Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital.

BACKGROUND: Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM: To improve overall understanding of this disease's diagnosis and prognosis. METHODS: We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS: Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin's lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION: Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

Endoscopic transgastric fenestration versus percutaneous drainage for management of (peri)pancreatic fluid collections adjacent to gastric wall (with video).

BACKGROUND: Percutaneous drainage (PCD) and endoscopic approaches have largely replaced surgical drainage as the initial approach for (peri) pancreatic fluid collections (PFC)s, while complications associated with endoscopic stent implantation are common. AIM: To introduce a novel endoscopic therapy named endoscopic transgastric fenestration (ETGF), which involves resection of tissue by endoscopic accessory between gastric and PFCs without stent implantation, and to evaluate its efficacy and safety compared with PCD for the management of PFCs adjacent to the gastric wall. METHODS: Patients diagnosed with PFCs adjacent to the gastric wall and who subsequently received ETGF or PCD were restrospectively enrolled. Indications for intervention were consistent with related guidelines. We analyzed patients baseline characteristics, technical and clinical success rate, recurrence and reintervention rate, procedure-related complications and adverse events. RESULTS: Seventy-two eligible patients were retrospectively identified (ETGF = 34, PCD = 38) from October 2017 to May 2021. Patients in the ETGF group had a significantly higher clinical success rate than those in the PCD group (97.1 vs 76.3%, P = 0.01). There were no statistically significant differences regarding recurrence, reintervention and incidence of complication between the two groups. While long-term catheter drainage was very common in the PCD group. CONCLUSION: Compared with PCD, ETGF has a higher clinical success rate in the management of PFCs adjacent to the gastric wall. ETGF is an alternative effective strategy for the treatment of PFCs adjacent to the gastric wall.

A bibliometric and visual analysis of cancer-associated fibroblasts.

Background: Cancer-associated fibroblasts (CAFs) represent the predominant stromal component within the tumour microenvironment (TME), exhibiting considerable heterogeneity and plasticity that significantly impact immune response and metabolic reprogramming within the TME, thereby influencing tumour progression. Consequently, investigating CAFs is of utmost importance. The objective of this study is to employ bibliometric analysis in order to evaluate the current state of research on CAFs and predict future areas of research and emerging trends. Methods: Conduct a comprehensive search for scholarly publications within the Web of Science Core Collection database, encompassing the time period from January 1, 2001, to December 31, 2022. Apply VOSviewer, CiteSpace, R software and Microsoft Excel for bibliometric analysis and visualisation. Results: This study involved a comprehensive analysis of 5,925 publications authored by 33,628 individuals affiliated with 4,978 institutions across 79 countries/regions. These publications were published in 908 journals, covering 14,495 keywords and 203,947 references. Notably, there was a significant increase in articles published between 2019 and 2022. China had the highest count of articles, while the United States emerged as the most frequently cited country. The primary research institutions in this field were Shanghai Jiao Tong University, Harvard University, and the University of Texas MD Anderson Cancer Center. Sotgia, Federica and Lisanti, Michael P from the University of Manchester, and Martinet, Wim from the University of Antwerp were the most prolific and highly cited authors. The journal Cancers had the highest number of publications, while Cancer Research was the most frequently cited journal. Molecular, biology, immunology, medicine and genetics were the main research disciplines in the field of CAFs. Key directions in CAFs research encompassed the study of transforming growth factor-ß, Fibroblast Activation Protein, breast cancer, as well as growth and metastasis. The findings from the analysis of keyword co-occurrence and literature co-citation have revealed several emerging hotspots and trends within the field of CAFs. These include STAT3, multidrug resistance, pancreatic ductal adenocarcinoma, pan-cancer analysis, preclinical evaluation, ionizing radiation, and gold nanoparticles. Conclusion: Targeting CAFs is anticipated to be a novel and effective strategy for cancer treatment. This study provides a comprehensive overview of the existing research on CAFs from 2001 to 2022, utilizing bibliometric analysis. The study identified the prominent areas of investigation and anticipated future research directions, with the aim of providing valuable insights and recommendations for future studies in the field of CAFs.

Epidural Anesthesia-Analgesia and Recurrence-free Survival after Lung Cancer Surgery: A Randomized Trial.

BACKGROUND: Regional anesthesia and analgesia reduce the stress response to surgery and decrease the need for volatile anesthesia and opioids, thereby preserving cancer-specific immune defenses. This study therefore tested the primary hypothesis that combining epidural anesthesia-analgesia with general anesthesia improves recurrence-free survival after lung cancer surgery. METHODS: Adults scheduled for video-assisted thoracoscopic lung cancer resections were randomized 1:1 to general anesthesia and intravenous opioid analgesia or combined epidural-general anesthesia and epidural analgesia. The primary outcome was recurrence-free survival (time from surgery to the earliest date of recurrence/metastasis or all-cause death). Secondary outcomes included overall survival (time from surgery to all-cause death) and cancer-specific survival (time from surgery to cancer-specific death). Long-term outcome assessors were blinded to treatment. RESULTS: Between May 2015 and November 2017, 400 patients were enrolled and randomized to general anesthesia alone (n = 200) or combined epidural-general anesthesia (n = 200). All were included in the analysis. The median follow-up duration was 32 months (interquartile range, 24 to 48). Recurrence-free survival was similar in each group, with 54 events (27%) with general anesthesia alone versus 48 events (24%) with combined epidural-general anesthesia (adjusted hazard ratio, 0.90; 95% CI, 0.60 to 1.35; P = 0.608). Overall survival was also similar with 25 events (13%) versus 31 (16%; adjusted hazard ratio, 1.12; 95% CI, 0.64 to 1.96; P = 0.697). There was also no significant difference in cancer-specific survival with 24 events (12%) versus 29 (15%; adjusted hazard ratio, 1.08; 95% CI, 0.61 to 1.91; P = 0.802). Patients assigned to combined epidural-general had more intraoperative hypotension: 94 patients (47%) versus 121 (61%; relative risk, 1.29; 95% CI, 1.07 to 1.55; P = 0.007). CONCLUSIONS: Epidural anesthesia-analgesia for major lung cancer surgery did not improve recurrence-free, overall, or cancer-specific survival compared with general anesthesia alone, although the CI included both substantial benefit and harm.

Clinical Characteristics and Outcome Analysis of 94 Children With Brain Abscess in Beijing: A Single-center Retrospective Study.

BACKGROUND: There are limit studies about pediatric brain abscess in China. The aim of this study was to analyze clinical characteristics and outcomes of pediatric brain abscess in recent years in China. METHODS: The clinical information of children with brain abscess hospitalized in Beijing Children's Hospital between January 1, 2007 and December 31, 2016 were retrospectively reviewed. RESULTS: Ninety-four children were enrolled in this study. A Streptococcus milleri group (13.8%) was identified as the most common causative organisms, followed by Staphylococcus aureus (6.4%). The overall mortality was 21.6%, with 50.0% of deaths happening in the first week after diagnosis. Long-term outcomes of 74 patients were assessed with Glasgow Outcome Scale-Extended Pediatric Reversion: 50 patients with a score of 1-2 (favorable outcome) and 24 patients with a score of 3-8 (unfavorable outcome). Patients with multiple abscesses (P = 0.029) and intraventricular rupture of brain abscess/hydrocephalus (P = 0.024) had higher risk of unfavorable outcomes. CONCLUSIONS: Brain abscess is a serious disease with high mortality in children; more aggressive treatments should be considered in the first week of diagnosis because of high risk of death, and for patients with multiple brain abscesses and intraventricular rupture of brain abscess/hydrocephalus because of their higher risk of unfavorable.

Thoracic Paravertebral Blockade Reduces Chronic Postsurgical Pain in Breast Cancer Patients: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of multilevel single-shot thoracic paravertebral blockade (PVB) on the occurrence of chronic postsurgical pain (CPSP) in patients undergoing breast cancer surgery. DESIGN: A randomized controlled trial with two parallel groups. SETTING: A tertiary hospital. METHODS: Patients scheduled for breast cancer surgery were randomized to receive either ultrasound-guided multilevel single-shot PVB from T2 to T5 (the PVB group) or nothing (the control group). Surgery was then performed under general anesthesia. Patients were followed up for 12 months after surgery. The primary end point was incidence of CPSP at six months after surgery. RESULTS: A total of 218 patients were enrolled and randomized; of these, 208 and 204 completed six- and 12-month follow-up, respectively. The incidence of CPSP at six months was significantly lower in the PVB group (12.5% [13/104]) than in the control group (24.0% [25/104], relative risk = 0.52, 95% CI = 0.28-0.96, P = 0.031). Pain scores within 48 hours both at rest and with movement were lower in the PVB group than the control group (P = 0.006 and P < 0.001, respectively). The percentages of patients with neuropathic pain were also lower in the PVB group than the control group at both six and 12 months after surgery (P = 0.016 and 0.028, respectively). Adverse events did not differ between groups. CONCLUSIONS: For patients undergoing breast cancer surgery, multilevel single-shot PVB reduces the incidence of CPSP at six months; it also improves early postoperative analgesia and reduces neuropathic pain at six and 12 months after surgery.

Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.

Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.

[Anti-radiation effect and mechanism studies of ethanol extracts from Spatholobus suberectus and its active component catechin].

To study the anti-radiation effect and mechanism of ethanol extracts from Spatholobus suberectus and its active component catechin, ICR mice were exposed to 6Gy irradiation and randomly divided into normal group, model group, positive control group (amifostine, 43.6 mg•kg⁻¹, iv 30 min before irradiation), SSD group (10, 20, 40 g•kg⁻¹) and catechin group (50, 100, 200 mg•kg⁻¹). The mice were administered the appropriate drugs once a day after irradiation for 28 consecutive days. Blood samples were collected from the tail end and the number of peripheral blood cells was counted before irradiation and on day 1, 3, 7, 14, 21 and 28 using a microcell counter. Changes of thymus and spleen index of mice on day 7 were observed. The serum SOD, GSH-Px activity and MDA level were detected by the colorimetric method. The colony forming ability of bone marrow hematopoietic progenitor cells on day 7 was detected by semi solid culture method. The HE staining was adopted to observe the pathological changes. The apoptosis of bone marrow cells was detected by flow cytometry. The expression of cleaved caspase-3 and Bax of bone marrow cells were measured separately by western-blotting and immunohistochemistry method. SSD and catechin can both significantly revert the irradiated-induced decline in hematological parameters (RBC, WBC, PLT, Hb), improve thymus and spleen index, significantly enhance serum SOD and GSH-Px activity and decrease the MDA level. The proliferation and differentiation of hematopoietic progenitor cells in bone marrow were promoted, the apoptosis of bone marrow cells was significantly up-regulated and the expression of cleaved caspase-3 and Bax was significantly reduced in SSD and catechin group. SSD and catechin have significant anti-radiation effect and its mechanism may be related to hematopoietic promoting, antioxidant and anti-apoptotic effects.

[Effect of six class of Kaixin San formulas on pharmacological and preliminary mechanism of Alzheimer's disease mice].

The efficacy of Chinese herbal formulas in treating Alzheimer has been proved in many studies. In this study, six different Kaixin San formulas were compared to investigate their effects on learning and memory decline, brain-derived neurotrophic factor (BDNF) in the hippocampus, tau protein, acetylcholinesterase (AChE) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Kunming mice were selected and established a mouse model of Alzheimer's by intraperitoneal injection of D-galactose and sodium nitrite, continued intragastric 4 weeks, using the ability of learning and memory in Morris water maze test to evaluate the animals in each group; the content of BDNF in the hippocampus of mice with Western blotting detected; ELISA method for the detection of each group of mice hippocampal tau protein,p-Tau protein, Aß,Ach,AchE and serum NT-proBNP levels. The results showed that, Kaixin San of Qianjin Yaofang three dose recorded significantly improved learning and memory ability of mice; increased the content of BDNF and Ach in the hippocampus; decreased the content of Aß, Tau protein, p-Tau protein in the hippocampus; high, middle dose significantly decreased the serum NT-proBNP and AchE in hippocampus, the effect is most significant. Part dose of Kaixin San of Yixin Fang, Kaixin Wan of Yimen Fang, Dingzhi Xiaowan of Beji Qianjin Yaofang and Dingzhi Wan of Guji Luyan could improve the learning and memory ability evaluation indicators, significantly increased BDNF and Ach in the hippocampus of AD model mice, reduced the Aß, Tau protein, p-Tau protein in hippocampus of AD model mice, decreased the NT-proBNP and AchE in serum of AD mice, the effect is more significant. Three does of Buxin Tang of Qianjin Yi had no effects of treatment in Alzheimer's disease. The results showed the treatment in AD of Kaixin San of Qianjin Yaofang is the most significant.

5-Hydroxymethylfurfural protects against ER stress-induced apoptosis in GalN/TNF-α-injured L02 hepatocytes through regulating the PERK-eIF2α signaling pathway.

5-Hydroxymethylfurfural (5-HMF), a water-soluble compound extracted from wine-processed Fructus corni, is a novel hepatic protectant for treating acute liver injury. The present study was designed to investigate the protective effect of 5-HMF in human L02 hepatocytes injured by D-galactosamine (GalN) and tumor necrosis factor-α (TNF-α) in vitro and to explore the underlying mechanisms of action. Our results showed that 5-HMF caused significant increase in the viability of L02 cells injured by GalN/TNF-α, in accordance with a dose-dependent decrease in apoptotic cell death confirmed by morphological and flow cytometric analyses. Based on immunofluorescence and Western blot assays, we found that GalN/TNF-α induced ER stress in the cells, as indicated by the disturbance of intracellular Ca(2+) concentration, the activation of protein kinase RNA (PKR)-like ER kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), and expression of ATF4 and CHOP proteins, which was reversed by 5-HMF pre-treatment in a dose-dependent manner. The anti-apoptotic effect of 5-HMF was further evidenced by balancing the expression of Bcl-2 family members. In addition, the knockdown of PERK suppressed the expression of phospho-PERK, phospho-eIF2α, ATF4, and CHOP, resulting in a significant decrease in cell apoptosis after the treatment with GalN/TNF-α. 5-HMF could enhance the effects of PERK knockdown, protecting the cells against the GalN/TNF-α insult. In conclusion, these findings demonstrate that 5-HMF can effectively protect GalN/TNF-α-injured L02 hepatocytes against ER stress-induced apoptosis through the regulation of the PERK-eIF2α signaling pathway, suggesting that it is a possible candidate for liver disease therapy.