Real-world evidence of combined treatment of biologics and exclusive enteral nutrition in patients with ileum-dominant Crohn's disease: A multicenter study.

BACKGROUND & AIMS: Although biologics were prescribed to achieve and maintain clinical remission of active Crohn's disease (CD), almost half of patients experienced a loss of response or intolerance. Here, we investigated the efficacy of combined treatment of biologics and 16-weeks exclusive enteral nutrition (EEN) in moderate-to-severe CD patients with small intestine lesions. METHODS: This was a real-world, multicenter retrospective study, from October 2016 to March 2023, medical records of patients registered at three IBD centers were reviewed for patients with ileal or ileocolonic CD in moderate-to-severe activity. All patients received treatment of biologics with concomitant 16-week EEN (BioEEN) or biologics alone (Bio). The clinical outcomes and endoscopic outcomes were assessed at week 16 and 52. RESULTS: There was no statistically significant difference between Bio (97 patients) and BioEEN group (100 patients) at baseline for demographic and clinical characteristics. Compared to treatment with biologics alone, patients with BioEEN treatment achieved higher rates of clinical response (95.0% vs. 66.0%), clinical remission (87.0% vs. 52.6%), endoscopic response (91.4% vs. 47.4%) including mucosal healing (85.7% vs. 23.7%) at week 16. The superiority of BioEEN sustained in maintenance, with 84.7% (vs. 49.1%) clinical response, 77.8% (vs. 38.6%) clinical remission, 69.2% (vs. 32.6%) endoscopic response and 51.9% (vs. 18.6%) mucosal healing at week 52. CONCLUSIONS: Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD.

Na3V2(PO4)3-decorated Na3V2(PO4)2F3 as a high-rate and cycle-stable cathode material for sodium ion batteries.

Since Na3V2(PO4)3 (NVP) possesses modest volume deformation and three-dimensional ion diffusion channels, it is a potential sodium-ion battery cathode material that has been extensively researched. Nonetheless, NVP still endures the consequences of poor electronic conductivity and low voltage platforms, which need to be further improved. On this basis, a high voltage platform Na3V2(PO4)2F3 was introduced to form a composite with NVP to increase the energy density. In this study, the sol-gel technique was successfully used to synthesize a Na3V2(PO4)2.75F0.75/C (NVPF·3NVP/C) composite cathode material. The citric acid-derived carbon layer was utilized to construct three-dimensional conducting networks to effectively promote ion and electron diffusion. Furthermore, the composites' synergistic effect accelerates the quick ionic migration and improves the kinetic reaction. In particular, NVP as the dominant phase enhanced the structural stability and significantly increased the capacitive contribution. Therefore, at 0.1C, the discharge capacity of the modified NVPF·3NVP/C composite is 120.7 mA h g-1, which is greater than the theoretical discharge capacity of pure NVP (118 mA h g-1). It discharged 110.9 mA h g-1 of reversible capacity even at an elevated multiplicity of 10C, and after 200 cycles, it retained 64.1% of its capacity. Thus, the effort produced an optimized NVPF·3NVP/C composite cathode material that may be used in the sodium ion cathode.

Comparative outcomes of obese and non-obese patients with lumbar disc herniation receiving full endoscopic transforaminal discectomy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the impact of full endoscopic transforaminal discectomy (FETD) on clinical outcomes and complications in both obese and non-obese patients presenting with lumbar disc herniation (LDH). METHODS: A systematic search of relevant literature was conducted across various primary databases until November 18, 2023. Operative time and hospitalization were evaluated. Clinical outcomes included preoperative and postoperative assessments of the Oswestry Disability Index (ODI) and visual analogue scale (VAS) scores, conducted to delineate improvements at 3 months postoperatively and during the final follow-up, respectively. Complications were also documented. RESULTS: Four retrospective studies meeting inclusion criteria provided a collective cohort of 258 patients. Obese patients undergoing FETD experienced significantly longer operative times compared to non-obese counterparts (P = 0.0003). Conversely, no statistically significant differences (P > 0.05) were observed in hospitalization duration, improvement of VAS for back and leg pain scores at 3 months postoperatively and final follow-up, improvement of ODI at 3 months postoperatively and final follow-up. Furthermore, the overall rate of postoperative complications was higher in the obese group (P = 0.02). The obese group demonstrated a total incidence of complications of 17.17%, notably higher than the lower rate of 9.43% observed in the non-obese group. CONCLUSION: The utilization of FETD for managing LDH in individuals with obesity is associated with prolonged operative times and a higher total complication rate compared to their non-obese counterparts. Nevertheless, it remains a safe and effective surgical intervention for treating herniated lumbar discs in the context of obesity.

Convergent gene losses and pseudogenizations in multiple lineages of stomachless fishes.

The regressive evolution of independent lineages often results in convergent phenotypes. Several teleost groups display secondary loss of the stomach, and four gastric genes, atp4a, atp4b, pgc, and pga2 have been co-deleted in agastric (stomachless) fish. Analyses of genotypic convergence among agastric fishes showed that four genes, slc26a9, kcne2, cldn18a, and vsig1, were co-deleted or pseudogenized in most agastric fishes of the four major groups. kcne2 and vsig1 were also deleted or pseudogenized in the agastric monotreme echidna and platypus, respectively. In the stomachs of sticklebacks, these genes are expressed in gastric gland cells or surface epithelial cells. An ohnolog of cldn18 was retained in some agastric teleosts but exhibited an increased non-synonymous substitution when compared with gastric species. These results revealed novel convergent gene losses at multiple loci among the four major groups of agastric fish, as well as a single gene loss in the echidna and platypus.

High CASC expression predicts poor prognosis of lung cancer: A systematic review with meta-analysis.

BACKGROUND: The long non-coding RNA cancer susceptibility candidate (CASC) has abnormal expression in lung cancer tissues and may correlate with lung cancer prognosis. This study aimed to comprehensively evaluate the association between CASC expression and the cancer prognosis. METHODS: PubMed, Embase, Web of Science, Google Scholar, Cochrane Library, and China National Knowledge Infrastructure databases were searched until April 1, 2023, to obtain the relevant literature. Studies that met the predefined eligibility criteria were included, and their quality was independently assessed by 2 investigators according to the Newcastle-Ottawa Scale (NOS) score. Detailed information was obtained, such as first author, year of publication, and number of patients. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted and grouped to assess the relationship between CASC expression and cancer prognosis. The dichotomous data was merged and shown as the odds ratio (OR) with a 95% CI was extracted to assess the relationship between CASC expression and clinicopathological parameters. RESULTS: A total of 12 studies with 746 patients with lung cancer were included in the meta-analysis. The expression levels of lncRNA CASC2 and CASC7 were decreased, while those of CASC9, 11, 15, and 19 were induced in lung cancer tissues compared with paracancerous tissues. In the population with low CASC expression (CASC2 and CASC7), high CASC expression indicated a good lung cancer prognosis (HR = 0.469; 95% CI, 0.271-0.668). Conversely, in the population with high CASC expression (CASC9, 11, 15, and 19), high CASC expression predicted a poor lung cancer outcome (HR = 1.910; 95% CI, 1.628-2.192). High CASC expression also predicted worse disease-free survival (DFS) (HR = 2.803; 95% CI, 1.804-6.319). Combined OR with 95% CI revealed an insignificant positive association between high CASC expression and advanced TNM stage (OR = 1.061; 95% CI, 0.775-1.454), LNM (OR = 0.962; 95% CI, 0.724-1.277), tumor size (OR = 0.942; 95% CI, 0.667-1.330), and histological grade (OR = 1.022; 95% CI, 0.689-1.517). CONCLUSION: The CASC expression levels negatively correlate with lung cancer prognosis. Therefore, CASC expression may serve as a prognostic marker and a potential therapeutic target for lung cancer.

Carbon dioxide capture and functionalization by bis(N-heterocyclic carbene)-borylene complexes.

Derivatives of free monocoordinated borylenes have attracted considerable interest due to their ability to exhibit transition-metal-like reactivity, in particular small molecules capture. However, such complexes are rare as the formation is either endergonic, or the resulting adduct is a transient intermediate that is prone to reaction. Here, we present the synthesis of two bis(N-heterocyclic carbene)-borylene complexes capable of capturing and functionalizing carbon dioxide. The capture and subsequent functionalization of CO2 by the bis(NHC)-disilylamidoborylene 1 is demonstrated by the formation of the bis(NHC)-isocyanatoborylene-carbon dioxide complex 3. Reversible capture of CO2 is observed using the bis(NHC)-mesitylborylene 2, and the persistent bis(NHC)-mesitylborylene-carbon dioxide adduct 4 can be stabilized by hydrogen bonding with boric acid. The reactions of 4 with ammonia-borane and aniline demonstrate that the captured CO2 can be further functionalized.

Association of advanced glycation end products with ear lobe crease: A cross-sectional study.

OBJECTIVE: Several studies have demonstrated a significant association between the presence of the ear lobe crease (ELC) and cardiovascular disease. Advanced glycation end-products (AGEs) can affect the structures and functions of proteins and contribute to the development of diabetic complications. However, few studies have reported the relationship between AGEs and ELC. The purpose of this study was to investigate the correlation of skin autofluorescence (SAF)-AGEage (SAF-AGEs × age/100) with ELC. METHODS: This cross-sectional study enrolled 6500 eligible participants from two communities in Beijing. Skin autofluorescence (SAF) was used to measure skin AGEs (SAF-AGEs). SAF-AGEage was defined as AGEs × age/100. Binary logistic regression analysis and linear regression analysis nested in logistic models were applied to test outcomes. RESULTS: The overall prevalence of ELC with an average age of 62.7 years participants was 57.1% (n = 3714). Age, fasting blood glucose, systolic blood pressure, and lipoprotein cholesterol were all greater in participants with ELC. ELC-positive participants had higher prevalence of coronary heart disease. Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGEage and ELC (odds ratio [OR] 1.526, 95% CI 1.324-1.759; OR 2.072, CI 1.791-2.396; and OR 2.983, CI 2.551-3.489) for the multivariate-adjusted models, respectively. Stratified research revealed that those with a history of diabetes, hypertension, or coronary heart disease experienced the connection between SAF-AGEage and ELC. CONCLUSION: ELC is associated with coronary heart disease, and the SAF-AGE has a potential role in ELC development in elder people.

Identification of tumor heterogeneity associated with KRAS/TP53 co-mutation status in lung adenocarcinoma based on single-cell RNA sequencing.

Lung cancer stands as the predominant cause of cancer-related mortality globally. Lung adenocarcinoma (LUAD), being the most prevalent subtype, garners extensive attention due to its notable heterogeneity, which significantly influences tumor development and treatment approaches. This research leverages single-cell RNA sequencing (scRNA-seq) datasets to delve into the impact of KRAS/TP53 co-mutation status on LUAD. Moreover, utilizing the TCGA-LUAD dataset, we formulated a novel predictive risk model, comprising seven prognostic genes, through LASSO regression, and subjected it to both internal and external validation sets. The study underscores the profound impact of KRAS/TP53 co-mutational status on the tumor microenvironment (TME) of LUAD. Crucially, KRAS/TP53 co-mutation markedly influences the extent of B cell infiltration and various immune-related pathways within the TME. The newly developed predictive risk model exhibited robust performance across both internal and external validation sets, establishing itself as a viable independent prognostic factor. Additionally, in vitro experiments indicate that MELTF and PLEK2 can modulate the invasion and proliferation of human non-small cell lung cancer cells. In conclusion, we elucidated that KRAS/TP53 co-mutations may modulate TME and patient prognosis by orchestrating B cells and affiliated pathways. Furthermore, we spotlight that MELTF and PLEK2 not only function as prognostic indicators for LUAD, but also lay the foundation for the exploration of innovative therapeutic approaches.

[Contamination Characteristics，Detection Methods，and Control Methods of Antibiotic Resistance in Pharmaceutical Wastewater].

Pharmaceutical industry wastewater contains a large number of emerging pollutants such as antibiotics， antibiotic resistant bacteria （ARBs）， and antibiotic resistance genes （ARGs）. The present biological water treatment processes cannot effectively remove these pollutants. Eventually， they are discharged into various water bodies or penetrate into soil with the effluent， causing environmental pollution and affecting human health. Therefore， exploring the pollution characteristics of antibiotics， ARBs， and ARGs in pharmaceutical wastewater and knowing the methods to detect and control antibiotic resistance pollution in wastewater are crucial for reducing the contamination of antibiotics and ARGs and assessing the ecological risks of antibiotic resistance. Aiming at the problem of antibiotic resistance pollution in a pharmaceutical wastewater treatment plant （PWWTPs）， the pollution status of antibiotics， ARBs， and ARGs in pharmaceutical wastewater was discussed. Different assessment methods of antibiotic resistance in pharmaceutical wastewater were summarized. Finally， the wastewater treatment technologies commonly used to remove antibiotics and ARGs in PWWTPs were summarized in order to provide a theoretical basis for the ecological risk assessment and scientific control of antibiotics and ARGs in the environment.

Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

Geographic differences in psychological symptoms, sleep quality, and quality of life in patients with inflammatory bowel disease: A multicenter study in China.

OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.

Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf.

Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis.

ASK1/ p38 axis inhibition blocks the release of mitochondrial "danger signals" from hepatocytes and suppresses progression to cirrhosis and liver cancer.

BACKGROUND AND AIMS: Apoptosis Signal-regulating Kinase 1 (ASK1) is activated by various pathological stimuli and induces cell apoptosis through downstream p38 activation. We studied the effect of pharmacological ASK1 inhibition on cirrhosis and its sequelae using comprehensive preclinical in vivo and in vitro systems. APPROACH AND RESULTS: Short-term (4-6 wk) and long-term (24-44 wk) ASK1 inhibition using small molecule GS-444217 was tested in thioacetamide-induced and BALB/c. Mdr2-/- murine models of cirrhosis and HCC, and in vitro using primary hepatocyte cell death assays. Short-term GS-444217 therapy in both models strongly reduced phosphorylated p38, hepatocyte death, and fibrosis by up to 50%. Profibrogenic release of mitochondrial DAMP mitochondrial deoxyribonucleic acid from dying hepatocytes was blocked by ASK1 or p38 inhibition. Long-term (24 wk) therapy in BALBc.Mdr2 - / - model resulted in a moderate 25% reduction in bridging fibrosis, but not in net collagen deposition. Despite this, the development of cirrhosis was effectively prevented, with strongly reduced p21 + hepatocyte staining (by 72%), serum ammonia levels (by 46%), and portal pressure (average 6.07 vs. 8.53 mm Hg in controls). Extended ASK1 inhibition for 44 wk in aged BALB/c. Mdr2-/- mice resulted in markedly reduced tumor number and size by ~50% compared to the control group. CONCLUSIONS: ASK1 inhibition suppresses the profibrogenic release of mitochondrial deoxyribonucleic acid from dying hepatocytes in a p38-dependent manner and protects from liver fibrosis. Long-term ASK1 targeting resulted in diminished net antifibrotic effect, but the progression to liver cirrhosis and cancer in BALBc/ Mdr2- / - mice was effectively inhibited. These data support the clinical evaluation of ASK1 inhibitors in fibrotic liver diseases.

Psychological symptoms and quality of life in patients with inflammatory bowel disease in China: A multicenter study.

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study.

The incidence and mortality of hepatocellular carcinoma (HCC) in Sub-Saharan Africa is projected to increase sharply by 2040 against a backdrop of limited diagnostic and therapeutic options. Two large South African-based case control studies have developed a serum-based miRNome for Hepatitis B-associated hepatocellular carcinoma (HBV-HCC), as well as identifying their gene targets and pathways. Using a combination of RNA sequencing, differential analysis and filters including a unique molecular index count (UMI) ≥ 10 and log fold change (LFC) range > 2: <-0.5 (p < 0.05), 91 dysregulated miRNAs were characterized including 30 that were upregulated and 61 were downregulated. KEGG analysis, a literature review and other bioinformatic tools identified the targeted genes and HBV-HCC pathways of the top 10 most dysregulated miRNAs. The results, which are based on differentiating miRNA expression of cases versus controls, also develop a serum-based miRNA diagnostic panel that indicates 95.9% sensitivity, 91.0% specificity and a Youden Index of 0.869. In conclusion, the results develop a comprehensive African HBV-HCC miRNome that potentially can contribute to RNA-based diagnostic and therapeutic options.

Low Bone Mineral Density and the Risk of Benign Paroxysmal Positional Vertigo.

OBJECTIVE: This study aimed to comprehensively analyze the relationship between low bone mineral density (BMD) and the risk of benign paroxysmal positional vertigo (BPPV) based on the large prospective population-based UK Biobank (UKB) cohort. STUDY DESIGN: Prospective population-based cohort study. SETTING: The UKB. METHODS: This prospective cohort study included UKB participants recruited between 2006 and 2010 who had information on BMD and did not have BPPV before being diagnosed with low BMD. Univariable and multivariable logistic regression models were constructed to assess the association between low BMD (overall low BMD, osteopenia, and osteoporosis) and BPPV. We further conducted sex and age subgroup analysis, respectively. Finally, the effects of antiosteoporosis and female sex hormone medications on BPPV in participants with osteoporosis were evaluated. RESULTS: In total, 484,303 participants were included in the final analysis, and 985 developed BPPV after a maximum follow-up period of 15 years. Osteoporosis was associated with a higher risk of BPPV (odds ratio [OR] = 1.37, P = .0094), whereas osteopenia was not. Subgroup analyses suggested that the association between osteoporosis and BPPV was significant only in elderly females (≥60 years, OR = 1.51, P = .0007). However, no association was observed between antiosteoporosis or female sex hormone medications and BPPV in the participants with osteoporosis. CONCLUSION: Osteoporosis was associated with a higher risk of developing general BPPV, especially in females aged ≥ 60 years old, whereas osteopenia was not associated with BPPV.