epidermidis , with MIC and MBC values of 2.5 and 5.0 mg/mL, respectively. A postcontact effect assay also confirmed the essential oil had a significant effect on the growth rate of surviving S. epidermidis . The antibacterial activity of the essential oil from green huajiao may be due to the increase in permeability of cell membranes, and the leakage of intracellular constituents, on the basis of the cell constituents' release assay and electron microscopy observations.

Fish oil-supplemented parenteral nutrition in severe acute pancreatitis patients and effects on immune function and infectious risk: a randomized controlled trial.

The human leukocyte antigen (HLA)-DR expression on monocytes and plasma Interleukin (IL)-10 levels are key indicators of immune response during the acute phase of severe acute pancreatitis (SAP). We designed a pilot study to investigate whether omega-3 fatty acids (FAs) supplemented parenteral nutrition (PN) could improve immune response in SAP patients. Fifty-six SAP patients were enrolled (28 patients in each group) and received isocaloric and isonitrogenous parenteral nutrition, providing 1.0 g/kg/day standard soybean-oil based fat (omega-6 FAs group) or 0.8 g/kg/day soybean oil +0.2 g/kg/day omega-3 FAs based fat (omega-3 FAs group). IL-10, HLA-DR and the ratio of CD4(+) to CD8(+) were determined before PN treatment and on day 6 after starting PN. The infection and surgery rates were recorded until hospital discharge. A significant IL-10 increase was associated with the administration of omega-3 FAs (p = 0.04, vs omega-6 FAs group). Monocyte HLA-DR expression improved in both groups after 5 days of PN treatment. This increase was significantly higher in the omega-3 FAs group compared to omega-6 FAs (p = 0.01). There was no significant difference of CD4(+)/CD8(+), infection and surgery rates between the two groups. In conclusion, omega-3 FAs supplemented PN can elevate the IL-10 level and HLA-DR expression in SAP patients. A larger trial is required to see whether omega-3 FAs supplemented PN treatment in SAP patients would result in better clinical outcomes than omega-6 FAs.

Omega-3 fatty acids-supplemented parenteral nutrition decreases hyperinflammatory response and attenuates systemic disease sequelae in severe acute pancreatitis: a randomized and controlled study.

BACKGROUND: The objective of this study was to investigate whether altering the fatty acid (FA) profile by omega-3 FA supplementation affects inflammatory response and systemic disease sequelae in severe acute pancreatitis. METHODS: Forty severe acute pancreatitis patients were enrolled and randomly assigned to receive parenteral nutrition (PN) for 5 days in a double-blind manner. Patients received PN with identical amounts of amino acids (1.25 g/kg/d), glucose (3 g/kg/d), and fat (1 g/kg/d) but different lipid compositions: the control group received a soybean oil (SO; Lipovenos 20%; Fresenius, Germany)-based fat solution and the omega-3 FA group was supplemented with 0.15 - 0.2 g/kg/d fish oil (FO; Omegaven 10%; Fresenius, Germany). Serum concentrations of eicosapentaenoic acid (EPA), interleukin-6, C-reactive protein (CRP), white blood cell count, and routine respiratory and renal parameters were measured before PN, and again on day 6 after starting PN. Outcomes such as infection morbidity, mortality, intensive care unit time, and length of hospital stay were recorded. RESULTS: Patients treated with FO had a significantly higher EPA concentration (P < .01), lower CRP level (P < .05), and better oxygenation index (P < .05) after 5 days of PN. Moreover, the number of days of continuous renal replacement therapy (CRRT) in the omega-3 FAs group was significantly less than that in the control group (P < .05). CONCLUSIONS: PN supplemented with omega-3 FAs diminishes the hyperinflammatory response by the EPA increase and the proinflammatory cytokine decrease in severe acute pancreatitis. This, together with improved respiratory function and shortened CRRT time, suggests that the systemic response to pancreatic and organ injury is attenuated.