BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a cause of acute-on-chronic liver failure (ACLF). AIM: To investigate the risk factors of ACLF within 1 year after TIPS in patients with cirrhosis and construct a prediction model. METHODS: In total, 379 patients with decompensated cirrhosis treated with TIPS at Nanjing Drum Tower Hospital from 2017 to 2020 were selected as the training cohort, and 123 patients from Nanfang Hospital were included in the external validation cohort. Univariate and multivariate logistic regression analyses were performed to identify independent predictors. The prediction model was established based on the Akaike information criterion. Internal and external validation were conducted to assess the performance of the model. RESULTS: Age and total bilirubin (TBil) were independent risk factors for the incidence of ACLF within 1 year after TIPS. We developed a prediction model comprising age, TBil, and serum sodium, which demonstrated good discrimination and calibration in both the training cohort and the external validation cohort. CONCLUSION: Age and TBil are independent risk factors for the incidence of ACLF within 1 year after TIPS in patients with decompensated cirrhosis. Our model showed satisfying predictive value.
Photoinduced Pd-catalyzed bisfunctionalization of butadienes with a readily available organic halide and a nucleophile represents an emerging and attractive method to assemble versatile alkenes bearing various functional groups at the allylic position. However, enantiocontrol and/or diastereocontrol in the C-C or C-X bond-formation step have not been solved due to the open-shell process. Herein, we present a cascade asymmetric dearomatization reaction of indoles via photoexcited Pd-catalyzed 1,2-biscarbonfunctionalization of 1,3-butadienes, wherein asymmetric control on both the nucleophile and electrophile part is achieved for the first time in photoinduced bisfunctionalization of butadienes. This method delivers structurally novel chiral spiroindolenines bearing two contiguous stereogenic centers with high diastereomeric ratios (up to >20 : 1â dr) and good to excellent enantiomeric ratios (up to 97 : 3â er). Experimental and computational studies of the mechanism have confirmed a radical pathway involving excited-state palladium catalysis. The alignment and non-covalent interactions between the substrate and the catalyst were found to be essential for stereocontrol.
The asymmetric hydrogenation (AH) of N-unprotected indoles is a straightforward, yet challenging method to access biologically interesting NH chiral indolines. This method has for years been limited to 2/3-monosubstituted or 2,3-disubstituted indoles, which produce chiral indolines bearing endocyclic chiral centers. Herein, we have reported an innovative Pd-catalyzed AH of racemic α-alkyl or aryl-substituted indole-2-acetates using an acid-assisted dynamic kinetic resolution (DKR) process, affording a range of structurally fascinating chiral indolines that contain exocyclic stereocenters with excellent yields, diastereoselectivities, and enantioselectivities. Mechanistic studies support that the DKR process relies on a rapid interconversion of each enantiomer of racemic substrates, leveraged by an acid-promoted isomerization between the aromatic indole and nonaromatic exocyclic enamine intermediate. The reaction can be performed on a gram scale, and the products can be derivatized into non-natural ß-amino acids via facile debenzylation and amino alcohol upon reduction.
Objective: This study aims to evaluate inpatient services in 49 tertiary comprehensive hospitals using indicators from the diagnosis related groups (DRG) payment system. Method: DRG data from 49 tertiary comprehensive hospitals were obtained from the quality monitoring platform for provincial hospitals, and relevant indicators were identified. The analytic hierarchy process (AHP) was used to compute the weight of each indicator. The rank sum ratio method was used to calculate the weight rank sum ratio (WRSR) value and the corresponding probit value of each hospital. The hospitals were divided into four grades based on the threshold value: excellent, good, fair, and poor. Results: Eight indicators of the 49 hospitals were scored, and the hospital rankings of indicators varied. The No. 1 hospital ranked first in the indicators of "total number of DRG", "number of groups", and "proportion of relative weights (RW) ≥ 2". The WRSR value of the No.1 hospital was the largest (0.574), and the WRSR value of the No. 44 hospital was the smallest (0.139). The linear regression equation was established: WRSRpredicted =-0.141+0.088*Probit, and the regression model was well-fitted (F = 2066.672, p < 0.001). The cut-off values of the three WRSRspredicted by the four levels were 0.167, 0.299, and 0.431, respectively. The 49 hospitals were divided into four groups: excellent (4), good (21), average (21), and poor (3). There were significant differences in the average WRSR values of four categories of hospitals (p < 0.05). Conclusion: There were notable variances in the levels of inpatient services among 49 tertiary comprehensive hospitals, and hospitals of the same category also showed different service levels. The evaluation results contribute to the health administrative department and the hospital to optimize the allocation of resources, improve the DRG payment system, and enhance the quality and efficiency of inpatient services.
Diagnosis-Related Groups , Inpatients , Humans , Hospitals
The role of this study was to evaluate the impact of gut microbiota depletion on the progression of osteoarthritis (OA) and osteoporosis (OP). We conducted an experimental mouse model of OA and OP over an 8-week period. The model involved destabilization of the medial meniscus and bilateral ovariectomy (OVX). To deplete the gut microbiota, we administered a course of antibiotics for 8 weeks. The severity of OA was assessed through micro-CT scanning, X-rays, and immunohistochemical staining. Microbiome analysis was performed using PCR of 16S DNA on fecal samples, and the levels of serum lipopolysaccharide, interleukin 6, tumor necrosis factor-α (TNF-α), osteocalcin, and estrogen were measured using enzyme-linked immunosorbent assay. We found that in comparison to the OVX+OA group, the OVX+OA+ABT group exhibited increased bone mineral density (P < 0.0001), bone volume fraction (P = 0.0051), and trabecular number (P = 0.0023) in the metaphyseal bone. Additionally, cartilage injury and levels of matrix metalloproteinase 13 were reduced in the OVX+OA+ABT group compared to the OVX+OA group. Moreover, the OVX+OA+ABT group demonstrated decreased relative abundance of Bacteroidetes, serum lipopolysaccharide (P = 0.0005), TNF-α (P < 0.0001), CTX-1 (P = 0.0002), and increased expression of bone formation markers. These findings were further supported by correlation network analyses. Depletion of gut microbiota was shown to protect against bone loss and cartilage degradation by modulating the composition of the gut microbiota in osteoporosis and osteoarthritis.
Microbiota , Osteoarthritis , Osteoporosis , Female , Mice , Animals , Humans , Tumor Necrosis Factor-alpha , Anti-Bacterial Agents/pharmacology , Dysbiosis , Lipopolysaccharides , Cartilage/metabolism , Osteoarthritis/metabolism , Osteoarthritis/pathology , Ovariectomy
Chiral cyclopentadienyl-rhodium(III) Cpx Rh(III) catalysis has been demonstrated to be competent for catalyzing highly enantioselective aziridination of challenging unactivated terminal alkenes and nitrene sources. The chiral Cpx Rh(III) catalysis system exhibited outstanding catalytic performance and wide functional group tolerance, yielding synthetically important and highly valuable chiral aziridines with good to excellent yields and enantioselectivities (up to 99 % yield, 93 % ee). This protocol presents a novel and effective strategy for synthesizing enantioenriched aziridines from simple alkenes. Various transformations were performed on the aziridine products, illustrating the versatility and synthetic potential of this protocol for constructing highly functionalized compounds.
In this study, carrageenase immobilization was evaluated with a concise and efficient strategy. Pomelo peel cellulose (PPC) modified by polyethyleneimine (PEI) using the physical absorption method was used as a carrier to immobilize carrageenase and achieved repeated batch catalysis. In addition, various immobilization and reaction parameters were scrutinized to enhance the immobilization efficiency. Under the optimized conditions, the enzyme activity recovery rate was more than 50% and 4.1 times higher than immobilization with non-modified pomelo peels. The optimum temperature and pH of carrageenase after immobilization by PEI-modified pomelo peel, at 60°C and 7.5 respectively, were in line with the free enzyme. The temperature resistance was reduced, inconsistent with free enzyme, and pH resistance was increased. A significant loss of activity (46.8%) was observed after reusing it thrice under optimal reaction conditions. In terms of stability, the immobilized enzyme conserved 76.0% of the initial enzyme activity after 98 days of storage. Furthermore, a modest decrease in the kinetic constant (Km) value was observed, indicating the improved substrate affinity of the immobilized enzyme. Therefore, modified pomelo peel is a verified and promising enzyme immobilization system for the synthesis of inorganic solvents.
Enzymes, Immobilized , Polyethyleneimine , Enzymes, Immobilized/metabolism , Enzyme Stability , Polyethyleneimine/chemistry , Hydrogen-Ion Concentration , Kinetics , Temperature
Phenyl polyhedral oligomeric silsesquioxane (POSS) is modified onto the GO surface by using the strong π-π coupling between a large number of benzene rings at the end of the phenyl POSS structure and the graphite structure in the GO sheet, realizing the non-covalent functionalization of GO (POSS-GO). The POSS-GO-reinforced EP (POSS-GO/EP) composite material is prepared using the casting molding process. The surface morphology of GO before and after modification and its peel dispersion in EP are examined. Furthermore, the mechanical properties, cross-sectional morphology, and reinforcement mechanism of POSS-GO/EP are thoroughly examined. The results show that the cage-like skeleton structure of POSS is embedded between the GO layers, increasing the spacing between the GO layers and leading to a steric hindrance effect, which effectively prevents their stacking and aggregation and improves the dispersion performance of GO. In particular, the 0.4 phr POSS-GO/EP sample shows the best mechanical properties. This is because, on the one hand, POSS-GO is uniformly dispersed in the EP matrix, which can more efficiently induce crack deflection and bifurcation and can also cause certain plastic deformations in the EP matrix. On the other hand, the POSS-GO/EP fracture cross-section with a stepped morphology of interlaced "canine teeth" shape is rougher and more uneven, leading to more complex crack propagation paths and greater energy consumption. Moreover, the mechanical meshing effect between the rough POSS-GO surface and the EP matrix is stronger, which is conducive to the transfer of interfacial stress and the strengthening and toughening effects of POSS-GO.
BACKGROUND: Hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids (PA-HSOS) is a complication of drug-induced liver damage. Few studies have examined the relationship between pathological changes and clinical circumstances in PA-HSOS. The Drum Tower Severity Scoring System (DTSS) was developed using prognostic indicators from clinical treatment outcomes. We hypothesized that the severity of pathological damage is consistent with DTSS. AIMS: We aimed to improve our understanding and assessment of vascular liver injury disease histopathology by studying larger sample sizes of human histopathological samples. We also wanted to confirm the link between histopathological findings and DTSS. METHODS: The study included 62 patients with PA-HSOS who underwent transjugular liver biopsy. Their hepatic pathological tissues were evaluated. Analyses of linear regression and Spearman's correlation were employed to examine the relationship between DTSS and pathological characteristics. RESULTS: Clinical performance and the DTSS score were used to determine histopathological severity. The sinusoidal congestion area (SCA), central venous endothelial injury (CVEI), and fibrinoid exudation in congestion foci (FECF) were significant indicators. SCA was linearly related to the DTSS score. CONCLUSION: Our findings show that hepatic pathological characteristics correlate with DTSS scores in PA-HSOS. SCA, CVEI, and FECF may be helpful for determining PA-HSOS severity.
Belamcanda chinensis (L.) DC, commonly used with florfenicol in Chinese veterinary clinics for respiratory tract infections, contains the major effective isoflavone, tectoridin (TEC). This study aimed to investigate the impact of TEC co-administration on the pharmacokinetics of florfenicol in vivo.Male rats received oral TEC (50 mg/kg BW) or sterile water for seven days, followed by a single oral dose of florfenicol (25 mg/kg BW) on the 8th day. Non-compartmental methods analysed the pharmacokinetics of florfenicol, while real-time reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analyses measured expression levels of cytochrome P450 (CYP) isoforms in the liver and P-glycoprotein (P-gp) in the jejunum.TEC significantly decreased florfenicol's AUC(0-∞), MRT(0-∞), t1/2z, Vz/F, and Cmax by 24.75%, 18.43%, 55.47%, 43.05%, and 19.48%, while increasing CLz/F by 33.33%. TEC also up-regulated hepatic CYP1A2 and CYP3A1 mRNA expression, as well as intestinal MDR1, by 1.39-fold, 1.85-fold, and 1.65-fold. This coincided with a respective increase in protein expression by 1.37-fold, 1.39-fold, and 1.43-fold.These findings suggest that TEC-induced alterations in the pharmacokinetics of florfenicol may be attributed to increased CYP and P-gp expression. Further investigations are warranted to understand the implications of these findings on the clinical effectiveness of florfenicol in veterinary practice.
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Isoflavones , Rats , Male , Animals , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Cytochrome P-450 Enzyme System/metabolism , Cytochrome P-450 CYP3A/metabolism
The quest to understand how the development of the brain supports the development of complex cognitive functions is fueled by advances in cognitive neuroscience methods. Intracranial EEG (iEEG) recorded directly from the developing human brain provides unprecedented spatial and temporal resolution for mapping the neurophysiological mechanisms supporting cognitive development. In this paper, we focus on episodic memory, the ability to remember detailed information about past experiences, which improves from childhood into adulthood. We review memory effects based on broadband spectral power and emphasize the importance of isolating narrowband oscillations from broadband activity to determine mechanisms of neural coordination within and between brain regions. We then review evidence of developmental variability in neural oscillations and present emerging evidence linking the development of neural oscillations to the development of memory. We conclude by proposing that the development of oscillations increases the precision of neural coordination and may be an essential factor underlying memory development. More broadly, we demonstrate how recording neural activity directly from the developing brain holds immense potential to advance our understanding of cognitive development.
Brain , Electrocorticography , Humans , Child , Brain/physiology , Cognition/physiology , Mental Recall/physiology , Brain Mapping , Electroencephalography
OBJECTIVE: Risk stratification plays a critical role in patients with asymptomatic carotid atherosclerotic stenosis. Heavy macrophage infiltration (HMC) is an important factor of plaque destabilization. However, in vivo imaging technologies and screening criteria for HMC remain limited. We aimed to (i) introduce algorithms for in vivo detection of macrophage infiltrations using optical coherence tomography (OCT) and (ii) to investigate the threshold of HMC and its association with plaque vulnerability. METHODS: Ex vivo OCT images were co-registered with histopathology in 282 cross-sectional pairs from 19 carotid endarterectomy specimens. Of these, 197 randomly selected pairs were employed to define the parameters, and the remaining 85 pairs were used to evaluate the accuracy of the OCT-based algorithm in detecting macrophage infiltrations. Clinical analysis included 93 patients receiving carotid OCT evaluation. The prevalence and burden of macrophage infiltration were analyzed. Multivariable and subgroup analysis were performed to investigate the association between HMC and plaque rupture. RESULTS: The sensitivity and specificity of algorithm for detecting macrophage infiltration were 88.0% and 74.9%, respectively. Of 93 clinical patients, ruptured plaques exhibited higher prevalence of macrophage infiltration than nonruptured plaques (83.7% [36/43] vs 32.0% [16/50], p < 0.001). HMC was identified when the macrophage index was greater than 60.2 (sensitivity = 74.4%, specificity = 84.0%). Multivariable analysis showed that HMC and multiple calcification were independent risk factors for non-lipid-rich plaque rupture. INTERPRETATION: This study provides a novel approach and screening criteria for HMC, which might be valuable for atherosclerotic risk stratification.
Plaque, Atherosclerotic , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Cross-Sectional Studies , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Sensitivity and Specificity , Macrophages
Informal landfills pose potential threats to the environment and human health due to the lack of anti-seepage measures. However, little research has been conducted on the distribution of pollutants in informal landfill sites situated in arid climates, as well as the underlying interaction mechanisms between environmental factors and microbial structure. In this study, we sought to investigate the pollution characteristics and microbial community succession of the landfill in northern China. The results revealed that heavy metals in the landfill showed poor mobility and migration. The lower layers of the garbage samples had higher water-soluble contents of heavy metals compared to the upper layers. The landfill-derived dissolved organic matter (DOM) was found to originate from microbial production, and four fluorescent components were identified, including fulvic acid-like substances, humus-like substances, and protein-like components. Fluorescence intensity and humification degree increased with increasing depth. The microbial diversity and richness decreased with sampling depth. The most abundant phyla in the samples were Proteobacteria, unidentified_Bacteria, Bacteroidota, Firmicutes, Myxococcota, Gemmatimonadota, Actinobacteria, and Deinococcota. As the sampling depth increased, Proteobacteria decreased, while Bacteroidota and Firmicutes showed a remarkable increase, with little variation observed in the other phyla. The partial least-squares path model (PLS-PM) results indicated that pH had the most significant effect on microbial abundance and diversity (direct effect value = -5.560), while DOM and heavy metals had the opposite effect, with direct effects of 1.838 and 3.231, respectively. DOM was identified as the driving factor for the variation in other environmental factors. The redundancy analysis (RDA) showed that the dominant genera were greatly influenced by Cu, humic-like substances, and protein-like substances. Among them, Bacillus, Alcanivorax, Devosia, and Chryseolinea may play important roles in the remediation of landfills. Our study not only gains a deeper understanding of the pollution risk of informal landfills in arid climates, but also provides a scientific basis for the future treatment and restoration of contaminated sites associated with landfills.
Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were stimulated with LPS+ATP to build the in vitro model. CA significantly alleviated inflammation and oxidative stress in both the in vivo and in vitro models of ALI through the inhibition of NLR family pyrin domain-containing 3 (NLRP3)-mediated pyroptosis. In addition, CA attenuated mitochondrial damage to suppress NLRP3-mediated pyroptosis in the in vivo and in vitro models of ALI by suppressing the production of reactive oxygen species (ROS) via inhibiting the Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. CA inhibited the interaction between Akt at T308 and phosphoinositide-dependent kinase-1 (PDPK1) at S549, thus promoting the phosphorylation of the Akt protein. Furthermore, CA directly targeted the PDPK1 protein and accelerated PDPK1 ubiquitination, indicating that 91-GLY, 111-LYS, 126-TYR, 162-ALA, 205-ASP, and 223-ASP might be responsible for the interaction between PDPK1 and CA. In conclusion, CA from Lettuce alleviated NLRP3-mediated pyroptosis in the ALI model through ROS-induced mitochondrial damage by activating Akt/Nrf2 pathway via PDPK1 ubiquitination. The present study suggests that CA might be a potential therapeutic drug to treat or prevent ALI in pneumonia or COVID-19.
Acute Lung Injury , COVID-19 , Mice , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Reactive Oxygen Species/metabolism , Proto-Oncogene Proteins c-akt , Pyroptosis , 1-Phosphatidylinositol 4-Kinase , Lipopolysaccharides/adverse effects , NF-E2-Related Factor 2/metabolism , Mice, Inbred C57BL , Acute Lung Injury/etiology , Acute Lung Injury/chemically induced , Inflammation/drug therapy
This study aimed to examine the effect of subanesthetic esketamine on postoperative fatigue in patients who underwent laparoscopic colorectal surgery. A total of 62 patients, including 32 in the esketamine group and 30 in the control group, were analysed in this study. Compared with the control group, the patients in the esketamine group had reduced Identity-Consequence Fatigue Scale (ICFS) on the 3rd and 7th days after surgery (P<0.05). There were also significant differences in the Positive and Negative Affect Schedule (PANAS) scale between the two groups. The positive affect scale was higher on postoperative day 3 (POD3), while the negative affect scale was lower on POD3 and postoperative day 7 (POD7) in the esketamine group than in the control group. However, the scores of postoperative hand grip strength, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Numeric Rating Scale (NRS) and Athens Insomnia Scale (AIS) were not significantly different between the two groups. Furthermore, mediation analysis showed that esketamine played an anti-fatigue role through improving emotional heath. Importantly, no adverse reactions occurred at this dosage of esketamine. Finally, our study suggested that subanesthetic esketamine improved postoperative fatigue, stabilized postoperative mood, reduced intraoperative remifentanil consumption, and promoted postoperative intestinal function recovery without increasing adverse reactions.
ABSTRACT: Background: Pulmonary sepsis and abdominal sepsis have pathophysiologically distinct phenotypes. This study aimed to compare their clinical characteristics and predictors of mortality. Methods: In this multicenter retrospective trial, 1,359 adult patients who fulfilled the Sepsis-3 criteria were enrolled and classified into the pulmonary sepsis or abdominal sepsis groups. Plasma presepsin was measured, and the scores of Acute Physiology and Chronic Health Evaluation (APACHE) II, Mortality in Emergency Department Sepsis (MEDS), and Simplified Acute Physiology Score (SAPS) II were calculated at enrollment. Data on 28-day mortality were collected for all patients. Results: Compared with patients with abdominal sepsis (n = 464), patients with pulmonary sepsis (n = 895) had higher 28-day mortality rate, illness severity scores, incidence of shock and acute kidney injury, and hospitalization costs. Lactate level and APACHE II and MEDS scores were independently associated with 28-day mortality in both sepsis types. Independent predictors of 28-day mortality included Pa o2 /F io2 ratio (hazard ratio [HR], 0.998; P < 0.001) and acute kidney injury (HR, 1.312; P = 0.039) in pulmonary sepsis, and SAPS II (HR, 1.037; P = 0.017) in abdominal sepsis. A model that combined APACHE II score, lactate, and MEDS score or SAPS II score had the best area under the receiver operating characteristic curve in predicting mortality in patients with pulmonary sepsis or abdominal sepsis, respectively. Interaction term analysis confirmed the association between 28-day mortality and lactate, APACHE II score, MEDS score, SAPS II score, and shock according to the sepsis subgroups. The mortality of patients with pulmonary sepsis was higher than that of patients with abdominal sepsis among patients without shock (32.9% vs. 8.8%; P < 0.001) but not among patients with shock (63.7 vs. 48.4%; P = 0.118). Conclusions: Patients with pulmonary sepsis had higher 28-day mortality than patients with abdominal sepsis. The study identified sepsis subgroup-specific mortality predictors. Shock had a larger effect on mortality in patients with abdominal sepsis than in those with pulmonary sepsis.
Acute Kidney Injury , Intraabdominal Infections , Sepsis , Adult , Humans , Retrospective Studies , Prognosis , ROC Curve , Lactic Acid , Peptide Fragments , Lipopolysaccharide Receptors
Postoperative fatigue is prevalent, but non-small cell lung cancer (NSCLC) patients receive poor treatment after video-assisted thoracoscopic surgery (VATS). The main objective of the present trial is to observe the anti-fatigue function of pregabalin in NSCLC patients after surgery. Patients requiring VATS pneumonectomy were randomized into two groups (n=33): the experimental and control groups. The results showed that the experimental group's Identity-Consequence Fatigue Scale (ICFS) scores on days 1, 3, 7, and 30 after the operation decreased more than those of the control group. On days 1, 2, and 3 following surgery, there were significant differences in the Visual Analog Scale (VAS) scores, the incidence rate of anxiety and depression, and the Athens Insomnia Scale (AIS) scores between the two groups. Furthermore, we discovered that the ICFS scores were positively related to the VAS scores, Hospital Anxiety and Depression Scale (HADS) scores, and AIS scores. Postoperative fatigue and pain, on the other hand, were more closely related. Finally, this analysis suggested that perioperative pregabalin can reduce postoperative fatigue in NSCLC patients by relieving postoperative pain, anxiety, and depression, improving postoperative sleep quality, and promoting early recovery.
OBJECTIVE: To determine whether peroral endoscopic myotomy (POEM) improves esophageal peristalsis and to investigate the association between recovery of esophageal peristalsis after POEM and clinical features of the patients. METHODS: In this single-center retrospective study, data were collected from medical records of the patients with achalasia who underwent POEM between January 2014 and May 2016. Demographics data, high-resolution esophageal manometry parameters, Eckardt score, and gastroesophageal reflux disease questionnaire (GERD-Q) score were collected. Weak and fragmented contraction was defined as partial recovery of esophageal peristalsis based on the Chicago classification version 3.0. Logistic regression analysis was used to identify variables associated with the partial recovery of peristalsis after POEM. RESULTS: A total of 103 patients were enrolled. Esophageal contractile activity was observed in the distal two-thirds of the esophagus in 24 patients. The Eckardt score, integrated relaxation pressure, and lower esophageal sphincter (LES) resting pressure were significantly decreased after POEM. Multivariate analysis revealed that preprocedural LES resting pressure (P = 0.013) and preprocedural Eckardt score (P = 0.002) were related to the partial recovery of peristalsis after POEM. Symptoms of gastroesophageal reflux and reflux esophagitis after POEM were less frequent in those with partial recovery of peristalsis (both P < 0.05). CONCLUSIONS: Normalization of esophagogastric junction relaxation pressure achieved by POEM is associated with the partial recovery of esophageal peristalsis in patients with achalasia. Preprocedural LES resting pressure and the Eckardt score are predictive of the recovery of esophageal peristalsis.
Esophageal Achalasia , Esophagitis, Peptic , Gastroesophageal Reflux , Myotomy , Natural Orifice Endoscopic Surgery , Humans , Esophageal Achalasia/surgery , Peristalsis , Retrospective Studies , Esophagoscopy , Natural Orifice Endoscopic Surgery/adverse effects , Manometry , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/surgery , Treatment Outcome , Esophageal Sphincter, Lower/surgery
OBJECTIVES: Nobiletin is a flavonoid found in the peel of Citrus sinensis (oranges). The purpose of this study is to investigate whether Nobiletin can alleviate the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and explore the underlying mechanisms. METHODS: The PAH rat model was replicated by subcutaneous injection of MCT. Nobiletin (1, 5 and 10 mg/kg) was administered by gavage from day 1 to day 21. After 21 days of MCT injection, the mean pulmonary artery pressure, pulmonary vascular resistance, Fulton Index, pulmonary artery remodelling, blood routine parameters, liver and kidney functions was measured. The level of inflammatory cytokines and PI3K/Akt/STAT3 were detected by qPCR, ELISA and western blot, the proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by CCK-8. KEY FINDINGS: Nobiletin (10 mg/kg) inhibited the MCT-induced increase in mean pulmonary artery pressure and pulmonary vascular resistance, right ventricular hypertrophy and pulmonary artery remodelling in rats. Nobiletin decreased the levels of inflammatory cytokines and phosphorylation level of PI3K/Akt/STAT3 in lungs of MCT-treated rats. Nobiletin inhibited the proliferation and lowered the inflammatory cytokines level induced by PDGF-BB in PASMCs. CONCLUSION: Nobiletin attenuates MCT-induced PAH, and the potential mechanism is to inhibit inflammation through PI3K/Akt/STAT3 pathway.
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Rats , Animals , Pulmonary Arterial Hypertension/chemically induced , Pulmonary Arterial Hypertension/drug therapy , Pulmonary Arterial Hypertension/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/metabolism , Monocrotaline/adverse effects , Monocrotaline/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Pulmonary Artery , Cytokines/metabolism , Disease Models, Animal
Obviously, immune cells like T cells and macrophages play a major role in rheumatoid arthritis (RA). On one hand, the breakdown of immune homeostasis directly induces systemic inflammation; on the other hand, these cells initiate and perpetuate synovitis and tissue damages through the interaction with fibroblast-like synoviocytes (FLS). In recent years, the pathological link between metabolic disorders and immune imbalance has received increasing attention. High energy demand of immune cells leads to the accumulation of metabolic byproducts and inflammatory mediators. They act on various metabolism-sensitive signal pathways as well as relevant transcription factors, such as HIF-1α, and STATs. These molecular events will impact RA-related effectors like circulating immune cells and joint-resident cells in return, allowing the continuous progression of systemic inflammation, arthritic manifestations, and life-threatening complications. In other words, metabolic complications are secondary pathological factors for the progression of RA. Therefore, the status of energy metabolism may be an important indicator to evaluate RA severity, and in-depth explorations of the mechanisms underlying the mystery of how RA-related metabolic disorders develop will provide useful clues to further clarify the etiology of RA, and inspire the discovery of new anti-rheumatic targets. This article reviews the latest research progress on the interactions between immune and metabolism systems in the context of RA. Great importance is attached to the changes in certain pathways controlling both immune and metabolism functions during RA progression.
