Anchoring Cs+ Ions on Carbon Vacancies for Selective CO2 Electroreduction to CO at High Current Densities in Membrane Electrode Assembly Electrolyzers.

Electrolyte cations have been demonstrated to effectively enhance the rate and selectivity of the electrochemical CO2 reduction reaction (CO2RR), yet their implementation in electrolyte-free membrane electrode assembly (MEA) electrolyzer presents significant challenges. Herein, an anchored cation strategy that immobilizes Cs+ on carbon vacancies was designed and innovatively implemented in MEA electrolyzer, enabling highly efficient CO2 electroreduction over commercial silver catalyst. Our approach achieves a CO partial current density of approximately 500 mA cm-2 in the MEA electrolyzer, three-fold enhancement compared to pure Ag. In situ Raman and theoretical analyses, combined with machine learning potentials, reveal anchored Cs induces an electric field that significantly promotes the adsorption of *CO2 - intermediates through performing muti-point energy calculations on each structure. Furthermore, reduced adsorption of *OH intermediates effectively hampers competing hydrogen evolution reaction, as clarified by disk electrode experiments and density functional theory studies. Additionally, coupling our system with commercial polysilicon solar cells yields a notable solar-to-CO energy conversion efficiency of 8.3 %. This study opens a new avenue for developing effective cation-promoting strategy in MEA reactors for efficient CO2RR.

Insulin or blood purification treatment for hypertriglyceridaemia-associated acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Hypertriglyceridaemia increases risks from acute pancreatitis (HTG-AP) over other aetiologies, but optimal management for HTG-AP remains undefined. We performed a systematic review and meta-analysis of studies of insulin-based treatment (IT) versus blood purification treatment (BPT) for HTG-AP. METHODS: Searches were conducted to identify randomised trials and observational studies published between 1946 and 2022 that compared IT and BPT for HTG-AP reporting baseline and post-treatment serum triglyceride (TG) levels with clinical outcomes. The primary outcome was serum TG reduction (Δ-TG) from baseline while secondary outcomes included complications, length of stay, adverse events, and cost. RESULTS: Fifteen (1 randomised, 2 prospective case-controlled, and 12 retrospective cohort) studies were analysed comprising 909 cases with HTG-AP. Pooled results demonstrated IT was significantly less efficient than BPT in Δ-TG at 24 h (WMD -666.06, 95% CI -1130.18 to -201.94, P = 0.005; 12 studies), at 48 h (WMD -672.60, 95% CI -1233.44 to -111.77; 8 studies), and overall Δ-TG by day 7 (WMD -385.81, 95% CI -711.07 to -60.54; 8 studies) (both P = 0.02). IT, however, was associated with significantly fewer adverse events (OR 0.09, 95% CI 0.03 to 0.27, P < 0.0001; 7 studies) and significantly reduced cost (WMD -2.50, 95% CI -3.61 to -1.39, P < 0.00001; 3 studies). Other secondary outcomes were not significantly different between the two regimens (all P ≥ 0.11). In subgroup analysis Δ-TG at 24 h and overall Δ-TG became insignificant, while other results were unaffected. CONCLUSION: Our findings support the general use of IT for inpatient management of HTG-AP, restricting BPT to those predicted or found to respond poorly to IT.

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis.

BACKGROUND/AIMS: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients. METHODS: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared. RESULTS: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone. CONCLUSIONS: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes.

Predicting persistent organ failure on admission in patients with acute pancreatitis: development and validation of a mobile nomogram.

BACKGROUND: Early prediction of persistent organ failure (POF) is important for triage and timely treatment of patients with acute pancreatitis (AP). METHODS: All AP patients were consecutively admitted within 48 h of symptom onset. A nomogram was developed to predict POF on admission using data from a retrospective training cohort, validated by two prospective cohorts. The clinical utility of the nomogram was defined by concordance index (C-index), decision curve analysis (DCA), and clinical impact curve (CIC), while the performance by post-test probability. RESULTS: There were 816, 398, and 880 patients in the training, internal and external validation cohorts, respectively. Six independent predictors determined by logistic regression analysis were age, respiratory rate, albumin, lactate dehydrogenase, oxygen support, and pleural effusion and were included in the nomogram (web-based calculator: https://shina.shinyapps.io/DynNomapp/). This nomogram had reasonable predictive ability (C-indexes 0.88/0.91/0.81 for each cohort) and promising clinical utility (DCA and CIC). The nomogram had a positive likelihood ratio and post-test probability of developing POF in the training, internal and external validation cohorts of 4.26/31.7%, 7.89/39.1%, and 2.75/41%, respectively, superior or equal to other prognostic scores. CONCLUSIONS: This nomogram can predict POF of AP patients and should be considered for clinical practice and trial allocation.

Intranasal fluticasone furoate in pediatric allergic rhinitis: randomized controlled study.

BACKGROUND: Intranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of fluticasone furoate nasal spray (FFNS) in a Chinese pediatric population. METHODS: In this phase 4 randomized, double-blind, placebo-controlled, multicenter study, pediatric AR patients aged 2-12 years were randomized 1:1:1, receiving either FFNS 55 µg or 110 µg or placebo. Electronic diary cards were completed to record symptoms, rescue medication use, and treatment compliance. Anterior rhinoscopy and overall response to therapy were evaluated and recorded. RESULTS: Patients treated with FFNS at either dose experienced a significantly greater reduction in daily reflective total nasal symptom score compared with placebo. This was maintained in a younger subset of patients (2-6 years). Drug-related adverse events occurred in <20% of patients in all groups. FFNS was well tolerated at both doses. CONCLUSIONS: This study demonstrates favorable efficacy and safety profiles for FFNS 55 µg or 110 µg in Chinese pediatric populations (2-12 years), supporting its use in clinical treatment for AR children, including younger children aged 2-6 years. IMPACT: The aim of this study was to investigate the efficacy and safety of intranasal fluticasone furoate in Chinese pediatric allergic rhinitis. This research not only addresses the deficiency in efficacy and safety data for intranasal corticosteroids in very young patients (aged 2-6 years) worldwide but also demonstrates that fluticasone furoate nasal spray shows a favorable benefit/risk profile at different dose levels. Our data will be of interest to the broad readership of Pediatric Research and will positively contribute to the dialog regarding the treatment of allergic rhinitis in children aged 2-6 years.

Assessment of the Quality and Content of Clinical Practice Guidelines on Irritable Bowel Syndrome Using the AGREE II Instrument.

OBJECTIVES: The aim of the study was to assess the quality of guidelines on irritable bowel syndrome (IBS) using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument and identify concordance of different commendations. MATERIALS AND METHODS: A systematic search was undertaken from inception to May 2018. Two reviewers independently selected the titles and abstracts. The guidelines included were assessed using the AGREE II instrument. The consistency of evaluations was calculated using intra-class correlation coefficients with 95% CI. RESULTS: From 994 records, 7 guidelines were included. Most of guidelines got a moderate score of AGREE II. The highest median scores were achieved for scope and purpose and clarity and presentation (69.4%), while the lowest median scores across guidelines were for applicability (50.0%). Most of the nonpharmacologic management recommendations for IBS were similar. However, there also existed some differences on pharmacologic between different guidelines. CONCLUSIONS: The guidelines on IBS varied in quality and there were discrepancies about recommendations and recommendation grades. There is some space to improvement the quality of methodological rigor in development and reporting within clinical guidelines.

Ethyl pyruvate and analogs as potential treatments for acute pancreatitis: A review of in vitro and in vivo studies.

Ethyl pyruvate (EP) has been shown to improve outcomes from multiple organ dysfunction syndrome (MODS) in experimental animal models of critical illness. This review aimed to summarise in vitro and in vivo effects of EP analogs on acute pancreatitis (AP) with the objective of proposing medicinal chemistry modifications of EP for future research. In vitro studies showed that both sodium pyruvate and EP significantly reduced pancreatic acinar necrotic cell death pathway activation induced by multiple pancreatic toxins. In vivo studies using different murine AP models showed that EP (usually at a dose of 40 mg/kg every 6 h) consistently reduced pain, markers of pancreatic injury, systemic inflammation and MODS. There was also a significant increase in survival rate, even when EP was administered 12 h after disease induction (compared with untreated groups or those treated with Ringer's lactate solution). Experimental studies suggest that EP and analogs are promising drug candidates for treating AP. EP or analogs can undergo medicinal chemistry modifications to improve its stability and deliverability. EP or analogs could be evaluated as a supplement to intravenous fluid therapy in AP.

The effect of bladder catheterization on the incidence of urinary tract infection in laboring women with epidural analgesia: a meta-analysis of randomized controlled trials.

INTRODUCTION AND HYPOTHESIS: There is conflicting evidence on whether intermittent catheterization (IC) is less associated with urinary tract infection (UTI) and more likely to prevent urinary retention than continuous catheterization (CC). We aimed to compare the effect of IC with that of CC on the incidence of postpartum UTI, urinary retention and hemorrhage in laboring women with epidural analgesia. METHODS: Electronic searches were performed in PubMed, EMBASE and Cochrane Library from their inception to October 2018. We selected RCTs comparing IC with CC in laboring women with epidural analgesia. A meta-analysis was performed using the RevMan software, and a random-effects model was used to pool the effect size. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence. RESULTS: Six RCTs (N = 850) were included in this review. The meta-analyses indicated that there was no significant difference between the IC and CC group in the incidence of postpartum UTI (RR = 1.25, 95% CI: 0.91 to 1.71, P = 0.16), postpartum urinary retention (RR = 0.76, 95% CI: 0.21 to 2.77, P = 0.68) and postpartum hemorrhage (RR = 1.72, 95% CI: 0.60 to 4.95, P = 0.31). GRADE assessment results showed that the quality of evidence was low. CONCLUSIONS: Based on the available evidence, there is no measurable difference in rates of UTI between CC and IC, not that neither stragety decreases UTI, since the included trials do not address this.

Hypertriglyceridaemia-associated acute pancreatitis: diagnosis and impact on severity.

BACKGROUND: The level of hypertriglyceridaemia (HTG) at which the risk of acute pancreatitis (AP) increases and the impact of HTG on AP attributable to other aetiologies remains unclear. METHODS: We compared clinical outcomes of patients admitted within 48 h of the onset of abdominal pain from a first episode of AP and admission serum triglyceride levels of either <5.65 mmol/l (<500 mg/dl) or ≥5.65 to <11.3 mmol/l (moderate HTG) or ≥11.3 mmol/l (≥1000 mg/dl, severe HTG). RESULTS: Among a cohort of 1,233 patients with AP there were significant progressive increases in all major deleterious clinical outcomes including mortality (all Ptrend < 0.05) that were directly dependent on admission triglyceride levels. Outcomes were improved by earlier presentation (<24 h compared to 24-48 h from abdominal pain onset). Patients with severe HTG and a concomitant aetiology (n = 68) had significantly more persistent organ failure, pancreatic necrosis and longer hospital stays (P < 0.05) than those with severe HTG alone (n = 206). CONCLUSIONS: There appears to be an association between HTG grade and the severity of AP. Severe HTG significantly increased the severity of AP, over AP attributable to other aetiologies. Moderate as well as severe HTG can be used as a criterion for the diagnosis of HTG-associated AP.

Development and validation of dissolution testings in acidic media for rabeprazole sodium delayed-release capsules.

Rabeprazole sodium (RAB) dissolved in acidic media is accompanied by its degradation in the course of dissolution testing. To develop and establish the accumulative release profiles of ACIPHEX(®) Sprinkle (RAB) delayed-release capsules (ACIPHEX(®) Sprinkle) in acidic media using USP apparatus 2 (paddle apparatus) as a dissolution tester, the issues of determination of accumulative release amount of RAB in these acidic media and interference of hydroxypropylmethyl cellulose phthalate were solved by adding appropriate hydrochloric acid (HCl) into dissolution samples coupled with centrifugation so as to remove the interference and form a solution of degradation products of RAB, which is of a considerably stable ultraviolet (UV) absorbance at the wavelength of 298 nm within 2.0 h. Therefore, the accumulative release amount of RAB in dissolution samples at each sample time points could be determined by UV-spectrophotometry, and the accumulative release profiles of ACIPHEX(®) Sprinkle in the media of pH 1.0, pH 6.0, and pH 6.8 could be established. The method was validated per as the ICH Q2 (R1) guidelines and demonstrated to be adequate for quality control of ACIPHEX(®) Sprinkle and the accumulative release profiles can be used as a tool to guide the formulation development and quality control of a generic drug for ACIPHEX(®) Sprinkle.

Effects of integrated traditional Chinese and Western medicine for acute pancreatitis: A real-world study in a tertiary teaching hospital.

AIM: This study aimed to evaluate whether integrated traditional Chinese medicine (TCM) and Western medicine (WM) is more effective than WM for acute pancreatitis (AP). METHODS: Patients with AP were enrolled and divided into the TCM and WM (TCM&WM) and WM groups according to the therapeutic protocol in real clinical settings. We applied 1:3 propensity score matching, which was to adjust confounding factors. The primary outcome was mortality, whereas the secondary outcomes were organ failure, organ supportive therapies, local complications, hospitalization cost, and length of hospital stay. Sensitivity and subgroup analyses were also performed. RESULTS: Of 5442 patients with AP, 4691 and 751 were included in the TCM&WM and WM groups, respectively. After PSM, patient baseline characteristics were well balanced. Compared with the WM group (n = 734), the TCM&WM group (n = 2096) had lower overall mortality rate (1.7% vs. 3.4%; risk ratio, 0.482; 95% confidence interval, 0.286-0.810; p = 0.005). The TCM&WM group was associated with lower risk of persistent renal failure, multiple organ failure, and infection, lower utilization of organ supportive therapies, shortened lengths of hospital and intensive care unit stay, and lower hospital costs. Sensitivity analyses showed similar results. Subgroup analysis favored TCM&WM treatment for patients aged < 60 years, with hypertriglyceridic etiology, and with admission interval between 24 and 48 h. CONCLUSION: TCM&WM treatment can achieve lower risks of mortality and organ failure and better economic effectiveness in patients with AP than WM treatment. This study provides a promising alternative of TCM&WM treatment for AP in the real-world setting.

Chaiqin chengqi decoction treatment mitigates hypertriglyceridemia-associated acute pancreatitis by modulating liver-mediated glycerophospholipid metabolism.

BACKGROUND: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored. PURPOSE: To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP. METHODS: Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 µg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes. RESULTS: HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes. CONCLUSION: Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.

Cost and Effectiveness of Percutaneous Endoscopic Interlaminar Discectomy versus Microscope-Assisted Tubular Discectomy for L5-S1 Lumbar Disc Herniation.

OBJECTIVE: To assess the cost and effectiveness of percutaneous endoscopic interlaminar discectomy (PEID) and microscope-assisted tubular discectomy (MATD) for patients with L5/S1 lumbar disc herniation (LDH). METHODS: The medical and financial records of patients diagnosed with L5/S1 LDH and who underwent either PEID or MATD from April 2021 to April 2022 were retrospectively collected. Demographic and baseline information, perioperative observational index, clinical outcomes, and inpatient costs were analyzed. RESULTS: Sixty patients were included, with 30 patients in the PEID group and 30 patients in the MATD group. No significant difference was found in demographic and baseline information between the 2 groups (P > 0.05). The PEID group showed significantly shorter incision length, less intraoperative blood loss, shorter hospital stays, and higher intraoperative fluoroscopy frequency compared with the MATD group (P < 0.05). There were no significant differences in visual analog scale back/leg score, Oswestry Disability Index, and 36-Item Short-Form Survey score between PEID and MATD groups before the surgery and at any follow-up time points (P > 0.05). The total cost, surgery cost, and surgical instruments/materials cost were significantly higher in the PEID group compared with the MATD group (P < 0.05). In contrast, the drug and nursing costs were significantly higher in the MATD group than in the PEID group (P < 0.05). CONCLUSIONS: PEID and MATD provide equivalent clinical efficacy and safety in treating LDH at L5/S1 segment within a 1-year follow-up. However, PEID is less invasive and MATD is less costly. No one surgical technique is superior in all aspects and patients should make decisions according to their top concern.

Novel one-pot strategy for fabrication of a pH-Responsive bone-targeted drug self-frame delivery system for treatment of osteoporosis.

Osteoporosis (OP) is a systemic metabolic orthopedic disorder prevalent in elderly people, that is characterized by a decrease in bone mass. Although many therapeutics have been adopted for OP treatment, many of them are still not well satisfied clinical requirements and therefore development of novel therapeutics is of great significance. In this work, a novel bone-targeting drug self-frame delivery system (DSFDS) with high drug loading efficiency and pH responsive drug release was fabricated by condensation of curcumin (Cur), amino group terminated polyethylene glycol (NH2-PEG), and alendronate (ALN) using hexachlorocyclotriphosphonitrile (HCCP) as the linker. The final product named as HCCP-Cur-PEG-ALN (HCPA NPs) displayed excellent water dispersity with small size (181.9 â€‹± â€‹25.9 â€‹nm). Furthermore, the drug loading capacity of Cur can reach 25.8%, and Cur can be released from HCPA NPs under acidic environment. Owing to the introduction of ALN, HCPA NPs exhibited strong binding to HAp in vitro and excellent bone-targeting effect in vivo. Results from cellular and biochemical analyses revealed that HCPA NPs could effectively inhibit the formation and differentiation function of osteoclasts. More importantly, we also demonstrated that HCPA NPs could effectively reduce bone loss in OVX mice with low toxicity to major organs. The above results clearly demonstrated that HCPA NPs are promising for OP treatment. Given the simplicity and well designability of fabrication strategy, explicit therapy efficacy and low toxicity of HCPA NPs, we believe that this work should be of great interest for fabrication of various DSFDS to deal with many diseases.

Facile synthesis of curcumin-containing poly(amidoamine) dendrimers as pH-responsive delivery system for osteoporosis treatment.

Osteoporosis is an age-related metabolic disease of bone, resulting in bone pain and even bone fragility and brittle fracture. Inhibiting overactive osteoclasts while promoting osteoblast activity is an ideal way to treat osteoporosis. Previous studies have demonstrated that natural compounds, such as curcumin (Cur) have dual roles both in promoting bone formation and inhibiting bone resorption, making them promising candidates for osteoporosis treatment. However, their poor water solubility, high dosage of curative effect and significant toxicity to other organs have largely limited their clinical translations. In this study, a novel method was reported to conjugate Cur and poly(amidoamine) dendrimers (PAD) using hexachlorocyclotriphosphazene (HCCP) as the linkage through a one-pot reaction, forming stable and uniform Cur loaded nanospheres (HCCP-Cur-PAD, HCP NPs). Owing to the hydrophilicity of PAD and hydrophobicity of Cur, HCP NPs can self-assemble into nanoparticles with particle size of 138.8 ± 78.7 nm and display excellent water dispersity. The loading capacity of Cur can reach 27.2% and it can be released from HCP NPs with pH-responsiveness. In vitro experimental results demonstrated that the HCP NPs entered lysosomes by endocytosis and proved dual anti-osteoporosis effects of inhibiting osteoclasts and promoting osteoblasts.

Enhanced photocatalytic activity and structural stability by hybridizing Ag3PO4 nanospheres with graphene oxide sheets.

Graphene oxide (GO)-Ag(3)PO(4) nanocomposites synthesized through a facile solution approach via electrostatic interaction were investigated as excellent photocatalysts for the degradation of rhodamine B (RhB) under visible light irradiation. SEM and TEM observations indicate that Ag(3)PO(4) nanospheres of ~120 nm in diameter were well dispersed and anchored onto the exfoliated GO sheets. The characterizations of FTIR and Raman demonstrated the existence of strong charge interactions between GO sheets and Ag(3)PO(4) nanospheres. As compared to Ag(3)PO(4) nanospheres alone, the attachments of GO sheets led to a band gap narrowing (2.10 eV) and a strong absorbance in the near infrared region (NIR). The photoluminescence (PL) analysis indicates a more efficient separation of electron-hole pairs in the GO-Ag(3)PO(4) nanocomposites. Notably, the incorporation of GO sheets not only significantly enhances the photocatalytic activity but also improves the structural stability of Ag(3)PO(4). The positive synergistic effects between Ag(3)PO(4) nanospheres and GO sheets are proposed to contribute to the improved photocatalytic properties. A possible photocatalytic mechanism of the GO-Ag(3)PO(4) nanocomposites was assumed as well. The integration of these advantages enables such GO-Ag(3)PO(4) hybrid material to be a nice photocatalyst for broad applications in a sewage treatment system.

Role of Seipin in Human Diseases and Experimental Animal Models.

Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). BSCL2 gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia's encephalopathy), and BSCL2-associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. In the current study, we comprehensively summarise phenotypes, underlying mechanisms, and treatment of human diseases caused by BSCL2 gene mutations, paralleled by animal studies including systemic or specific Bscl2 gene knockout, or Bscl2 gene overexpression. In various animal models representing diseases that are not related to Bscl2 mutations, differential expression patterns and functional roles of seipin are also described. Furthermore, we highlight the potential therapeutic approaches by targeting seipin or its upstream and downstream signalling pathways. Taken together, restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment. Meanwhile, seipin-related pathways are also considered to have potential therapeutic value in diseases that are not caused by BSCL2 gene mutations.

Impact of admission and early persistent stress hyperglycaemia on clinical outcomes in acute pancreatitis.

Background: To determine the impact of glucose levels at admission and during first week (early phase) on clinical outcomes in patients with acute pancreatitis (AP) and to investigate the relationship between stress hyperglycaemia (SHG) and hypertriglyceridaemia (HTG). Methods: Two independent and prospective databases were retrospectively analysed (n = 1792). Patients admitted with pain of less than 48 hours and confirmed AP were included. SHG was defined as admission blood glucose ≥ 10.00 mmol/L (non-diabetic) or ≥ 16.67 mmol/L (diabetic). Blood glucose records for the first week were inspected to determine whether SHG lasted ≥ 48 hours (persistent) or < 48 hours (transient). Clinical outcomes were compared between designated patient groups using multivariate and trend analyses. The correlation between SHG and HTG (serum triglyceride ≥ 5.65 mmol/L) was also analysed. Results: On admission, SHG was present in 27.8% (499/1792) patients; during the first 48 hours of admission, transient and persistent SHG was found in 31% (556/1792) and 8.0% (144/1792) patients, respectively. Admission SHG was associated with higher incidence of persistent organ failure, acute necrotic collection, major infection, and mortality as well as prolonged length of hospital stay (all P < 0.05). Duration of SHG was also associated with worsened clinical outcomes (all P < 0.05). In HTG-AP patients, more severe clinical outcomes were observed in those who concomitantly had SHG (P < 0.05). Conclusions: Admission and persistent SHG during the first week of admission worsens clinical outcomes of AP patients. These effects are more pronounced when admission HTG co-existed.

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis via Oxidative Stress and PI3K/Akt Signaling Pathway.

Obesity-related acute pancreatitis (AP) is characterized by increasing prevalence worldwide and worse clinical outcomes compared to AP of other etiologies. Chaiqin chengqi decoction (CQCQD), a Chinese herbal formula, has long been used for the clinical management of AP but its therapeutic actions and the underlying mechanisms have not been fully elucidated. This study has investigated the pharmacological mechanisms of CQCQD in a novel mouse model of obesity-related alcohol-induced AP (OA-AP). The mouse OA-AP model was induced by a high-fat diet for 12 weeks and subsequently two intraperitoneal injections of ethanol, CQCQD was administered 2 h after the first injection of ethanol. The severity of OA-AP was assessed and correlated with changes in transcriptomic profiles and network pharmacology in the pancreatic and adipose tissues, and further docking analysis modeled the interactions between compounds of CQCQD and their key targets. The results showed that CQCQD significantly reduced pancreatic necrosis, alleviated systemic inflammation, and decreased the parameters associated with multi-organ dysfunction. Transcriptomics and network pharmacology analysis, as well as further experimental validation, have shown that CQCQD induced Nrf2/HO-1 antioxidant protein response and decreased Akt phosphorylation in the pancreatic and adipose tissues. In vitro, CQCQD protected freshly isolated pancreatic acinar cells from H2O2-elicited oxidative stress and necrotic cell death. The docking results of AKT1 and the active compounds related to AKT1 in CQCQD showed high binding affinity. In conclusion, CQCQD ameliorates the severity of OA-AP by activating of the antioxidant protein response and down-regulating of the PI3K/Akt signaling pathway in the pancreas and visceral adipose tissue.